BackgroundDepression is a common, debilitating and costly disorder. The best-evidenced psychological therapy – cognitive–behavioural therapy (CBT) – is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative.ObjectivesTo determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months’ follow-up, and to investigate the processes of treatments.DesignRandomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation.SettingThree community mental health services in England.ParticipantsAdults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services.InterventionsBA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists.OutcomesPrimary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months.ResultsWe recruited 440 participants (BA,n = 221; CBT,n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) –1.3 to 1.5 PHQ-9 points,p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI –1.5 to 1.6 PHQ-9 points,p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235;p < 0.001), but no differences in non-intervention (hospital, community health, social care and medication costs) or total (non-intervention plus intervention) costs. Costs were lower and QALY outcomes better in the BA group, generating an incremental cost-effectiveness ratio of –£6865. The probability of BA being cost-effective compared with CBT was almost 80% at the National Institute for Health and Care Excellence’s preferred willingness-to-pay threshold of £20,000–30,000 per QALY. There were no trial-related adverse events.LimitationsIn this pragmatic trial many depressed participants in both groups were also taking antidepressant medication, although most had been doing so for a considerable time before entering the trial. Around one-third of participants chose not to complete a PP dose of treatment, a finding common in both psychotherapy trials and routine practice.ConclusionsWe found that BA is as effective as CBT, more cost-effective and can be delivered by MHWs with no professional training in psychological therapies.Future workSettings and countries with a paucity of professionally qualified psychological therapists, might choose to investigate the delivery of effective psychological therapy for depression without the need to develop an extensive and costly professional infrastructure.Trial registrationCurrent Controlled Trials ISRCTN27473954.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 46. See the NIHR Journals Library website for further project information.