SSRI withdrawal syndrome in children and adolescents: a narrative literature review.

INTRODUCTION: While there is considerable published evidence regarding the nature and severity of Selective Serotonin Reuptake Inhibitor (SSRI) discontinuation symptoms in the adult population, information relating to the child and adolescent population remains scarce. This narrative review examined the published literature on SSRI withdrawal symptoms in the under-18-year-old age group. MEDLINE and PsycINFO were comprehensively searched from inception to 5 May 2023. AREAS COVERED: This review highlights the importance of recognizing SSRI withdrawal in children and adolescents and summarizes available literature and guidelines for safe discontinuation. EXPERT OPINION: Evidence of the presence of SSRI withdrawal phenomenon in children and adolescents mainly originates from case reports and extrapolated adult data. Existing data on SSRI withdrawal syndrome in children and adolescents is therefore limited, and there is a need for formal research in this specific population to establish with more certainty the nature and extent of SSRI withdrawal syndrome. Nevertheless, there is currently enough evidence available for prescribing clinicians to provide psychoeducation to patients and families about the possibility of withdrawal symptoms when SSRI treatment is considered. The need for gradual and planned discontinuation should also be discussed for safe withdrawal.

Long-acting antipsychotics in the treatment of schizophrenia: opportunities and challenges.

INTRODUCTION: Maintenance antipsychotic treatment improves multiple outcomes in people with schizophrenia. These benefits are challenged by medication nonadherence, which is a common occurrence. Long-acting injectable antipsychotic (LAI) formulations were developed to reduce nonadherence and thereby improve outcomes. This narrative review is based on a PubMed search (January 2000 - August 2022) for studies on LAI antipsychotics. AREAS COVERED: Opportunities and challenges associated with LAIs are reviewed. Advantages, compared to oral antipsychotics (OAs), include improved adherence, reduced relapse and hospitalization risk, delayed and lower relapse risk after stopping treatment, and the ability to differentiate true treatment resistance from 'pseudo'-resistance. Additionally, LAIs are associated with lower all-cause mortality than OAs. LAIs are under-used in many services, partly reflecting negative attitudes, misconceptions, and lack of knowledge among clinicians, patients, and carers. Practical barriers to LAI use include acquisition costs and inadequate service structures to administer/monitor LAI treatment. EXPERT OPINION: The education and engagement of clinicians, patients and caregivers can assist more informed decision-making regarding LAIs. Future research regarding LAIs should encompass multiple complementary designs, focus on functionality and recovery outcomes, and include groups at high risk of relapse, including those with comorbid substance use disorders and early in the course of schizophrenia.

Patients' and primary carers' views on clozapine treatment for schizophrenia: A cross-sectional study in Qatar.

Subjective views of clozapine treatment among patients with schizophrenia in the Middle East and North African MENA Region have not previously been assessed. Globally, few studies have assessed the views of carers to clozapine treatment. We conducted a cross-sectional survey, using a clinician administered structured interview, of patients with schizophrenia/schizoaffective disorder prescribed clozapine in Qatar, and their primary carers. Participants were asked to rate clozapine against prior their antipsychotic treatment in terms of specific benefits and side effects. Forty-two patients and 33 carers participated in the study. Of the patients, two thirds were male, approximately half were Qatari and the mean age was 33.9 years. Patients and carers rated clozapine as superior to prior antipsychotic treatment on all 7 potential benefits inquired about. The greatest perceived benefit was improved mood. Patients rated clozapine as less likely to cause extrapyramidal side effects but more likely to cause 18 other potential side effects compared to prior antipsychotic treatment, with the greatest difference being for nocturnal salivation, increased appetite, and constipation. Nearly half of patients (48 %) and two thirds of carers (64 %) stated that they would have preferred to start clozapine earlier in their illness. Sixty percent of patients and 37 % of carers regarded the information that they had received from health professionals on clozapine as inadequate. Less than half of patients and approximately-two thirds of carers had adequate knowledge of haematological monitoring for clozapine. Generally, there were significantly positive correlation between patients and carers regarding the overall side effects of clozapine treatment. Likewise, improvement in hearing voices paranoid thoughts correlated with improved quality of life. In summary, the results show that patients and carers appreciate the benefits of clozapine despite its side effects being problematic. The results support clozapine being offered earlier in treatment and services providing more information on clozapine to patients and carers.

COVID-19 perceived stigma among survivors: A cross-sectional study of prevalence and predictors

Background and objectivesPerceived stigma related to infectious diseases is of public health importance and can adversely impact patients' physical and mental health. This study aims to identify the level of perceived stigma among COVID-19 survivors in Qatar and investigate its predictors.MethodsAn analytical cross-sectional design was employed. Four hundred and four participants who had a positive COVID-19 PCR test were randomly selected from medical records. The selected participants were interviewed to collect sociodemographic and health-related information. Perceived stigma was assessed using the COVID-19 perceived stigma scale-22 (CPSS-22) that was developed by the researchers. A descriptive analysis followed by a bivariate analysis investigated possible associations between the perceived stigma levels and independent variables. A multivariable analysis was performed using logistic regression to identify any significant associations with perceived stigma. The validity and reliability of the developed tool were also tested.ResultsThe prevalence of COVID-19 perceived stigma was twenty-six percent (n = 107, 26.4%) at 95% CI [22.4–30.4]. Factors associated with higher COVID-19 perceived stigma were male gender, being a manual worker, non-Arabic ethnicity, low educational level, living alone, and being isolated outside the home. However, only occupation, ethnicity, and low educational level predicted COVID-19 perceived stigma in multivariable analysis. The CPSS-22 showed excellent reliability (Cronbach's alpha 0.92).ConclusionPerceived stigma was relatively common among participants. Designing programs and interventions targeting male manual workers and those of low-educational levels may assist policymakers in mitigating the stigma related to COVID-19. (AU)

COVID-19 perceived stigma among survivors: A cross-sectional study of prevalence and predictors.

Background and objectives: Perceived stigma related to infectious diseases is of public health importance and can adversely impact patients' physical and mental health. This study aims to identify the level of perceived stigma among COVID-19 survivors in Qatar and investigate its predictors. Methods: An analytical cross-sectional design was employed. Four hundred and four participants who had a positive COVID-19 PCR test were randomly selected from medical records. The selected participants were interviewed to collect sociodemographic and health-related information. Perceived stigma was assessed using the COVID-19 perceived stigma scale-22 (CPSS-22) that was developed by the researchers. A descriptive analysis followed by a bivariate analysis investigated possible associations between the perceived stigma levels and independent variables. A multivariable analysis was performed using logistic regression to identify any significant associations with perceived stigma. The validity and reliability of the developed tool were also tested. Results: The prevalence of COVID-19 perceived stigma was twenty-six percent (n = 107, 26.4%) at 95% CI [22.4-30.4]. Factors associated with higher COVID-19 perceived stigma were male gender, being a manual worker, non-Arabic ethnicity, low educational level, living alone, and being isolated outside the home. However, only occupation, ethnicity, and low educational level predicted COVID-19 perceived stigma in multivariable analysis. The CPSS-22 showed excellent reliability (Cronbach's alpha 0.92). Conclusion: Perceived stigma was relatively common among participants. Designing programs and interventions targeting male manual workers and those of low-educational levels may assist policymakers in mitigating the stigma related to COVID-19.

Trends in prevalence of depression and anxiety symptoms and effects of sociodemographic variables before and after the first wave of COVID-19 in Qatar.

BACKGROUND: Prevalence trends from Arabic speaking countries on psychiatric symptoms before and after the first wave of the COVID-19 pandemic are lacking. We estimated the point prevalence and change in depression and anxiety symptoms scores in relation to sociodemographic variables following the resolution of the first wave in Qatar compared with before the pandemic. METHODS: We conducted a trend analysis using repeated nationally representative cross-sectional surveys spanning 2017, 2018, 2020/2021 and using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) to assess depressive and anxiety symptoms. Negative binomial regression was used to model changes in these symptoms in relation sociodemographics and survey year. RESULTS: The two-week prevalence of depressive symptoms (≥10 on the PHQ-9) was 6.6% in 2017 and 6.5% in 2020/2021 (p = 0.986). The two-week prevalence of anxiety symptoms (≥10 on the GAD-7) was 3.6% in 2018 and 5.1% in 2020/2021 (p = 0.062). The data for 2020/21 showed a 35.1% and 29.2% decrease in depression and anxiety symptoms scores compared to pre-pandemic years (2017/2018) after adjusting for sociodemographic factors. LIMITATIONS: Screening tools rather than structured interviews were used to assess depressive and anxiety symptoms CONCLUSIONS: The prevalence of depression and anxiety after the first COVID wave did not differ significantly to pre-pandemic estimates. The end of the first wave of the pandemic weakened the associations of these symptoms with traditional sociodemographic risk factors. The 2020/21 depression and anxiety symptoms scores remained high for Qataris and Arabs, suggesting that these cultural groups may benefit most from public mental health interventions.

Abnormal corneal nerve morphology and brain volume in patients with schizophrenia.

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35-0.86 and P = 0.50) or cognitive function (P = 0.35-0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61-0.64) or diabetes (P = 0.057-0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.

Support and attitudes of Qatar mental health professionals to a proposed mental health inpatient smoking ban: Results of a cross-sectional survey.

WHAT IS KNOWN ON THE SUBJECT?: Smoking is more common among people with serious mental illness, and it contributes to a reduced life expectancy. Several Western countries have successfully introduced smoke-free policies in inpatient mental health units. There is virtually no information about attitudes to smoking bans in mental health units from countries in the Middle East and North Africa region. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We surveyed mental health professionals working in Qatar's main mental health service to determine support for and attitudes towards a proposed total smoking ban in psychiatric wards. Most staff who completed the survey supported an inpatient smoking ban. However, further analysis, both quantitative and qualitative, showed markedly ambivalent attitudes, that is staff simultaneously held attitudes that supported and opposed a smoking ban. Professionals who did not support a ban were more likely to have not received smoking cessation training in the last 5 years, to be a psychiatrist rather than a nurse or allied mental health professional, to be current smokers and to be a Middle Eastern and North African national. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Further staff training is necessary to achieve more consistent attitudes that support a total smoking ban and increase the likelihood of successful implementation. The attitudes in this study showed similarities and differences to those reported for mental health professionals in Western countries. This highlights that local research is necessary to help shape training and successfully implement smoke-free policies. ABSTRACT: Introduction Despite the fact that patients with serious mental illness (SMI) have high rates of smoking and an increased standardized mortality, there is virtually no information about attitudes to smoking bans in mental health units from countries in the Middle East and North Africa region. Aim To assess support for, and attitudes towards, a proposed total smoking ban in psychiatric wards among mental health clinicians in Qatar. Method Cross-sectional survey of mental health professionals working in Qatar's primary mental health service. Results The response rate was 68% (353/520). Support for a ban was assessed with a single-item question; 73% of respondents supported a ban with opposition significantly (p < .05) associated with being a current smoker, a Middle Eastern and North African (MENA) national, a psychiatrist versus a mental health nurse or allied health professional and not receiving smoking cessation training in the last 5 years. A 21-item questionnaire assessed attitudes to a total smoking ban. It showed marked ambivalence with multiple linear regression identifying MENA nationality, male gender and current smoking status as independent variables influencing attitudes. The most strongly held attitude supporting a ban was concern about passive smoking and against a ban was concern it may increase patient agitation. Qualitative data confirmed ambivalent views. Discussion The results show similarities and differences to research from other countries suggesting that cultural factors influence some attitudes to smoke-free policies. Implications for Practice Staff support and smoking cessation education are necessary to achieve more consistent staff attitudes to support smoke-free policies.

Psychiatric inpatients' views of their mental health, and their experience of social change, during the pandemic: A report from Qatar.

WHAT IS KNOWN ON THE SUBJECT?: There is only limited information on how the COVID-19 pandemic has affected people diagnosed with mental health disorders, especially people admitted to psychiatric wards. We surveyed the views of inpatients at Qatar's only psychiatric hospital regarding how the pandemic had affected their mental health and social changes they had experienced during the pandemic. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Nearly half (43%) of those who completed the survey reported that the pandemic had led to a deterioration in their mental health. Those who reported deterioration in their mental health during the pandemic were significantly more likely to have experienced negative social changes during the pandemic. Examples included increased stress from the home and reduced ability to discuss emotions/feelings with family members. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health services need to ensure ongoing support for patients during and after the pandemic. Mental health nurses have a pivotal role including identifying early warning signs of relapse of mental disorders, delivering talking treatments and providing practical advice and COVID-19-related education. Further work is needed to assess the views of people diagnosed with mental health problems in different countries and at a different time point during the pandemic. ABSTRACT: Introduction The impact of the COVID-19 pandemic on people under the care of mental health services has received relatively little attention in the scientific literature. Aim To assess psychiatric inpatients' views regarding their mental health and experience of social change during the pandemic. Method Cross-sectional survey of consecutive patients admitted to Qatar's only psychiatric hospital between mid-June and mid-October 2020. Results Data were analysed for 114/284 (40%) patients admitted during the study period. 8 (7%) reported a history of COVID-19. 43% reported that the pandemic had led to deterioration in their mental health, 11% to an improvement and 39% that there had been no attributable change. Those reporting worsened mental health, attributable to the pandemic, were significantly more likely to report having experienced four negative social changes during the pandemic, namely reduced ability to discuss emotions/feelings with family members, decreased time spent exercising, decreased time spent relaxing and increased stress from the home. Demographic factors did not distinguish those reporting worsened mental health from those whose mental health was improved or unchanged. Discussion A large proportion of psychiatric inpatients reported negative social and mental health changes during the pandemic. However, the study cannot determine causality. Implications for practice Mental health services should consider the psychological and social aspects of people's lives, including their interactions with family, friends and the community. This is especially relevant during the COVID-19 pandemic due to its wide impact on society. Interventions for people diagnosed with mental health disorders should address their psychological and social needs.

Buspirone in the management of refractory irritable bowel syndrome: A case report.

RATIONALE: Irritable bowel syndrome (IBS) is a chronic and debilitating functional disorder of the gastrointestinal tract manifested by abdominal pain and bowel habit dysregulation. The pathophysiology is complex and management targets symptom resolution. Therapeutic interventions range from dietary modification, psychological interventions, exercise, to the use of antispasmodics, antibiotics, and antidepressants. Anecdotal reports have suggested that buspirone may be beneficial in the treatment of functional dyspepsia and IBS and its physiological effect of reducing gastric tone provides a rational for its benefit. PATIENT CONCERNS: A 28-year-old man with unremarkable past medical and psychiatric history presented with worsening abdominal pain, bloating, and bowel movement dysregulation of over 6-year duration. DIAGNOSES: Physical examination revealed mild distension and discomfort on deep palpation. Thorough blood investigations, stool analysis and culture, and imaging were unremarkable except for the detection of mucus with stool. The patient was diagnosed with irritable bowel syndrome with mixed habits. INTERVENTIONS: Dietary adjustment and a range of medications (mebeverine, simethicone, loperamide, rifaximin, sertraline and amitriptyline) yielded unsatisfactory response of were not tolerated. Buspirone was eventually introduced. OUTCOMES: Buspirone was associated with a significant and sustained improvement in IBS symptoms and quality of life. LESSONS: This case suggests that buspirone was effective in treating refractory IBS. Further research is needed to assess the role of buspirone in IBS management.

Mania and hypomania associated with COVID-19: a series of 15 cases seen by the consultation-liaison psychiatry service in Qatar.

BACKGROUND: A range of neuropsychiatric diagnoses have been reported in association with coronavirus disease 2019 (COVID-19). However, only sporadic cases of mania or hypomania have been reported in patients with COVID-19. This study aimed to report clinical characteristics of 15 consecutive cases of COVID-19-associated mania or hypomania seen in three general hospitals in Qatar in the early months of the pandemic in 2020. METHODS: This study is a retrospective case-note review of 15 cases of COVID-19-associated mania or hypomania (confirmed by polymerase chain reaction test), seen as inpatient consultations out of the first 100 consecutive patients managed by consultation-liaison psychiatric teams in Qatar between 2 March 2020 and 7 July 2020. RESULTS: The mean age of the 15 patients was 40 years. Twelve patients had mania, and three had hypomania. Regarding the physical severity of COVID-19, 10 patients were asymptomatic, two had upper respiratory tract symptoms alone and three had pneumonia. None of the patients were intubated. Potential risk factors for mania/hypomania included pandemic-related psychosocial stress before admission (n = 9), past history of mania/bipolar disorder (n = 6) or psychosis (n = 2), raised inflammatory markers (n = 7) and steroid use (n = 3). None had a history of recent substance misuse. Other than one patient with advanced cancer, none had comorbidity regarded as likely to have caused mania or hypomania. Three patients had mild white matter ischaemic changes on brain imaging. Standard pharmacological treatment for mania (i.e. antipsychotic medication supplemented by prn benzodiazepines) was effective. Ten patients were discharged home from the COVID-19 facility where they presented, but five required transfer to Qatar's psychiatric hospital for further treatment of mania. CONCLUSION: The association of mania or hypomania with COVID-19 may be spurious (e.g. representing an initial presentation of bipolar disorder) or causal. The reported cases illustrate a range of potential aetiological mechanisms by which COVID-19 could cause mania or hypomania. Cohort studies are necessary to determine the incidence, aetiology and prognosis of COVID-19-associated mania/hypomania.

Delirious mania in a patient with COVID-19 pneumonia.

Delirious mania (the coexistence of delirium and mania) is described in the literature but not recognised in standard nosologies. We report a woman in her late 30s, with no psychiatric history, who presented with concurrent symptoms of mania and delirium. She was diagnosed with COVID-19 pneumonia (positive reverse transcription-PCR test). There was no history of substance misuse or concurrent medical illness. CT head scan was normal as were blood investigations, other than elevated inflammatory markers. She received standard treatment for COVID-19 pneumonia and lorazepam and quetiapine to treat her neuropsychiatric symptoms. She made a full recovery after 9 days. She was apyrexial with normal oxygen saturation throughout her illness. The case shows that severe neuropsychiatric symptoms can complicate otherwise mild COVID-19 pneumonia with neuroinflammation being a possible mechanism. A diagnosis of delirious mania appears to better capture the complexity of the presentation than a diagnosis of mania or delirium alone.

The COVID-19 pandemic: an opportunity to make mental health a higher public health priority.

Coronavirus disease 2019 (COVID-19) was first recognised in December 2019. The subsequent pandemic has caused 4.3 million deaths and affected the lives of billions. It has increased psychosocial risk factors for mental illness including fear, social isolation and financial insecurity and is likely to lead to an economic recession. COVID-19 is associated with a high rate of neuropsychiatric sequelae. The long-term effects of the pandemic on mental health remain uncertain but could be marked, with some predicting an increased demand for psychiatric services for years to come. COVID-19 has turned a spotlight on mental health for politicians, policy makers and the public and provides an opportunity to make mental health a higher public health priority. We review longstanding reasons for prioritising mental health and the urgency brought by the COVID-19 pandemic, and highlight strategies to improve mental health and reduce the psychiatric fallout of the pandemic.

Prevalence and Potential Determinants of COVID-19 Vaccine Hesitancy and Resistance in Qatar: Results from a Nationally Representative Survey of Qatari Nationals and Migrants between December 2020 and January 2021.

Global COVID-19 pandemic containment necessitates understanding the risk of hesitance or resistance to vaccine uptake in different populations. The Middle East and North Africa currently lack vital representative vaccine hesitancy data. We conducted the first representative national phone survey among the adult population of Qatar, between December 2020 and January 2021, to estimate the prevalence and identify potential determinants of vaccine willingness: acceptance (strongly agree), resistance (strongly disagree), and hesitance (somewhat agree, neutral, somewhat disagree). Bivariate and multinomial logistic regression models estimated associations between willingness groups and fifteen variables. In the total sample, 42.7% (95% CI: 39.5-46.1) were accepting, 45.2% (95% CI: 41.9-48.4) hesitant, and 12.1% (95% CI: 10.1-14.4) resistant. Vaccine resistant compared with hesistant and accepting groups reported no endorsement source will increase vaccine confidence (58.9% vs. 5.6% vs. 0.2%, respectively). Female gender, Arab ethnicity, migrant status/type, and vaccine side-effects concerns were associated with hesitancy and resistance. COVID-19 related bereavement, infection, and quarantine status were not significantly associated with any willingness group. Absence of or lack of concern about contracting the virus was solely associated with resistance. COVID-19 vaccine resistance, hesitance, and side-effects concerns are high in Qatar's population compared with those globally. Urgent public health engagement should focus on women, Qataris (non-migrants), and those of Arab ethnicity.

Long-Acting Injectable Antipsychotics: A Systematic Review of Their Non-Systemic Adverse Effect Profile.

INTRODUCTION: Long acting injectable (LAI) antipsychotics are commonly used in the treatment of schizophrenia to improve adherence and clinical outcomes. Concerns have been reported in relation to their non-systemic or injection site adverse effect profile. As such, this study aims to review and evaluate all evidence reporting injection site adverse effects with LAI antipsychotics. METHODS: An electronic search was systematically conducted through four databases (PubMed, Embase, SCOPUS, Cochrane) in order to identify studies investigating injection-site reactions associated with LAI antipsychotics. Unpublished studies such as conference proceedings and clinical trial registries were also searched. The search was limited to literature published in English without year limits. RESULTS: Of a total of 189 citations that were identified from the electronic database search, 12 were selected for inclusion in this review. Various injection site reactions were reported in these studies, including pain, bleeding, and swelling. Overall, the studies reported a low incidence of these injection site reactions. Only a minority of the included articles compared injection site reactions between different LAI antipsychotics. CONCLUSION: Injection site pain was the most commonly reported injection site adverse effect across all articles reviewed. The low incidence of injection site adverse effects associated with LAI antipsychotics indicates that these formulations appear to be well tolerated by patients. More head-to-head trials comparing second generation LAI antipsychotics are needed.

Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics. METHODS: We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries. FINDINGS: 7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I2=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I2=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I2=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I2=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I2=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I2=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations. INTERPRETATION: During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation. FUNDING: None.