Cognitive neuropsychological models propose that antidepressants exert their therapeutic effects by modifying negative emotional processing biases early in treatment. However, evidence from large, long-term clinical samples is limited.

We conducted a mechanistic analysis within the Antidepressants to Prevent Relapse in Depression randomized controlled trial, which compared maintenance antidepressant treatment with placebo substitution in adults with recurrent depression who were currently well (N = 478). Participants completed a computerized facial emotion recognition task at baseline, 12 weeks, and 52 weeks, in which faces morphed from happy to sad. The primary outcome was the number of faces classified as happy (0–45). Linear and longitudinal mixed-effects models were used to compare treatment groups and examine associations with depressive (PHQ-9) and anxiety (GAD-7) symptoms.

Of the 462 participants completing at least one task, there was no evidence that discontinuing antidepressants altered performance compared with maintenance at 12 weeks (adjusted mean difference = 0.23, 95% CI –0.5 to 1.0, p = 0.5) or 52 weeks (0.29, –0.5 to 1.2, p = 0.5). Depressive symptoms were negatively associated with happy face classifications both cross sectionally (β = –0.20 per PHQ-9 point, p = 0.02) and longitudinally (β = –0.09, p = 0.05). Anxiety symptoms were positively associated with happy classifications (β = 0.11, p = 0.047).

Maintenance antidepressant treatment did not sustain positive emotional processing biases as indexed by facial emotion recognition, despite robust associations between such biases and depressive symptoms. These findings challenge the generalizability of laboratory evidence on emotional bias modification to long-term clinical treatment and highlight the need for further mechanistic research on antidepressant action.

Antidepressants are pivotal in treating major depressive disorder and other psychiatric conditions. However, despite their widespread use, evidence regarding the serious adverse effects of prolonged antidepressant use and withdrawal in complex older-adult populations remains limited.

We aimed to investigate the association between phases of antidepressant treatment with emergency hospital admission and hospital admissions related to adverse drug reactions in older adults with polypharmacy in English primary care.

We conducted a case–control study using linked primary and secondary care electronic health record data from the Clinical Practice Research Databank GOLD and Aurum. We included individuals aged 65–100 years with polypharmacy (i.e. those who were prescribed five or more medicines). We used conditional logistic regression to investigate the associations between the phases of antidepressant treatment and hospital admission risks.

We found 626 199 emergency hospital admission cases and matched with 3 639 740 controls. The initiation phase of antidepressants was associated with the greatest increase in the risk of emergency hospital admission (adjusted odds ratio 2.30, 95% CI 2.23–2.38), followed by short treatment gap or early discontinuation after short-term use (adjusted odds ratio 1.41, 95% CI 1.37–1.45). We found that patients had a higher risk of serotonin-related symptoms, falls and trauma, and cardiovascular events during antidepressant use phases, and the risks tend to decrease in past exposure phases for most conditions.

Individuals who are on the initiation and short treatment gap or early discontinuation after short-term use of antidepressant treatment are associated with a higher risk of hospital admission. This study highlights the need for vigilant monitoring of antidepressant initiation and withdrawal in older-adult polypharmacy patients.

Psychotropic medication use has been shown to be associated with decreased bone mineral density (BMD) and quality, and increased fracture risk. Less is known about psychotropic use and associated bone loss over time.

To determine the association between psychotropic medication use and bone loss in men.

Data from 940 men (aged ≥20 years) participating in the Geelong Osteoporosis Study were used in this longitudinal study. BMD (g/cm2) at the spine and hip were measured with dual-energy X-ray absorptiometry at baseline, and 5 and 15 years post-baseline. Body mass index (BMI) was calculated, lifestyle factors and medication use was self-reported, and socioeconomic status was determined. Mood and anxiety disorders were identified through a clinical interview. Multivariable linear regression was used to determine the associations.

Over the study period (median 13.2 years), psychotropic use was associated with change in BMD at the spine (unadjusted mean difference −0.063 g/cm2, 95% CI −0.096 to −0.031, p < 0.001) and hip (−0.038 g/cm2, 95% CI −0.059 to −0.017, p < 0.001). BMI was identified as an effect modifier. Psychotropic use was associated with spine and hip bone loss at the 25th (adjusted mean difference −0.077g/cm2 (95% CI −0.122 to −0.033); and −0.058 g/cm2 (95% CI −0.084 to −0.032), respectively) and 50th percentile (adjusted mean difference −0.053 g/cm2 (95% CI −0.089 to −0.018) and −0.038 g/cm2 (95% CI −0.059 to −0.017), respectively), but not the 75th percentile of BMI (p = 0.121 and p = 0.106, respectively).

Psychotropic use was associated with bone loss in non-obese men, highlighting the need for regular monitoring and preventive strategies to protect bone health.

Recent decades have seen a steady increase in antidepressant prescribing, but little is known about prescribing trends during and following the COVID-19 pandemic.

This preregistered systematic review, following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, aimed to investigate antidepressant prescribing trends for adults in the UK and Republic of Ireland during and after the pandemic. It also compared prescriptions by drug and location.

We searched six databases: APA PsycInfo, CINAHL, MEDLINE, Scopus, medRxiv and Preprints.org. The review included primary research articles reporting trends in antidepressant prescriptions, including at least one time point after March 2020 in the UK and Republic of Ireland. This review has been preregistered on PROSPERO (ID: CRD42024498503).

We identified 7,320 studies, of which ten met the search criteria for the review. Studies were grouped on the basis of time period (2020: n = 5; 2021: n = 3; 2022: n = 2), location (England, Scotland, Northern Ireland, Republic of Ireland, UK) and drug type (serotonin–noradrenaline reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclics, and others (e.g. monoamine oxidase inhibitors)). Most studies (eight of ten) demonstrated increased antidepressant prescribing over time. Two studies highlighted a decrease between March and May 2020. Demographic variables reflected higher rates of prescribing for women, and the modal group receiving antidepressants comprised middle-aged adults.

The commonly reported increase in antidepressant prescribing corroborates pre-pandemic trends and may suggest further, increased demands for mental health support to meet the unique challenges of the pandemic. Future research is required to evaluate the appropriateness of treatment decisions and to explore psychosocial factors that influence individual prescribing choices.

Trazodone is commonly used in the treatment of major depressive disorder (MDD) in adults. This study aimed to establish consensus on the clinical scenarios and patient profiles for which trazodone treatment is considered suitable.

A two-round Delphi process was conducted across eight European countries. Statements regarding trazodone were rated by a panel of 32 experts for agreement or disagreement using a 9-point Likert scale; those with <70% agreement among panelists were revised and reassessed by the panel.

There was strong consensus agreement on 68 out of 91 statements (75%) related to trazodone. According to the panel, trazodone is well tolerated, with low anticholinergic activity, minimal impact on sexual function, weight neutrality, and low potential for clinically relevant drug–drug interactions. Consensus agreement supported trazodone use across a broad spectrum of patients with MDD, including those with insomnia, anxiety, psychomotor agitation, substance use, physical comorbidities, neurological conditions, and treatment-resistant depression; consensus agreement was also achieved for trazodone use in elderly patients, and those experiencing adverse effects with other antidepressants.

This study suggests that trazodone is useful in the treatment of MDD across multiple patient profiles. These findings offer practical guidance to support individualized and evidence-based decision-making in clinical practice.

Exposure to workplace bullying is associated with an increased risk of mental health conditions, yet it is debated whether the association is causal. This study aims to address this by examining whether onset of workplace bullying is associated with initiating treatment with psychotropic medication, here used as a proxy measure for onset of common mental disorders.

We used two longitudinal datasets from Sweden and Denmark (mean age: 47.4, women: 52.8%), combined with national registry data on psychotropic medication purchases. Using a target trial approach, the study population (N = 25 309) consisted of employees free of workplace bullying and psychotropic medication use at baseline. We used Cox proportional hazards regression (adjusted for sociodemographic variables, depressive symptoms and psychosocial work characteristics) to assess the association between onset of exposure to workplace bullying and incident treatment with psychotropic medication during 2 years.

In total, 1490 individuals (5.9%) experienced onset of workplace bullying. Bullying onset was associated with incident treatment with any psychotropic medication (HR: 1.42, 95% CI 1.15–1.77, model adjusted for sociodemographic variables). This association was attenuated in the fully adjusted model (HR: 1.24, 95% CI 0.99–1.53). In analyses focusing on antidepressant treatment, the estimates were stronger (HR: 1.55, 95% CI: 1.15–2.09, fully adjusted model). The results further demonstrated an exposure–response relationship, such that higher frequency of bullying exposure was associated with an increased risk of initiating any psychotropic treatment and antidepressants.

Individuals experiencing onset of workplace bullying were at higher risk of starting antidepressant treatment within 2 years. This is the first study showing that onset of workplace bullying can contribute to the development of mental health conditions requiring medical treatment. These results underline the importance of preventive interventions that reduce workplace bullying.

The Maudsley 3-item visual analogue scale (M3VAS) was developed as a novel and intuitive patient-reported measure for depression, focusing on core symptoms and suicidality.

To evaluate the longitudinal validity of M3VAS for capturing symptom change over time.

Both M3VAS and the Patient Health Questionnaire (PHQ-9, as reference standard) were administered in an observational study (RHAPSODY, no. NCT04939818) at weeks 0, 2 and 4 to both depressed patients (n = 50) and matched controls (n = 24). We serially tested factor structure, internal consistency and convergence (correlation) over time, assessing responsiveness by both correlation of change in score and effect of time across scales (analysis of variance and effect size).

M3VAS exhibited strong factor loadings and high item interrelatedness (Cronbach’s alpha 0.78–0.83) at all time points. Total scores correlated strongly with PHQ-9 at each time point (r > 0.8, P < 0.001). Correlation of score change over the study period (r = 0.65, P < 0.001) also confirmed responsiveness. In the depressed group, an effect of time on score was seen for both M3VAS (F = 4.942, P = 0.010) and PHQ-9 (F = 12.505, P < 0.001), with standard response mean (Cohen’s d) of 0.58 and 0.74, respectively. No effect of time was seen in the control group.

Following previous cross-sectional validation against the Quick Inventory of Depressive Symptomatology–Self-report, this present study demonstrated appropriate longitudinal measurement properties for M3VAS as a measure of depression, including responsiveness. Evaluating the ability of M3VAS to discern responses with a variety of treatments is a key future goal.

The smallest worthwhile difference (SWD) represents the smallest beneficial effect of an intervention that patients deem worthwhile given the harms, expenses and inconveniences of the intervention. The SWD facilitates interpretation of the patient-perceived importance of intervention effects. We previously estimated the SWD for antidepressants for depression, but the SWD for psychotherapy remains unknown.

To estimate the SWD of recommended psychotherapies for depression compared with no treatment.

We estimated the SWD through a patient required difference in response rates between psychotherapy and no treatment after 2 months. We recruited using Prolific, an online cross-sectional survey platform, in the UK and USA in January 2025. We also queried a random subset of respondents to replicate our previous SWD estimation for antidepressants.

In the primary study, we recruited 526 participants (mean age: 36.7 years (s.d. = 12.5); 54% women and 61% White individuals). Of these, 6% reported that they would not initiate psychotherapy with a 100% treatment response. For those willing to initiate psychotherapy, 87 reported moderate-to-severe depressive symptoms but were not in treatment, 184 were in treatment and 131 reported absent-to-mild symptoms with or without previous treatment. The median SWD for people with moderate-to-severe depressive symptoms, not in treatment and willing to consider psychotherapies was a 20% (interquartile range: 10–35%) difference in response rates comparing psychotherapy with no treatment. This was similar to the SWD for antidepressant drugs (SWD = 20%, interquartile range: 10–30%; n = 104). Participant characteristics were not meaningfully associated with the SWD.

Current empirically supported psychotherapy response rates of 15% were sufficient for one in three people to initiate psychotherapy given the burdens, but two in three expected greater treatment benefits or fewer burdens. The SWD for psychotherapy was not materially different from the estimated SWD for antidepressants. Individual patient value judgements and preferences merit greater attention. These findings should be replicated with diverse samples from different geographical locations.

With the increased prevalence of major depressive episodes with mixed features specifier (MDE-MFS), the pharmacological treatment for MDE-MFS has attracted great clinical attention. This study aimed to investigate the efficacy and safety of medication use for MDE-MFS.

Commonly used databases were searched for the meta-analysis. Primary efficacy outcomes included response rate and the change in the Young Mania Rating Scale scores; the primary safety outcome was the rate of treatment-emergent hypomania/mania. Effects were expressed as relative risk (RR) or standardized mean difference (SMD).

In patients with MDE-MFS, antipsychotics significantly improved depressive (RR = 1.46 [95% CI: 1.31, 1.61]) and manic (SMD = −0.35 [95% CI: −0.53, −0.17]) symptoms without increasing the risk of manic switch (RR = 0.91 [95% CI: 0.53, 1.55]). However, subgroup analysis of bipolar disorder (BD) patients with MDE-MFS indicated that antipsychotics had limited effects on manic symptoms. Mood stabilizers, especially valproate, demonstrated significant effects in BD patients with MDE-MFS by relieving depressive and manic symptoms. For MDE-MFS in patients with major depressive disorder, trazodone has shown potential effectiveness in retrospective studies, while the effectiveness of antidepressants on BD patients with MDE-MFS lacked evidence.

While antipsychotics are first options for MDE-MFS, their effect on manic symptoms in BD patients with MDE-MFS is still unclear. Mood stabilizers may also be considered, and the use of antidepressants remains a topic of controversy. Since our findings are mostly based on post-hoc analyses, the evidence remains preliminary, highlighting the need for further research to produce more conclusive evidence.