Duloxetine Treatment in Elderly With Dysthymia

NCT01852383 | Completed Phase 4 Results DMC

• 1 other identifier: 6143R
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Dysthymic Disorder

Keywords

Duloxetine; Antidepressant; Depression; Dysthymic Disorder; Side Effects; Elderly

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 12

  Week 0 and 12

Other Outcomes (2)

• Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12.

  0 and 12 weeks

• Maximum Duloxetine Oral Dose

  Week 0, 1, 2, 4, 6, 8, 10, 12

Study Arms (1)

Duloxetine

EXPERIMENTAL

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

Interventions

Duloxetine 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.

Also known as: Cymbalta

Duloxetine

Eligibility Criteria

• Age: 60 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (4)

• 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.

  PMID: 8666563 BACKGROUND

• 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.

  PMID: 15533993 BACKGROUND

• 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.

  PMID: 15653941 BACKGROUND

• 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.

  PMID: 17590215 BACKGROUND

MeSH Terms

Conditions

Depression; Dysthymic Disorder

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. D.P. Devanand
• Organization: New York State Psychiatric Institute

dpd3@columbia.edu

(646) 774-8658

Study Officials

• Davangere Devanand, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Study Start: January 1, 2006
• Primary Completion: September 1, 2010
• Study Completion: March 1, 2013
• Last Updated: May 1, 2014
• Results First Posted: May 1, 2014

Record last verified: 2014-02

Locations

US (1)