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.

Some patients return for further psychological treatment in routine services, although it is unclear how common this is, as scarce research is available on this topic.

To estimate the treatment return rate and describe the clinical characteristics of patients who return for anxiety and depression treatment.

A large dataset (N=21,029) of routinely collected clinical data (2010–2015) from an English psychological therapy service was analysed using descriptive statistics.

The return rate for at least one additional treatment episode within 1–5 years was 13.7%. Furthermore, 14.5% of the total sessions provided by the service were delivered to treatment-returning patients. Of those who returned, 58.0% continued to show clinically significant depression and/or anxiety symptoms at the end of their first treatment, while 32.0% had experienced a demonstrable relapse before their second treatment.

This study estimates that approximately one in seven patients return to the same service for additional psychological treatment within 1–5 years. Multiple factors may influence the need for additional treatment, and this may have a major impact on service activity. Future research needs to further explore and better determine the characteristics of treatment returners, prioritise enhancement of first treatment recovery, and evaluate relapse prevention interventions.

Nowadays, relapses are typical in patients with schizophrenia and may have serious implications due to most of them are caused by a lack of adherence to treatment.Therefore, numerous long-acting injectable antipsychotics (LAI) have been developed as aripiprazole depot who need a proper oral supplementation. Since November 2020, FDA approved a new treatment indication with a double injection start and a single dose of 20mg of oral aripiprazole, with the aim of avoiding oral supplementation during the next 14 days.

The purpose of our study is to expose our experience with the new double injection start with aripiprazole LAI, regarding the rehospitalization rate.

A prospective study (n=17 patients) has been developed between November 2020 and October 2021 with the purpose of studying the rehospitalization and antipsychotic adherence after the new guideline of aripiprazole

After an 11-month-follow-up, it is noticed a 65% non-rehospitalization rate and a 76% proper treatment persistence rate. The 94% did not present any kind of side effects, only one patient had a case report of bullous pemphigoid. Regarding the concomitant use of other antipsychotics, 82% of the patients remained in monotherapia. The average stay time was shortened (11 days) regarding the standard dose (14 days).

The new LAI regimen is well tolerated in our patients obtaining a high treatment persistence after several months of hospital discharge. It was already possible to shorten the time of rehospitalization, not having to add oral aripiprazole for 14 days. Most patients were discharged are on antipsychotic monotherapy and have not been rehospitalized in the short term.

No significant relationships.

Polypharmacy can be the cause of deliberate discontinuation of medication and consequent relapse of schizophrenia.

To establish the one-year rate of relapse in the patients with schizophrenia with regard to monotherapy or polypharmacy.

The sample of all hospitalized patients with schizophrenia in a five-year period was analyzed. Descriptive statistics were used.

Total of 87 participants (57 women), the median age was 43 years. Antipsychotic monotherapy was used in 31 (35.6%) of the participants. In one year period, 32 (36.8%) of all participants had a relapse. Prior to relapse, significantly more participants were treated with polypharmacy (p<0,05).

Antipsychotic polypharmacy is related to a higher rate of relapse in patients with schizophrenia.

No significant relationships.

People with schizophrenia could be more substantially influenced by the emotional stress brought on by the COVID-19 pandemic, resulting in relapses or worsening of an already existing mental health condition because of the high susceptibility to stress.

This study aimed to assess the presence of relapse and its risk factors among patients with schizophrenia during the era of COVID 19 pandemic.

This study included 90 adults who met DSM-5 criteria for schizophrenia and were diagnosed by (SCID-I) Arabic version and who are following up at the outpatient psychiatric clinic, Zagazig University Hospital, Egypt, Positive and Negative Syndrome Scale (PANSS) measuring severity of symptoms, Compliance Rating Scale (CRS) and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). scales were conducted on those patients before COVID-19 pandemic from January to April 2019 and repeated on September to November 2020 during COVID 19 pandemic to compare clinical parameters between those two periods as to detect any deterioration in their clinical state.

The mean score of compliance rating scale (CRS) was decreased after COVID-19 pandemic compared to before COVID 19 (P<0.001).The mean score of PANSS scale positive subscale (P) had increased after COVID-19 pandemic compared to before COVID 19 (P<0.001).

There was a deterioration of the clinical state of schizophrenic patients during COVID-19 pandemic especially the positive symptoms and following up the news about COVID-19 regularly, decreased level of family support, lower level of compliance with treatment, and having a family member with COVID-19 infection or death were the risk factors for relapse.

No significant relationships.

Introduction: Residual depressive symptoms are common after a successful acute treatment of late-life depression (LLD), and their presence predicts increased risk of relapse. While electroconvulsive therapy (ECT) is the most effective treatment for LLD, little is known about which particular symptoms remain and impact long-term outcome after a successful acute ECT course.

Objectives: We aimed to assess the association between specific residual depressive symptoms after an effective acute ECT course for LLD and relapse at six-month follow-up.

Methods: In this prospective cohort study, including 110 patients aged 55 years and older with LLD, information about relapse was collected six months after the acute ECT course. Relapse was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15, hospital admission or restart of ECT. We used multivariable stepwise logistic regression models including the scores on the 10 individual MADRS items at the end of the acute ECT course to predict relapse.

Results: Of the 80 responders with available six-month follow-up data, 29 patients (36.25%) had suffered relapse. Higher scores on the MADRS items ‘reduced sleep’ (odds ratio (OR)=2.03, 95% confidence interval (CI)=1.11-3.69, p=0.0214) and ‘lassitude’ (OR=1.62, 95% CI=1.00-2.62, p=0.0497) at the end of the acute ECT course were significantly associated with increased risk of relapse at six-month follow-up.

Conclusions: Some residual depressive symptoms, including sleep disturbance and fatigue, may help better identify patients vulnerable to relapse following a successful acute ECT course for LLD. Future studies assessing interventions that target specific residual symptoms may further reduce post-ECT depressive relapse.

No significant relationships.

Maintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.

We aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.

Clinical records of 44 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated.

Nearly half of the patients were male (n:24, 54%). 43,2% of the patients were married. The mean age was 36.6±11.9 years and the mean duration of education was 11.5±3.9 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (65.9%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. Ten of the patients discontinued the treatment due to the side effects and extrapyramidal side effects was the most common side effect. Relapse was observed in 25% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.

LAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.

No significant relationships.

Clinical relapses in schizophrenia remain a frequent event. Long-acting injectable (LAI) antipsychotics enhance adherence, but low blood levels can sometimes be observed despite an adequate posology. Nonetheless, the evaluation of this parameter is uncommon in clinical practice.

To explore the potential advantages of therapeutic drug monitoring (TDM) of LAIs as a predictor of relapse in clinically stable outpatients with schizophrenia.

44 individuals who had reached the pharmacokinetic steady state of LAI treatment (paliperidone, olanzapine, aripiprazole) underwent an anamnestic and psychopathological assessment. LAI blood levels were measured using liquid chromatography-mass spectrometry and classified as “in range” or “under range” according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guideline values. Individuals who relapsed during the one-year follow-up were compared to non-relapsers (Fisher’s exact test, χ2 or Mann-Whitney U). An exploratory binary logistic regression tested the role of other possible relevant predictors of relapse.

No differences were observed in baseline use of mood stabilisers (p=0.211), antidepressants (p=0.530), or prescribed LAI (p=0.563). Other comparisons are presented in the table: among these variables, in-range LAI levels were the only significant predictor of relapse (F=5.95, p=0.015; OR 0.04, 95%CI 0.02-0.56).

TDM of LAIs may optimise the clinical management of schizophrenia by highlighting a suboptimal dosage and a consequent higher relapse risk. Large-scale, drug-specific assessments are needed to confirm these findings.

No significant relationships.

Relapses in major depression are frequent and are associated with a high burden of disease. Although short-term studies suggest a normalisation of depression-associated brain functional alterations directly after treatment, long-term investigations are sparse.

To examine brain function during negative emotion processing in association with course of illness over a 2-year span.

In this prospective case–control study, 72 in-patients with current depression and 42 healthy controls were investigated during a negative emotional face processing paradigm, at baseline and after 2 years. According to their course of illness during the study interval, patients were divided into subgroups (n = 25 no-relapse, n = 47 relapse). The differential changes in brain activity were investigated by a group × time analysis of covariance for the amygdala, hippocampus, insula and at whole-brain level.

A significant relapse × time interaction emerged within the amygdala (PTFCE-FWE = 0.011), insula (PTFCE-FWE = 0.001) and at the whole-brain level mainly in the temporal and prefrontal cortex (PTFCE-FWE = 0.027), resulting from activity increases within the no-relapse group, whereas in the relapse group, activity decreased during the study interval. At baseline, the no-relapse group showed amygdala, hippocampus and insula hypoactivity compared with healthy controls and the relapse group.

This study reveals course of illness-associated activity changes in emotion processing areas. Patients in full remission show a normalisation of their baseline hypo-responsiveness to the activation level of healthy controls after 2 years. Brain function during emotion processing could further serve as a potential predictive marker for future relapse.

Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis.

Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse.

Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical−striatal−thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse.

MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.