Safety and effectiveness of olanzapine and droperidol for chemical restraint for non-consenting adults: a systematic review and meta-analysis.

BACKGROUND: Chemical restraint (CR) is emergency drug management for acute behavioural disturbances in people with mental illness, provided with the aim of rapid calming and de-escalating potentially dangerous situations. AIMS: To describe a systematic review of Randomised Controlled Trials (RCTs) reporting on short-term safety and effectiveness of drugs used for CR, administered to non-consenting adults with mental health conditions, who require emergency management of acute behavioural disturbances. A meta-analysis was conducted of those RCTs with comparable interventions, outcome measures and measurement timeframes. METHOD: Academic databases were searched for RCTs published between 1 January 1996 and 20th April 2020. Relevant RCTs were critically appraised using the 13-item JBI checklist. All RCTs were described, and step-wise filters were applied to identify studies suitable for meta-analysis. For these, forest and funnel plots were constructed, and Q and I2 statistics guided interpretation of pooled findings, tested using MedCalc Version 19.1. RESULTS: Of 23 relevant RCTs, 18 (78.2% total) had excellent methodological quality scores (at least 90%). Eight RCTs were potentially relevant for meta-analysis (six of excellent quality), reporting 20 drug arms in total. Adverse events for 6-36% patients were reported in all 20 drug arms. Four drug arms from two homogenous studies of N = 697 people were meta-analysed. These RCTs tested two antipsychotic drugs (droperidol, olanzapine) delivered intravenously in either 5 mgs or 10 mg doses, with outcomes of time to calm, percentage calm within five or 10 min, and adverse events. There were no significant differences between drug arms for either measure of calm. However, 5 mg olanzapine incurred significantly lower risk of adverse events than 10 mg olanzapine (OR 0.4 (95%CI 0.2-0.8)), although no dose differences were found for droperidol. CONCLUSION: 5 mg intravenous olanzapine is recommended for quick, safe emergency management of people with acute behavioural disturbances associated with mental illness.

Effectiveness of mandatory peer review to reduce antipsychotic prescriptions for Medicaid-insured children.

BACKGROUND: Prior authorization of prescription medications is a policy tool that can potentially impact care quality and patient safety. OBJECTIVE: To examine the effectiveness of a mandatory peer-review program in reducing antipsychotic prescriptions among Medicaid-insured children, accounting for secular trends that affected antipsychotic prescribing nationally. DATA SOURCE: Medicaid Analytical eXtracts (MAX) with administrative claims for health services provided between January 2006 and December 2011. STUDY DESIGN: This retrospective, observational study examined prescription claims records from Washington State (Washington) and compared them to a synthetic control drawing from 20 potential donor states that had not implemented any antipsychotic prior authorization program or mandatory peer review for Medicaid-insured children during the study period. This method provided a means to control for secular trends by simulating the antipsychotic use trajectory that the program state would have been expected to experience in the absence of the policy implementation. PRINCIPAL FINDINGS: Before the policy implementation, antipsychotic use prevalence closely tracked those of the synthetic control (6.17 per 1000 in Washington vs. 6.21 in the synthetic control group). Within two years after the policy was implemented, prevalence decreased to 4.04 in Washington and remained stable in the synthetic control group (6.47), corresponding to an approximately 38% decline. CONCLUSION: Prior authorization program designs and implementations vary widely. This mandatory peer-review program, with an authorization window and two-stage rollout, was effective in moving population level statistics toward safe and judicious use of antipsychotic medications in children.

The efficacy and safety of sulforaphane as an adjuvant in the treatment of bipolar depressive disorder: Study protocol for a randomized, double-blinded, placebo-controlled, parallel-group clinical trial.

BACKGROUND: Bipolar disorder (BD) is a chronic and disabling psychiatric disorder. The treatment of BD still remains a significant clinical challenge due to the complex nature of the disease. Nutraceutical therapy as adjunctive role is a promising therapy for BD. Sulforaphane (SFN), a broccoli extract, was reported to be effective for emotional problems and cognitive impairment. However, clinical research of SFN in the treatment of BD was rare. Therefore, this study is designed to evaluate the adjuvant role of SFN in the treatment of BD. METHODS: This is a randomized, double-blinded, placebo-controlled, parallel-group clinical trial. A total of 100 patients who meet inclusion criteria will be assigned to receive quetiapine plus SFN or quetiapine plus placebo in a 1:1 ratio. The total duration of the study will be 12 weeks including 5 follow ups. The primary outcome is in the Montgomery-Asberg depression rating scale. The secondary outcomes are the quick inventory of depressive symptomatology-self report, Hamilton anxiety rating scale, young mania rating scale, cognitive function, inflammatory factors, and intestinal flora. Any adverse events will be recorded throughout the trial. DISCUSSION: This trial will provide evidences to evaluate the efficacy and safety of SFN combined with quetiapine in the treatment of BD patients, as well as the adjuvant role of SFN in combination. TRIAL REGISTRATION: This study protocol was registered at the Chinese clinical trial registry (ChiCTR2000028706).

The use of olanzapine as an antiemetic in palliative medicine: a systematic review of the literature.

BACKGROUND: Olanzapine is an atypical antipsychotic that has affinity for many central nervous system receptors. Its efficacy is supported by several studies in the prevention and treatment of chemotherapy-induced nausea and vomiting. No recommendations exist on the antiemetic use of olanzapine in the palliative care setting. The aim of this work is to complete the initial work of Fonte et al. published in 2015, to determine whether the literature supports the use of olanzapine as an antiemetic in palliative situations and, in practice, to propose a therapeutic schema adapted to the palliative setting. METHODS: Systematic review of the literature according to the PRISMA criteria. We searched the PubMed, Cochrane, RefDoc, EMBase databases and the gray literature databases. The bibliographic search was conducted between November 2016 and August 2017. RESULTS: Thirteen articles were included: 2 case studies, 3 case series, 3 retrospective studies, 2 prospective studies, 2 literature reviews. All studies concluded on the efficacy of olanzapine as an antiemetic in the palliative care setting. No serious adverse effects were reported. Based on the data from the literature review, we propose a therapeutic scheme adapted to the palliative care context. CONCLUSION: Action of olanzapine on many receptors and its tolerance profile make it an interesting antiemetic treatment in palliative medicine. But to date, studies are scarce and have a low statistical power. Further investigation is therefore needed to determine the benefit of this treatment in palliative care patients, compared to usual treatments.

Paranoid delusions • ideas of reference • sleep problems • Dx?

► Paranoid delusions ► Ideas of reference ► Sleep problems ► Multiple, vague somatic symptoms.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Long-term use of antipsychotics and antidepressants is not evidence-based.

BACKGROUND: The widespread use of psychiatric drugs does not appear to be evidence-based but seems to be driven mainly by commercial pressures. I studied whether two widely differing drug classes, antipsychotics and antidepressants, showed similar patterns in long-term usage. METHODS: I constructed usage curves over a ten-year period, from 2006 to 2016, based on data from Statistics Denmark. RESULTS: In 2006, a total of 110,235 patients deemed a prescription for an antipsychotic and 395,018 for an antidepressant, corresponding to 2.0% and 7.3% of the Danish population. Only 21,846 vs. 79,030 of these were first-time users (19.8% vs. 20.0%). The percentage of current users who redeemed a prescription for the same or a similar drug in each of the following years was remarkably similar for the two classes of drugs, and after ten years, it was 35% vs. 33%.Using the requirement that the patients identified in 2006 needed to redeem the prescription only once during the next ten years, 42% vs. 43% were taking a drug in 2016. This suggests that most patients identified at any given point in time as drug users continue taking such drugs for many years, with little or no interruption in drug intake.For first-time users, the drop in usage was much quicker. The percentage of first-time users who redeemed a prescription for the same or a similar drug in each of the following years fell to about one-third (29% vs. 36%) already after two years.Using 2011 as the starting year yielded similar results. CONCLUSIONS: If we accept the evidence-based premises that antipsychotics and antidepressants do not have clinically relevant effects and that the patients dislike them, the data suggest massive overuse of the drugs, to a remarkably similar degree. We need to focus on helping patients withdraw slowly and safely from the drugs they are on instead of telling them that they need to stay on them.

Improving quality of antipsychotic polypharmacy: a pilot study.

Background: Concurrent prescription of more than one type of antipsychotic for the same patient - antipsychotic polypharmacy (APP) - is associated with increased incidence of side effects, uncertain therapeutic benefit and general guidelines advise against it. Nevertheless, APP is common and there is little evidence about possible interventions to improve practice.Aims: To investigate the prevalence and documentation quality of APP in specialized psychiatric care and assess the feasibility and effect of a simple intervention to improve clinical practice.Methods: We examined the prevalence and the quality of documentation of APP in medical records from a large inpatient treatment department before and 6 months after an intervention, which consisted of giving feedback to doctors on their prescription practices as well as teaching about current guidelines. Prescription and documentation before and after intervention were compared between intervention and control wards.Results: One hundred and twenty-one medical records were examined at baseline. 43% of these had APP, of these 27% was satisfactory documented. After the intervention, the proportion with APP was reduced from 42% to 29% in the intervention group. There was a statistically significant interaction effect of the intervention group and the after-intervention condition on this reduction. The percentage with satisfactory documentation of APP was increased after the intervention in both groups, but we found no corresponding interaction effect.Conclusion: APP is prevalent in inpatient treatment of patients with mainly psychotic disorders but documentation of this is insufficient. Simple education and feedback on prescription and records documentation practices may increase adherence to guidelines.

Stratified medicine in schizophrenia: how accurate would a test of drug response need to be to achieve cost-effective improvements in quality of life?

OBJECTIVE: Stratified medicine refers to the use of tests that predict treatment response to drive treatment decisions for individual patient. The pharmacoeconomic implications of this approach in schizophrenia are unknown. We aimed to assess the cost-effectiveness of a hypothetical stratified medicine algorithm (SMA) compared with treatment as usual (TAU), for patients with schizophrenia who failed a first-line antipsychotic. METHODS: A decision analytic model with embedded Markov process was constructed, which simulated the health and cost outcomes for patients followed SMA or TAU over a lifetime horizon, from healthcare and social care perspective. In the base-case analysis, sensitivity and specificity of the stratifier were both set as 60%. Extensive sensitivity analyses were conducted to test the impact of uncertainty around the value of important parameters. The primary outcome was the incremental cost per quality-adjusted life year (QALY) gained. RESULTS: When both sensitivity and specificity of the stratified test were set at 60%, SMA appeared to be the optimal strategy as it produces more QALYs and incurs lower costs than TAU. This is robust to all scenarios tested. At a willingness-to-pay threshold of £20,000 per QALY, the probability for SMA to be the optimal strategy is 82.4%. CONCLUSIONS: Our results suggest that use of any stratifier with a sensitivity and specificity over 60% is very likely to be cost-effective comparing to TAU, for psychotic patients who failed a first-line antipsychotic. This finding, however, should be interpreted with caution due to lack of evidence for clozapine as a second-line antipsychotic.

Early intervention for bipolar disorder - Do current treatment guidelines provide recommendations for the early stages of the disorder?

BACKGROUND: Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. METHODS: We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. RESULTS: We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. LIMITATION: The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. CONCLUSIONS: There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances.

Numerous stationary phases have been developed with the aim to provide desired performances during chromatographic analysis of the basic solutes in their protonated form. In this work, the procedure for the characterization of bonded stationary phase performance, when both qualitative and quantitative chromatographic factors were varied in chaotropic chromatography, was proposed. Risperidone and its three impurities were selected as model substances, while acetonitrile content in the mobile phase (20-30%), the pH of the aqueous phase (3.00-5.00), the content of chaotropic agents in the aqueous phase (10-100 mM), type of chaotropic agent (NaClO4, CF3COONa), and stationary phase type (Zorbax Eclipse XDB, Zorbax Extend) were studied as chromatographic factors. The proposed procedure implies the combination of D-optimal experimental design, indirect modeling, and polynomial-modified Gaussian model, while grid point search method was selected for the final choice of the experimental conditions which lead to the best possible stationary phase performance for basic solutes. Good agreement between experimentally obtained chromatogram and simulated chromatogram for chosen experimental conditions (25% acetonitrile, 75 mM of NaClO4, pH 4.00 on Zorbax Eclipse XDB column) confirmed the applicability of the proposed procedure. The additional point was selected for the verification of proposed procedure ability to distinguish changes in solutes' elution order. Simulated chromatogram for 21.5% acetonitrile, 85 mM of NaClO4, pH 5.00 on Zorbax Eclipse XDB column was in line with experimental data. Furthermore, the values of left and right peak half-widths obtained from indirect modeling were used in order to evaluate performances of differently modified stationary phases applying a half-width plots approach. The results from half-width plot approach as well as from the proposed procedure indicate higher efficiency and better separation performance of the stationary phase extra densely bonded and double end-capped with trimethylsilyl group than the stationary phase with the combination of end-capping and bidentate silane bonding for chromatographic analysis of basic solutes in RP-HPLC systems with chaotropic agents. Graphical abstract ᅟ.

Clozapine Rechallenge After Major Adverse Effects: Clinical Guidelines Based on 259 Cases.

BACKGROUND: Clozapine is widely prescribed for treatment-refractory schizophrenia, but its use is limited by many potentially life-threatening adverse effects. The risk of rechallenge after these complications has never been comprehensively assessed in controlled studies. Thus, clinical guidelines must rely on the published case reports. The number of such reports is likely to increase over time, and updated analyses of larger samples are needed, as they may lead to changes in clinical guidelines. STUDY QUESTIONS: How safe is the clozapine rechallenge after life-threatening adverse effects? STUDY DESIGN: The published case reports of clozapine rechallenge were identified in a MEDLINE search. We added 121 cases reported from 2012 through 2017 to the 138 cases reported from 1972 through 2011 analyzed by us in a previous publication. The 95% confidence intervals (CIs) of the successful rechallenge rate were calculated for each adverse effect with at least 5 published case reports. The rechallenge was considered a valid clinical option when the lower end of the CI range was at least 50%. RESULTS: A successful outcome was documented in 128/203 patients rechallenged after neutropenia (63.0%, CI, 56.0%-69.6%), 3/17 after agranulocytosis (17.7%, CI, 4.7%-44.2%), 11/17 after myocarditis (64.7%, CI, 38.6%-84.7%), and 7/7 after neuroleptic malignant syndrome (100%, CI, 56.1%-100%). Among the 15 patients with other clozapine-induced adverse effects, the rechallenge was successful in those with eosinophilia, cardiac complications other than myocarditis (QTc prolongation, pericarditis, cardiomyopathy, and atrial flutter), and gastrointestinal hypomotility. The rechallenge failed in patients who had developed pancreatitis or renal insufficiency. CONCLUSION: Clozapine rechallenge is a reasonable clinical option after return to baseline for patients who had developed neutropenia and neuroleptic malignant syndrome, but not after agranulocytosis or myocarditis. Data are insufficient to formulate rechallenge guidelines for any other clozapine-related adverse effects.

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia.

BACKGROUND: Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD. METHODS: Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primary-care practice for at least 3 years in Northwestern Virginia. RESULTS: PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management. CONCLUSIONS: PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development.

Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop antipsychotics; to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: The overall team comprised 9 clinicians (1 family physician, 1 family physician specializing in long-term care, 1 geriatric psychiatrist, 2 geriatricians, 4 pharmacists) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated from a Cochrane systematic review of antipsychotic deprescribing trials for the behavioural and psychological symptoms of dementia, and a systematic review was conducted to assess the evidence behind the benefits of using antipsychotics for insomnia. A review of reviews of the harms of continued antipsychotic use was performed, as well as narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality-of-evidence ratings were used to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. RECOMMENDATIONS: We recommend deprescribing antipsychotics for adults with behavioural and psychological symptoms of dementia treated for at least 3 months (symptoms stabilized or no response to an adequate trial) and for adults with primary insomnia treated for any duration or secondary insomnia in which underlying comorbidities are managed. A decision-support algorithm was developed to accompany the guideline. CONCLUSION: Antipsychotics are associated with harms and can be safely tapered. Patients and caregivers might be more amenable to deprescribing if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice or management. This guideline provides recommendations for making decisions about when and how to reduce the dose of or stop antipsychotics. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients and families.

Update in perioperative medicine: practice changing evidence published in 2016.

This summary reviews 18 key articles published in 2016 which have significant practice implications for the perioperative medical care of surgical patients. Due to the multi-disciplinary nature of the practice of perioperative medicine, important new evidence is published in journals representing a variety of medical and surgical specialties. Keeping current with the evidence that drives best practice in perioperative medicine is therefore challenging. We set out to identify, critically review, and summarize key evidence which has the most potential for practice change. We integrated the new evidence into the existing body of medical knowledge and identified practical implications for real world patient care. The articles address issues related to anticoagulation, transfusion threshold, immunosuppressive medications, postoperative delirium, myocardial injury after noncardiac surgery, postoperative pain management, perioperative management of antihypertensives, perioperative fasting, and perioperative diabetic control.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines.

Background: This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity. Methods: The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines. Results: The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option. Conclusion: The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper.

Development and validation of HILIC-ESI/MS/MS methods for simultaneous quantitation of several antipsychotics in human plasma and blood.

BACKGROUND: Knowledge of antipsychotic drug levels at point of care (POC) may significantly aid therapeutic decision-making. To support the development of future POC devices and to validate the use of fingerstick capillary blood sampling, two robust hydrophilic interaction LC-ESI/MS/MS methods were developed and validated. Two PK studies were completed evaluating the correlation between fingerstick blood and plasma concentrations with corresponding venous blood and plasma concentrations for several commonly prescribed atypical antipsychotics and selected metabolites. Sensitive and reliable LC-MS/MS bioanalytical assays were developed to support these studies. RESULTS: Three methods, requiring only 25-µl matrix volumes, were developed using supported liquid extraction with hydrophilic interaction LC-MS/MS detection and validated according to regulatory guidance. CONCLUSION: Robust and efficient LC-MS/MS assays were established and were effective in providing antipsychotic drug matrix comparator results in the intended clinical studies.

The safety, efficacy and tolerability of Abilify Maintena for the treatment of schizophrenia.

Relapse in schizophrenia has been associated with poor adherence to oral medication. A possible method to optimize medication adherence could be to switch patients from oral to depot medication. In this respect, aripiprazole long acting injectable (ALAI) significantly delayed time to impending relapse when compared with placebo (p < 0.0001), while ALAI was generally well tolerated during both short-term and long-term studies. A literature search, using PubMed was conducted to identify relevant publications. Available evidence suggests that ALAI may be a viable treatment option for patients with schizophrenia, but before it can be concluded whether or not all schizophrenia patients could benefit from a switch to depot formulations, several questions remain to be answered. Thus, there is a great need for randomized controlled trials comparing depot medications with their oral equivalents.