Venlafaxine is used to treat depression worldwide. Previous reviews have demonstrated that venlafaxine lowers scores on depression rating scales, producing statistically significant results but the relevance to patients remains uncertain. Knowledge of the incidence of the adverse effects associated with venlafaxine has previously been based on the results of non-randomised studies. Our primary objective was to assess the risks of adverse events with venlafaxine in the treatment of adults with major depressive disorder in randomised trials.

We searched relevant databases and other sources from inception to 7 March 2024 for randomised clinical trials comparing venlafaxine versus placebo or no intervention in adults with major depressive disorder. Data were synthesised using meta-analysis and Trial Sequential Analysis. The primary outcomes were suicides or suicide attempts, serious adverse events and non-serious adverse events.

We included 28 trials randomising 6,253 participants to venlafaxine versus placebo. All results were at high risk of bias, and the certainty of the evidence was very low. All trials assessed outcomes at a maximum of 12 weeks after randomisation. Meta-analysis and Trial Sequential Analysis showed insufficient information to assess the effects of venlafaxine on the risks of suicides or suicide attempts. Meta-analysis showed evidence of harm of venlafaxine versus placebo on serious adverse events (risk ratio: 2.66; 95% confidence interval: 1.67–4.25; p < 0.01; 22 trials), mainly due to a higher risk of sexual dysfunction and anorexia. Meta-analysis showed that venlafaxine also increased the risk of several non-serious adverse events: nausea, dry mouth, dizziness, sweating, somnolence, constipation, nervousness, insomnia, asthenia, tremor and decreased appetite.

Short-term results show that venlafaxine has uncertain effects on the risks of suicides but increases the risks of serious adverse events (especially sexual dysfunction and anorexia) and many non-serious adverse events. The long-term effects of venlafaxine for major depressive disorder are unknown. It is a particular cause for concern that there are no data on the long-term adverse effects of venlafaxine given that so many people use these drugs for several years.

Cannabis abuse in psychotic patients is associated with rehospitalizations, reduced adherence and increased symptom severity. Previous psychosocial interventions have been ineffective in cannabis use, possibly because of low sample sizes and short interventions. We investigated whether adding CapOpus to treatment as usual (TAU) reduces cannabis use in patients with cannabis use disorder and psychosis.

A total of 103 patients with psychosis and cannabis use disorder were centrally randomized to 6 months of CapOpus plus TAU (n = 52) or TAU (n = 51). CapOpus consisted mainly of motivational interviewing and cognitive behaviour therapy (CBT). TAU was targeted primarily at the psychotic disorder. The primary outcome was self-reported days with cannabis use in the preceding month.

Pre-randomization cannabis use frequency was 14.9 [95% confidence interval (CI) 12.7–17.1] days/month. Post-treatment, the ratio of days/month with cannabis use in CapOpus versus TAU was 0.76 (95% CI 0.38–1.50) (p = 0.42), and 0.80 (95% CI 0.21–3.10) (p = 0.75) at the 4-month follow-up. From 46.4 (95% CI 36.4–56.3) monthly joints pre-randomization, consumption fell to 27.3 (95% CI 12.6–41.9) joints in CapOpus and 48.2 (95% CI 31.8–64.6) in TAU (p = 0.06). Follow-up amounts were 28.4 (95% CI 13.5–43.2) and 41.6 (95% CI 25.2–58.0) joints (p = 0.23). Several subgroup analyses suggested benefits of CapOpus.

CapOpus did not reduce the frequency, but possibly the amount, of cannabis use. This is similar to the findings of previous trials in this population. Implementation of CapOpus-type interventions is thus not warranted at present but subgroup analyses call for further trials.

Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews.

Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors.

We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference −1.02, 95% confidence interval (CI) −2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference −1.29, 95% CI −2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events.

Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.