Trial Outcomes & Findings for Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism (NCT NCT02901041)

Results Overview

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

81 participants

Primary outcome timeframe

Pre-treatment

Results posted on

2023-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Zonisamide & Computerized Psychotherapy Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Overall Study STARTED	40	41
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	11	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Zonisamide & Computerized Psychotherapy Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Overall Study Withdrawal by PI	4	8
Overall Study Withdrawal by Subject	7	3

Baseline Characteristics

Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide & Computerized Psychotherapy n=40 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.	Total n=81 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=93 Participants	41 Participants n=4 Participants	81 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	43.28 years STANDARD_DEVIATION 12.61 • n=93 Participants	40.39 years STANDARD_DEVIATION 10.64 • n=4 Participants	41.81 years STANDARD_DEVIATION 11.67 • n=27 Participants
Sex: Female, Male Female	17 Participants n=93 Participants	9 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	32 Participants n=4 Participants	55 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=93 Participants	35 Participants n=4 Participants	71 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	6 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	35 Participants n=93 Participants	37 Participants n=4 Participants	72 Participants n=27 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Region of Enrollment United States	40 participants n=93 Participants	41 participants n=4 Participants	81 participants n=27 Participants
Alcohol Use Disorder Clinical Severity Rating	5.35 units on a scale STANDARD_DEVIATION 0.92 • n=93 Participants	5.02 units on a scale STANDARD_DEVIATION 0.91 • n=4 Participants	5.19 units on a scale STANDARD_DEVIATION 0.92 • n=27 Participants

PRIMARY outcome

Timeframe: Pre-treatment

Population: All participants were assessed on this measure at baseline.

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=40 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Average Standard Drinking Units Per Day	4.50 standard drinking units per day Standard Deviation 3.89	4.48 standard drinking units per day Standard Deviation 2.44

PRIMARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=29 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=29 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Average Standard Drinking Units Per Day	2.23 standard drinking units per day Standard Deviation 2.15	3.06 standard drinking units per day Standard Deviation 1.99

PRIMARY outcome

Timeframe: Pre-treatment

Population: All participants were analyzed for this measure.

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=40 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Percentage of Drinking Days	72.77 Percentage of drinking days Standard Deviation 26.13	79.62 Percentage of drinking days Standard Deviation 19.78

PRIMARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=29 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=29 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Percentage of Drinking Days	51.27 percentage of drinking days Standard Deviation 32.35	68.14 percentage of drinking days Standard Deviation 32.24

PRIMARY outcome

Timeframe: Pre-treatment

Population: All participants were analyzed for this measure.

TLFB was be used to estimate participants' daily drinking. In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB was used to gather information on participants' daily drinking. In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead. Heavy drinking days refers to the percentage of heavy drinking days within that window (4 or more drinks for women, 5 or more for men).

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=40 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Percent Heavy Drinking Days	46.43 percentage of heavy drinking days Standard Deviation 30.86	43.82 percentage of heavy drinking days Standard Deviation 32.49

PRIMARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

TLFB was be used to estimate participants' daily drinking. (See outcome measure 1 for more details description.) In this assessment, participants are presented with a calendar and asked to provide retrospective estimates of their daily alcohol consumption over a specified time period. TLFB data from 28 days before post-treatment were used to calculate post-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead. Heavy drinking days refers to the percentage of heavy drinking days within that window (4 or more drinks for women, 5 or more for men).

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=29 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=29 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Percent Heavy Drinking Days	19.83 Percent heavy drinking days Standard Deviation 23.22	31.12 Percent heavy drinking days Standard Deviation 30.38

PRIMARY outcome

Timeframe: Pre-treatment

Population: All participants were analyzed for this measure.

Timeline follow back is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. These standards, which can be found the NIAAA website, were used to calculate participant's average drinking units.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=40 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Average Weekly Standard Drinking Units (SDUs)	31.51 standard drinking units per week Standard Deviation 27.23	31.37 standard drinking units per week Standard Deviation 17.11

PRIMARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

Timeline followback (TLFB) was used to collect information on participant's daily drinking. TLFB is a form of interview used to collect retroactive data related to participant's drinking. Participants are presented with a calendar are asked to report what they drank each day for a specified timeframe (e.g. in the past week). Participants were encouraged to give their best estimate in the absence of total certainty regarding their drinking on a given day. Study assessors then used these responses to identify how many standard drinking units participants drank each day. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) defines "one standard drinking unit" as containing 14 grams of pure alcohol, and provide guidelines for calculating standard drinking units based on the alcohol content and size of a given drink. TLFB data from 28 days before BL were used to calculate pre-treatment outcomes. In instances where 28 days of data were not available, 21 days were used instead.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=29 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=29 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Average Weekly Standard Drinking Units (SDUs)	15.64 standard drinking units per week Standard Deviation 15.03	21.43 standard drinking units per week Standard Deviation 13.96

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

In this online task, participants are presented with a balloon. Clicking a button will pump the balloon, causing it to inflate and the participant to be awarded a certain amount of money. This happens until a threshold when a pump will cause the balloon to explode and all money would be lost. At any point in time, participants can choose between pumping the balloon further and risking it exploding, or not pumping the balloon and collecting the money they have already earned. 90 trials are conducted and the average number of pumps delivered are used to measure levels of risk-taking. Higher numbers of balloon pumps are associated with greater risk-taking.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=31 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Balloon Analogue Risk Task: Total Pump Count	709.23 pumps Standard Deviation 370.01	682.16 pumps Standard Deviation 307.33

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

In this online task, participants are presented with a balloon. Clicking a button will pump the balloon, causing it to inflate and the participant to be awarded a certain amount of money. This happens until a threshold when a pump will cause the balloon to explode and all money would be lost. At any point in time, participants can choose between pumping the balloon further and risking it exploding, or not pumping the balloon and collecting the money they have already earned. 90 trials are conducted and the average number of pumps delivered are used to measure levels of risk-taking. Higher numbers of balloon pumps are associated with greater risk-taking.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=22 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=26 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Balloon Analogue Risk Task: Total Pump Count	829.09 pumps Standard Deviation 409.84	730.04 pumps Standard Deviation 312.94

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

In this online task, participants are first presented with a go or a no-go cue, and are then presented with a go or no-go target. Participants are instructed to respond to a go target by clicking on a button, and not to respond to a no-go target. The cues have a high probability of signaling a correct target (valid cues), and a low probability of signaling an incorrect target (invalid cues). Incorrect responses to the no-go target are used to assess inhibitory control, which reflect impulse control. A test includes 250 trials and takes approximately 15 minutes to complete. Here, inhibition error is reported as the error rate (as a percentage) for trials where a go cue was followed by a no-go target. Larger error rates reflect less inhibitory control.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=28 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Cued Go/No-go Task: Inhibition Error	2.48 percentage of incorrect responses Standard Deviation 6.43	1.63 percentage of incorrect responses Standard Deviation 3.02

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out. One participant was excluded from the analyses due to highly elevated error rates (\>80%).

In this online task, participants are first presented with a go or a no-go cue, and are then presented with a go or no-go target. Participants are instructed to respond to a go target by clicking on a button, and not to respond to a no-go target. The cues have a high probability of signaling a correct target (valid cues), and a low probability of signaling an incorrect target (invalid cues). Incorrect responses to the no-go target are used to assess inhibitory control, which reflect impulse control. A test includes 250 trials and takes approximately 15 minutes to complete. Here, inhibition error is reported as the error rate (as a percentage) for trials where a go cue was followed by a no-go target. Larger error rates reflect less inhibitory control.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=19 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Cued Go No-Go: Inhibition Error	0.63 percentage of incorrect responses Standard Deviation 1.50	1.05 percentage of incorrect responses Standard Deviation 2.61

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study. Two participants were excluded from the analyses due to highly elevated error rates (\>80%)

The CPT includes two attention tasks, the second one being more difficult than the first. In the first task (reported on here), participants are presented a series of letters, one letter by one letter, and are asked to click on a button when the letter X appears. The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. An omission occurs when the X appears but the participant does not click the button within 0.69 seconds after it appears. The omission rate is calculated by dividing the number of omissions by the number of X presentations and converting that to a percentage. Higher omission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=28 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT) - X Test Omission Rate	23.51 percentage of omitted responses Standard Deviation 8.42	23.37 percentage of omitted responses Standard Deviation 8.20

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out. One participant was excluded from the analyses due to highly elevated error rates (\>80%).

The CPT includes two attention tasks, the second one being more difficult than the first. In the first task (reported on here), participants are presented a series of letters, one letter by one letter, and are asked to click on a button when the letter X appears. The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. An omission occurs when the X appears but the participant does not click the button within 0.69 seconds after it appears. The omission rate is calculated by dividing the number of omissions by the number of X presentations and converting that to a percentage. Higher omission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=18 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT): X Test Omission Rate	29.76 percentage of omitted responses Standard Deviation 16.58	26.42 percentage of omitted responses Standard Deviation 8.76

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

The CPT includes two attention tasks, the second one being more difficult than the first. In the first task (reported on here), participants are presented a series of letters, one letter by one letter, and are asked to click on a button when the letter X appears. The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. A commission occurs when a participant clicks a button when something other than the letter X has been presented. The commission rate is calculated by dividing the number of commissions by the total number of non-X presentations and converting that to a percentage. Higher commission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=30 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT): X Test Commission Rate	0.74 percentage of commission responses Standard Deviation 1.20	0.42 percentage of commission responses Standard Deviation 0.45

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

The CPT includes two attention tasks, the second one being more difficult than the first. In the first task (reported on here), participants are presented a series of letters, one letter by one letter, and are asked to click on a button when the letter X appears.The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. A commission occurs when a participant clicks a button when something other than the letter X has been presented. The commission rate is calculated by dividing the number of commissions by the total number of non-X presentations and converting that to a percentage. Higher commission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT): X Test Commission Rate	0.84 percentage of commission responses Standard Deviation 1.09	0.43 percentage of commission responses Standard Deviation 0.48

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study. One participant was excluded from the analyses due to highly elevated error rates (\>80%).

The CPT includes two attention tasks, the second one being more difficult than the first. In the second task (reported on here), participants are presented with a series of letters, and are instructed to click on the button only when the letter X appears directly after the letter A appears (an AX presentation). The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. An omission occurs when a participant does not click the button when the letter X appears directly after the letter A. The omission rate is calculated by dividing the number of omissions by the total number of AX presentations and converting that to a percentage. Higher omission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=29 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT): AX Test Omission Rate	6.40 percentage of omission responses Standard Deviation 9.92	3.33 percentage of omission responses Standard Deviation 4.76

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

The CPT includes two attention tasks, the second one being more difficult than the first. In the first task, participants are presented a series of 31 letters, one letter by one letter, and are asked to click on a button when the letter X appears. In the second task (reported on here), participants are presented with a series of 31 letters, and are instructed to click on the button only when the letter X appears directly after the letter A appears (an AX presentation). The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. An omission occurs when a participant does not click the button when the letter X appears directly after the letter A. The omission rate is calculated by dividing the number of omissions by the total number of AX presentations and converting that to a percentage. Higher omission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task (CPT): AX Test Omission Rate	8.76 percentage of omission responses Standard Deviation 13.99	5.58 percentage of omission responses Standard Deviation 9.88

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

The CPT includes two attention tasks, the second one being more difficult than the first. In the second task (reported on here), participants are presented with a series of letters, and are instructed to click on the button only when the letter X appears directly after the letter A appears (an AX presentation). The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. A commission occurs when a participant presses the button at any time other than following an AX presentation (i.e. during a non-AX presentation). The commission rate is calculated by dividing the number of commissions by the number of non-AX presentations and converting that to a percentage. Higher commission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=30 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=32 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continous Performance Task: AX Test Commission Rate	.80 percentage of commission responses Standard Deviation 1.03	0.40 percentage of commission responses Standard Deviation 0.43

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

The CPT includes two attention tasks, the second one being more difficult than the first. In the second task (reported on here), participants are presented with a series of letters, and are instructed to click on the button only when the letter X appears directly after the letter A appears (an AX presentation). The letters appear at approximately 0.92s intervals, and responses are scored correctly if the button is clicked within 0.69s after the letter appears. A commission occurs when a participant presses the button at any time other than following an AX presentation (i.e. during a non-AX presentation). The commission rate is calculated by dividing the number of commissions by the number of non-AX presentations and converting that to a percentage. Higher commission rates indicate worse performance on this attentional task.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Connor's Continuous Performance Task: AX Test Commission Rate	0.87 percentage of commission responses Standard Deviation 1.65	0.84 percentage of commission responses Standard Deviation 1.59

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. "Mean percent bet" refers to the overall mean percentage of their points participants bet across trials.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=28 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=31 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Mean Percent Bet	61.51 percentage of points bet Standard Deviation 14.18	59.48 percentage of points bet Standard Deviation 14.93

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: The number of participants analyzed at pre-treatment exceeds the number of participants analyzed at post-treatment due to participant dropout.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. "Mean percent bet" refers to the overall mean percentage of their points participants bet across trials.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Mean Percent Bet	56.01 percentage of points bet Standard Deviation 15.28	61.62 percentage of points bet Standard Deviation 13.07

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. Risk adjustment is a measure of the difference between their risk taking behavior during ascending versus descending trials, and represents whether the participant changes their bet based on the odds of winning. There are no min or max scores, and a higher score indicates the subject is more likely to change the wager depending on the probability of winning.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=28 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=31 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Risk Adjustment	0.67 score on a scale Standard Deviation 0.66	0.94 score on a scale Standard Deviation 0.57

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. Risk adjustment is a measure of the difference between their risk taking behavior during ascending versus descending trials, and represents whether the participant changes their bet based on the odds of winning. There are no min or max scores, and a higher score indicates the subject is more likely to change the wager depending on the probability of winning.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Risk Adjustment	0.55 score on a scale Standard Deviation 0.74	0.91 score on a scale Standard Deviation 0.61

SECONDARY outcome

Timeframe: Pre-treatment

Population: Not all participants completed the neurocognitive tests associated with the study.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. Delay aversion is the difference between the risk-taking score in the descend and ascend conditions. There is no min or max score. Participants who find delays aversive tend to select an amount to bet early in the sequence; i.e., a large bet in the descend condition, and a small bet in the ascend condition. Thus, they will have a higher risk aversion score.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=28 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=31 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Delay Aversion	0.32 score on a scale Standard Deviation 0.34	0.30 score on a scale Standard Deviation 0.29

SECONDARY outcome

Timeframe: Post-treatment (Week 12)

Population: Fewer participants were analyzed at post-treatment (compared to pre-treatment) due to participant drop-out.

Participants are given 10 boxes. Some of these boxes are red, the others are blue. They are told that a yellow token is hidden under one of these boxes and they have to guess the color of the box under which the yellow token is hidden. Once they decide on the color, they are asked to bet points on this choice: the computer provides the bets in either ascending (bets get bigger) or descending order (bets get smaller) and participants are asked to click on a bet when they want to bet this number of points. If they win, the bet number is added to their total points. If they lose the bet number is taken away from their total points. Delay aversion is the difference between the risk-taking score in the descend and ascend conditions. There is no min or max score. Participants who find delays aversive tend to select an amount to bet early in the sequence; i.e., a large bet in the descend condition, and a small bet in the ascend condition. Thus, they will have a higher risk aversion score.

Outcome measures

Outcome measures
Measure	Zonisamide & Computerized Psychotherapy n=19 Participants Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=22 Participants Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Roger's Risk Task: Delay Aversion	0.16 score on a scale Standard Deviation 0.60	0.30 score on a scale Standard Deviation 0.42

Adverse Events

Zonisamide & Computerized Psychotherapy

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo & Computerized Psychotherapy

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zonisamide & Computerized Psychotherapy n=40 participants at risk Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 participants at risk Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
Blood and lymphatic system disorders Metabolic acidosis	2.5% 1/40 • Number of events 1 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Blood and lymphatic system disorders Agranulocytosis	2.5% 1/40 • Number of events 1 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Cardiac disorders Episodic heart fluttering	0.00% 0/40 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	2.4% 1/41 • Number of events 1 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.

Other adverse events

Additional Information

Dr. Todd Farchione

Boston University

Phone: (617) 353-9610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Zonisamide & Computerized Psychotherapy n=40 participants at risk Zonisamide capsules (with a target maintenance dose of 400 mg daily) and a seven module computerized psychotherapy for alcohol use disorders called Take Control (9 sessions) will be administered over the course of 12 weeks, followed by a two week medication taper. Zonisamide: ZONEGRAN® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. A dose of 400 mg daily will be used as the target maintenance dose in this study but dosing will be modified if needed to adjust for subject tolerance of drug dosing. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic	Placebo & Computerized Psychotherapy n=41 participants at risk Placebo capsules (for zonisamide) and a seven module computerized psychotherapy for alcohol use disorders called Take Control will be administered over the course of 14 weeks. Take Control: Take Control is a seven module computer-based intervention which presents evidence-based alcohol education that includes motivational interviewing and cognitive-behavioral skills building. This program is derived from the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) self-help approach, Rethinking Drinking. Starting on March 23, 2020, participants will participate in a simplified Take Control treatment at home due to the COVID-19 pandemic Placebo (for Zonisamide): Sugar pills manufactured to mimic Zonisamide capsules.
General disorders Nausea	7.5% 3/40 • Number of events 5 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Gastrointestinal disorders Decreased appetite	7.5% 3/40 • Number of events 6 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	2.4% 1/41 • Number of events 1 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Weight loss	10.0% 4/40 • Number of events 9 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	7.3% 3/41 • Number of events 4 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Headache	27.5% 11/40 • Number of events 22 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	12.2% 5/41 • Number of events 5 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Dizziness/Fainting	7.5% 3/40 • Number of events 3 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	14.6% 6/41 • Number of events 7 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Psychiatric disorders Nervousness/anxiety	5.0% 2/40 • Number of events 21 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	9.8% 4/41 • Number of events 10 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Psychiatric disorders Memory problems	5.0% 2/40 • Number of events 2 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	2.4% 1/41 • Number of events 2 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Psychiatric disorders Insomnia	12.5% 5/40 • Number of events 13 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	14.6% 6/41 • Number of events 11 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Drowsiness	0.00% 0/40 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	9.8% 4/41 • Number of events 4 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Tiredness/Fatigue	7.5% 3/40 • Number of events 11 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	12.2% 5/41 • Number of events 17 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Cough	2.5% 1/40 • Number of events 1 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	7.3% 3/41 • Number of events 3 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Diarrhea	7.5% 3/40 • Number of events 3 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	2.4% 1/41 • Number of events 2 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Dry mouth	5.0% 2/40 • Number of events 2 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Taste change	12.5% 5/40 • Number of events 6 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Fever	5.0% 2/40 • Number of events 2 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	0.00% 0/41 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
General disorders Congestion	7.5% 3/40 • Number of events 5 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	9.8% 4/41 • Number of events 5 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Psychiatric disorders Depression	5.0% 2/40 • Number of events 20 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	2.4% 1/41 • Number of events 12 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.
Psychiatric disorders Concentration difficulties	5.0% 2/40 • Number of events 6 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.	4.9% 2/41 • Number of events 3 • 14 weeks Serious adverse events were those that required immediate reporting to Boston University's Institutional Review Board according to their definitions of SAEs. All other adverse events were collected using the Modified SAFTEE form, administered by study physicians on a weekly basis. Percentages reflect the percent of participants who endorsed a given adverse event at any time during the trial.