Antipsychotic Discontinuation Research Articles

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

National surveillance using a clinical quality indicator for prolonged antipsychotic use among older Australians with dementia who access aged care services.

Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC. Retrospective cohort study, including older individuals with dementia who accessed HCPs (n=50,257) or PRAC (n=250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n=2367) and PRAC (n=15,597) using the cumulative incidence function. Between 2011-12 and 2015-16, antipsychotic use for >90days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively. While small decreases in antipsychotic use >90days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized.

Withdrawal syndrome after antipsychotics discontinuation: an analysis of the WHO database of spontaneous reports (Vigibase) between 2000 and 2022.

Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data. We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors. The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094). Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.

Guanfacine Used With Antipsychotics May Cause Bradycardia to Become Apparent After Discontinuation of Antipsychotics.

Guanfacine Used With Antipsychotics May Cause Bradycardia to Become Apparent After Discontinuation of Antipsychotics.

The effects of antipsychotic discontinuation or maintenance on the process of recovery in remitted first-episode psychosis patients - A systematic review and meta-analysis of randomized controlled trials.

The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients. CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach. Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2=0%; n=128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups. Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

Antipsychotic Prescribing in Older Adults after In-Hospital Initiation.

In older adults, the use of antipsychotics to treat delirium or the behavioural and psychological symptoms of dementia is potentially inappropriate and may be associated with adverse effects. Antipsychotics newly initiated in hospital may be inadvertently continued after discharge. In the Saskatchewan Health Authority (SHA) - Regina area, the frequency and duration of antipsychotic continuation for older adults after initiation during a hospital stay is unknown. To describe potentially inappropriate antipsychotic use in older adults after discharge from hospital, specifically rates of postdischarge antipsychotic therapy after initiation in hospital and continuation up to 180 days after discharge; prescribing regimens used; risk factors associated with continuation; pharmacist involvement; and plans for antipsychotic discontinuation, tapering, and/or follow-up. This retrospective chart review included inpatients 65 years of age or older who were discharged from medicine units at SHA - Regina area hospitals between September 30, 2021, and June 28, 2022. Outpatient dispensing histories were also gathered. Of the 189 patients included in the analysis, 60 (31.7%) had continuation of antipsychotic therapy at discharge. Of these, 48 (80.0%), 33 (55.0%), and 24 (40.0%) had continuation of antipsychotic therapy at 30, 90, and 180 days after discharge, respectively. Of the patients with continuing antipsychotic therapy, 53 (88.3%) were 75 years of age or older, and 9 (15.0%) had documentation of an outpatient antipsychotic follow-up plan. Postdischarge continuation of antipsychotics was similar to that reported in the literature. Patients continued on antipsychotics after discharge were at a greater than 50% risk of continuation at 90 days and were unlikely to have a follow-up plan. Future quality improvement efforts should include standardized prioritization of medication reviews, documentation of indications, and regular reassessment of therapy.

Changes in substance use and engagement in gaming/gambling in persons with severe mental illness during the COVID-19 pandemic and earthquakes: a community study in two points.

External stressors, such as COVID-19 pandemic and earthquake, can cause an increase in substance use and addictive behavior in persons with severe mental illnesses (SMI). We analyzed the changes and predictors of substance use and addictive behavior in SMI during these double disasters in Croatia. Questionnaires exploring the presence of substance or behavior addiction disorder, mental ill health [Depression Anxiety Stress Scales-21 (DASS-21), Insomnia Severity Index (ISI), Perceived Stress Scale (PSS), Obsessive-Compulsive Inventory-Revised], coping mechanisms, and perceived social support [Multidimensional Scale of Perceived Social Support (MSPSS)] were administered among 90 participants with SMI included in the RECOVER-E study in May/June 2020 (first COVID-19 wave, Zagreb earthquake) and in December 2020/January 2021 (second COVID-19 wave, Petrinja earthquake). In both time points, a major increase was observed in tobacco smoking (25.0%; 28.6%, respectively) predicted by discontinuation of antidepressants and higher DASS-21 score. Increased sedative use was observed (24.4%; 23.8%, respectively) predicted by higher PSS and ISI scores, lower MSPSS scores, antipsychotic discontinuation and not receiving community mental health team (CMHT) service. In persons with SMI during a double disaster special attention needs to be given to reducing mental-ill health and stress, providing social support and continuity of psychiatric care, through medications and CMHTs.

Predictors of hospitalisation and recovery following full antipsychotic discontinuation in first episode psychosis. A naturalistic retrospective cohort study.

Whilst antipsychotic medication reduces risk of relapse following a first episode of psychosis (FEP), some individuals can discontinue medication and remain relapse free. We aimed to identify patient and service-specific factors which influence clinical outcome following antipsychotic discontinuation. The outcomes 'admission to hospital' and 'remaining free from psychotic symptoms', both within one year from discontinuation, were explored retrospectively in an established naturalistic cohort of 354 patients with FEP. Logistic regression analysis was used to explore influence of routinely available baseline and treatment course variables on these outcomes. Seventy-seven individuals (22%) fully discontinued antipsychotic treatment within a year, at mean 102days from initiation. Only antipsychotic type had significant association with discontinuation; aripiprazole was discontinued more than olanzapine (p=0.028). Seventeen individuals required admission to hospital; significantly associated with prior admission at first illness onset (p=0.004), and prior legal detention to hospital (p=0.001). Admission was less likely in those discontinuing aripiprazole vs olanzapine (p=0.044). Twenty-four patients remained psychosis symptom free and were most significantly likely to have received clinician support in discontinuation; this group had no association with either initial duration of untreated psychosis or prior duration of antipsychotic treatment. Future studies exploring outcomes following antipsychotic discontinuation require consistency of choice of outcome measures and sample stratification by vulnerability factors including severity of first illness episode, whether remaining symptom free after first episode, which medication switched from and baseline functioning. The impact and nature of clinician support to discontinue requires further exploration alongside its association with abruptness of discontinuation.

Time-dependent effect of antipsychotic discontinuation and dose reduction on social functioning and subjective quality of life–a multilevel meta-analysis

Meta-analyses indicate superiority of antipsychotic maintenance treatment over discontinuation within up to 24 months after treatment initiation for patients with schizophrenia-spectrum disorders. In terms of functional recovery, long-term trials show improved functioning after discontinuation, suggesting a time-dependent effect of antipsychotic maintenance. However, these trials were not included in previous meta-analyses. We therefore investigated whether the effect of antipsychotic maintenance treatment vs. discontinuation on social functioning and quality of life varies by trial length. The study was preregistered with PROSPERO (CRD42021248933). PubMed, PsycINFO, Web of Science, Embase and trial registers were systematically searched on 8th November 2021 and updated on 25th June, 2023 and 10th August, 2023 for studies that compared antipsychotic maintenance to discontinuation and reported data on social functioning or subjective quality of life in patients with schizophrenia-spectrum disorders. Risk of bias was assessed with the RoB 2, the ROBINS-I and the RoB-ME tools. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. We included k=35 studies (N=5924) with follow-ups between one month and 15 years. Overall, maintenance and discontinuation did not differ on social functioning (k=32; n=5330; SMD=0.204; p=0.65; 95% CI [-0.69, 1.10]) or quality of life (k=10; n=943; SMD=-0.004; p=0.97; 95% CI [-0.22, 0.21]), whilst subgroup analyses of middle- (2-5 years; k=7; n=1032; SMD=0.68; 95% CI [0.06, 1.28]) and long-term follow-ups (>5 years; k=2; n=356; SMD=1.04; 95% CI [0.82, 1.27]) significantly favoured discontinuation. However, the quality of evidence was rated as very low. Although our findings suggest a time-dependent decrease in the effect of maintenance treatment on social functioning, interpretation of these findings is limited by the serious risk of bias in middle- and long-term trials. Therefore, any conclusions regarding the long-term benefits of antipsychotic treatment or discontinuation for functional recovery are premature and more high-quality trials tailored to comparing state of the art maintenance treatment vs. discontinuation are needed. None.

Receptor-Independent Therapies for Forensic Detainees with Schizophrenia-Dementia Comorbidity.

Forensic institutions throughout the world house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, psychiatric treatment, and nutrition led to an unmatched longevity in this population, which previously lived, on average, 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management, increasing healthcare expenditures. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who have aged on dopamine-blocking agents. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss may contribute to the development of early dementia. Taken together, increased lifespan and the subsequent cognitive deficit observed in long-term forensic institutions raise questions and dilemmas unencountered by the previous generations of clinicians. These include: does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? Can patients with schizophrenia and dementia meet the Dusky standard to stand trial? Should neurocognitive disorders in the elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we hypothesize that gray matter loss is the core symptom of schizophrenia which leads to dementia. We hypothesize further that strategies to delay or stop gray matter depletion would not only improve the schizophrenia sustained recovery, but also avert the development of major neurocognitive disorders in people living with schizophrenia. Based on this hypothesis, we suggest utilization of both receptor-dependent and independent therapeutics for chronic psychosis.

Does Slow and Steady Win the Race? Rates of Antipsychotic Discontinuation, Antipsychotic Dose, and Risk of Psychotic Relapse.

Antipsychotics are recommended for prevention of relapse in schizophrenia. It is unclear whether increased risk of relapse following antipsychotic discontinuation is predominantly associated with an absolute magnitude of dose reduction or rate of antipsychotic reduction. Establishing the responsible mechanism is important because prolonged withdrawal schedules have been suggested to reduce risk of relapse. Individual patient data from antipsychotic discontinuation studies were obtained. We estimated the occupancy of receptors over time using half-lives and median effective dose ED50 values obtained from pharmacokinetic and receptor occupancy studies. Hazard ratios for relapse events were calculated using Cox proportional hazards models to assess the influence of formulation (oral, 1-monthly, and 3-monthly injections). The change in hazard ratio over time was estimated, and the effect of time-varying covariates was calculated, including rate of occupancy reduction and absolute receptor occupancy. Five studies including 1388 participants with schizophrenia were identified (k = 2: oral, k = 2: 1-monthly injection, k = 1: 3-monthly injection). Withdrawal of long-acting injectable medication did not lead to a lower hazard ratio compared with withdrawal of oral medication, and this included the period immediately following randomization. Hazard ratios were not associated with the rate of decline of receptor occupancy; however, they were associated with reduced absolute occupancy in trials of long-acting injections (P = .038). Antipsychotic discontinuation is associated with an increased risk of psychotic relapse, related to receptor occupancy. Although relapse does not appear to be related to the rate of discontinuation, gradual discontinuation strategies may allow for easier antipsychotic reinstatement in case of symptomatic worsening.

Associations of comorbid substance use disorders with clinical outcomes in schizophrenia using electronic health record data.

Schizophrenia and comorbid substance use disorders (SUDs) are associated with poor treatment outcomes but differences between the associations of different SUDs with clinical outcomes are poorly characterized. This study examines the associations of comorbid SUDs with clinical outcomes in schizophrenia using a largescale electronic health record (EHR) database. Real-world data (RWD) analysis using the NeuroBlu database; de-identified EHR data were analysed. Multivariable logistic regression, Poisson and CoxPH models were used to compare the associations of specific comorbid SUDs with outcome variables. Comorbid SUD was significantly different on all outcome measures compared to no SUD (U=1.44e7-1.81e7, all ps<.001), except number of unique antipsychotics (U=1.61e7, p=.43). Cannabis (OR=1.58, p<.001) and polysubstance (OR=1.22, p=.007) use disorders were associated with greater CGI-S. Cannabis (IRR=1.13, p=.003) and polysubstance (IRR=1.08, p=.003) use disorders were associated with greater number of unique antipsychotics prescribed, while cocaine (HR=1.87, p<.001), stimulants (HR=1.64, p=.024), and polysubstance (HR=1.46, p<.001) use disorders were associated with a shorter time to antipsychotic discontinuation. Conversely, alcohol use (IRR=0.83, p<.001), cocaine use (IRR=0.61, p<.001), opioid use (IRR=0.61, p<.001), stimulant use (IRR=0.57, p<.001) and polysubstance use (IRR=0.87, p<.001) disorders were associated fewer inpatient days. Comorbid SUDs were generally associated with greater CGI-S and poorer clinical outcomes in patients with schizophrenia. Treatment strategies should target not only schizophrenia symptoms but also comorbid SUD to improve management of both conditions.

Experiences of reduction and discontinuation of antipsychotics: a qualitative investigation within the RADAR trial

Experiences of reduction and discontinuation of antipsychotics: a qualitative investigation within the RADAR trial

Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): an open, parallel-group, randomised controlled trial

Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse. RADAR was an open, parallel-group, randomised trial done in 19 National Health Service Trusts in England. Participants were aged 18 years and older, had a diagnosis of recurrent, non-affective psychotic disorder, and were prescribed an antipsychotic. Exclusion criteria included people who had a mental health crisis or hospital admission in the past month, were considered to pose a serious risk to themselves or others by a treating clinician, or were mandated to take antipsychotic medication under the Mental Health Act. Through an independent, internet-based system, participants were randomly assigned (1:1) to gradual, flexible antipsychotic reduction, overseen by treating clinicians, or to maintenance. Participants and clinicians were aware of treatment allocations, but assessors were masked to them. Follow-up was for 2 years. Social functioning, assessed by the Social Functioning Scale, was the primary outcome. The principal secondary outcome was severe relapse, defined as requiring admission to hospital. Analysis was done blind to group identity using intention-to-treat data. The trial is completed and has been registered with ISRCTN registry (ISRCTN90298520) and with ClinicalTrials.gov (NCT03559426). 4157 people were screened, of whom 253 were randomly allocated, including 168 (66%) men, 82 (32%) women, and 3 (1%) transgender people, with a mean age of 46 years (SD 12, range 22-79). 171 (67%) participants were White, 52 (21%) were Black, 16 (6%) were Asian, and 12 (5%) were of other ethnicity. The median dose reduction at any point during the trial was 67% in the reduction group and zero in the maintenance group; at 24 months it was 33% versus zero. At the 24-month follow-up, we assessed 90 of 126 people assigned to the antipsychotic dose reduction group and 94 of 127 assigned to the maintenance group, finding no difference in the Social Functioning Scale (β 0·19, 95% CI -1·94 to 2·33; p=0·86). There were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals. At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning. Our data can help to inform decisions about the use of long-term antipsychotic medication. National Institute for Health Research.

Network biomarkers in recovered psychosis patients who discontinued antipsychotics

There are no studies investigating topological properties of resting-state fMRI (rs-fMRI) in patients who have recovered from psychosis and discontinued medication (hereafter, recovered patients [RP]). This study aimed to explore topological organization of the functional brain connectome in the RP using graph theory approach. We recruited 30 RP and 50 age and sex-matched healthy controls (HC). The RP were further divided into the subjects who were relapsed after discontinuation of antipsychotics (RP-R) and who maintained recovered state without relapse (RP-M). Using graph-based network analysis of rs-fMRI signals, global and local metrics and hub information were obtained. The robustness of the network was tested with random failure and targeted attack. As an ancillary analysis, Network-Based Statistic (NBS) was performed. Association of significant findings with psychopathology and cognitive functioning was also explored. The RP showed intact network properties in terms of global and local metrics. However, higher global functional connectivity strength and hyperconnectivity in the interconnected component were observed in the RP compared to HC. In the subgroup analysis, the RP-R were found to have lower global efficiency, longer characteristic path length and lower robustness whereas no such abnormalities were identified in the RP-M. Associations of the degree centrality of some hubs with cognitive functioning were identified in the RP-M. Even though network properties of the RP were intact, subgroup analysis revealed more altered topological organizations in the RP-R. The findings in the RP-R and RP-M may serve as network biomarkers for predicting relapse or maintained recovery after the discontinuation of antipsychotics.

Racial and ethnic differences in patterns of use and discontinuation of long-acting injectable antipsychotics using Medicaid claims data.

In general, racial and ethnic differences exist in antipsychotic prescription practices. However, little is known about such differences between individual long-acting injectable (LAI) antipsychotic formulations, specifically. This study's primary objective was to determine racial and ethnic differences among LAI antipsychotic use. Secondary objectives were to identify if discontinuation rates differed between agents and by race or ethnicity. International Classification of Diseases, 10th edition (ICD-10) codes were used to identify patients with schizophrenia and related disorders (18-64 years) who received an LAI antipsychotic between 2016 and 2020 using Merative Multi-State Medicaid databases. Using National Drug Code numbers for LAI antipsychotics, pharmacy claims were identified and data analyzed. Cochran-Mantel-Haenszel tests and odds ratio estimators were used to investigate conditional association between race or ethnicity and medication, while controlling for age, sex, health plan, and prescription year. Kaplan-Meier survival curves were examined, and stratified log-rank tests were conducted to compare the time until discontinuation distributions by race or ethnicity. The analysis included 37 712 patients. Blacks received an LAI first-generation antipsychotic more often than Whites (OR: 1.64, 95% CI: [1.56, 1.73], Hispanics (OR: 1.46, 95% CI: [1.21, 1.75]) and others (OR: 1.44, 95% CI: [1.20, 1.73]). Aside from fluphenazine decanoate showing earlier discontinuation rates for Whites over Blacks (P = .02), no significant differences in discontinuation across race or ethnicity were identified. Despite no significant differences in second-generation antipsychotic LAI discontinuation rates between Blacks and other racial or ethnic groups, Blacks received second-generation antipsychotic LAIs significantly less often than other groups. Further studies are needed to determine why differences may be occurring.

Efficacy of low-dose risperidone in combination with sertraline in first-episode drug-naïve patients with schizophrenia: a randomized controlled open-label study

ObjectiveDespite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients.MethodsA total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up.ResultsRepeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6.ConclusionsOur study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ.Trial registration number: ClinicalTrials.gov, NCT04076371

Collaborative discontinuation of antipsychotics after the first episode of psychosis.

Collaborative discontinuation of antipsychotics after the first episode of psychosis.

Collaborative discontinuation of antipsychotics after the first episode of psychosis

Collaborative discontinuation of antipsychotics after the first episode of psychosis

Prevalence and impact of antipsychotic discontinuation among commercially-insured patients with bipolar disorder

BackgroundAntipsychotic discontinuation is common among patients with bipolar disorder, especially when psychotic symptoms are remitted. This analysis describes the prevalence, predictors, and economic impact of antipsychotic discontinuation among patients with bipolar disorder.MethodsA retrospective, observational study was conducted using administrative claims data in the IBM MarketScan Commercial Database. Patients with ≥1 claim with a diagnosis for bipolar disorder (manic or mixed) and newly-initiating antipsychotic therapy between 1 January 2011 and 30 June 2016 were included. Baseline characteristics were assessed in the 12 months prior to the initiation. Outcomes were assessed during a 24-month follow-up. Discontinuation of antipsychotic therapy was utilized as a predictor of healthcare costs in models adjusted for baseline characteristics. Using limited set of variables in the claims database, predictors of discontinuation were also assessed.ResultsA total of 18,259 commercially-insured patients were identified as initiators of antipsychotics. Common comorbidities among the cohorts included major depressive disorder and dyslipidemia. Discontinuation was very common among these patients (85%). Major depressive disorder, drug abuse, and other substance abuse/dependency were predictive of discontinuation. Controlling for differences in baseline characteristics, discontinuation was associated with 33% higher inpatient and emergency visit costs (p <.001) among those using these services, and 24% higher total healthcare costs (p <.001) for the overall cohort.ConclusionsMost patients with bipolar mania or mixed states discontinue antipsychotic treatment in less than 2 years. Antipsychotic discontinuation contributes to excess healthcare costs. Future research focusing on the reasons for discontinuation and tailoring disease management based on comorbidities may inform adherence improvement initiatives.