Antidepressant Treatment of Melancholia in Late Life
Condition: Depression; Melancholia
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to compare the safety and effectiveness of a select serotonin
      re-uptake inhibitor (SSRI, sertraline) and a tricyclic antidepressant (TCA, nortriptyline) in
      outpatients over the age of 60 who have major depression.

      SSRIs are effective in the treatment of major depression. However, there is also evidence
      that SSRIs may be significantly less effective than TCAs for patients with late-life major
      depression with melancholia. Since SSRIs seem to be easier to take than TCAs and are more
      widely prescribed, it is important to determine which of these types of antidepressants works
      best to treat these patients.

      Patients will be assigned randomly to receive either sertraline (a SSRI) or nortriptyline (a
      TCA) for 12 weeks. Patients will be monitored for symptoms, side effects, and quality of
      life. If a patient responds to treatment, he/she will participate in a 6-month continuation
      phase in which he/she will continue to receive the same medication.

      An individual may be eligible for this study if he/she:

      Has unipolar major depression (with some exceptions) and is over 60 years old.
    

Detailed description: 
      To compare the efficacy and safety of a select serotonin re-uptake inhibitor (SSRI,
      sertraline) and a tricyclic antidepressant (TCA, nortriptyline) in outpatients over the age
      of 60 who meet Diagnostic and Statistical Manuel-IV criteria for unipolar major depression,
      excluding patients who meet criteria for psychotic or atypical subtype. To test the
      hypothesis that medication condition interacts with diagnostic subtype (melancholic vs
      non-melancholic) in determining antidepressant response. To examine the roles of symptom
      severity and alternative diagnostic subtyping in contributing to this pattern.

      SSRIs are effective in the treatment of major depression. However, there is also evidence
      that SSRIs may be significantly less effective than TCAs for depressed patients with
      melancholia. This issue is of particular concern in late-life major depression. SSRIs have
      important safety advantages with respect to overdose and a benign cardiovascular profile.
      Furthermore, the SSRIs do not have significant anticholinergic effects, and appear to be
      better tolerated than the TCAs. Perhaps most important, the SSRIs currently are prescribed
      widely as the medication treatment of first choice for major depression in late life.
      Therefore, if it were determined that SSRIs are considerably less effective than TCAs in the
      treatment of melancholia in the elderly, there would be significant ramifications for
      clinical practice.

      Randomization to sertraline (a SSRI) or nortriptyline (a TCA) is stratified by the presence
      or absence of melancholia. Outcome measures for the 12-week acute phase include clinician and
      patient ratings of symptoms, side effects, and an evaluation of the health-related quality of
      life (HRQOL). At the end of the acute treatment phase, patients who meet criteria for
      clinical response participate in a 6-month continuation phase.
    

Intervention name(s): Sertraline; Nortriptyline
Intervention type(s): Drug; Drug
Intervention description(s): 12 week trial dose up to 200mgs; 12 week trial dose adjusted to therapeutic level
Other intervention name(s): nortiptyline
Intervention MeSH terms: Sertraline; Nortriptyline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Aged; Antidepressive Agents, Tricyclic; Depression; Female; Human; Male; Middle Age; Nortriptyline; Sertraline; Serotonin Uptake Inhibitors; Antidepressive Agents, Tricyclic -- *therapeutic use; Antidepressive Agents, Tricyclic -- adverse effects; Depression -- *drug therapy; Nortriptyline -- *therapeutic use; Nortriptyline -- adverse effects; Sertraline -- *therapeutic use; Sertraline -- adverse effects; Serotonin Uptake Inhibitors -- *therapeutic use; Serotonin Uptake Inhibitors -- adverse effects