Trial Outcomes & Findings for Does Dual Therapy Hasten Antidepressant Response? (NCT NCT00519428)

NCT ID: NCT00519428

Last Updated: 2017-10-04

Results Overview

Life Table Survival Analysis run twice, once comparing Dual Therapy (i.e., Bupropion + Escitalopram) to Bupropion alone (i.e., Bupropion + Placebo) and once comparing Dual Therapy to Escitalopram alone (i.e., Escitalopram + Placebo). Because both analyses must significantly favor Dual Therapy, each individual analysis must reach a critical alpha = .0916 in order to reach an over-all alpha = .05.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

245 participants

Primary outcome timeframe

12 weeks

Results posted on

2017-10-04

Participant Flow

Recruitment dates: August, 2007 to August 2011 Locations: 4 outpatient research clinics in two countries (US and Canada)

All patients had to be psychoactive drug-free for at least two weeks (five weeks for fluoxetine) prior to randomization and had to continue to meet study entry criteria at point of randomization

Participant milestones

Participant milestones
Measure	Escitalopram + Bupropion escitalopram plus bupropion	Escitalopram escitalopram monotherapy	Bupropion bupropion monotherapy
Overall Study STARTED	78	84	83
Overall Study COMPLETED	57	69	58
Overall Study NOT COMPLETED	21	15	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Escitalopram + Bupropion escitalopram plus bupropion	Escitalopram escitalopram monotherapy	Bupropion bupropion monotherapy
Overall Study Adverse Event	5	2	10
Overall Study Lost to Follow-up	7	7	6
Overall Study Withdrawal by Subject	8	3	7
Overall Study unstated	1	3	2

Baseline Characteristics

Does Dual Therapy Hasten Antidepressant Response?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=84 Participants escitalopram monotherapy	Bupropion n=83 Participants bupropion XL monotherapy	Total n=245 Participants Total of all reporting groups
Age, Continuous Age	40 years STANDARD_DEVIATION 10 • n=5 Participants	41 years STANDARD_DEVIATION 11 • n=7 Participants	40 years STANDARD_DEVIATION 11 • n=5 Participants	40 years STANDARD_DEVIATION 11 • n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	62 Participants n=7 Participants	49 Participants n=5 Participants	163 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	22 Participants n=7 Participants	34 Participants n=5 Participants	82 Participants n=4 Participants
Region of Enrollment United States	37 participants n=5 Participants	42 participants n=7 Participants	41 participants n=5 Participants	120 participants n=4 Participants
Region of Enrollment Canada	41 participants n=5 Participants	42 participants n=7 Participants	42 participants n=5 Participants	125 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: age 18-65 with Major Depressive Disorder (MDD), non-bipolar, non-psychotic, non-substance abusing, without intolerance to study drugs or adequate selective serotonin re-uptake inhibitor (SSRI) and/or bupropion treatment in current episode; physically healthy without contraindications to bupropion or escitalopram.

Outcome measures

Outcome measures
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=84 Participants escitalopram monotherapy	Bupropion n=83 Participants bupropion XL monotherapy
Time to Remission, Defined by the Week of Onset of Persistent Hamilton Rating Scale for Depression (HAM-D 17) <= 7, With no Subsequent HAM-D 17 > 7	8 weeks Standard Deviation 7	9 weeks Standard Deviation 7	10 weeks Standard Deviation 7

SECONDARY outcome

Timeframe: 12 weeks

Population: age 18-65 with MDD, non-bipolar, non-psychotic, non-substance abusing, without intolerance to study drugs or adequate SSRI/bupropion treatment in current episode; physically healthy without contraindications to bupropion or escitalopram.

Chi square comparison of rates of persistent remission (i.e., no subsequent Hamilton Rating Scale for Depression, 17 items \[HAMD-D 17\] \> 7 once HAMD-D 17 \<= 7); Dual rate vs. Escitalopram only rate and Dual rate vs. Bupropion only rate.

Outcome measures

Outcome measures
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=84 Participants escitalopram monotherapy	Bupropion n=83 Participants bupropion XL monotherapy
Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12	52 percentage of participants	46 percentage of participants	34 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks

Last summary score rating on the 17-item Hamilton Rating Scale for Depression Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Range 0-58. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥ 23 = Very Severe Depression

Outcome measures

Outcome measures
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=83 Participants escitalopram monotherapy	Bupropion n=84 Participants bupropion XL monotherapy
Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)	10 units on Hamilton Rating Scale for Depre Standard Deviation 8	9 units on Hamilton Rating Scale for Depre Standard Deviation 7	12 units on Hamilton Rating Scale for Depre Standard Deviation 8

SECONDARY outcome

Timeframe: 12 weeks

Population: All randomized patients; latest available Total SAS score used if week 12 score not available.

Social adjustment was measured using the Social Adjustment Scale (SAS). The SAS is a self-report scale that assesses depressive symptoms and functioning in nine social and work-related domains generating a total score that is indicative of a subject's overall level of social adjustment. Subjects rate their own social functioning over times on a 5-point scale on items covering work for pay, housework, extended family, parenting, marital status, social activity and leisure, family unit and student status (sub-scales). Mean values of all the sub-scales are used, with a range from 0-5. Higher score = worse outcome … worse functioning

Outcome measures

Outcome measures
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=83 Participants escitalopram monotherapy	Bupropion n=84 Participants bupropion XL monotherapy
Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score	2.65 units on the SAS scale Standard Deviation .69	2.63 units on the SAS scale Standard Deviation .69	2.74 units on the SAS scale Standard Deviation .71

SECONDARY outcome

Timeframe: 12 weeks

Population: All Randomized Subjects

The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) intends to measure quality of life in 16 domains. A summary score is computed by adding the scores and dividing by 16 (or the number of answered items if some are not answered). The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. Higher score means more satisfaction.

Outcome measures

Outcome measures
Measure	Escitalopram + Bupropion n=78 Participants escitalopram plus bupropion XL	Escitalopram n=83 Participants escitalopram monotherapy	Bupropion n=84 Participants bupropion XL monotherapy
Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)	3.0 units on the Q-LES-Q scale Standard Deviation .82	3.0 units on the Q-LES-Q scale Standard Deviation .76	3.1 units on the Q-LES-Q scale Standard Deviation .74

Adverse Events

Escitalopram + Bupropion

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Escitalopram

Serious events: 0 serious events

Other events: 80 other events

Deaths: 0 deaths

Bupropion

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jonathan W. Stewart, M.D.

NYSPInstitute

Phone: 212-543-5745

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Escitalopram + Bupropion n=78 participants at risk escitalopram plus bupropion XL escitalopram + bupropion: same dosing schedule as for monotherapy	Escitalopram n=84 participants at risk escitalopram monotherapy escitalopram: 10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted	Bupropion n=83 participants at risk bupropion XL monotherapy bupropion XL: 150mg/d increasing to 300 mg/d after 1 week and 450 mg/d after 3 weeks, all increases if tolerated and not remitted
General disorders Too much energy	6.4% 5/78 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	4.8% 4/84 • Number of events 4 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	8.4% 7/83 • Number of events 7 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Musculoskeletal and connective tissue disorders muscle tightness	16.7% 13/78 • Number of events 13 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	16.7% 14/84 • Number of events 14 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	21.7% 18/83 • Number of events 18 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
General disorders insomnia	30.8% 24/78 • Number of events 24 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	32.1% 27/84 • Number of events 27 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	37.3% 31/83 • Number of events 31 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders tremor	29.5% 23/78 • Number of events 23 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	16.7% 14/84 • Number of events 14 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	21.7% 18/83 • Number of events 18 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders trouble thinking	15.4% 12/78 • Number of events 12 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	15.5% 13/84 • Number of events 13 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	6.0% 5/83 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders trouble finding words	6.4% 5/78 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	7.1% 6/84 • Number of events 6 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	8.4% 7/83 • Number of events 7 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders spacey	16.7% 13/78 • Number of events 13 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	14.3% 12/84 • Number of events 12 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	6.0% 5/83 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Cardiac disorders dizzy	24.4% 19/78 • Number of events 19 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	23.8% 20/84 • Number of events 20 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	22.9% 19/83 • Number of events 19 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders headache	35.9% 28/78 • Number of events 28 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	33.3% 28/84 • Number of events 28 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	31.3% 26/83 • Number of events 26 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Gastrointestinal disorders dry mouth	34.6% 27/78 • Number of events 27 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	21.4% 18/84 • Number of events 18 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	33.7% 28/83 • Number of events 28 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Gastrointestinal disorders decreased appetite	21.8% 17/78 • Number of events 17 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	25.0% 21/84 • Number of events 21 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	25.3% 21/83 • Number of events 21 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Gastrointestinal disorders nausea, vomiting	32.1% 25/78 • Number of events 25 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	38.1% 32/84 • Number of events 32 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	33.7% 28/83 • Number of events 28 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
General disorders lethargy	12.8% 10/78 • Number of events 10 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	17.9% 15/84 • Number of events 15 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	12.0% 10/83 • Number of events 10 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Nervous system disorders daytime sleepiness	16.7% 13/78 • Number of events 13 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	20.2% 17/84 • Number of events 17 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	10.8% 9/83 • Number of events 9 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
General disorders sweating	24.4% 19/78 • Number of events 19 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	15.5% 13/84 • Number of events 13 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	6.0% 5/83 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
General disorders sexual dysfunction	25.6% 20/78 • Number of events 20 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	21.4% 18/84 • Number of events 28 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	10.8% 9/83 • Number of events 9 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
Psychiatric disorders anger, irritability	5.1% 4/78 • Number of events 4 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	6.0% 5/84 • Number of events 5 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.	16.9% 14/83 • Number of events 14 • 12 weeks A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.