Clinical trial NCT01852383: Duloxetine Treatment in Elderly With Dysthymia
Official title: An Open Treatment Trial of Duloxetine in Elderly Patients With Dysthymic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Dysthymic Disorder
Keywords: Duloxetine
Antidepressant
Depression
Dysthymic Disorder
Side Effects
Elderly
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2013-05-13
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Hamilton Rating Scale for Depression (HAM-D, 24-item) From 0 Weeks to 12 Weeks.
timeFrame: Screen (0) and 12 weeks
Secondary outcomes:
measure: Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 12
timeFrame: Week 0 and 12
Other outcomes:
measure: Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12.
timeFrame: 0 and 12 weeks
measure: Maximum Duloxetine Oral Dose
timeFrame: Week 0, 1, 2, 4, 6, 8, 10, 12
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: Columbia University
name: Davangere Devanand, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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. doi: 10.1176/appi.ajgp.13.1.59.
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. doi: 10.1111/j.1742-1241.2007.01476.x. Epub 2007 Jun 22.