The effects of cognitive therapy versus 'no intervention' for major depressive disorder

Abstract

Background: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews.

Methods/principal findings: We used The Cochrane systematic review methodology with meta-analyses and trial sequential analyses of randomized trials comparing the effects of cognitive therapy versus 'no intervention' for major depressive disorder. Participants had to be older than 17 years with a primary diagnosis of major depressive disorder to be eligible. Altogether, we included 12 trials randomizing a total of 669 participants. All 12 trials had high risk of bias. Meta-analysis on the Hamilton Rating Scale for Depression showed that cognitive therapy significantly reduced depressive symptoms (four trials; mean difference -3.05 (95% confidence interval (Cl), -5.23 to -0.87; P<0.006)) compared with 'no intervention'. Trial sequential analysis could not confirm this result. Meta-analysis on the Beck Depression Inventory showed that cognitive therapy significantly reduced depressive symptoms (eight trials; mean difference on -4.86 (95% CI -6.44 to -3.28; P = 0.00001)). Trial sequential analysis on these data confirmed the result. Only a few trials reported on 'no remission', suicide inclination, suicide attempts, suicides, and adverse events without significant differences between the compared intervention groups.

Discussion: Cognitive therapy might be an effective treatment for depression measured on Hamilton Rating Scale for Depression and Beck Depression Inventory, but these outcomes may be overestimated due to risks of systematic errors (bias) and random errors (play of chance). Furthermore, the effects of cognitive therapy on no remission, suicidality, adverse events, and quality of life are unclear. There is a need for randomized trials with low risk of bias, low risk of random errors, and longer follow-up assessing both benefits and harms with clinically relevant outcome measures.

Figure 1. The effect of cognitive therapy versus ‘no intervention’ at cessation of treatment on Hamilton Rating Scale for Depression (HDRS).

Below figure: All four trials used only individual cognitive therapy. The therapists' level of experience and/or education was classified as ‘high’ in Dozios (2009), as ‘intermediate’ in Murphy (1984) and Hollon (1992), and as ‘unclear’ in Scott (1997).

Figure 2. The effect of cognitive therapy versus ‘no intervention’ at cessation of treatment on Becks Depression Inventory (BDI).

Figure 3. Trial sequential analysis of the cumulative meta-analysis of the effect of cognitive therapy versus ‘no intervention’ for major depressive disorder on the Hamilton Rating Scale for Depression (HDRS).

Below figure: The required information size of 994 is calculated based on an intervention effect compared with ‘no intervention’, of 2 points on the HDRS, a variance of 126.5.04 on the mean difference, a risk of type I error of 5%, and a power of 80%. With these presumptions, the cumulated Z-curve (blue curve) do not cross the trial sequential monitoring boundaries (red inner sloping lines) implying that there is no firm evidence for a beneficial effect of cognitive therapy compared with no intervention.

Figure 4. Trial sequential analysis of the cumulative meta-analysis of the effect of cognitive therapy versus no ‘intervention’ for major depressive disorder on the Beck Depression Inventory (BDI).

Below figure: The required information size of 570 is calculated based on an intervention effect compared with ‘no intervention’, of 4 points on the BDI, a variance of 153.1 on the mean difference, a risk of type I error of 1% and a power of 90%. With these presumptions, the cumulated Z-curve (blue curve) crosses the trial sequential monitoring boundaries (red inner sloping lines) implying that there is no risk of random error in the estimate of a beneficial effect of cognitive therapy compared with no intervention. However, all trials were considered as high risk of bias, which could explain the positive findings.

Figure 5. Effect of cognitive therapy versus ‘no intervention’ on ‘no remission’ (HDRS>7) at cessation of treatment.

Figure 6. Trial sequential analysis of the cumulative meta-analysis of the effect of cognitive therapy versus no ‘intervention’ for no remission according to the Hamilton Rating Scale for Depression.

Below figure: The required information size of 303 is calculated based on a control event proportion of 62%, an assumed relative risk reduction of 30%, a type I error of 5%, a beta of 10% (power of 90%), and the heterogeneity in the meta-analysis. With these presumptions, the cumulated Z-curve (blue curve) do not cross the trial sequential monitoring boundaries (red inner sloping lines) implying that there is a risk of random error in the estimate of a beneficial effect of cognitive therapy compared with no intervention, either due to sparse data or repetitive testing in the cumulative meta-analysis. Furthermore, all trials were considered as high risk of bias, which could explain the positive findings in the conventional meta-analysis.