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

Condition	Treatment or Intervention	Phase
Depression	Drug: citalopram  Drug: BuproprionSR  Drug: buspirone  Drug: Lithium  Drug: mirtazapine  Drug: nortriptyline  Drug: sertraline  Drug: tranylcypromine  Drug: VenlafaxineXR  Behavior: Cognitive Therapy  Drug: T3 (Triiodothyronine)	Phase IV

Further Study Details: 

Expected Total Enrollment:  4000

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.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

- Outpatients aged 18 to 75 years old with nonpsychotic major depressive disorder (HAMD score 14 or greater)

Alabama
      Tuscaloosa VA Mental Health Clinic - Veterans Only, Tuscaloosa,  Alabama,  35404,  United States
      Tuscaloosa VA Primary Care Center, Tuscaloosa,  Alabama,  35404,  United States
      Birmingham VA Medical Center, Birmingham,  Alabama,  35223,  United States
California
      Harbor UCLA Family Health Care Center, Harbor City,  California,  90710,  United States
      UCLA Internal Medicine Clinic, Los Angeles,  California,  90024,  United States
      Harbor UCLA Medical Center, Torrance,  California,  90509,  United States
      Psychiatric Centers at San Diego, Chula Vista,  California,  91910,  United States
      Veterans Affairs Medical Center/FIRM Primary Care Clinic, San Diego,  California,  92161,  United States
      UCSD Outpatient Psychiatric Services, San Diego,  California,  92103,  United States
      UCLA General Outpatient Psychiatry Clinic, Los Angeles,  California,  90024,  United States
Illinois
      Northwestern Outpatient Treatment Care Center, Chicago,  Illinois,  60611,  United States
      Evanston Outpatient Clinic, Evanston,  Illinois,  60201,  United States
      University of Illinois at Chicago Clinic, Chicago,  Illinois,  60612,  United States
Kansas
      COMCARE of Sedgwick County, Wichita,  Kansas,  67203,  United States
      Psychiatric Outpatient Clinic, Wichita,  Kansas,  67214-2878,  United States
Massachusetts
      MGH/Charlestown Clinic, Charlestown,  Massachusetts,  02129,  United States
      MGH/Salem Professional, Salem,  Massachusetts,  01970,  United States
      Swampscott Family Doctors, Boston,  Massachusetts,  01907,  United States
      Internal Medicine Associates, Boston,  Massachusetts,  02114,  United States
Michigan
      Briarwood Family Practice Clinic, Ann Arbor,  Michigan,  48109-0708,  United States
      General Psychiatric Ambulatory Clinic, Ann Arbor,  Michigan,  48105-0722,  United States
New York
      LIJ/Zucker Hillside Adult Ambulatory Care Center, Glen Oaks,  New York,  11004,  United States
      LIJ North Shore Medical Group, Lake Success,  New York,  11040,  United States
North Carolina
      UNC Chapel Hill Adult Diagnostic & Treatment Clinic, Chapel Hill,  North Carolina,  27599-7160,  United States
      UNC Chapel Hill General Medicine Clinic, Chapel Hill,  North Carolina,  27599-7110,  United States
      UNC Chapel Hill Family Practice Clinic, Chapel Hill,  North Carolina,  27955,  United States
Oklahoma
      Springer Family Medicine, Tulsa,  Oklahoma,  74135,  United States
      Warren Clinic, Tulsa,  Oklahoma,  74136,  United States
      Laureate Psychiatric Clinic & Hospital, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      AMPN Corkery, Heise & Dainesi, Upper St. Clair,  Pennsylvania,  15317,  United States
      Diversified Human Services Clinic, Pittsburgh,  Pennsylvania,  15062,  United States
      Bellefield Clinic of WPIC, Pittsburgh,  Pennsylvania,  15213,  United States
      Latterman Family Health Center, Pittsburgh,  Pennsylvania,  15132,  United States
Tennessee
      Psychiatric Consultants, P.C., Nashville,  Tennessee,  37203,  United States
      Vanderbilt University Medical Center-Mental Health Center, Nashville,  Tennessee,  37212,  United States
      Vine Hill Community Clinic, Nashville,  Tennessee,  37212,  United States
      Centerstone/Luton Mental Health Services, Nashville,  Tennessee,  37217,  United States
Texas
      UT Southwestern Family Medicine Clinic, Dallas,  Texas,  75390,  United States
      The Holiner Psychiatric Group, Dallas,  Texas,  75230,  United States
Virginia
      MCV Family Counseling, Richmond,  Virginia,  23298-0268,  United States
      MCV Primary Care Clinic, Richmond,  Virginia,  23220,  United States

Study chairs or principal investigators

A. John Rush, MD,  Study Director,  University of Texas Southwestern Medical Center Department of Psychiatry   

Study ID Numbers:  N01MH90003
Record last reviewed:  December 2004
Last Updated:  December 21, 2004
Record first received:  July 20, 2001
ClinicalTrials.gov Identifier:  NCT00021528
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08