In patients with remitted psychosis, the dosage of antipsychotics can be lowered without increased risk of relapse. Whether dose tapering can lead to improved cognition is unclear. We compared changes in cognitive performance between patients undergoing dose tapering and those receiving a fixed maintenance dose.

A 2-year prospective trial of patients with stable schizophrenia-related psychotic disorders was conducted: one group received guided dose reduction (GDR) and one group received maintenance treatment. Cognitive function was assessed using the Wechsler Adult Intelligence Scale-Third Edition, Mandarin Chinese version, at baseline, 1, and 2 years. The relations between the ratio of reduced dose and the extent of cognitive improvement were examined by Spearman’s correlation coefficient. We also examined cognitive performance between aripiprazole (ARI) users and non-ARI users.

GDR patients exhibited significantly greater improvements in total intellectual quotient (IQ), particularly working memory, and information and arithmetic subtest scores, with no significant difference in relapse rates between groups. Statistically significant dose–response correlations were found between the degree of dose reduction and improvements in total IQ (n = 72, r = 0.242, p = 0.041), Working Memory Index (n = 72, r = 0.284, p = 0.016), and Arithmetic subtest (n = 72, r = 0.295, p = 0.012). There were no differences in cognitive changes between ARI users and non-users.

Lowering antipsychotic dosage may ameliorate patient performance in several cognitive domains. This finding is worthy of consideration while evaluating the risk-to-benefit ratio of tapering antipsychotics in patients with remitted psychosis.

Antipsychotic (AP) medication in individuals at clinical high risk for psychosis (CHR-P) is not routinely recommended by clinical guidelines but is commonly prescribed. Since little is known about the predictors of AP inception in CHR-P, we analyzed data from two observational cohorts.

To avoid baseline predictors being confounded by previous treatment, participants were selected for analysis from the 764 participants at CHR-P enrolled in NAPLS-2 and the 710 enrolled in NAPLS-3 by excluding those with lifetime histories of AP use. Baseline clinical variables available in both studies were employed as predictors of subsequent AP inception over the next 6 months in univariable and multivariable analyses.

Preliminary analyses indicated no important effects of sample. The final combined population included 79 AP inception participants and 580 participants who did not have AP inception. The AP medications most commonly prescribed were risperidone, aripiprazole, and quetiapine. Univariable analyses identified seven significant predictors of AP inception. The final logistic regression model including these variables was highly significant (χ2 = 36.53, df = 7, p = <0.001). Three variables (current major depression, fewer education years, and current benzodiazepine use) emerged as significant independent predictors of AP inception.

This study is the first to determine baseline characteristics that predict subsequent AP initiation in CHR-P. Some AP use in CHR-P appears to be intended as augmentation of antidepressant treatment for comorbid major depression. Some prescribers may not have detected the attenuated positive symptoms characteristic of CHR-P since their severity did not significantly predict AP inception.

Second-generation antipsychotics (SGAs) are moderately effective treatments for psychotic disorders but are associated with significant weight gain and metabolic complications. These contribute to a nearly 20-year reduction in life expectancy for individuals with enduring psychotic illness. Weight gain can also negatively impact adherence, increase relapse risk, and worsen psychosocial outcomes.

To highlight the mechanisms underlying antipsychotic-induced weight gain (AIWG), examine pharmacological strategies for its prevention and treatment, and argue for the early use of metformin.

This perspective article synthesises current evidence on the pathophysiology of AIWG and evaluates the role of metformin in mitigating these effects.

Weight gain can occur rapidly after initiating antipsychotic treatment, particularly in young people and those prescribed antipsychotics for non-psychotic indications. Presentation and response to interventions vary. Of all pharmacological strategies, metformin has the most robust evidence for both prevention and treatment of AIWG. It is a well-tolerated, low-cost antihyperglycaemic agent with an established safety profile. Metformin should be considered early in the course of antipsychotic treatment for all individuals, regardless of diagnosis, to prevent clinically significant weight gain and reduce long-term health risks. Early intervention may improve adherence, reduce relapse, and enhance overall quality of life.

The origins and treatment-target-related mechanisms of schizophrenia remain to be fully understood. Pharmacological and non-pharmacological treatments require expansion and improvements to meet peoples’ needs and goals. Nevertheless, antipsychotics are a cornerstone when managing schizophrenia, being essential for reducing symptom severity, preventing relapse, improving long-term functional outcomes, and reducing premature mortality risk.

This narrative review synthesizes key evidence on the efficacy and risks associated with antipsychotic medications. The concept of effect sizes is introduced, allowing to compare antipsychotics across trials with different rating instruments and across different conditions.

The available evidence in schizophrenia and comparison with medications used for medical conditions counters the sometimes-voiced criticism that antipsychotics “do not work.” Instead, for a substantial group of people with schizophrenia, positive psychotic symptoms and global psychopathology improve witha small-medium effect size of about 0.4 versus placebo. These results are comparable to median effect sizes across commonly used medications for somatic disorders. When patients with initial response are continued on antipsychotics, the effect size increases to 0.9 for relapse prevention, translating into a number needed to treat (NNT) of about 3 to prevent one more relapse versus no treatment. This NNT is 10–20 times higher than that for the prevention of poor outcomes in some common medical conditions.

Despite general efficacy and effectiveness of antipsychotics for schizophrenia, further development is needed regarding preventive interventions and medications with mechanisms other than postsynaptic dopamine receptor blockade, with broader efficacy for positive, negative, cognitive, suicidality, and/or reward dysregulation symptomatology, and the identification of illness mechanism/biomarker-targeting treatments to enhance treatment personalization.

Patients in forensic psychiatric care (FPC) are commonly treated with a wide range of psychotropic medications. There is, however, a lack of understanding regarding how pharmacological treatment and psychotropic polypharmacy are used throughout care.

This register-based cohort study included patients admitted to FPC in Sweden between 2009 and 2020. We estimated the prevalence of the use of major psychotropic medication, as well as psychotropic polypharmacy, at admission and discharge. We also examined the change in antipsychotic use after admission.

In total, 1962 patients were included. Antipsychotics were the most used psychotropic medication class, with 86.2% (95%CI: 84.5–87.8) of patients receiving at least one typical or atypical antipsychotic at admission. Changes in the antipsychotic regime were more common at the beginning of FPC, compared to later time points. Within the subgroup of patients discharged during the study period (n = 561), there was a reduction in the use of typical antipsychotics (admission: 34.9%; discharge: 26.6%) and hypnotics and sedatives (admission: 37.4%; discharge: 28.1%). Other major medication classes remained relatively stable. The prevalence of psychiatric polypharmacy at admission was 70.6% (95%CI: 68.5–72.7) and remained similar during care.

Our study documented a high prevalence of antipsychotic use and psychotropic polypharmacy through FPC. Further, a high level of off-label antipsychotic use and antipsychotic polypharmacy was observed. Stronger evidence regarding the effectiveness and safety of these treatment strategies is needed.

Clinical high risk for psychosis (CHR) is often managed with antipsychotic medications, but their effects on neurocognitive performance and clinical outcomes remain insufficiently explored. This study investigates the association between aripiprazole and olanzapine use and cognitive and clinical outcomes in CHR individuals, compared to those receiving no antipsychotic treatment.

A retrospective analysis was conducted on 127 participants from the Shanghai At Risk for Psychosis (SHARP) cohort, categorized into three groups: aripiprazole, olanzapine, and no antipsychotic treatment. Neurocognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were assessed through the Structured Interview for Prodromal Syndromes (SIPS) at baseline, 8 weeks, and one year.

The non-medicated group demonstrated greater improvements in cognitive performance, clinical symptoms, and functional outcomes compared to the medicated groups. Among the antipsychotic groups, aripiprazole was associated with better visual learning outcomes than olanzapine. Improvements in neurocognition correlated significantly with clinical symptom relief and overall functional gains at follow-up assessments.

These findings suggest potential associations between antipsychotic use and cognitive outcomes in CHR populations while recognizing that observed differences may reflect baseline illness severity rather than medication effects alone. Aripiprazole may offer specific advantages over olanzapine, underscoring the importance of individualized risk-benefit evaluations in treatment planning. Randomized controlled trials are needed to establish causality.

Patients with psychosis face an elevated risk of cardiovascular mortality and are more likely to disengage from care. While antipsychotics are essential for treatment, they further increase this risk. Despite this, Ghana lacks a national policy for monitoring cardiovascular risk factors in individuals on antipsychotics.

To evaluate disengagement in care and weight changes among newly diagnosed psychotic patients at Accra Psychiatric Hospital, and to inform clinical practice.

A retrospective review of medical records was conducted for patients newly diagnosed with non-affective psychotic disorders between June 2022 and May 2023. Patients were reviewed for 6 months, with assessments at baseline, 3 months and 6 months. Outcomes included antipsychotic prescription patterns, dropout rates, cardiovascular disease monitoring and weight changes. Descriptive statistics, multinomial logistic regression and linear mixed-effects models were used for analysis.

The number of patients disengaged from care within the first month was 53.1%, and within 6 months 75.5%; 62.8% received olanzapine at baseline. Weight gain was exponential, with 40% experiencing clinically significant weight gain at 3 months, increasing to 58% at 6 months. Less than 50% of patients had their blood sugar and lipid profiles checked before starting antipsychotics. Higher baseline weight was associated with increased weight over time (β = 0.96, t = 80, P < 0.001, 95% CI 0.93, 0.98).

High disengagement rates, low cardiovascular disease monitoring and exponential weight gain were observed. Targeted interventions, robust monitoring protocols and further research are needed to improve patient outcomes.

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.

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.

Catatonia in psychotic patients presents unique challenges. While antipsychotics are the cornerstone of schizophrenia treatment, their use in catatonic patients is sometimes discouraged for fear of worsening the signs. Reports on the successful use of second-generation antipsychotics have been published. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to describe the outcomes of antipsychotic-treated catatonic events.

We searched Medline and Web of Science databases from 2000 to 2023 using search terms including “catatonia” and “antipsychotic agents” for all original peer-reviewed articles, including clinical trials, observational studies, and case-reports. We included antipsychotic-treated catatonic events and extracted data on patient characteristics, pharmacological context, agent involved, and treatment outcomes for each antipsychotic trial.

After screening 6,219 records, 79 full-text articles were included. Among them, we identified 175 antipsychotic trials (in 110 patients). Only 41.1% of the patients benefited from a previous benzodiazepine trial. Antipsychotic use was considered beneficial in 60.0% of the trials, neutral in 29.1%, and harmful in 10.9%. Trials tended to be reported as beneficial for amisulpride, clozapine, and risperidone, equivocal for aripiprazole and olanzapine, and mostly detrimental for haloperidol and quetiapine. Psychotic disorders were the most common underlying etiology (65.8%).

Antipsychotics could be an option in the treatment of catatonia in psychotic patients. However, with few exceptions, we found non-beneficial outcomes with all second-generation antipsychotics in varying proportions in this largest review to date. Although olanzapine is widely used, it is associated with mitigated reported outcomes.

Venous thromboembolism (VTE) is a fatal condition affecting older people. This study aims to identify specific risk factors for VTE in older psychiatric in-patients within mental hospital settings. Using predefined search terms, we searched five databases to capture studies evaluating risk factors associated with the occurrence of deep vein thrombosis and pulmonary embolism in older psychiatric in-patients.

Thirteen studies were identified, and a narrative synthesis performed. Increasing age was a consistent risk factor for VTE. Diagnosis and psychotropic medication use were inconsistent. Depression, catatonia and use of restraint in people with dementia were associated with higher risks.

Older psychiatric in-patients differ from medical and surgical in-patients in their risk profiles. Screening tools used in general hospital patients are of limited use among older adults in psychiatric hospital settings. An exclusive screening tool to identify VTE risk factors in older psychiatric in-patients is needed.

Relatively little is known about mental healthcare-related harm, with patient safety incidents (PSIs) in community-based services particularly poorly understood. We aimed to characterize PSIs, contributory factors, and reporter-identified solutions within community-based mental health services for working-age adults.

We obtained data on PSIs reported within English services from the National Reporting and Learning System. Of retrieved reports, we sampled all incidents reportedly involving ‘Death’, ‘Severe harm’, or ‘Moderate harm’, and random samples of a proportion of ‘Low harm’ or ‘No harm’ incidents. PSIs and contributory factors were classified through qualitative content analysis using existing frameworks. Frequencies and proportions of incident types were computed, and reporter-identified solutions were inductively categorized.

Of 1825 sampled reports, 1443 were eligible and classified into nine categories. Harmful outcomes, wherein service influence was unclear, were widely observed, with self-harm the modal concern amongst ‘No harm’ (15.0%), ‘Low harm’ (62.8%), and ‘Moderate harm’ (37.6%) categories. Attempted suicides (51.7%) and suicides (52.1%) were the most frequently reported events under ‘Severe harm’ or ‘Death’ outcomes, respectively. Incidents common to most healthcare settings were identified (e.g. medication errors), alongside specialty-specific incidents (e.g. Mental Health Act administration errors). Contributory factors were wide-ranging, with situational failures (e.g. team function failures) and local working conditions (e.g. unmanageable workload) widely reported. Solution categories included service user-directed actions and policy introduction or reinforcement.

Study findings provide novel insights into incidents, contributory factors, and reported solutions within community-based mental healthcare. Targets for safety improvement are outlined, aimed at strengthening system-based prevention of incidents.

The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.