The comparability between self-reports and clinician-rated scales for measuring depression following treatment has been a long-standing debate, with studies finding mixed results. While the use of self-reports in psychotherapy trials is very common, it has been widely assumed that these tools pose a validity threat when masking of participants is not possible. We conducted a meta-analysis across randomized controlled trials (RCTs) of psychotherapy for depression to examine if treatment effect estimates obtained via self-reports differ from clinician-rated outcomes.

We identified studies from a living database of psychotherapies for depression (updated to 1 January 2023). We included RCTs measuring depression at post-treatment with both a self-report and a clinician-rated scale. As our main model, we ran a multilevel hierarchical meta-analysis, resulting in a pooled differential effect size (Δg) between self-reports and clinician ratings. Moderators of this difference were explored through multimodel inference analyses.

A total of 91 trials (283 effect sizes) were included. In our main model, we found that self-reports produced smaller effect size estimates compared to clinician-rated instruments (Δg = 0.12; 95% CI: 0.03–0.21). This difference was very similar when only including trials with masked clinicians (Δg = 0.10; 95% CI: 0.00–0.20). However, it was more pronounced for unmasked clinical ratings (Δg = 0.20; 95% CI: −0.03 to 0.43) and when trials targeted specific population groups (e.g., perinatal depression) (Δg = 0.20; 95% CI: 0.08–0.32). Effect sizes between self-reports and clinicians were identical in trials targeting general adults (Δg = 0.00; 95% CI: −0.14 to 0.14).

Self-report instruments did not overestimate the effects of psychotherapy for depression and were generally more conservative than clinician assessments. Patients’ perception of improvement should not be considered less valid by default, despite the inherent challenge of masking in psychotherapy.

Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.

To find the optimal dosage of aripiprazole augmentation.

Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose–effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4–12 weeks).

Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose–efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15–1.85) and 5 mg (OR = 1.93, 95% CI 1.33–2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52–2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.

Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.

Psychotherapies are the treatment of choice for panic disorder, but which should be considered as first-line treatment is yet to be substantiated by evidence.

To examine the most effective and accepted psychotherapy for the acute phase of panic disorder with or without agoraphobia via a network meta-analysis.

We conducted a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the most effective and accepted psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase, PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA guidelines were used. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO (CRD42020206258).

We included 136 RCTs in the systematic review. Taking into consideration efficacy (7352 participants), acceptability (6862 participants) and the CINeMA confidence in evidence appraisal, the best interventions in comparison with treatment as usual (TAU) were cognitive–behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = −0.67, 95% CI −0.95 to −0.39; CINeMA: moderate; for acceptability: relative risk RR = 1.21, 95% CI −0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic therapy (for efficacy: s.m.d. = −0.61, 95% CI −1.15 to −0.07; CINeMA: low; for acceptability: RR = 0.92, 95% CI 0.54–1.54; CINeMA: moderate). After removing RCTs at high risk of bias only CBT remained more efficacious than TAU.

CBT and short-term psychodynamic therapy are reasonable first-line choices. Studies with high risk of bias tend to inflate the overall efficacy of treatments. Results from this systematic review and network meta-analysis should inform clinicians and guidelines.

There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method.

Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects.

Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining.

An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.

The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.

We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.

The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.

The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.

Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals.

The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort.

In total, 37.0% (95% confidence interval 34.8–39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70–0.77) and 0.82 (0.79–0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively.

Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive–behavioural therapy (CBT) in comparison with pill placebo.

To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression.

A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data.

We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of –0.22 (95% CI –0.42 to –0.02, P = 0.03, I 2 = 0%).

Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.

Contradictions and initial overestimates are not unusual among highly cited studies. However, this issue has not been researched in psychiatry.

To assess how highly cited studies in psychiatry are replicated by subsequent studies.

We selected highly cited studies claiming effective psychiatric treatments in the years 2000 through 2002. For each of these studies we searched for subsequent studies with a better-controlled design, or with a similar design but a larger sample.

Among 83 articles recommending effective interventions, 40 had not been subject to any attempt at replication, 16 were contradicted, 11 were found to have substantially smaller effects and only 16 were replicated. The standardised mean differences of the initial studies were overestimated by 132%. Studies with a total sample size of 100 or more tended to produce replicable results.

Caution is needed when a study with a small sample size reports a large effect.

The value of family psychoeducation for schizophrenia has been well established, and indications for its use have recently expanded to include bipolar affective disorder. However, no study to date has adequately examined its use in depression.

To examine family psychoeducation in the maintenance treatment of depression and to investigate the influence of the family's expressed emotion (EE) on its effectiveness.

Of 103 patients diagnosed with major depression and their primary family members, 57 pairs provided written informed consent. The pairs were randomly allocated to the intervention (n = 25) or control (n = 32). One family in the intervention group and two in the control group withdrew their consent after randomisation. The intervention group underwent four psychoeducation sessions consisting of didactic lectures about depression and group problem-solving focusing on how to cope in high-EE situations. Patients did not attend these sessions. Patients in both the intervention and control groups received treatment as usual. The families' EE levels were evaluated through Five-Minute Speech Samples. The primary outcome was relapse.

Time to relapse was statistically significantly longer in the psychoeducation group than in the control group (Kaplan–Meier survival analysis, P = 0.002). The relapse rates up to the 9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI 0.04–0.66; number needed to treat 2.4, 95% CI 1.6–4.9). In Cox proportional hazard analysis, baseline EE did not moderate the effectiveness of the intervention.

Family psychoeducation is effective in the prevention of relapse in adult patients with major depression.

Panic disorder can be treated with psychotherapy, pharmacotherapy or a combination of both.

To summarise the evidence concerning the short- and long-term benefits and adverse effects of a combination of psychotherapy and antidepressant treatment.

Meta-analyses and meta-regressions were undertaken using data from all relevant randomised controlled trials identified by a comprehensive literature search. The primary outcome was relative risk (RR) of response.

We identified 23 randomised comparisons (21 trials involving a total of 1709 patients). In the acute-phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR=1.24, 95% CI 1.02–1.52) or psychotherapy (RR=1.16, 95%CI 1.03–1.30). After termination of the acute-phase treatment, the combined therapy was more effective than pharmacotherapy alone (RR=1.61, 95% CI 1.23–2.11) and was as effective as psychotherapy (RR=0.96, 95% CI 0.79–1.16).

Either combined therapy or psychotherapy alone may be chosen as first-line treatment for panic disorder with or without agoraphobia, depending on the patient's preferences.