Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world.

To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.

Discipline is a crucial aspect of parenting, shaping child development and behaviour. Time-out, a widely used disciplinary strategy with a strong evidence-base, has recently come under scrutiny with concerns about potential adverse effects on children's emotional development and attachment, particularly for those with a history of adversity.

To contribute critical empirical insights to the current controversy surrounding time-out by exploring the associations among time-out implementation, parent–child attachment and child mental health, and whether adversity exposure moderated these associations.

This cross-sectional study utilised a nationally representative sample of 474 primary caregivers in Australia, with children aged 6–8 years, who completed an online survey. Measures included the Implementation of Time-out Scale, Adverse Life Experiences Scale, Primary Attachment Style Questionnaire, Strengths and Difficulties Questionnaire and Spence Child Anxiety Scale.

Appropriately implemented time-out was associated with enhanced mental health and attachment, while inappropriate time-out correlated with adverse child outcomes. Exposure to adversity moderated the relationship between time-out implementation and child well-being, such that children exposed to adversity were most likely to experience attachment enhancement from appropriately implemented time-out.

Despite recent concerns of harm caused by time-out, particularly for children with a history of adversity, findings support the beneficial impact of time-out on child well-being and attachment when implemented in accordance with evidence-based parameters. Combatting misinformation and disseminating evidence-based time-out guidelines is crucial for promoting child well-being and attachment, especially for children who have experienced adversity.

Evidence is largely limited regarding the extent to which abnormal behavioural profiles, including physical inactivity, sedentary behaviour and inadequate sleep duration, impact long-term health conditions in individuals with pre-existing depression.

To investigate the associations between accelerometer-derived daily movement behaviours and mortality in individuals with pre-existing depression.

Between 2013 and 2015, a total of 10 914 individuals with pre-existing depression were identified from the UK Biobank through multiple sources including self-reported symptoms, records of antidepressant usage and diagnostic recording based on the 10th Revision of the International Classification of Diseases (ICD-10) codes F32–F33. These participants were subsequently followed up until 2021. Wrist-worn accelerometers were used for objective measurement of sleep duration, sedentary behaviour, moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA) over a span of seven consecutive days.

During a median follow-up of 6.9 years, 434 deaths occurred among individuals with pre-existing depression. We observed a U-shaped association between sleep duration and mortality in individuals with pre-existing depression, with the lowest risk occurring at approximately 9 h/day. Both MVPA and LPA exhibited an L-shaped pattern in relation to mortality, indicating that engaging in higher levels of physical activity was associated with lower risk of mortality in individuals with pre-existing depression, but the beneficial effect reached a plateau after 50 min/day for MVPA and 350 min/day for LPA. We found a positive association between sedentary time and mortality, and the risk apparently increased above 8 h/day. Moreover, substituting 1 hour/day of sedentary time with LPA or MVPA was significantly associated with a 12% (hazard ratio: 0.88, 95% CI: 0.83–0.94) and 24% (hazard ratio: 0.76, 95% CI: 0.61–0.94) lower risk of mortality, respectively.

Our study found the beneficial effect of adequate sleep duration, high levels of physical activity and short sedentary time on risk of mortality among individuals with pre-existing depression.

The clinical high risk for psychosis (CHR-p) syndrome enables early identification of individuals at risk of schizophrenia and related disorders. We differentiate between the stigma associated with the at-risk identification itself (‘labelling-related’ stigma) versus stigma attributed to experiencing mental health symptoms (‘symptom-related’ stigma) and examine their relationships with key psychosocial variables.

We compare labelling- and symptom-related stigma in rates of endorsement and associations with self-esteem, social support loss and quality of life.

We assessed stigma domains of shame-related emotions, secrecy and experienced discrimination for both types of stigma. Individuals at CHR-p were recruited across three sites (N = 150); primary analyses included those who endorsed awareness of psychosis risk (n = 113). Paired-sample t-tests examined differences in labelling- versus symptom-related stigma; regressions examined associations with psychosocial variables, controlling for covariates, including CHR-p symptoms.

Respondents reported greater symptom-related shame, but more labelling-related secrecy. Of the nine significant associations between stigma and psychosocial variables, eight were attributable to symptom-related stigma, even after adjusting for CHR-p symptoms.

Stigma attributed to symptoms had a stronger negative association with psychosocial variables than did labelling-related stigma among individuals recently identified as CHR-p. That secrecy related to the CHR-p designation was greater than its symptom-related counterpart suggests that labelling-related stigma may still be problematic for some CHR-p participants. To optimise this pivotal early intervention effort, interventions should address the holistic ‘stigmatising experience’ of having symptoms, namely any harmful reactions received as well as participants’ socially influenced concerns about what their experiences mean, in addition to the symptoms themselves.

Abrupt cessation of heavy cannabis use can cause a withdrawal syndrome characterised by irritability, anxiety, insomnia, reduced appetite and restlessness. Recent reports have also described people in whom cannabis withdrawal immediately preceded the acute onset of psychosis.

To identify cases of psychosis associated with cannabis withdrawal.

We completed a systematic review of the literature, which comprised case reports, case series and other studies. We also searched a large electronic database of psychiatric healthcare records.

The systematic review identified 44 individuals from 21 studies in whom cannabis withdrawal preceded the development of acute psychosis. In the health record study, we identified another 68 people, of whom 47 involved a first episode of psychosis and 21 represented further episodes of an existing psychotic disorder. Almost all people were daily cannabis users who had stopped using cannabis abruptly. Individuals who continued to use cannabis after the acute psychotic episode had a much higher risk of subsequent relapse than those who abstained (odds ratio 13.9 [95% CI: 4.1 to 56.9]; χ2 = 20.1, P < 0.00001).

Abrupt cannabis withdrawal may act as a trigger for the first episode of psychosis and a relapse of an existing psychosis. Acute psychotic symptoms can emerge after the cessation, as well as following the use, of cannabis.

Personalised management of recurrent depression, considering individual patient characteristics, is crucial.

This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity.

Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models.

A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points).

Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression.

ISRCTN26666654.

Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.

Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD)

To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities.

Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific (‘co-occurring’) psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty.

Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) −0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic–dissociative symptoms (SMD −0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD −0.44, P = 0.02; LCE) and anxious symptoms (SMD −1.11, P < 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic–dissociative symptoms (P = 0.001).

Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.