Duloxetine Treatment in Elderly With Dysthymia

NCT ID: NCT01852383

Last Updated: 2014-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2013-03-31

Brief Summary

Dysthymic disorder (DD) denotes chronic depression with fewer symptoms than major depressive disorder (MDD), and it affects ~ 2-4 % of adults with a similar prevalence in the elderly. In the elderly, dysthymic disorder (DD) has been shown to be associated with suffering and disability. The differences between young adult and elderly DD patients indicate that findings obtained in young adults with DD cannot be extrapolated to elderly DD patients who need to be studied separately. Data from epidemiologic studies support this view. In contrast to the data in young adult DD patients, there is a paucity of controlled data on the treatment of elderly DD patients. In our center, a double-masked, placebo-controlled study of 91 elderly DD patients did not find significant superiority for fluoxetine over placebo with response rates of 27.3% for fluoxetine and 19.6% for placebo in intent-to-treat analyses, and response rates of 37.5% for fluoxetine and 23.1% for placebo in completer analyses. Given the relative failure of selective serotonin reuptake inhibitor (SSRIs) to treat geriatric DD effectively, the investigators decided to evaluate the dual reuptake inhibitor, venlafaxine.

The investigators earlier completed an investigator-initiated, open-label 12-week venlafaxine (Effexor XR) trial. Of 23 elderly DD patients, 18 completed the trial. Fourteen (60.9%) were responders in intent-to-treat analyses with the last observation carried forward, and 77.8% were responders in completer analyses. Nearly half the sample (47.8%) met criteria for remission. In the intent-to-treat sample, increased severity of depression at baseline was associated with superior response and the presence of cardiovascular disease was associated with poorer response. These results with venlafaxine indicate that further treatment studies of dual serotonin-norepinephrine reuptake inhibitors like duloxetine are warranted in elderly patients with dysthymic disorder.

Detailed Description

HYPOTHESES:

1. Duloxetine will reduce depressive symptomatology over a period of 12 weeks in elderly DD patients.

2. Duloxetine-treated dysthymic patients will have significant improvement in measures of overall functioning.

This pilot trial enrolled 30 patients ≥ 60 years old with dysthymic disorder. Patients were recruited by clinician referral and by radio or newspaper advertisements that offered free evaluation by experienced clinicians for participation in clinical trials in the Adult and Late Life Depression Clinic at the New York State Psychiatric Institute. After a telephone screen to rule out exclusions for enrollment in the clinic, a psychiatrist conducted a detailed evaluation and completed the Cumulative Illness Rating Scale (CIRS)-Geriatric [CIRS-G]. Patients with a provisional clinical diagnosis of dysthymic disorder were interviewed by a research rater (social worker or nurse) with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I disorders- Patient edition (SCID-P). Based on the psychiatrist's evaluation and the SCID-P interview, a consensus DSM-IV diagnosis was made at a staff conference.

Conditions

Depression; Dysthymic Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Duloxetine

A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily.

At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects.

Administration was as a single a.m. dose.

Group Type: EXPERIMENTAL

Duloxetine

Intervention Type: DRUG

Patients were evaluated weekly for the first 6 weeks and every two weeks for the next 6 weeks. At 0, 1, 4, 8, and 12 weeks, the study psychiatrist completed the Cornell Dysthymia Rating Scale , Clinical Global Impression (CGI) scale, and side effect ratings using the Treatment Emergent Symptom Scale. The research rater completed a SCID-P at baseline and the 24-item HAM-D at each visit, and the patient completed the Beck Depression Inventory-II at each visit.

Adverse events: All adverse events and serious adverse events were documented.

The maximum duration of delay before active treatment (medication or psychotherapy) was 1 week.

Dropout: Patients who had a CGI score of 6 or 7 for two weeks during the second half of the study were dropped by the investigator from the trial.

Interventions

Duloxetine

Patients were evaluated weekly for the first 6 weeks and every two weeks for the next 6 weeks. At 0, 1, 4, 8, and 12 weeks, the study psychiatrist completed the Cornell Dysthymia Rating Scale , Clinical Global Impression (CGI) scale, and side effect ratings using the Treatment Emergent Symptom Scale. The research rater completed a SCID-P at baseline and the 24-item HAM-D at each visit, and the patient completed the Beck Depression Inventory-II at each visit.

Adverse events: All adverse events and serious adverse events were documented.

The maximum duration of delay before active treatment (medication or psychotherapy) was 1 week.

Dropout: Patients who had a CGI score of 6 or 7 for two weeks during the second half of the study were dropped by the investigator from the trial.

Intervention Type: DRUG

Other Intervention Names

Cymbalta

Eligibility Criteria

Inclusion Criteria

• Diagnosis of dysthymic disorder (SCID and DSM-IV)
• Age 60 - 95
• Mini-Mental State Score ≥ 24
• 24-item Hamilton Rating Scale for Depression score 12-25
• Willing and capable of giving informed consent

Exclusion Criteria

• Current major depressive episode (SCID and DSM-IV)
• Alcohol or substance dependence during the last year (SCID and DSM-IV)
• Bipolar disorder, schizophrenia and other psychotic disorders(SCID and DSM-IV)
• Clinical stroke, dementia, Huntington's disease, epilepsy or other major neurological disease
• Acute unstable medical conditions
• Active suicidal ideation or plan
• Non-response to duloxetine (minimum 90 mg/day for 6 weeks) during the past year
• A positive urine drug screen for substances of abuse or dependence
• Sensitivity with intolerability to duloxetine
• Use of other medications that may interact with duloxetine, including inhibitors of cytochrome P450 1A2 (CYP1A2) and cytochrome P450 2D6 (CYP2D6), e.g., quinolone antibiotics and type 1-C anti-arrhythmics. Several antidepressant medications, including most SSRIs, are inhibitors of CYP2D6 but these medications are not permitted during this antidepressant treatment trial.
• Patients with hypertension (BP >140/90 mm Hg on 2 consecutive measurements). For patients with treated hypertension and BP >140/90, written approval must be obtained from patient's internist allowing them to participate in this study.
• Known liver damage or disease

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Davangere Devanand, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

References

Nobler MS, Devanand DP, Kim MK, Fitzsimons LM, Singer TM, Turret N, Sackeim HA, Roose SP. Fluoxetine treatment of dysthymia in the elderly. J Clin Psychiatry. 1996 Jun;57(6):254-6.

Reference Type: BACKGROUND

PMID: 8666563 (View on PubMed)

Devanand DP, Juszczak N, Nobler MS, Turret N, Fitzsimons L, Sackeim HA, Roose SP. An open treatment trial of venlafaxine for elderly patients with dysthymic disorder. J Geriatr Psychiatry Neurol. 2004 Dec;17(4):219-24. doi: 10.1177/0891988704269818.

Reference Type: BACKGROUND

PMID: 15533993 (View on PubMed)

Devanand DP, Nobler MS, Cheng J, Turret N, Pelton GH, Roose SP, Sackeim HA. Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder. Am J Geriatr Psychiatry. 2005 Jan;13(1):59-68. doi: 10.1176/appi.ajgp.13.1.59.

Reference Type: BACKGROUND

PMID: 15653941 (View on PubMed)

Wise TN, Wiltse CG, Iosifescu DV, Sheridan M, Xu JY, Raskin J. The safety and tolerability of duloxetine in depressed elderly patients with and without medical comorbidity. Int J Clin Pract. 2007 Aug;61(8):1283-93. doi: 10.1111/j.1742-1241.2007.01476.x. Epub 2007 Jun 22.

Reference Type: BACKGROUND

PMID: 17590215 (View on PubMed)

Other Identifiers

6143R

Identifier Type: -

Identifier Source: org_study_id