The optimal duration for maintaining antidepressant treatment in individuals with obsessive-compulsive disorder (OCD) who achieve symptom stabilization remains unclear.

This systematic review and pairwise meta-analysis of double-blind randomized placebo-controlled trials (DBRPCTs) compared antidepressant maintenance and antidepressant discontinuation groups in terms of relapse rate at each DBRPCT study endpoint (primary outcome), OCD symptom improvement, all-cause discontinuation, and adverse event-related discontinuation. Furthermore, relapse rates at 4, 8, 12, 16, 20, and 24 weeks were compared between the groups. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The absolute risk reduction (ARR) and number needed to treat to benefit (NNTB) for relapse rates were also estimated.

Nine trials (n = 1084; mean age: 32.8 years; proportion of males: 53.3%) were included. The antidepressant maintenance group had lower relapse rates at each DBRPCT study endpoint (RR [95% CI] = 0.53 [0.42–0.68]; ARR = 21.0%; NNTB = 5) and lower all-cause and adverse event-related discontinuation rates than the antidepressant discontinuation group. The maintenance group also exhibited lower relapse rates at 4 weeks (RR [95% CI] = 0.47 [0.31–0.70]; ARR: not significant; NNTB: not significant), 8 weeks (0.42 [0.31–0.57]; 12.0%; 8), 12 weeks (0.43 [0.32–0.56]; 18.0%; 6), 16 weeks (0.41 [0.32–0.52]; 25.0%; 4), 20 weeks (0.43 [0.34–0.53]; 26.0%; 4), and 24 weeks (0.42 [0.33–0.52]; 27.0%; 4) than the discontinuation group. Moreover, the maintenance group outperformed the discontinuation group regarding OCD symptom improvement.

Individuals with OCD may benefit from continued antidepressant treatment, provided that it is well tolerated.

Cannabis use is linked to treatment non-adherence and relapses in psychotic disorders. Antipsychotic medication is effective for relapse prevention in primary psychoses, but its effectiveness after cannabis-induced psychosis (CIP) remains unclear.

To examine the effectiveness of antipsychotic medication for relapse prevention following the first clinically diagnosed CIP.

A cohort of 1772 patients (84.1% men) with incident CIP was identified from the Swedish National Patient and Micro Data for Analyses of Social Insurance registers. The primary outcome was hospitalisation due to any psychotic episode. Drug use data were collected from the Prescribed Drug Register and modelled into drug use periods using the PRE2DUP method. A within-individual Cox regression model was used to study the risk of outcomes during the use of different oral or long-acting injectable (LAI) antipsychotics compared with non-use.

The mean age at first diagnosis was 26.6 years (s.d. = 8.3). Of the cohort, 1343 (75.8%) used antipsychotics and 914 (51.3%) experienced psychosis hospitalisation during the follow-up. Any antipsychotic use was associated with a decreased risk of psychosis hospitalisation (adjusted hazard ratio (aHR) 0.75; 95% CI 0.67–0.84). Specific antipsychotics associated with decreased risk included aripiprazole LAI (aHR 0.27; 95% CI 0.14–0.51), olanzapine LAI (aHR 0.28; 95% CI 0.15–0.53), clozapine (aHR 0.55; 95% CI 0.34–0.90), oral aripiprazole (aHR 0.64; 95% CI 0.45–0.91), antipsychotic polytherapy (aHR 0.74; 95% CI 0.63–0.87) and oral olanzapine (aHR 0.81; 95% CI 0.69–0.94).

In particular, LAIs, clozapine and oral aripiprazole were associated with a decreased risk of psychosis relapse following CIP. Prescribers should consider using more LAIs for better treatment outcomes after CIP.

Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.

We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.

Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.

Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.

Having a relapse of schizophrenia or recurrent psychosis is feared by patients, can cause social and personal disruption and has been suggested to cause long-term deterioration, possibly because of a toxic biological process.

To assess whether relapse affected the social and clinical outcomes of people enrolled in a 24-month randomised controlled trial of antipsychotic medication dose reduction versus maintenance treatment.

The trial involved participants with a diagnosis of schizophrenia or recurrent, non-affective psychosis. Relapse was defined as admission to hospital or significant deterioration (assessed by a blinded end-point committee). We analysed the relationship between relapse during the trial and social functioning, quality of life, symptom scores (Positive and Negative Syndrome Scale) and rates of being in employment, education or training at 24-month follow-up. We also analysed changes in these measures during the trial among those who relapsed and those who did not. Sensitivity analyses were conducted examining the effects of ‘severe’ relapse (i.e. admission to hospital).

During the course of the trial, 82 out of 253 participants relapsed. There was no evidence for a difference between those who relapsed and those who did not on changes in social functioning, quality of life, symptom scores or overall employment rates between baseline and 24-month follow-up. Those who relapsed showed no change in their social functioning or quality of life, and a slight improvement in symptoms compared to baseline. They were more likely than those who did not relapse to have had a change in their employment status (mostly moving out of employment, education or training), although numbers changing status were small. Sensitivity analyses showed the same results for those who experienced a ‘severe’ relapse.

Our data provide little evidence that relapse has a detrimental effect in the long term in people with schizophrenia and recurrent psychosis.

Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.

Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.

A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).

This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.

1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.

Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.

ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.

Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies.

Probands and relatives with current DSM-IV BED (n = 156) from a family study of BED (‘baseline’) were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints.

Of participants with follow-up data (n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables.

Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.

Studies investigating parenthood and how it affects long-term outcomes are lacking among individuals with schizophrenia spectrum disorders. This study aimed to examine the life of participants 20 years after their first diagnosis with a special focus on parenthood, clinical illness course, and family-related outcomes.

Among 578 individuals diagnosed with first-episode schizophrenia spectrum disorder between 1998 and 2000, a sample of 174 participants was reassessed at the 20-year follow-up. We compared symptom severity, remission, clinical recovery, and global functioning between 75 parents and 99 non-parents. Also, family functioning scored on the family assessment device, and the children's mental health was reported. We collected longitudinal data on psychiatric admission, supported housing, and work status via the Danish registers.

Participants with offspring had significantly lower psychotic (mean (s.d.) of 0.89 (1.46) v. 1.37 (1.44), p = 0.031) negative (mean [s.d.] of 1.13 [1.16] v. 1.91 [1.07], p < 0.001) and disorganized symptom scores (mean [s.d.] of 0.46 [0.80] v. 0.85 [0.95], p = 0.005) and more were in remission (59.5% v. 22.4%, p < 0.001) and in clinical recovery (29.7% v. 11.1%, p = 0.002) compared to non-parents. When investigating global functioning over 20 years, individuals becoming parents after their first diagnosis scored higher than individuals becoming parents before their first diagnosis and non-parents. Regarding family-related outcomes, 28.6% reported unhealthy family functioning, and 10% of the children experienced daily life difficulties.

Overall, parents have more favorable long-term outcomes than non-parents. Still, parents experience possible challenges regarding family functioning, and a minority of their children face difficulties in daily life.

Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia.

This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK.

Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%).

PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.

Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.

One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.

Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.

Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression.

An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months.

Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse.

The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.