Duloxetine Treatment in Elderly With Dysthymia
Condition: Depression; Dysthymic Disorder
MeSH terms: Depression; Dysthymic Disorder
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Duloxetine
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Cymbalta
Intervention MeSH terms: Duloxetine Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Duloxetine; Antidepressant; Depression; Dysthymic Disorder; Side Effects; Elderly