[Self-harming behavior and suicide attempts in autism spectrum disorder: A systematic overview].

Recent research indicates that the risk of suicide attempts in autism spectrum disorder is substantially higher than in the general population. Although a number of factors may play a role in suicide, in the present review we focused on the meta-analyses that examined self-injurious behavior and suicide attempts in autism due to the importance of these factors. Results to date suggest that the risk of self-harming behavior and suicide attempts in autism is approximately three-times higher than in the general population. Of concern, are findings that suggest that women with autism are 5-13 times more likely to complete suicide than women without autism. It is noteworthy that the high-functioning autistic group has a significantly higher risk of suicide than the low-functioning group. By contrast, the risk of death from somatic causes is higher in the low-functioning autistic group. The results of this systematic overview of the available meta-analyses may help health care professionals, decision-makers, affected persons and their relatives to recognize self-injurious behavior and suicide risk in time, thereby facilitating prevention.

[How could forensic psychiatry be made more attractive?] / Hogyan lehetne az igazságügyi pszichiátriát vonzóbbá tenni?

INTRODUCTION: Decrease in the number of forensic psychiatric experts recently reached a critical level. Shortage of forensic experts caused difficulties in the health care as well as in the justice system. OBJECTIVE: Surveying of how the field of forensic psychiatry and the forensic psychiatric expert work can be made more attractive. METHOD: We performed an online survey among forensic psychiatric experts and specialists in psychiatry. We complied a questionnaire that beside demographic data contained questions in 4 areas. The first 2 areas of the questionnaire - simplifying the forensic psychiatry training (10 items), decreasing the cost of the forensic psychiatry training (5 items) - consisted of simple tatements. Responders had to indicate on a 10-point Likert scale their level of agreement. In the last 2 areas, participants were asked to describe in unstructured format whether they see any circumstance that makes forensic psychiatry attractive or unattractive. The questionnaire was sent out in electronic form to the forensic psychiatric experts on the mailing list of the Hungarian Forensic Expert Chamber, and all specialists in psychiatry on the mailing list of the Hungarian Medical Chamber. RESULTS: Altogether 171 persons filled in the questionnaire with a mean age of 57.26 ± 11.57 years. There were 122 (71.3%) females among the participants. The following proposals received the highest ratings from the forensic psychiatric experts as well as from the specialists in psychiatry: increasing the number of the training institutes; decreasing the costs of the training; making the Hungarian Forensic Expert Chamber course free of charge; and introducing a stipend to cover the costs of the training. DISCUSSION: Results of the survey indicate that active forensic psychiatric experts and specialists in psychiatry representing a potential professional resource, concur that forensic psychiatry training can be made more attractive mainly with increasing the number of training institutes and decreasing the total costs of the training which is compiled from different constituents. CONCLUSION: Due to the critical lack of necessary professionals, urgent action is needed to make forensic psychiatry more popular and the forensic psychiatry qualification easier to obtain. Orv Hetil. 2023; 164(35): 1373-1380.

[Psychiatric disorders are associated with high mortality rates: somatic comorbidity and mortality in autism spectrum disorder and schizophrenia]. / A pszichiátriai betegségekre jelentos korai halálozási arányszámok jellemzok: szomatikus komorbiditás és mortalitás autizmusspektrum-zavarban és szkizofréniában.

A significant proportion of the high mortality associated with psychiatric illness is due to premature death in comorbidity with somatic illness, and to a lesser extent suicide and accidents. In our literature review, we demonstrate that the risk of mortality for individuals diagnosed with autism spectrum disorder and schizophrenia is more than twice of that of controls. With respect to schizophrenia diagnosis, national data from Hungary are available, and consistent with the international data show an increased risk of mortality. In Hungary, the mortality risk of persons with a diagnosis of schizophrenia is about 2.4 times higher than that of controls matched by age, sex and postcode. In particular, the risk of dying from schizophrenia is increased among young people (7-10 times) and we highlight that although the risk of death in schizophrenia is higher for men than for women, the risk of dying from schizophrenia for women diagnosed with schizophrenia is higher than for men compared to the female control group (relative risk). Considering the high prevalence of psychiatric disorders, an important prerequisite for improving the national mortality rates recorded for somatic illnesses is the early diagnosis and treatment of psychiatric illnesses comorbid with somatic illnesses. The data presented here can help to support the reforms needed in medical education and training and in the organization of health care to reduce mortality. Orv Hetil. 2023; 164(33): 1287-1293.

Electrophysiological underpinnings of dysfunctional inhibitory control in adults with attention-deficit/hyperactivity disorder: evidence for reduced NoGo anteriorization.

Our aim was to delineate the electrophysiological basis of dysfunctional inhibitory control of adult ADHD via investigating the anteriorization of the P3 component of the event-related brain response associated with the NoGo task condition (i.e., NoGo anteriorization, NGA). NGA is a neurophysiological measure of brain topography for cognitive response control, which indexes an overall shift of the brain's electrical activity in anterior direction towards the prefrontal areas. While the NoGo P3 received considerable attention in the adult ADHD literature, the brain topography of this component, which reflects the inhibitory process, remains largely unaddressed. EEG recordings were obtained during a Go/NoGo task from 51 subjects (n = 26 adult patients with ADHD, n = 25 healthy controls) using a high-density, 128-channel BioSemi ActiveTwo recording system. ADHD patients had significantly lower P3 NGA response compared to controls. The decrease in NGA was related to impulsivity scores as measured by the Conners' Adult ADHD Rating Scale: patients with higher impulsivity scores had significantly lower NGA. Treatment with stimulant medication, as compared to the lack of such treatment, was associated with a correction of the lower NGA response in ADHD patients. The current study revealed a lower NGA in adult ADHD, a finding which is consistent with the inhibitory control and frontal lobe dysfunctions described in the disorder. Our finding of the inverse relationship between NGA and impulsivity suggests that clinically more severe impulsivity is linked to a more pronounced frontal dysfunction in adult ADHD subjects.

Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence.

BACKGROUND: Summarizing evidence from clinical trials of patients with schizophrenia with predominant or prominent negative symptoms (NS), a prior meta-analysis reported a large placebo effect in negative symptoms (Cohen's d = 2.909). Assuming that such an effect was clinically not plausible, we performed a critical re-assessment and an update of the previous results with newly available data from add-on and monotherapy studies. STUDY DESIGN: Random-effect meta/regression analysis of trials that focused on predominant or prominent NS; and adopted a double-blind, randomized, placebo-controlled design. The final pooled meta-analytic database, based on the available add-on and monotherapy studies combined, included 24 publications containing data on a total of 25 studies (21 add-on, 4 monotherapy). STUDY RESULTS: The pooled overall estimate for the placebo effect from the primary analysis for all included studies had a medium effect size, with a Cohen's d value of 0.6444 (SE = 0.091). The estimates were similar in the add-on and monotherapy studies. Meta-regression indicated that the high placebo response was significantly associated with clinical trial characteristics, including the high ratio of patients assigned to active vs. placebo treatment and short trial duration. CONCLUSIONS: These results represent a major downward correction for a current effect size estimate of the placebo response in the negative symptoms of schizophrenia. Our findings also pinpoint certain clinical trial characteristics, which may serve as important predictors of the placebo response. The knowledge of these factors can have important implications for drug development and trial design for new drugs for negative symptoms of schizophrenia.

What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial.

Introduction: Minimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence. Methods: Data of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression-Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID1); as the difference between the PANSS-FSNS change associated with the first instance and the PANSS-FSNS changes associated with the last recorded clinically unchanged status across all visits (MCID2); with the effect size approach (MCID3); as the Youden Index based cut-off value between no clinical change and minimal improvement (MCID4); as the relative likelihood of minimal improvement (MCID5). Results: The MCID1 and MCID2 resulted in, respectively, a 3.8-point (18.5%) and a 1.5-point (7.3%) decrease from baseline severity on the PANSS-FSNS. Greater values were required for the MCID at later evaluation times. The cut-off between minimum improvement and no clinical change defined by the Youden Index was a-3-point (15%) change in the PANSS-FSNS. The effect size approach indicated the 1.5-point difference between minimally improved and unchanged patients to be a medium effect (ES = 0.6). Conclusion: Applying different methods led to different results, ranging between 7.3 and 18.5% improvement from the baseline for the MCID at its earliest occurrence in patients with predominantly negative symptoms of schizophrenia.

Separate pathways to violent behavior in schizophrenia and in the general population.

Violence in schizophrenia is best investigated within the broader context of violent behavior in the general population. Two important domains of general pathology which allow us to take such an approach include impairment in emotion processing, as manifested by faulty facial emotion recognition, and aggressive reactivity which consists of heightened sensitivity to provocation. To test this approach, we included 135 subjects: 38 violent (VS's) and 33 nonviolent patients with schizophrenia, 32 healthy controls and 32 non-psychotic violent subjects (NPV's). We measured violence with the Life History of Aggression Scale, recognition of facial emotions with the Emotion Recognition Task, and aggressive reactivity through the Buss-Perry Aggression Questionnaire. Adolescent antisocial behavior was evaluated as a potential precursor to these deficits. We found that impairment in fear recognition (IFR) and aggressive reactivity have a significant effect on violence in the violent groups. These two impairments interact in different ways in these groups. In NPV's they contribute in an additive fashion to violence, whereas in VS's they represent separate pathways; aggressive reactivity leads to violence only when there is no IFR. Adolescent antisocial behavior has a differential effect on these 2 impairments in the 2 groups. Thus, these findings provide insights on the differential role of IFR and aggressive reactivity for violence in schizophrenia compared to the general population. In NPV's, both dysfunctions represent antisocial features and contribute jointly to violence. In schizophrenia, they have different etiologies and constitute alternative pathways to violence. This has important implications for the conceptualization and treatment of violence.

Behaviour and Experience: The Two Sides of the Negative Syndrome - A Comparison of Andreasen's Negative Syndrome and Huber's Basic Symptoms.

Negative symptoms in schizophrenia and schizoaffective disorder are present both in behavior and in the subjective experience of the patients, however the relationships between these two components have not been sufficiently studied. Standardized assessment methods were utilized in a study of 96 acutely exacerbated inpatients and 26 stabilized outpatients with the diagnosis of schizophrenia and schizoaffective disorder for the measurement of nega tive symptoms, subjective experiences, depression, general psychopathology and neurological side effects. Halo - peridol blood levels were controlled in the inpatient group. Results of this study suggest that the behavioral symptoms and the subjective experiences of the negative syndrome are not correlated with each other. The subjective experiences of negative symptoms were highly correlated with depression in the acutely exacerbated inpatients, but not in the outpatients. Medication levels and neurological side effects were not related either to the behavioral or the experiential aspects of the negative syndrome.

A meta-analysis of effectiveness of real-world studies of antipsychotics in schizophrenia: Are the results consistent with the findings of randomized controlled trials?

Randomized controlled trials (RCTs) have been considered as gold standard for establishing the efficacy and safety of investigational new drugs; nonetheless, the generalizability of their findings has been questioned. To address this issue, an increasing number of naturalistic studies and real-world database analyses have been conducted. The question of how much information from these two approaches is congruent or discrepant with each other is of great importance for the clinical practice. To answer this question, we focused on data from the antipsychotic (AP) treatment of schizophrenia. Our aim was two-fold: to conduct a meta-analysis of real-world studies (RWS), and to compare the results of RWS meta-analysis with previously published meta-analyses of RCTs. The principal measure of effectiveness was all-cause treatment discontinuation for both RWS and RCTs (when not available, then drop out for RCTs). We included publications for 8 selected APs (oral formulations of amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and long-acting injectable (LAI) risperidone). We identified 11 RWS and 7 RCT meta-analyses for inclusion. Our results indicated that the RWS yielded statistically conclusive and consistent findings across individual investigations. For the overwhelming majority of the comparisons where both RWS and RCT meta-analyses were available, there was good congruency between the RWS and the RCT results. Our results support that RCTs, despite their limitations, provide evidence which is generalizable to real-world settings. This is an important finding for both regulators and clinicians. RWS can provide guidance for situations where no evidence is available from double-blind clinical trials.

Atypical resting-state gamma band trajectory in adult attention deficit/hyperactivity disorder.

Decreased gamma activity has been reported both in children and adults with attention deficit/hyperactivity disorder (ADHD). However, while ADHD is a lifelong neurodevelopmental disorder, our insight into the associations of spontaneous gamma band activity with age is limited, especially in adults. Therefore, we conducted an explorative study to investigate trajectories of resting gamma activity in adult ADHD patients (N = 42) versus matched healthy controls (N = 59). We investigated the relationship of resting gamma activity (30-48 Hz) with age in four right hemispheric electrode clusters where diminished gamma power in ADHD had previously been demonstrated by our group. We found significant non-linear association between resting gamma power and age in the lower frequency gamma1 range (30-39 Hz) in ADHD as compared to controls in all investigated locations. Resting gamma1 increased with age and was significantly lower in ADHD than in control subjects from early adulthood. We found no significant association between gamma activity and age in the gamma2 range (39-48 Hz). Alterations of gamma band activity might reflect altered cortical network functioning in adult ADHD relative to controls. Our results reveal that abnormal gamma power is present at all ages, highlighting the lifelong nature of ADHD. Nonetheless, longitudinal studies are needed to confirm our results.

The Importance of Conduct Disorder in the Treatment of Violence in Schizophrenia: Efficacy of Clozapine Compared With Olanzapine and Haloperidol.

OBJECTIVE: Treatment of violence in schizophrenia remains a challenging problem, especially in patients with conduct disorder. Previous clinical studies did not select patients on the basis of violence and did not focus on conduct disorder. This study is a head-to-head comparison of clozapine, olanzapine, and haloperidol in the treatment of violent schizophrenia patients with and without conduct disorder. METHODS: Physically assaultive schizophrenia patients (N=99) were randomly assigned to receive clozapine, olanzapine, or haloperidol in a 12-week double-blind trial. They were characterized on the basis of the presence or absence of conduct disorder before age 15. Assaults were recorded; their frequency and severity were scored on the Modified Overt Aggression Scale. Psychiatric symptoms were evaluated through the Positive and Negative Syndrome Scale. RESULTS: Patients with a history of conduct disorder had more frequent and severe assaults than those without conduct disorder during the 12-week trial. Clozapine was superior to haloperidol and olanzapine in reducing assaults; olanzapine was superior to haloperidol. Clozapine's greater antiaggressive efficacy over haloperidol was substantially more pronounced in patients with conduct disorder than in patients without conduct disorder. In patients with conduct disorder, clozapine was four times more likely than haloperidol to result in lower violence; in patients without conduct disorder, it was three times more likely to do so. Olanzapine's superiority over haloperidol was also more pronounced in patients with conduct disorder. CONCLUSIONS: This study is the first to examine the effect of clozapine in violent schizophrenia patients with conduct disorder. When conduct disorder is present, clozapine is the optimal treatment.

Impaired early information processing in adult ADHD: a high-density ERP study.

BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) often demonstrate sensory processing difficulties in the form of altered sensory modulation, which may contribute to their symptomatology. Our objective was to investigate the neurophysiological correlates of sensory processing deficits and the electrophysiological characteristics of early information processing in adult ADHD, measured by the P1 event-related potential (ERP). METHODS: We obtained ERPs during a Go/NoGo task from 26 adult patients with ADHD and 25 matched controls using a high-density 128-channel BioSemi ActiveTwo recording system. RESULTS: ADHD patients had a significantly reduced P1 component at occipital and inferotemporal scalp areas compared to controls. The reduction was associated with inattention and hyperactivity symptom severity, as measured by the Conners' Adult ADHD Rating Scale. ADHD patients with higher inattention scores had significantly smaller P1 amplitudes at posterior scalp sites, while higher hyperactivity scores were associated with higher P1 amplitudes. CONCLUSIONS: Deficits in early sensory processing, as measured by the P1 ERP component, are present in adult ADHD patients and are associated with symptom severity. These findings are suggestive of bottom-up cognitive deficits in ADHD driven by impairments in early visual processing, and provide evidence that sensory processing problems are present at the neurophysiological level in this population.

Multivariate patterns of EEG microstate parameters and their role in the discrimination of patients with schizophrenia from healthy controls.

Quasi-stable electrical fields in the EEG, called microstates carry information on the dynamics of large scale brain networks. Using machine learning techniques, we explored whether abnormalities in microstates can be used to classify patients with schizophrenia and healthy controls. We applied multivariate pattern analysis of microstate features to create a specified feature set to represent microstate characteristics. Machine learning approaches using these features for classification of patients with schizophrenia were compared with prior EEG based machine learning studies. Our microstate segmentation in both patients with schizophrenia and healthy controls yielded topographies that were similar to the normative database established earlier by Koenig et al. Our machine learning model was based on large sample size, low number of features and state-of-art K-fold cross-validation technique. The multivariate analysis revealed three patterns of correlated features, which yielded an AUC of 0.84 for the group separation (accuracy: 82.7%, sensitivity/specificity: 83.5%/85.3%). Microstate segmentation of resting state EEG results in informative features to discriminate patients with schizophrenia from healthy individuals. Moreover, alteration in microstate measures may represent disturbed activity of networks in patients with schizophrenia.

Attention deficit hyperactivity disorder: Last in, first out - delayed brain maturation with an accelerated decline?

While early neurodevelopmental processes during the emergence of ADHD in childhood received considerable attention, the neurobiological mechanisms that underlie the changes in ADHD in adulthood remain largely unaddressed. We wanted to delineate neurodevelopmental changes in adult ADHD using an electrophysiological measure, the fronto-central NoGo P3 event-related potential (ERP), which is an important neurophysiological index of brain functioning in ADHD, and biomarker for response inhibition and aging. ERPs were obtained from 45 ADHD and 41 healthy subjects using a 128-channel BioSemi recording-system, applying emotionally-valenced and neutral stimuli in a response inhibition task. Our results indicated that ADHD subjects manifested delayed developmental P3-trajectory in young-adulthood as compared to controls; they also showed P3 reduction across all emotional valences, and the reduction was most pronounced at younger ages. The differences in P3 diminished by mid-adulthood, and started to increase again at more advanced ages. Thus, similar to structural-MRI indices, developmental brain differences in the fronto-central NoGo P3 in ADHD largely normalize in young-adulthood. However, a reduction of P3 occurs again starting from mid-adulthood. As the fronto-central NoGo P3 reflects the functioning of the frontal areas (which show delayed maturation in ADHD), our findings are consistent with the ''last in, first out'' hypothesis, which refers to a mirroring pattern of brain development and aging, and posits that brain regions that develop relatively late degenerate relatively early with age. Thus, ADHD may not only be associated with delayed neurodevelopment, but also with a premature age-related deterioration, at least in some measures of electrophysiological functioning.

[How we see the development of clinical trials from the investigators' side?]

This is a discussion paper on research in clinical pharmacology in the field of psychiatry. In addition to other factors the decline in discovery and development of new drugs in the field of psychiatry and the developments and growing complexity in the field of clinical trial technology, including outsourcing and risk based monitoring, reduced the number of young clinical researchers interested in this important field. The challenges posed by the restructuring within the pharmacological industry - including digitalization - should induce changes in the structure and in the processes of clinical pharmacology research and in the training of clinical research staff members. The approval of esketamine nasal spray for treatment resistant depression by the FDA and the results of research with psychedelics call for more education and training in this specific field.

ADHD: a hidden comorbidity in adult psychiatric patients.

Adult attention-deficit/hyperactivity disorder (aADHD) has recently been better recognized and treated in many European countries. In spite of this development, aADHD still features as a "hidden" comorbidity, often not diagnosed even in patients under psychiatric treatment for other psychiatric disorders. The aim of this study was to establish the prevalence rates of unrecognized aADHD in academic centers providing regular psychiatric services in the Czech Republic and Hungary. In a population of psychiatric in-and outpatients, Adult ADHD Self-Report Scale was administered. All positively and about half of the negatively screened subjects were clinically interviewed and the DSM diagnosis of ADHD was determined based on the symptom list and Conners' Adult ADHD Rating Scale. The estimated point prevalence rate of unrecognized comorbid aADHD among psychiatric in-and out patients was 6.99% (95% lower CI: 5.11, 95% upper CI 8.86) according to the DSM-IV-TR criteria and 9.27% (95% lower CI: 7.13, 95% upper CI 11.40) according to the DSM-5 criteria. Current suicide risk was significantly associated with the presence of undiagnosed aADHD; however, life time suicide attempts, depression, dysthymia, alcohol and substance dependence, anxiety and stress related disorders were not. Further educational efforts are needed to improve the recognition and treatment of aADHD in adults.

Alterations in resting-state gamma activity in patients with schizophrenia: a high-density EEG study.

Alterations of EEG gamma activity in schizophrenia have been reported during sensory and cognitive tasks, but it remains unclear whether changes are present in resting state. Our aim was to examine whether changes occur in resting state, and to delineate those brain regions where gamma activity is altered. Furthermore, we wanted to identify the associations between changes in gamma activity and psychopathological characteristics. We studied gamma activity (30-48 Hz) in 60 patients with schizophrenia and 76 healthy controls. EEGs were acquired in resting state with closed eyes using a high-density, 256-channel EEG-system. The two groups were compared in absolute power measures in the gamma frequency range. Compared to controls, in patients with schizophrenia the absolute power was significantly elevated (false discovery rate corrected p < 0.05). The alterations clustered into fronto-central and posterior brain regions, and were positively associated with the severity of psychopathology, measured by the PANSS. Changes in gamma activity can lead to disturbed coordination of large-scale brain networks. Thus, the increased gamma activity in certain brain regions that we found may result in disturbances in temporal coordination of task-free/resting-state networks in schizophrenia. Positive association of increased gamma power with psychopathology suggests that altered gamma activity provides a contribution to symptom presentation.

Decreased resting gamma activity in adult attention deficit/hyperactivity disorder.

Objectives: To delineate task-free gamma activity in adult ADHD and healthy control subjects based on high-density EEG recordings. Relationship of gamma activity with symptom severity was also examined, since gamma activity is considered to be an index of network functions in the brain that underlie higher-order cognitive processes.Methods: Spontaneous EEG was recorded in adult ADHD subjects (N = 42; 25 methylphenidate-naïve and 17 on methylphenidate treatment) and controls (N = 59) with eyes open. EEG absolute power gamma was investigated in the gamma1 (30.25-39 Hz) and gamma2 (39.25-48 Hz) frequency bands.Results: Gamma1 and gamma2 activity was diminished in ADHD compared with healthy control subjects. The difference between ADHD and controls was the most pronounced in the right centroparietal region for both gamma1 and gamma2. Inverse associations were found between gamma1 and gamma2 activity and ADHD symptoms in centroparietal scalp regions.Conclusions: Gamma activity is reduced in adult ADHD, and the reduction has a predominantly right centroparietal distribution. Our findings are consistent with childhood ADHD literature with respect to diminished posterior gamma activity in patients, which may reflect altered dorsal attention network functions. Gamma abnormalities might provide a link between neurophysiological functioning and neuropsychological deficiencies, thereby offering an opportunity to investigate the neurobiological mechanisms that underlie the clinical symptoms of ADHD.

Efficacy of typical and atypical antipsychotic medication on hostility in patients with psychosis-spectrum disorders: a review and meta-analysis.

As violence against self and others is an important outcome in the treatment of patients with psychosis-spectrum disorders and hostility is an important indicator for violence, we set out to evaluate the effects of different types of antipsychotic agents in reducing hostility. We performed a systematic literature search, which provided 18 suitable randomized studies comparing typical to atypical antipsychotics for at least 4 weeks in patients with psychotic disorders. Results showed a small (0.26) but significant effect for atypical as compared to typical antipsychotics, with high heterogeneity, even though the mean dose of typical antipsychotics was higher. This effect size remained similar when separately analyzing sponsored and non-sponsored studies. When differentiating between high and low-dose studies, the high-dose group showed a significant difference between typical and atypical antipsychotics whereas the low-dose group did not. An analysis comparing clozapine to typical antipsychotics showed a moderate effect size (0.415), with low heterogeneity. These results are important for clinicians to help their shared decision making with patients when choosing maintenance treatment, as next to efficacy for psychosis and tolerability, safety for the patient and their environment is an important outcome.