Duloxetine Treatment in Elderly With Dysthymia
Condition: Depression; Dysthymic Disorder
MeSH terms: Depression; Dysthymic Disorder
Intervention: Duloxetine
Intervention description: 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.
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 60 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Duloxetine; Antidepressant; Depression; Dysthymic Disorder; Side Effects; Elderly

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.
    

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