Metacognitive Therapy versus Cognitive Behaviour Therapy in Adults with Major Depression: A Parallel Single-Blind Randomised Trial.

In the last forty years therapy outcomes for depression have remained the same with approximately 50% of patients responding to treatments. Advances are urgently required. We hypothesised that a recent treatment, metacognitive therapy (MCT), might be more effective, by targeting mental control processes that directly contribute to depression. We assessed the clinical efficacy of MCT compared to current best psychotherapy practice, CBT, in adults with major depressive disorder. A parallel randomized single-blind trial was conducted in a primary care outpatient setting. This trial is registered with the ISCRTN registry, number ISRCTN82799488. In total 174 adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder were eligible and consented to take part. 85 were randomly allocated to MCT and 89 to CBT. Randomisation was performed independently following pre-treatment assessment and was stratified for severity of depression (low < 20 vs high > =20) on the Hamilton Depression Rating Scale (HDRS) and on sex (male/female). Assessors and trial statisticians were blind to treatment allocation. Each treatment arm consisted of up to 24 sessions of up to 60 minutes each, delivered by trained clinical psychologists. The co-primary outcome measures were assessor rated symptom severity on the HDRS and self-reported symptom severity on the Beck Depression Inventory II (BDI-II) at post treatment. Secondary outcomes were scores six months post treatment on these measures and a range of symptom and mechanism variables. A key trial design feature was that each treatment was implemented to maximize individual patient benefit; hence time under therapy and number of sessions delivered could vary. Treated groups in the trial were very similar on most baseline characteristics. Data were analyzed on the basis of intention to treat (ITT). No differences were found on the HDRS at post treatment or follow-up (-0.95 [-2.88 to 0.98], p = 0.336; and -1.61 [-3.65 to 0.43], p = 0.122), but floor effects on this outcome were high. However, a significant difference favouring MCT was found on the BDI-II at post treatment (-5.49 [95% CI -8.90 to -2.08], p = 0.002), which was maintained at six-month follow-up (-4.64 [-8.21 to -1.06], p = 0.011). Following MCT 74% of patients compared with 52% in CBT met formal criteria for recovery on the BDI-II at post treatment (odds-ratio=2.42 [1.20 to 4.92], p = 0.014). At follow-up the proportions were 74% compared to 56% recovery (odds-ratio=2.19 [1.05 to 4.54], p = 0.036). Significant differences favouring MCT, also maintained over time, were observed for most secondary outcomes. The results were robust against controlling for time under therapy and when outcomes were assessed at a common 90 day mid-term time-point. Limitations of the study include the use of only two therapists where one treated 69% of patients, possible allegiance effects as the study was conducted in an established CBT clinic and the chief investigator is the originator of MCT and group differences in time under therapy. Never the less evidence from this study suggests that MCT had considerable beneficial effects in treating depression that may exceed CBT.