Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      STAR*D focuses on non-psychotic major depressive disorder in adults who are seen in
      outpatient settings. The primary purpose of this research study is to determine which
      treatments work best if the first treatment with medication does not produce an acceptable
      response. Participants will first receive citalopram, an SSRI medication; if symptoms remain
      after 8-12 weeks of treatment, up to four other levels of treatment will be offered,
      including cognitive therapy and other medications. There are no placebo treatments. Some
      patients may require a combination of two or more treatments to obtain full benefit.
      Participation could last from 15 to 27 months and involve up to 30 clinic visits.
      Participants will be interviewed by telephone throughout the study about their symptoms,
      daily functioning, treatment side effects, use of the health care system, and satisfaction
      with treatment. There will be a one-year follow up for participants once their depression has
      been successfully treated
    

Detailed description: 
      The STAR*D project will enroll 4,000 outpatients (ages 18 -75) diagnosed with nonpsychotic
      Major Depressive Disorder. Participants will be initially treated (open label) with
      citalopram, the Level 1 treatment, for a minimum of 8 weeks. Patients who experience minimal
      benefit will be strongly encouraged to complete 12 weeks of treatment in order to maximize
      the chances of symptom remission (unless no benefit at all is seen after 8 weeks). All
      participants will also receive a brief depression educational program.

      At each level change, participants will be asked to indicate the unacceptability of the
      potential treatment strategies (e.g, to augment or to switch medications). Participants will
      then be eligible for random assignment to one of the acceptable and medically safe treatment
      options.

      Level 2: Participants who either did not have an adequate response to or could not tolerate
      citalopram are eligible for Level 2. The Level 2 treatment strategies are:

      i) Medication and Psychotherapy Switch: switch to sertraline, venlafaxineXR, bupropionSR, or
      cognitive therapy (CT).

      ii) Medication and Psychotherapy Augmentation: add to citalopram either a) buspirone, b)
      bupropionSR, or c) CT.

      iii) Medication Only Switch or Medication Only Augmentation options are available for
      participants for whom CT is unacceptable.

      iv)Psychotherapy Only Switch or Psychotherapy Only Augmentation options are available for
      participants for whom additional medication is unacceptable at this point in the study
      (participants must be willing to continue citalopram)

      Level 2A: Participants without a satisfactory response to their Level 2 treatment are
      eligible for random assignment to additional treatment at Level 2A (if medically safe and
      acceptable). Level 2A is included so that all participants entering Level 3 have had an
      opportunity to respond to at least 2 medications. Level 2A consists of Medication Switch to
      one of two antidepressant medications (venlafaxineXR or bupropion SR).

      Level 3: Participants without satisfactory response to Level 2 and,if appropriate Level 2A,
      are eligible for random assignment to one of the following treatments (if acceptable and
      medically safe):

      i) Medication Switch to: a) mirtazapine or b) nortriptyline, a tricyclic antidepressant.

      ii) Medication Augmentation: Add (to current Level 2 or Level 2A medication) either: a)
      lithium or b) thyroid hormone (T3).

      Level 4: Participants without an adequate response to Level 3 are eligible for random
      assignment to Level 4 treatment (if acceptable and medically safe). Level 4 includes two
      Medication Switch options: to tranylcypromine [a monoamine oxidase inhibitor (MAOI)], or to
      mirtazapine plus venlafaxineXR.

      After Level 4, participants without an adequate response will discuss other acceptable
      treatment options with their physician.

      Once an adequate response is achieved at Levels 2, 2A, 3 or 4, participants are eligible to
      enter the 12-month follow-up, during which time they will remain on their current
      treatment(s) and will be asked about their symptoms and other relevant information monthly by
      telephone. ONLY PATIENTS BEING TREATED AT THE PARTICIPATING CLINICS ARE ELIGIBLE FOR THIS
      STUDY.
    

Intervention name(s): citalopram; BuproprionSR; buspirone; Lithium; mirtazapine; nortriptyline; sertraline; tranylcypromine; VenlafaxineXR; Cognitive Therapy; T3 (Triiodothyronine)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Behavioral; Drug
Intervention MeSH terms: Mirtazapine; Buspirone; Tranylcypromine; Sertraline; Citalopram; Nortriptyline
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sequential Treatment; Major Depression; Treatment Resistant Depression