Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
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
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.
- Outpatients aged 18 to 75 years old with nonpsychotic major depressive disorder (HAMD
 score 14 or greater)