Maintenance Treatment Of Schizophrenia Research Articles

Impact of the COVID-19 Pandemic on Medication Adherence and Maintenance Treatment for Schizophrenia: A Reconsideration [Letter].

Impact of the COVID-19 Pandemic on Medication Adherence and Maintenance Treatment for Schizophrenia: A Reconsideration [Letter].

Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report

Lurasidone is an atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia. Recently, lurasidone was also extended FDA approval for adults with major depressive episodes associated with bipolar I disorder (bipolar depression), as either a monotherapy or as adjunctive therapy with lithium or valproate. The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis, but little has yet been studied on first episode cannabis-induced psychosis. For its particular performance and tolerability, lurasidone is becoming an important option for the treatment of first-episode psychosis in youth. Case presentation four patients experiencing first cannabis-induced psychotic episode were treated with lurasidone. In all patients, there was an improvement in the clinical picture of psychosis. The recovery was positive, not only with the remission of positive and negative symptoms, but also regarding disruptive behaviour, with the return of functioning. All the patients were treated with lurasidone, with a target dose of 74-128 mg/day. No significant side effects were reported. There are non-controlled studies for the use of lurasidone in first episode psychosis cannabis induced. These findings suggest that lurasidone is an atypical antipsychotic beneficial in this clinical picture. Treatment with medium-high doses of lurasidone could be effective and tolerable in this phase of the disorder. Randomized control trials with longer follow-up are recommended to confirm these positive results.

Features of Clinical Use of Brexpiprazole, the New Atypical Antipsychotic of the Third Generation: Experience and Perspectives

Background: personalized approach considering the effectiveness and safety of the medication is the main goal of contemporary psychopharmacotherapy. Knowing special characteristics of any given drug allows a practitioner to choose the tactic meeting needs of the particular patient.The aim of this narrative review was to summarize the data about use Brexpiprazole of in pharmacotherapy of different mental disorders.Method: using the keywords “brexpiprazole”, “psychoses”, “treatment” we performed a scientific publications search in PubMed and PsychInfo databases over the last 10 years.Results: brexpiprazole is supposed to resemble such third generation antypsychotics as aripiprazole and cariprazine, lacking their drawbacks. There is a history of using brexpiprazole in schizophrenia and unipolar depression. Pilot studies and clinical cases were presented on the possible perspectives in use of brexpiprazole, such as Alzheimer disease, posttraumatic stress disorder, borderline personality disorder and bipolar affective disorder. On the basis of the reviewed data we conclude that brexpiprazole is effective for cupping and maintenance treatment of schizophrenia, for augmentation in recurrent depressive disorder and is also perspective in other fields of psychiatry. Brexpiprazole has a favorable safety profile with low incidence of metabolic, extrapyramidal and hyperstimulation symptoms.

Maintenance Treatment With Antipsychotic Drugs in Schizophrenia: A Cochrane Systematic Review and Meta-analysis.

Antipsychotic drugs are the mainstay of treatment of schizophrenia, and are known to reduce acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotics are effective for relapse prevention, compared to withdrawing these agents for people with schizophrenia or schizophrenia-like psychoses, based on evidence from randomized trials. The current report of the update of the review is focused on some newly investigated outcomes: rates of remission and recovery, change in social functioning and in quality of life. The updated review included 75 randomized controlled trials (RCTs) published from 1959 to 2017, involving 9145 participants. Although some potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear and robust to a series of sensitivity analyses. Antipsychotic drugs were more effective than placebo in preventing relapse at 1 year (drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR = 0.38, 95% CI = 0.32 to 0.45) and in reducing hospitalization (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR = 0.43, 95% CI = 0.32 to 0.57). Quality of life appeared to be better in drug-treated participants (7 RCTs, n = 1573, SMD = -0.32, 95% CI = -0.57 to -0.07); the same for social functioning (15 RCTs, n = 3588, SMD = -0.43, 95% CI = -0.53 to -0.34). Although based on data from fewer studies, maintenance treatment apparently increased the possibility to achieve remission of symptoms (drug 53%, placebo 31%; 7 RCTs, 867 participants; RR = 1.73, 95% CI = 1.20 to 2.48) and to sustain it over 6 months (drug 36%, placebo 26%; 8 RCTs, 1807 participants; RR = 1.67, 95% CI = 1.28 to 2.19). There were no data on recovery. Antipsychotic drugs as a group were associated with more participants experiencing side effects such as movement disorders (e.g., at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI = 1.25 to 1.85) and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR = 1.69, 95% CI = 1.21 to 2.35, NNTH = 25, 95% CI = 20 to 50). For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs does not only prevent relapses and rehospitalizations, but that patients also benefit in terms of quality of life, functioning and sustained remission. These positive effects must be weighed against the backdrop of the adverse effects of antipsychotics.

Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia.

Background and HypothesisOptimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study MethodsWe studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study ResultsAmong the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11–0.25, 1.4–<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%–45% lower risk of rehospitalization (P < .001) than the standard dose of 0.9–1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). ConclusionsFor most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4–<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.

Calling for policy actions to increase access to long-acting antipsychotics in low-income and middle-income countries.

Schizophrenia-spectrum disorders are associated with substantial impairment and disability. Lack of treatment adherence is a major issue, especially in low- and middle-income countries (LMICs). Despite growing evidence supporting second-generation long-acting antipsychotics (LAIs) as an effective strategy to ensure continued maintenance treatment in schizophrenia, access to these technologies has been very limited in constrained-resource settings. Including second-generation LAIs in national and international essential medicines lists and evidence-based guidelines, promoting public health-oriented patent pooling and extending their availability to primary health care settings, are key actions that should urgently be implemented to increase access to long-acting technologies. Implementing these policy actions can pragmatically improve treatment adherence, ultimately tackling schizophrenia-related impairment and disability in LMICs, which can be regarded as a global health priority.

Combination Therapy of Long-Acting Injectable Second-Generation Antipsychotics and Oral Antipsychotics: A Retrospective Chart Review and Prescribers' Attitude Survey.

Although long-acting injectable antipsychotics (LAI-APs) have been considered as a monotherapeutic option in the maintenance treatment of schizophrenia, it has been recently reported that the combination therapy of LAI-APs and oral antipsychotics (OAPs) is common. We conducted a retrospective chart review to examine the situation of the combination therapy of LAI second-generation antipsychotics (LAI-SGAs) and OAPs, and a questionnaire survey to investigate prescribers' attitudes toward the combination therapy. We included patients who received any LAI-SGAs for 1 month or longer and classified them into monotherapy and combination therapy groups. We collected information on age, sex, primary psychiatric diagnosis, and concomitant psychotropic medications. Of the 132 patients, 39 (29.5%) received the combination therapy of LAI-SGAs and OAPs. Long-acting injectable risperidone was significantly associated with receiving the combination therapy compared with LAI aripiprazole. Olanzapine was the most common OAP in combination with LAI-SGAs. Only 8 patients (20.5%) concurrently received the same type of OAPs as LAI-SGAs. More than 60% of the patients received OAP polypharmacy before the initiation of LAI-SGAs. The psychiatrists in charge prescribed LAI-SGAs mainly because of a concern about adherence, and OAPs mainly because of insufficient dose of LAI-SGAs, to patients in the combination therapy group. They estimated that adherence to OAPs in two thirds of the patients in the combination therapy group was 80% or higher. The present study showed that the combination therapy of LAI-SGAs and OAPs is often conducted in real-world clinical practice. Considering the reason for the introduction of LAI-APs, clinicians should carefully monitor patients' adherence to OAPs concurrently used with LAI-APs.

Development and Optimization of Asenapine Sublingual Film Using QbD Approach.

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6min) and higher asenapine permeation (~ 80% in 90min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

The Patient, Investigator, Nurse, Carer Questionnaire (PINC-Q): a cross-sectional, retrospective, non-interventional study exploring the impact of less frequent medication administration with paliperidone palmitate 3-monthly as maintenance treatment for schizophrenia

BackgroundTo understand the implications of switching from paliperidone palmitate 1-monthly (PP1M) to paliperidone palmitate 3-monthly (PP3M) treatment of schizophrenia from the perspective of four key stakeholders: patients, physicians, nurses and carers.MethodsThis was a cross-sectional, retrospective, non-interventional study comprising a one-time questionnaire (PINC-Q) for adult patients (aged ≥18 years) with schizophrenia (International Classification of Diseases; ICD-10) and their physician, nurse and carer. Questionnaires were developed in association with patient and carer advocacy groups (GAMIAN and EUFAMI) and following an advisory board formed of psychiatrists and nurses. The degree of alignment between stakeholders was also examined.ResultsResponses were received from a total of 224 evaluable patients. For most patients (88.4%), responses were received from at least two other stakeholders. Patients were moderately ill with mild-to-moderate lack of insight and had received PP1M for a mean (standard deviation [SD]) of 23.9 (21.28) months before switching to PP3M (duration mean [SD] 12.8 [3.72] months). The most frequently reported reasons to switch from PP1M to PP3M were ‘to live life as normally as possible’ and ‘patient convenience’. Over 79% of responses within each stakeholder group stated that PP3M helped the patients, with increased patient activity and social involvement, improved frequency and quality of physician–patient and nurse–patient communication and decreased perceived stigma.ConclusionsThe results of this study add to the increasing body of evidence supporting the benefits of PP3M in a population of patients with schizophrenia representative of real-world clinical practice.

Maintenance treatment for schizophrenia during the COVID-19 pandemic: the views of Japanese psychiatrists

Maintenance treatment for schizophrenia during the COVID-19 pandemic: the views of Japanese psychiatrists

[Cariprazine: from receptor affinities to therapeutic effects. Review in schizophrenic spectrum disorders and expert opinion].

Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional and social adjustments. Antipsychotics (APs) are the first-line treatment for schizophrenia that may modify the course of the disease in most cases, by decreasing the institutionalization risk, although they may induce severe side effects. It is worth noting that APs may well control positive symptoms, while their efficacy on negative and cognitive symptoms is low. Cariprazine is one of the latest third-generation APs acting as a partial agonist at dopamine receptor of the type 2 and 3 with a broader spectrum of activities, recently approved for the treatment of adult schizophrenia. The aim of this paper was to review and comment on the available literature on the effectiveness and tolerability of cariprazine in schizophrenia, with a main focus on possibly specific symptoms, as well as in those peculiar patients' populations that could mostly benefit from this latest AP, when compared with previous APs. The current literature would indicate that cariprazine is significantly more effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative and cognitive symptoms, than other APs. In any case, cariprazine has a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its advantages over other APs, cariprazine appears to represent a promising treatment for schizophrenic spectrum disorders.

Cariprazine as a therapeutic option for schizophrenia: a drug evaluation

ABSTRACT Introduction: Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional, and social adjustments. Antipsychotics (APs), the first-line treatment for schizophrenia, in many cases modify the course of the disease, by reducing the institutionalization risk, at the price of severe and invalidating side effects. Cariprazine is one of the latest second-generation APs (SGAs) acting as a partial agonist of type 2 and 3 dopamine receptors, which was recently approved for the treatment of adult schizophrenia. Areas covered: The authors provide a critical review and commentary on the currently available data on the effectiveness and tolerability of cariprazine in schizophrenic patients, with a particular focus on its specific target symptoms. Expert opinion: Cariprazine appears significantly effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative, and cognitive symptoms, slightly more than other SGAs. It shows a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its precise advantages over other SGAs, cariprazine seems a promising compound not only in schizophrenia, but also in a broad range of psychiatric conditions, including perhaps bipolar and addictive disorders.

Long Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Bipolar Disorder.

Schizophrenia and bipolar disorder (BD) are psychiatric disorders with economic and social effects that cause disability. Treatment non-compliance is one of the major problems faced by clinicians in both schizophrenia and BD. Treatment non-compliance is associated with recurrence and impaired functionality. Treatment compliance increases with long-acting injectable antipsychotics (LAIAs) and recurrence times are prolonged, hospitalization rates decrease compared to those who use an equivalent oral form of the same drug. The use of LAIAs in the maintenance treatment of schizophrenia has also been associated with a low mortality rate, decrease in caregiver burden, and increase in patient satisfaction. Studies show that LAIAs are cost-effective compared to their oral forms. Data on the use of LAIAs in first-episode schizophrenia and BD are relatively limited. The results of studies on the use of LAIAs in patients with first-episode schizophrenia indicate that LAIAs have advantageous in preventing relapse and re-hospitalization compared to oral antipsychotics. In BD, with the use of LAIAs, the rate of hospitalization due to mood episodes and the frequency of manic episodes have been decreased. LAIAs have not been found to be as effective in preventing depressive episodes in BD as manic episodes. Although there are many studies supporting the use of LAIAs in maintenance treatment of schizophrenia and BD, more studies are needed on this issue. In this article, studies on the use of LAIAs in schizophrenia, first episode schizophrenia and BD are reviewed and the place of LAIAs in treatment was discussed.

Maintenance treatment with antipsychotic drugs for schizophrenia.

The symptoms and signs of schizophrenia have been linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotic drugs are also effective for relapse prevention. This is the updated version of the aforesaid review. To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (12 November 2008, 10 October 2017, 3 July 2018, 11 September 2019). We included all randomised trials comparing maintenance treatment with antipsychotic drugs and placebo for people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) or standardised mean differences (SMD), again based on a random-effects model. The review currently includes 75 randomised controlled trials (RCTs) involving 9145 participants comparing antipsychotic medication with placebo. The trials were published from 1959 to 2017 and their size ranged between 14 and 420 participants. In many studies the methods of randomisation, allocation and blinding were poorly reported. However, restricting the analysis to studies at low risk of bias gave similar results. Although this and other potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR 0.38, 95% CI 0.32 to 0.45, number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 3; high-certainty evidence). Hospitalisation was also reduced, however, the baseline risk was lower (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR 0.43, 95% CI 0.32 to 0.57, NNTB 8, 95% CI 6 to 14; high-certainty evidence). More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at seven to 12 months: drug 36% versus placebo 62%, 24 RCTs, n = 3951, RR 0.56, 95% CI 0.48 to 0.65, NNTB 4, 95% CI 3 to 5; high-certainty evidence) and due to inefficacy of treatment (at seven to 12 months: drug 18% versus placebo 46%, 24 RCTs, n = 3951, RR 0.37, 95% CI 0.31 to 0.44, NNTB 3, 95% CI 3 to 4). Quality of life might be better in drug-treated participants (7 RCTs, n = 1573 SMD -0.32, 95% CI to -0.57 to -0.07; low-certainty evidence); probably the same for social functioning (15 RCTs, n = 3588, SMD -0.43, 95% CI -0.53 to -0.34; moderate-certainty evidence). Underpowered data revealed no evidence of a difference between groups for the outcome 'Death due to suicide' (drug 0.04% versus placebo 0.1%, 19 RCTs, n = 4634, RR 0.60, 95% CI 0.12 to 2.97,low-certainty evidence) and for the number of participants in employment (at 9 to 15 months, drug 39% versus placebo 34%, 3 RCTs, n = 593, RR 1.08, 95% CI 0.82 to 1.41, low certainty evidence). Antipsychotic drugs (as a group and irrespective of duration) were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI 1.25 to 1.85, number needed to treat for an additional harmful outcome (NNTH) 20, 95% CI 14 to 50), sedation (drug 8% versus placebo 5%, 18 RCTs, n = 4078, RR 1.52, 95% CI 1.24 to 1.86, NNTH 50, 95% CI not significant), and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR 1.69, 95% CI 1.21 to 2.35, NNTH 25, 95% CI 20 to 50). For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs prevents relapse to a much greater extent than placebo for approximately up to two years of follow-up. This effect must be weighed against the adverse effects of antipsychotic drugs. Future studies should better clarify the long-term morbidity and mortality associated with these drugs.

Longitudinal changes in antipsychotic dose in patients treated with long-acting injectable second-generation antipsychotics.

Only a few studies have investigated changes in the dose of long-acting injectable second-generation antipsychotics (LAI-SGAs) over the long term in the maintenance treatment of schizophrenia. In this retrospective cohort study, we examined longitudinal changes in antipsychotic dose over a 3-year period in patients with schizophrenia who had been taking LAI-SGAs for at least 1 year. We compared the total daily chlorpromazine equivalent dose of antipsychotics at 12, 24 and 36 months with the baseline dose at 3 months after initiation of LAI-SGAs. We also performed multiple regression analysis to explore factors associated with change in total daily dose 12 months after treatment initiation. A total of 154 patients fulfilled the inclusion criteria. There was no significant difference in total daily antipsychotic dose between 3 months and 12, 24 or 36 months after treatment initiation. Total daily dose was increased in 43 (27.9%), 31 (34.8%) and 22 patients (36.7%) at 12, 24 and 36 months, respectively. Age and total antipsychotic dose at 3 months were significantly negatively associated with change in total daily dose. Antipsychotic dose was basically unchanged during long-term treatment in patients treated with LAI-SGAs in the maintenance phase, although there was an increase in some patients.

Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data.

Cariprazine is one of the newest dopamine-serotonin partial agonists, also known as ‘atypical’ second generation antipsychotics. Originally approved for acute and maintenance treatment of schizophrenia as well as for acute mania and mixed mania/depression, cariprazine has now been approved for bipolar I depression. Additionally, post hoc analyses of bipolar I depressed subjects show that both those with and those without concurrent manic features were improved following treatment with cariprazine. Maintenance studies are in progress in bipolar disorder, as are studies to augment antidepressants in unipolar major depressive episodes insufficiently responsive to treatment. Here, we review specifically the efficacy and safety data of cariprazine in bipolar I disorder and discuss the hypothesized mechanism of action of cariprazine and how it could theoretically be linked to caprazine’s broad therapeutic actions across the mood disorder spectrum.

P.391 Patient, investigator, nurse, carer questionnaire: exploring the impact of less frequent medication administration in the maintenance treatment of schizophrenia

P.391 Patient, investigator, nurse, carer questionnaire: exploring the impact of less frequent medication administration in the maintenance treatment of schizophrenia

Antipsychotic treatment in the maintenance phase of schizophrenia: An updated systematic review of the guidelines and algorithms

BackgroundWe updated our previous systematic review regarding clinical guidelines and algorithms on antipsychotic treatment in the maintenance phase of schizophrenia (doi: 10.1016/j.schres.2011.11.021) to incorporate and synthesize more recent findings to guide clinical practice. MethodsWe conducted a systematic literature search to identify clinical guidelines and algorithms describing antipsychotic treatment in the maintenance phase of schizophrenia using MEDLINE and Embase. We assessed overall quality of the guidelines/algorithms according to the AGREE II instrument and extracted information on treatment recommendations. ResultsWe identified 20 guidelines/algorithms from various regions, including 11 updated or newly launched ones after the previous systematic review in 2012. All of the guidelines/algorithms satisfied a certain level of quality. Where mentioned, endorsements were sorted into “recommended”, “partially recommended”, or “not recommended”. As for antipsychotic discontinuation strategy, a majority of guidelines/algorithms that mentioned this strategy did not recommend it for multiple-episode schizophrenia (N = 5/6). On the other hand, the guidelines/algorithms tended to shift from “not recommended” to “partially recommended” both for schizophrenia in general (N = 7/13, N = 7/8 for those published after 2013) and first-episode schizophrenia (N = 10/11, N = 7/7 for those published after 2013) regarding this strategy. All guidelines/algorithms (N = 9/9) converged to discourage antipsychotic intermittent/targeted strategy. Similar to antipsychotic discontinuation strategy, all of the updated or new guidelines/algorithms (N = 6/6) endorsed antipsychotic dose reduction/lower dose strategy. ConclusionRecent clinical guidelines and algorithms on antipsychotic maintenance treatment in schizophrenia shifted more toward a possibility of antipsychotic discontinuation and dose reduction/lower dose strategies. Nonetheless, clinicians need to contemplate on the risk-benefit balance of these strategies for individual patients.

Antipsychotic polypharmacy reduces risk of hospital stay compared to monotherapy

In a finding contrary to treatment guidelines that discourage antipsychotic polypharmacy in the maintenance treatment of schizophrenia, a cohort study has reported that any polypharmacy combination reduced risk of psychiatric rehospitalization compared with antipsychotic monotherapy. The combination of clozapine and aripiprazole was associated with the lowest risk of rehospitalization, the researchers found. Study results were published online Feb. 20 in JAMA Psychiatry.

Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons.

Second-generation antipsychotics (SGAs) are recommended for maintenance treatment in schizophrenia. However, comparative long-term effectiveness among SGAs is unclear. Here we provide a systematic review and meta-analysis of randomized trials lasting ≥⃒6 months comparing SGAs head-to-head in schizophrenia and related disorders. The primary outcome was all-cause discontinuation. Secondary outcomes included efficacy and tolerability, i.e., psychopathology, inefficacy-related and intolerability-related discontinuation, relapse, hospitalization, remission, functioning, quality of life, and adverse events. Pooled risk ratio and standardized mean difference were calculated using random-effects models. Across 59 studies (N=45,787), lasting 47.4±32.1 weeks (range 24-186), no consistent superiority of any SGA emerged across efficacy and tolerability outcomes. Regarding all-cause discontinuation, clozapine, olanzapine and risperidone were significantly (p<0.05) superior to several other SGAs, while quetiapine was inferior to several other SGAs. As to psychopathology, clozapine and olanzapine were superior to several other SGAs, while quetiapine and ziprasidone were inferior to several other SGAs. Data for other efficacy outcomes were sparse. Regarding intolerability-related discontinuation, risperidone was superior and clozapine was inferior to several other SGAs. Concerning weight gain, olanzapine was worse than all other compared non-clozapine SGAs, and risperidone was significantly worse than several other SGAs. As to prolactin increase, risperidone and amisulpride were significantly worse than several other SGAs. Regarding parkinsonism, olanzapine was superior to risperidone, without significant differences pertaining to akathisia. Concerning sedation and somnolence, clozapine and quetiapine were significantly worse than some other SGAs. In summary, different long-term SGA efficacy and tolerability patterns emerged. The long-term risk-benefit profiles of specific SGAs need to be tailored to individual patients to optimize maintenance treatment outcomes.