Duloxetine Treatment in Elderly With Dysthymia

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01852383
• Other study ID #: 6143R
• Status: Completed
• Phase: Phase 4
• First received: May 8, 2013
• Last updated: April 1, 2014
• Start date: January 2006
• Est. completion date: March 2013

Study information

• Verified date: February 2014
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2013
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 95 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Dysthymic Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Jun 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12.	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	No
Other	Maximum Duloxetine Oral Dose	Maximum duloxetine oral dose	Week 0, 1, 2, 4, 6, 8, 10, 12	No
Primary	Change in Hamilton Rating Scale for Depression (HAM-D, 24-item) From 0 Weeks to 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	No
Secondary	Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 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	No