Peterson 2010.

Study characteristics
Methods	Design: double‐blind randomised placebo‐controlled trial Prerandomisation phase Phase 1: open‐label acute treatment with fluoxetine 20 mg/d (8 weeks) Phase 2: open‐label continuation treatment (fluoxetine increase to fixed dose of 40 mg/d) with and without CBT (12 weekly sessions, then 7 biweekly) (28 weeks) Duration post randomisation: 80 weeks Aim: to evaluate the effectiveness of CBT and fluoxetine and fluoxetine alone in preventing recurrence of depressive disorder during maintenance treatment for patients with remitted MDD
Participants	Country: USA Setting: outpatients from Depression Clinical and Research Program (DCRP) of Massachusetts General Hospital 1992‐1998 Type of antidepressant: fluoxetine Duration of antidepressant treatment prerandomisation: 36 weeks Duration of AD treatment post stabilisation: 28 weeks Number of participants: 391 entered phase 1, 132 entered phase 2 (66 entered fluoxetine study arm and 66 fluoxetine and CBT arm) Total number of randomised participants: 55 (antidepressant only 15, placebo only 17, CBT and placebo 12, CBT and antidepressant 11) Primary diagnosis ‐ recurrent depression (history of 3 or more episodes) ‐ chronic depression (onset of continuous depressive symptoms > 36 months before the study) ‐ history of poor inter‐episode recovery ‐ both MDD and dysthymia Number of previous episodes: fluoxetine 4.2 (± 5.6), placebo 4.2 (± 5.6), CBT placebo 8.6 (± 15.1), CBT and fluoxetine 2.3 (± 1.5) Severity of depressive symptoms: HAM‐D 17, mean (SD): fluoxetine 5.5 (2.1), placebo 4.3 (3.7), CBT and placebo 2.8 (2.5), CBT and fluoxetine 5.4 (4.5) Mean age, years (SD): fluoxetine 43.5 (8.8), placebo 43.2 (9.8), CBT and placebo 42.9 (9.3), CBT and fluoxetine 45.1 (8.1) Female: fluoxetine 47%, placebo 53%, CBT and placebo 70%, CBT and fluoxetine 67% Inclusion criteria ‐ participants were drug‐free outpatients who met criteria for MDD, as diagnosed with the Structured Clinical Interview for DSM‐III‐R ‐ initial HAM‐D 17 score of 16 ‐ 18 to 65 years of age ‐ required to meet at least 1 of the following criteria: history of ≥ 3 major depressive episodes, with the prior episode no more than 2.5 years before onset of the current episode; diagnosis of current episode as chronic (onset of continuous depressive symptoms > 36 months before the study); history of poor inter‐episode recovery; or both MDD and dysthymia Definition of remission: HAMD‐17 ≤ 7 for 3 consecutive weeks Exclusion criteria ‐ pregnant women and women of childbearing potential who were not using a medically accepted means of contraception ‐ women of childbearing potential taking a birth control pill, or women who were currently lactating ‐ patients with serious risk of suicide, seizure disorder history, major unstable medical illness, history of multiple adverse drug reactions, or allergy to the study drugs ‐ antisocial personality disorder, or a DSM‐III‐R comorbid diagnosis of Axis I pathology other than anxiety disorders ‐ patients currently using non‐study‐related psychotropic drugs or exhibiting evidence of hypothyroidism Patients were excluded if their depression failed to respond in the past to a trial of (1) a higher dose of fluoxetine (60 to 80 mg/d), (2) the combination of fluoxetine and desipramine, or (3) the combination of fluoxetine and lithium. Finally, patients were excluded if they failed to respond during the course of their current major depressive episode to at least 1 adequate antidepressant trial, defined as 6 weeks or more of treatment with 150 mg of imipramine (or its tricyclic equivalent) or 60 mg of phenelzine (or its monoamine oxidase inhibitor equivalent)
Interventions	Intervention 1: placebo Intervention 2: fluoxetine 40 mg/d Intervention 3: CBT and placebo Intervention 4: CBT and fluoxetine 40 mg/d Tapering scheme: not described Medication: psychopharmacologists followed a standard protocol for medication management visits and were instructed not to engage in cognitive or behavioural interventions CBT  Description: cognitive therapy was conducted by highly trained doctoral‐level psychologists according to a treatment manual adapted from Beck et al. (1979) and Mercier and Leahy (1992). Each session followed a conventional cognitive therapy format, which includes symptom check, agenda setting, homework review, cognitive and behavioural exercises for specific problem areas, and assignment of new homework. CBT was modified to address residual symptoms specifically and to enhance patient coping skills. The therapy used for this study was designed specifically to target symptoms and issues common to remitted depressed patients, who are at high risk for relapse and recurrence. Three content domains are emphasised when working with remitted depressed patients. The first is recovery, which involves working to resolve any residual symptoms that are present after clinical remission. Such residual symptoms are common and include irritability, neurovegetative disturbances, and hopelessness. The second content area is re‐entry, which entails working to improve a patient’s functioning in key life roles such as student, family member, spouse, and employee. An acute depressive episode typically results in lowered levels of functioning in 1 or more of these areas, thus the gap between current and optimal psychosocial functioning may be significant. One common target of this content area is avoidant behaviour, which is often activated by a patient to maintain tentative short‐term stability but in turn prevents return to premorbid levels of functioning. The third content area, risk, involves focusing on maladaptive cognitive and behavioural patterns that contribute to heightened relapse rates. Such patterns include lack of assertiveness and self‐care, as well as perfectionism and unrealistic self‐expectations Frequency: the structure of therapy for the maintenance phase of this protocol (an 80‐week period) consisted of 7 biweekly, 50‐minute sessions followed by 16 monthly, 50‐minute sessions Integrity of delivery and compliance: no independent ratings of treatment quality and fidelity
Outcomes	‐ depressive recurrence Definition of relapse: meeting criteria for MDD and ≥ 15 in the HAM‐D 17; confirmed 1 week later with another clinician blind to treatment status Depressive symptoms and improvement: HAM‐D 17, CGI‐S, CGI‐I, 92‐item Symptom Questionnaire (SQ), Beck Hopelessness Scale (BHS), Beck Depression Inventory (BDI), Patient Global Impression of Improvement (PGI‐I), Beck Anxiety Inventory (BAI), monthly
Notes	Funding: not reported COI: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: information insufficient to permit judgement Quote: “patients were randomised”
Allocation concealment (selection bias)	Unclear risk	Comment: information insufficient to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: information insufficient to permit judgement Quote: "double‐blind"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: information insufficient to permit judgement Quote: "another clinician blind to treatment status"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: low withdrawals post randomisation (1 CBT and placebo group, 1 medication only group, 1 placebo only group); reasons stated
Selective reporting (reporting bias)	High risk	Comment: neither withdrawal symptoms nor adverse events were reported.
Other bias	Unclear risk	Source of funding was not reported