Discontinuation Of Antipsychotic Treatment Research Articles

Predicting psychotic relapse following randomised discontinuation of paliperidone in individuals with schizophrenia or schizoaffective disorder: an individual participant data analysis

Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment discontinuation, using machine learning. For this individual participant data analysis, we searched the Yale University Open Data Access Project's database for placebo-controlled, randomised antipsychotic discontinuation trials with participants with schizophrenia or schizoaffective disorder (aged ≥18 years). We included studies in which participants were treated with any antipsychotic study drug and randomly assigned to continue the same antipsychotic drug or to discontinue it and receive placebo. We assessed 36 prespecified baseline variables at randomisation to predict time to relapse, using univariate and multivariate proportional hazard regression models (including multivariate treatment group by variable interactions) with machine learning to categorise the variables as general prognostic factors of relapse, specific predictors of relapse, or both. We identified 414 trials, of which five trials with 700 participants (304 [43%] women and 396 [57%] men) were eligible for the continuation group and 692 participants (292 [42%] women and 400 [58%] men) were eligible for the discontinuation group (median age 37 [IQR 28-47] years for continuation group and 38 [28-47] years for discontinuation group). Out of the 36 baseline variables, general prognostic factors of increased risk of relapse for all participants were drug-positive urine; paranoid, disorganised, and undifferentiated types of schizophrenia (lower risk for schizoaffective disorder); psychiatric and neurological adverse events; higher severity of akathisia (ie, difficulty or inability to sit still); antipsychotic discontinuation; lower social performance; younger age; lower glomerular filtration rate; benzodiazepine comedication (lower risk for anti-epileptic comedication). Out of the 36 baseline variables, predictors of increased risk specifically after antipsychotic discontinuation were increased prolactin concentration, higher number of hospitalisations, and smoking. Both prognostic factors and predictors with increased risk after discontinuation were oral antipsychotic treatment (lower risk for long-acting injectables), higher last dosage of the antipsychotic study drug, shorter duration of antipsychotic treatment, and higher score on the Clinical Global Impression (CGI) severity scale The predictive performance (concordance index) for participants who were not used to train the model was 0·707 (chance level is 0·5). Routinely available general prognostic factors of psychotic relapse and predictors specific for treatment discontinuation could be used to support personalised treatment. Abrupt discontinuation of higher dosages of oral antipsychotics, especially for individuals with recurring hospitalisations, higher scores on the CGI severity scale, and increased prolactin concentrations, should be avoided to reduce the risk of relapse. German Research Foundation and Berlin Institute of Health.

A longitudinal analysis of electronic health records to investigate antipsychotic side effects and treatment discontinuation in first episode psychosis

A longitudinal analysis of electronic health records to investigate antipsychotic side effects and treatment discontinuation in first episode psychosis

Effectiveness of Antipsychotic Use for Reducing Risk of Work Disability: Results From a Within-Subject Analysis of a Swedish National Cohort of 21,551 Patients With First-Episode Nonaffective Psychosis.

The authors sought to determine whether antipsychotic use, compared with nonuse, is associated with lower work disability in first-episode nonaffective psychosis, and if so, for how long. A within-subject design was used to study the risk of sickness absence or disability pension during antipsychotic use compared with nonuse during a maximum of 11 years of follow-up (2006-2016) in a Swedish nationwide cohort of patients with first-episode nonaffective psychosis (N=21,551; age range, 16-45 years). The within-subject analyses were conducted with stratified Cox regression models, adjusted for time-varying factors, using each individual as her or his own control to eliminate selection bias. The primary outcome was work disability (sickness absence or disability pension). Overall, 45.9% of first-episode patients had work disability during the median length of follow-up of 4.8 years. The risk of work disability was lower during use compared with nonuse of any antipsychotic (adjusted hazard ratio [aHR]=0.65, 95% CI=0.59-0.72). The lowest adjusted hazard ratios emerged for long-acting injectable antipsychotics (aHR=0.46, 95% CI=0.34-0.62), oral aripiprazole (aHR=0.68, 95% CI=0.56-0.82), and oral olanzapine (aHR=0.68, 95% CI=0.59-0.78). Long-acting injectables were associated with lower risk than olanzapine, the most commonly used oral antipsychotic (aHR=0.68, 95% CI=0.50-0.94). Adjusted hazard ratios were similar during the periods of <2 years, 2-5 years, and >5 years since diagnosis. Among individuals with first-episode nonaffective psychosis, antipsychotic treatment (with long-acting injectables in particular) was associated with about 30%-50% lower risk of work disability compared with nonuse of antipsychotics in the same individuals, which held true beyond 5 years after first diagnosis. These findings are informative regarding the important topic of early discontinuation of antipsychotic treatment after a first episode of nonaffective psychosis, but they need replication.

One-Year Clinical Outcomes Following Electroconvulsive Therapy for Patients with Schizophrenia: A Nationwide Health Insurance Data-Based Study.

BackgroundAlthough the use of electroconvulsive therapy (ECT) in the treatment of schizophrenia has decreased since the advent of antipsychotic drugs, ECT is still implemented in several clinical indications. However, a few population-based studies have examined its real-world effectiveness in schizophrenia.MethodsWe used data from 2010 to 2019 from the Health Insurance Review and Assessment Service database in the Republic of Korea. We selected 380 schizophrenia patients having more than six ECT sessions and 1140 patient controls matched for age, sex, calendar year at entry, and the number of psychiatric hospitalizations before the time point of start of psychiatric hospitalization for ECT. Antipsychotic treatment discontinuation, psychiatric hospitalization, and direct medical costs were used as measures of clinical outcomes. Multiple regression analysis was used for any group-by-time interaction effect, and 1-year pre- and post-ECT periods were compared within and between the groups.ResultsWe found a significantly lower number of antipsychotic treatment discontinuations in the ECT group during the 1-year post-ECT period (t=2.195, p=0.028). A larger decrease was found in the number of psychiatric hospitalizations in the ECT group, with a group-by-time interaction effect (p=0.043). The direct medical costs in the 1-year pre- (t=−8.782, p<0.001) and post-ECT periods (t=−9.107, p<0.001) were higher in the ECT group than in the control group, with no significant change across both periods.ConclusionWe found that the ECT group had a larger decrease in the number of psychiatric hospitalizations in the 1-year post-ECT period than the control group.

Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up "Real World" Study in China.

Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083). Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.

An analysis of views about supported reduction or discontinuation of antipsychotic treatment among people with schizophrenia and other psychotic disorders

BackgroundAntipsychotic medication can reduce psychotic symptoms and risk of relapse in people with schizophrenia and related disorders, but it is not always effective and adverse effects can be significant. We know little of patients’ views about continuing or discontinuing antipsychotic treatment.AimsTo explore the views of people with schizophrenia and other psychotic disorders about continuing their antipsychotic medication or attempting to reduce or discontinue this medication with clinical support.MethodsWe collected quantitative and qualitative data by conducting semi-structured interviews in London, UK. Factors predicting a desire to discontinue medication were explored. Content analysis of qualitative data was undertaken.ResultsWe interviewed 269 participants. 33% (95% CI, 27 to 39%) were content with taking long-term antipsychotic medication. Others reported they took it reluctantly (19%), accepted it on a temporary basis (24%) or actively disliked it (18%). 31% (95% CI, 25 to 37%) said they would like to try to stop medication with professional support, and 45% (95% CI, 39 to 51%) wanted the opportunity to reduce medication. People who wanted to discontinue had more negative attitudes towards the medication but were otherwise similar to other participants. Wanting to stop or reduce medication was motivated mainly by adverse effects and health concerns. Professional support was identified as potentially helpful to achieve reduction.ConclusionsThis large study reveals that patients are commonly unhappy about the idea of taking antipsychotics on a continuing or life-long basis. Professional support for people who want to try to reduce or stop medication is valued.

Relapse in Dementia-related Psychosis and Clinical Decisions.

Patients with dementia can experience hallucinations and delusions because of their underlying neurodegenerative condition, a syndrome known as dementia-related psychosis. Dementia-related psychosis contributes to morbidity and mortality among patients with dementia and increases the burden on caregivers and the health care system. With no pharmacological treatment currently approved in the United States for this condition, patients are often treated off-label with antipsychotics. Though typical and atypical antipsychotics have demonstrated variable to modest efficacy in dementia-related psychosis, serious safety concerns arise with their use. Accordingly, clinical and Centers for Medicare & Medicaid Services guidelines recommend trying antipsychotics only when other therapies have failed and encourage treatment discontinuation of antipsychotics after 4 months to assess whether ongoing therapy is needed. Discontinuation of effective antipsychotic treatment, however, may increase the risk for relapse of symptoms and the associated morbidities that accompany relapse. A randomized medication withdrawal clinical trial design allows assessment of relapse risk after discontinuation and can provide initial information on longer-term safety of therapy for dementia-related psychosis. Given the substantial unmet need in this condition, new, well-tolerated therapies that offer acute and sustained reduction of symptoms while also preventing recurrence of symptoms of psychosis are critically needed.

From Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a Wave

From Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a Wave

Real-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIs

Back to table of contents Previous article Next article Clinical & ResearchFull AccessReal-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:8 Oct 2021https://doi.org/10.1176/appi.pn.2021.9.32AbstractAn analysis of national VA health databases shows clozapine along with long-acting formulas of aripiprazole and paliperidone have lower discontinuation rates than oral olanzapine, while oral quetiapine and ziprasidone have higher discontinuation rates.Patients with schizophrenia may be less likely to discontinue treatment if prescribed clozapine or long-acting injectable (LAI) formulations of second-generation antipsychotics, according to a report in AJP in Advance. The findings, which also revealed that patients who were taking multiple antipsychotics (polypharmacy) had lower discontinuation rates, were based on data from the U.S. Department of Veterans Affairs (VA).Though the data was limited to veterans, lead author Marc Weiser, M.D., head of the Division of Psychiatry at Sheba Medical Center in Ramat Gan, Israel, noted the findings mirrored those of a 2017 study that used Swedish medical data. “Replicating research findings is difficult,” Weiser noted. “When you have nearly identical outcomes from two studies done by different investigators in different countries using different patient populations, it points to the results being broadly applicable.”Weiser and colleagues compiled VA clinical and pharmacy data from all patients who received a schizophrenia diagnosis and at least one antipsychotic prescription lasting 60 days or more between October 2010 and September 2015. To keep the data robust, the investigators focused on antipsychotics with at least 150 prescriptions during the analysis period. The final sample included 37,368 patients with 62,056 antipsychotic prescriptions among 15 categories: nine oral medications (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and all first-generation antipsychotics), five LAI formulations (first-generation drugs fluphenazine and haloperidol and second-generation aripiprazole, paliperidone, and risperidone), and patients receiving polypharmacy.The investigators compared the treatment discontinuation rates and hospital admission rates associated with all the medications relative to olanzapine. Weiser noted olanzapine was chosen as the reference since it is considered the most well-tolerated oral antipsychotic and it was used as the reference drug in the 2017 Swedish study.After adjusting for patient sociodemographic factors, Weiser and colleagues found that five groups had a lower risk of treatment discontinuation than olanzapine. These included patients taking clozapine (with nearly 60% less discontinuation risk than olanzapine), a trio of second-generation LAIs (aripiprazole, paliperidone, and risperidone), and patients on polypharmacy. Patients taking oral quetiapine, oral ziprasidone, oral aripiprazole, oral risperidone, and oral first-generation antipsychotics all had higher risks of discontinuation than those taking olanzapine. In a secondary analysis, the investigators found that all three second-generation LAIs were associated with lower risks of discontinuation with the oral formulations of the medications.Weiser told Psychiatric News that he was not surprised by the findings that clozapine was associated with a lower risk of treatment discontinuation than the other antipsychotics. “Since clozapine requires patients to check in regularly, physicians tend to prescribe it to patients who they believe will be compliant; there is a pre-screening process built in.”The polypharmacy findings were a bit more surprising, he noted. “Giving patients multiple antipsychotics is considered a no-no in clinical settings, but this finding supports that giving the right combination of drugs can boost their effectiveness,” he said. Future studies should look at which combinations may offer the most symptom improvement along with lowest risks of side effects.In contrast to the discontinuation findings, none of the medications were found to reduce the risk of psychiatric hospitalization compared with olanzapine. Weiser noted this was the one of the few divergences from the Swedish study, which found clozapine to be superior to olanzapine.While no antipsychotics were superior to olanzapine in terms of hospitalizations, several were associated with increased hospitalization risk: these included oral and LAI first-generation antipsychotics, as well as oral lurasidone, quetiapine, and ziprasidone.Weiser noted that he was particularly concerned about the quetiapine finding, being that this was the second most-prescribed medication in the sample (behind oral risperidone) and this medication was associated with a 36% increased risk of hospitalization. “It is interesting since in the general population, quetiapine is not used that extensively for schizophrenia,” he said. Rather, quetiapine is more commonly prescribed off-label for conditions like anxiety or insomnia.This study was supported by the Stanley Medical Research Institute. Weiser also serves on the staff of the Stanley Institute. ■“Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs” is posted here.The 2017 analysis, “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” is posted here. ISSUES NewArchived

Dopaminergic mechanisms underlying the expression of antipsychotic-induced dopamine supersensitivity in rats

Antipsychotic treatment can produce a dopamine-supersensitive state, potentiating the response to dopamine receptor stimulation. In both schizophrenia patients and rats, this is linked to tolerance to ongoing antipsychotic treatment. In rodents, dopamine supersensitivity is often confirmed by an exaggerated psychomotor response to d-amphetamine after discontinuation of antipsychotic exposure. Here we examined in rats the dopaminergic mechanisms mediating this enhanced behavioural response, as this could uncover pathophysiological processes underlying the expression of antipsychotic-evoked dopamine supersensitivity. Rats received 0.5 mg/kg/day haloperidol via osmotic minipump for 2 weeks, before treatment was discontinued. After cessation of antipsychotic treatment, rats showed a supersensitive psychomotor response to the D2 agonist quinpirole, but not to the D1 partial agonist SKF38393 or the dopamine reuptake blocker GBR12783. Furthermore, acute D1 receptor blockade (using SCH39166) decreased the exaggerated psychomotor response to d-amphetamine in haloperidol-pretreated rats, whereas acute D2 receptor blockade (using sulpiride) enhanced it. Thus, after discontinuation of antipsychotic treatment, D1- and D2-mediated transmission differentially modulate the expression of a supersensitive response to d-amphetamine. This supersensitive behavioural response was accompanied by enhanced GSK3β activity and suppressed ERK1/2 activity in the nucleus accumbens (but not caudate-putamen), suggesting increased mesolimbic D2 transmission. Finally, after discontinuing haloperidol treatment, neither increasing ventral midbrain dopamine impulse flow nor infusing d-amphetamine into the cerebral ventricles triggered the expression of already established dopamine supersensitivity, suggesting that peripheral effects are required. Thus, while dopamine receptor-mediated signalling regulates the expression of antipsychotic-evoked dopamine supersensitivity, a simple increase in central dopamine neurotransmission is insufficient to trigger this supersensitivity.

Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs.

Effectiveness of antipsychotic drugs is inferred from relatively small randomized clinical trials conducted with carefully selected and monitored participants. This evidence is not necessarily generalizable to individuals treated in daily clinical practice. The authors compared the clinical effectiveness between all oral and long-acting injectable (LAI) antipsychotic medications used in the treatment of schizophrenia in the U.S. Department of Veterans Affairs (VA) health care system. This was an observational study utilizing VA pharmacy data from 37,368 outpatient veterans with schizophrenia. Outcome measures were all-cause antipsychotic discontinuation and psychiatric hospitalizations. Oral olanzapine was used as the reference group. In multivariable analysis, clozapine (hazard ratio=0.43), aripiprazole long-acting injectable (LAI) (hazard ratio=0.71), paliperidone LAI (hazard ratio=0.76), antipsychotic polypharmacy (hazard ratio=0.77), and risperidone LAI (hazard ratio=0.91) were associated with reduced hazard of discontinuation compared with oral olanzapine. Oral first-generation antipsychotics (hazard ratio=1.16), oral risperidone (hazard ratio=1.15), oral aripiprazole (hazard ratio=1.14), oral ziprasidone (hazard ratio=1.13), and oral quetiapine (hazard ratio=1.11) were significantly associated with an increased risk of discontinuation compared with oral olanzapine. No treatment showed reduced risk of psychiatric hospitalization compared with oral olanzapine; quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine. In a national sample of veterans with schizophrenia, those treated with clozapine, two of the LAI second-generation antipsychotics, and antipsychotic polypharmacy continued the same antipsychotic therapy for a longer period of time compared with the reference drug. This may reflect greater overall acceptability of these medications in clinical practice.

PMH54 Impact of Bipolar Disorder Treatment Discontinuation on Healthcare Utilization and Costs in the Real-World Setting

To describe the real-world antipsychotic (AP) treatment discontinuation patterns and the association between treatment discontinuation and healthcare costs among bipolar disorder patients. A retrospective observational study was conducted using administrative claims data the IBM® MarketScan Commercial Database. Patients with at least 1 medical claim with a diagnosis of bipolar disorder (manic or mixed sub-type) and newly initiating AP therapy between 1/1/11-6/30/16 were included. Baseline patient characteristics were assessed in the 12 months prior to the AP initiation. Total healthcare costs and healthcare utilization were assessed during a 24-month follow-up. Discontinuation of index AP therapy, defined as a gap of at least 60 days without the medication on-hand, was utilized as a predictor of healthcare costs and utilization outcomes in generalized linear and logistic regression models adjusted for baseline characteristics. Predictors of discontinuation were also assessed via logistic regression. A total of 18,259 bipolar disorder patients were identified as new initiators of APs. The cohort was 61% female and had an average age of 39 years. The most commonly initiated AP was quetiapine (33.6%), followed by aripiprazole (29.3%). A total of 15,460 patients (85%) discontinued their index regimen. Patients with baseline substance use disorders, depression, and other anxiety disorders were significantly more likely to discontinue. More than half of the cohort utilized emergency room services (53%) and 33% had at least one inpatient admission during the follow-up. The median total healthcare costs were $24,861 during the 24-month follow-up. Controlling for differences in baseline characteristics, discontinuation of AP therapy was associated with 24% higher total healthcare costs (Cost ratio: 1.24; p<0.001) and 33% higher inpatient+ER costs (1.33; p<0.001). Discontinuation of AP therapy among bipolar disorder patients is high and contributes to excess healthcare costs and high-cost services. Future research focusing on the reasons for discontinuation may inform medication adherence initiatives.

Predictors of long-acting injectable antipsychotic treatment discontinuation in outpatients with schizophrenia: relevance of the Drug Attitude Inventory-10.

Given the importance of patients' subjective experience and attitudes in the management of severe mental illness, the present study evaluated their potential role as predictors of future continuation of long-acting injectable antipsychotic maintenance treatment (LAI-AMT) in clinically stable outpatients with schizophrenia switching from an oral therapy. Retrospective data from 59 subjects receiving LAI-AMT for at least 6 months were collected. Patients who continued LAI treatment (n = 32) were compared to those who discontinued it (n = 27), assessing baseline socio-demographic and clinical characteristics, psychopathological features (Positive And Negative Syndrome Scale, Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale) and patient-reported experience of treatment through Drug Attitude Inventory 10-item (DAI-10) and Subjective Well-being under Neuroleptics short form. Binary logistic and Cox regression analyses explored the predictive role of the mentioned variables on treatment discontinuation. The Kaplan-Meier estimator compared dropout from LAI treatment in subsamples with different characteristics. Unemployment and lower baseline DAI-10 scores predicted LAI-AMT discontinuation. No major differences were detected in other socio-demographic, clinical or psychometric indexes. When switching from oral to LAI-AMT, the preliminary assessment of attitude towards drug might be clinically relevant, allowing the identification of patients at risk for treatment discontinuation.

Early intervention services, patterns of prescription and rates of discontinuation of antipsychotic treatment in first-episode psychosis.

Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. A total of 310 FEP patients were assessed across seven early intervention teams (mean age=30.2 years; SD=11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.

Three-year longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder.

The longitudinal course of neuropsychological functioning after the first manic episode in bipolar disorder is unknown. The present study evaluated cognitive change in bipolar disorder in the first 3years after the initial manic episode. Ninety-one newly diagnosed patients with bipolar disorder and 61 demographically similar healthy participants received a neuropsychological evaluation assessing multiple cognitive domains at baseline, 1-year, and 3-year time points. Patients also received clinical assessments including mood ratings at all time points. Patients showed deficits in all domains at baseline, but similar longitudinal trajectories across time relative to healthy participants in most cognitive domains. For processing speed, patients showed more gains than controls from baseline to 1year, but these gains stabilized thereafter. Patients with alcohol/substance abuse showed an initial delay but subsequent recovery in executive functioning. Patients who discontinued antipsychotic treatment showed better cognitive outcomes in verbal memory. Appropriately treated patients with bipolar disorder showed favorable cognitive outcome in the first 3years after experiencing an initial manic episode, arguing against cognitive neuroprogression at this stage of the illness. Discontinuation of antipsychotic treatment may be associated with better cognitive outcomes, but clarification of the role of antipsychotics on cognitive functioning requires further investigation.

Continuation of schizophrenia treatment with three long-acting injectable antipsychotics in South Korea: A nationwide population-based study

Long-acting injectable (LAI) antipsychotics have been developed to prevent symptom relapse in patients with schizophrenia; relapse has a detrimental clinical impact and high social burden. However, data on treatment continuation rates of LAI antipsychotics are inconsistent, primarily because of study design; limited data exist for patients taking oral psychotropic medications taken along with LAI antipsychotics, and factors related to LAI antipsychotics treatment discontinuation. Patients with schizophrenia in the South Korea Health Insurance Review Agency database from 2007 to 2016 who had received LAI haloperidol, LAI paliperidone, or LAI risperidone were included. Treatment continuation rates and proportions of patients using concurrent oral psychotropic medications were calculated. Cox proportional hazard ratios were used for analysis related to discontinuation. There was a significant difference in treatment continuation rates at 6 months after initiation (36.8% LAI haloperidol, 57.5% LAI paliperidone, and 34.5% LAI risperidone). A substantial proportion of patients in all three groups were prescribed oral antipsychotics during LAI antipsychotics treatment. In the LAI paliperidone group, type of hospital was significantly associated with a higher risk of treatment discontinuation, with a hazard ratio of 1.195–1.598. Early discontinuation of LAI antipsychotic treatment occurs in a large number of patients with schizophrenia. Intervention strategies for improving the LAI antipsychotics treatment adherence are needed.

Rates and predictors of one-year antipsychotic treatment discontinuation in first-episode schizophrenia: Results from an open-label, randomized, “real world” clinical trial

Antipsychotic treatment discontinuation is a major challenge in the treatment of first-episode schizophrenia (FES) patients. However, the rate and predictors remain unclear. Five hundred and sixty-nine FES patients were randomized to risperidone (n = 190), olanzapine (n = 185) or aripiprazole (n = 194) in a six-site study in China with 1-year follow-up. Patients failing the initially assigned antipsychotic were switched to one of the other 2 antipsychotics. By 52 weeks, 47.1% of FES patients discontinued all antipsychotics. In the 8-week acute phase, an antipsychotic switch was protective against antipsychotic discontinuation, whereas higher positive symptoms at the endpoint predicted discontinuation. In the maintenance phase, discontinuation was predicted by male gender and higher CGI-S score at the endpoint. The findings indicate that in China nearly half of patients with FES discontinued antipsychotic treatment during one year treatment. Clinicians should employ strategies other than medication choice to keep them from discontinuing.

Study supports continuous antipsychotic treatment for first-episode schizophrenia

The Brown University Psychopharmacology UpdateVolume 29, Issue 8 p. 3-3 What's New in Research Study supports continuous antipsychotic treatment for first-episode schizophrenia First published: 09 July 2018 https://doi.org/10.1002/pu.30344Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract A nationwide cohort study of patients with first-episode schizophrenia has found that, contrary to common belief, risk of treatment failure after discontinuation of antipsychotic treatment does not decrease with longer exposure to medication. The findings suggest that in the eight years following a first episode, it is not possible to define a safe time point for discontinuation of antipsychotic treatment. Volume29, Issue8August 2018Pages 3-3 RelatedInformation

Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis.

Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance. This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18-24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model. Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18-24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant). Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18-24 months) did not experience a relapse.

20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia.

It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that after stabilization, antipsychotic treatment should be continued for 1-5 years, and longer exposure should be avoided if possible. However, there is no published evidence to substantiate this view. The authors used nationwide databases to investigate this issue. Prospectively gathered nationwide register data were used to study the risk of treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment. Multivariate Cox regression was used to assess outcomes among all patients hospitalized for the first time with a schizophrenia diagnosis in Finland during the period of 1996-2014 (N=8,719). The lowest risk of rehospitalization or death was observed for patients who received antipsychotic treatment continuously (adjusted hazard ratio=1.00), followed by patients who discontinued antipsychotic use immediately after discharge from the first hospital treatment (hazard ratio=1.63, 95% CI=1.52-1.75), within 1 year (hazard ratio=1.88, 95% CI=1.57-2.24), within 1-2 years (hazard ratio=2.12, 95% CI=1.43-3.14), within 2-5 years (hazard ratio=3.26, 95% CI=2.07-5.13), and after 5 years (a median of 7.9 years) (hazard ratio=7.28, 95% CI=2.78-19.05). Risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years. Whatever the underlying mechanisms, these results provide evidence that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotic treatment is associated with increased survival.