Duloxetine Treatment in Elderly With Dysthymia

April 1, 2014 updated by: New York State Psychiatric Institute

An Open Treatment Trial of Duloxetine in Elderly Patients With Dysthymic Disorder

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.

Other Names:
  • Cymbalta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hamilton Rating Scale for Depression (HAM-D, 24-item) From 0 Weeks to 12 Weeks.
Time Frame: Screen (0) and 12 weeks
The research rater completed the 24-item Hamilton Rating Scale for Depression (HAM-D) and documented the scores on each visit. Hamilton Rating Scale for Depression scores range from 0-50 with low scores or decreasing scores representing decreased severity and better outcome, and higher scores or increasing scores representing more severe depressive symptoms and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.
Screen (0) and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 12
Time Frame: Week 0 and 12
Cornell Dysthymia Rating Scale scores from range 0-64. Lower or decreasing scores represent decreased severity and a better outcome, while higher or increasing scores represent more severe depression and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.
Week 0 and 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12.
Time Frame: 0 and 12 weeks
The Treatment Emergent Symptom Scale (TESS) documents the presence of common side effects. There are 26 items and the total score range is 0-26. Low scores or decrease in scores represent less side effects and high scores or increase in scores represent more side effects. The change in side effect severity scores was calculated by subtracting the Week 12 score from the Week 0 score.
0 and 12 weeks
Maximum Duloxetine Oral Dose
Time Frame: Week 0, 1, 2, 4, 6, 8, 10, 12
Maximum duloxetine oral dose
Week 0, 1, 2, 4, 6, 8, 10, 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

May 8, 2013

First Submitted That Met QC Criteria

May 10, 2013

First Posted (Estimate)

May 13, 2013

Study Record Updates

Last Update Posted (Estimate)

May 1, 2014

Last Update Submitted That Met QC Criteria

April 1, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6143R

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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