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BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
Acta Neuropsychiatrica Aug 2023Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect... (Review)
Review
OBJECTIVES
Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.
METHODS
We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).
RESULTS
According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination.
CONCLUSION
Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.
Topics: Selective Serotonin Reuptake Inhibitors; Apathy; Olanzapine; Antidepressive Agents; Bupropion
PubMed: 36644883
DOI: 10.1017/neu.2023.6 -
Journal of Psychopharmacology (Oxford,... Oct 2023Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations.
AIMS
We hypothesized that QTP-IR is inferior to QTP-ER at any dose in efficacy for the acute treatment in schizophrenia and tested using a dose-response model-based network meta-analysis (NMA).
METHODS
We searched PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov for randomized placebo-controlled trials comparing QTP-IR and/or QTP-ER for acute psychosis in patients with schizophrenia up to September 21, 2022. A random effect Bayesian dose-response model-based NMA was performed to compare the dose-response relationships between QTP-IR and QTP-ER.
RESULTS
The relationship between doses and antipsychotic effects was partially bell-shaped for QTP-IR but not for QTP-ER. The respective peak effect dose was 279.7 mg for QTP-IR and 557.2 mg for QTP-ER, with no significant difference in peak effect. QTP-IR ranging from 100 to 300 mg were significantly superior to QTP-ER at the same doses. In addition, QTP-IR ranging from 100 to 400 mg were significantly better than placebo, whereas QTP-ER ranging from 500 to 800 mg were significantly more effective than placebo. Moreover, QTP-IR 600 mg was significantly less effective than QTP-ER at the same dose. Furthermore, QTP-IR 700 mg was significantly superior to placebo, but significantly inferior to QTP-ER 600 mg.
CONCLUSIONS
QTP-IR may reach comparable peak responses and exhibit enhanced antipsychotic effects at lower doses than QTP-ER; the converse may be true at relatively high doses. Collectively, we propose a novel strategy to enhance the efficacy of QTP administration.
Topics: Humans; Quetiapine Fumarate; Antipsychotic Agents; Network Meta-Analysis; Bayes Theorem; Psychotic Disorders; Schizophrenia; Delayed-Action Preparations
PubMed: 37740667
DOI: 10.1177/02698811231200020 -
The Cochrane Database of Systematic... Aug 2023Antipsychotic medications are regularly prescribed in care home residents for the management of behavioural and psychological symptoms of dementia (BPSD) despite... (Review)
Review
BACKGROUND
Antipsychotic medications are regularly prescribed in care home residents for the management of behavioural and psychological symptoms of dementia (BPSD) despite questionable efficacy, important adverse effects, and available non-pharmacological interventions. Prescription rates are related to organisational factors, staff training and job satisfaction, patient characteristics, and specific interventions. Psychosocial intervention programmes aimed at reducing the prescription of antipsychotic drugs are available. These programmes may target care home residents (e.g. improving communication and interpersonal relationships) or target staff (e.g. by providing skills for caring for people with BPSD). Therefore, this review aimed to assess the effectiveness of these interventions, updating our earlier review published in 2012.
OBJECTIVES
To evaluate the benefits and harms of psychosocial interventions to reduce antipsychotic medication use in care home residents compared to regular care, optimised regular care, or a different psychosocial intervention.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 14 July 2022.
SELECTION CRITERIA
We included individual or cluster-randomised controlled trials comparing a psychosocial intervention aimed primarily at reducing the use of antipsychotic medication with regular care, optimised regular care, or a different psychosocial intervention. Psychosocial interventions were defined as non-pharmacological intervention with psychosocial components. We excluded medication withdrawal or substitution interventions, interventions without direct interpersonal contact and communication, and interventions solely addressing policy changes or structural interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Critical appraisal of studies addressed risks of selection, performance, attrition and detection bias, as well as criteria related to cluster randomisation. We retrieved data on the complex interventions on the basis of the TIDieR (Template for Intervention Description and Replication) checklist. Our primary outcomes were 1. use of regularly prescribed antipsychotic medication and 2.
ADVERSE EVENTS
Our secondary outcomes were 3. mortality; 4. BPSD; 5. quality of life; 6. prescribing of regularly psychotropic medication; 7. regimen of regularly prescribed antipsychotic medication; 8. antipsychotic medication administered 'as needed'; 9. physical restraints; 10. cognitive status; 11. depression; 12. activities of daily living; and 13.
COSTS
We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included five cluster-randomised controlled studies (120 clusters, 8342 participants). We found pronounced clinical heterogeneity and therefore decided to present study results narratively. All studies investigated complex interventions comprising, among other components, educational approaches. Because of the heterogeneity of the results, including the direction of effects, we are uncertain about the effects of psychosocial interventions on the prescription of antipsychotic medication. One study investigating an educational intervention for care home staff assessed the use of antipsychotic medication in days of use per 100 resident-days, and found this to be lower in the intervention group (mean difference 6.30 days, 95% confidence interval (CI) 6.05 to 6.66; 1152 participants). The other four studies reported the proportion of participants with a regular antipsychotic prescription. Of two studies implementing an intervention to promote person-centred care, one found a difference in favour of the intervention group (between-group difference 19.1%, 95% CI 0.5% to 37.7%; 338 participants), while the other found a difference in favour of the control group (between-group difference 11.4%, 95% CI 0.9% to 21.9%; 862 participants). One study investigating an educational programme described as "academic detailing" found no difference between groups (odds ratio 1.06, 95% CI 0.93 to 1.20; 5363 participants). The fifth study used a factorial design to compare different combinations of interventions to supplement person-centred care. Results showed a positive effect of medication review, and no clear effect of social interaction or exercise. We considered that, overall, the evidence about this outcome was of low certainty. We found high-certainty evidence that psychosocial interventions intended primarily to reduce antipsychotic use resulted in little to no difference in the number of falls, non-elective hospitalisations, or unplanned emergency department visits. Psychosocial interventions intended primarily to reduce antipsychotic use also resulted in little to no difference in quality of life (moderate-certainty evidence), and BPSD, regular prescribing of psychotropic medication, use of physical restraints, depression, or activities of daily living (all low-certainty evidence). We also found low-certainty evidence that, in the context of these interventions, social interaction and medication review may reduce mortality, but exercise does not.
AUTHORS' CONCLUSIONS
All included interventions were complex and the components of the interventions differed considerably between studies. Interventions and intervention components were mostly not described in sufficient detail. Two studies found evidence that the complex psychosocial interventions may reduce antipsychotic medication use. In addition, one study showed that medication review might have some impact on antipsychotic prescribing rates. There were no important adverse events. Overall, the available evidence does not allow for clear generalisable recommendations.
Topics: Humans; Antipsychotic Agents; Psychosocial Intervention; Activities of Daily Living; Quality of Life; Restraint, Physical
PubMed: 37650479
DOI: 10.1002/14651858.CD008634.pub3 -
Journal of Managed Care & Specialty... Feb 2024Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT)... (Review)
Review
A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.
BACKGROUND
Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs.
OBJECTIVE
To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine.
METHODS
We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified.
RESULTS
We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment.
CONCLUSIONS
Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.
Topics: Adult; Humans; United States; Antipsychotic Agents; Schizophrenia; Lurasidone Hydrochloride; Paliperidone Palmitate; Quetiapine Fumarate
PubMed: 38308625
DOI: 10.18553/jmcp.2024.30.2.183 -
Human Psychopharmacology Mar 2024N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
N-acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta-analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders.
METHODS
PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop-out rates.
RESULTS
A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24 weeks and >24 weeks). There was also no statistical difference in drop-out rates between the two groups.
CONCLUSION
For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.
Topics: Humans; Acetylcysteine; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37712506
DOI: 10.1002/hup.2880 -
Psychological Medicine Dec 2023Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common.
METHODS
We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events.
RESULTS
We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of -6.45 [95% confidence interval (CI) -8.13 to -4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects ( = 0.003) and also weight gain ( < 0.00001), sedation ( < 0.00001) and increased appetite ( = 0.001) in the antipsychotic group.
CONCLUSIONS
There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.
Topics: Child; Humans; Antipsychotic Agents; Aripiprazole; Risperidone; Psychotic Disorders; Autism Spectrum Disorder; Randomized Controlled Trials as Topic
PubMed: 37539448
DOI: 10.1017/S003329172300212X -
Neuroscience and Biobehavioral Reviews Feb 2024People living with dementia commonly experience anxiety, which is often challenging to manage. We investigated the effectiveness of treatments for the management of... (Meta-Analysis)
Meta-Analysis Review
Clinical effectiveness of pharmacological and non-pharmacological treatments for the management of anxiety in community dwelling people living with dementia: A systematic review and meta-analysis.
People living with dementia commonly experience anxiety, which is often challenging to manage. We investigated the effectiveness of treatments for the management of anxiety in this population. We conducted a systematic review and meta-analysis of randomised controlled trials, and searched EMBASE, CINAHL, MEDLINE and PsycInfo. We estimated standardised mean differences at follow-up between treatments relative to control groups and pooled these across studies using random-effects models where feasible. Thirty-one studies were identified. Meta-analysis demonstrated non-pharmacological interventions were effective in reducing anxiety in people living with dementia, compared to care as usual or active controls. Specifically, music therapy (SMD-1.92(CI:-2.58,-1.25)), muscular approaches (SMD-0.65(CI:-1.02,-0.28)) and stimulating cognitive and physical activities (SMD-0.31(CI:-0.53,-0.09)). Pharmacological interventions with evidence of potential effectiveness included Ginkgo biloba, probiotics, olanzapine, loxapine and citalopram compared to placebo, olanzapine compared to bromazepam and buspirone and risperidone compared to haloperidol. Meta-analyses were not performed for pharmacological interventions due to studies' heterogeneity. This has practice implications when promoting the use of more non-pharmacological interventions to help reduce anxiety among people living with dementia.
Topics: Humans; Independent Living; Olanzapine; Anxiety; Treatment Outcome; Dementia
PubMed: 38097097
DOI: 10.1016/j.neubiorev.2023.105507 -
The Cochrane Database of Systematic... Dec 2023This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30%... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects.
OBJECTIVES
To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 3 October 2022 with no language restrictions. CRS Web includes randomised and quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials.
DATA COLLECTION AND ANALYSIS
For this update, two review authors independently selected trials and extracted data. Our primary outcome was 50% or greater reduction in seizure frequency. Our secondary outcomes were treatment withdrawal, adverse effects, cognitive effects, and quality of life. Primary analyses were by intention-to-treat. We performed sensitivity best- and worse-case analyses to account for missing outcome data. We calculated pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) for dichotomous outcomes.
MAIN RESULTS
We identified no new studies for this update, so the results and conclusions of the review are unchanged. We included five parallel-group studies in adults or children, eight cross-over studies in adults or children, and one parallel study with a responder-enriched design in infants. In total, these 14 studies enroled 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks and treatment phases ranged from eight to 36 weeks. We rated 11 studies (1243 participants) at low overall risk of bias and three (697 participants) at unclear overall risk of bias due to lack of information on study design. Four studies (563 participants) reported effective blinding. Lamotrigine compared with placebo probably increases the likelihood of achieving 50% or greater reduction in seizure frequency (RR 1.80, 95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence). There is probably little or no difference in risk of treatment withdrawal for any reason among people treated with lamotrigine versus people treated with placebo (RR 1.11, 95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). Lamotrigine compared with placebo is probably associated with a greater risk of ataxia (RR 3.34, 99% Cl 2.01 to 5.55; 12 trials; 1525 participants; moderate-certainty evidence), dizziness (RR 1.76, 99% Cl 1.28 to 2.43; 13 trials; 1768 participants; moderate-certainty evidence), nausea (RR 1.81, 99% CI 1.22 to 2.68; 12 studies, 1486 participants; moderate-certainty evidence), and diplopia (RR 3.79, 99% Cl 2.15 to 6.68; 3 trials, 944 participants; moderate-certainty evidence). There is probably little or no difference in the risk of fatigue between lamotrigine and placebo (RR 0.82, 99% CI 0.55 to 1.22; 12 studies, 1552 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs.
Topics: Adult; Child; Humans; Lamotrigine; Diplopia; Dizziness; Drug Therapy, Combination; Anticonvulsants; Seizures; Drug Resistant Epilepsy; Ataxia; Drug-Related Side Effects and Adverse Reactions; Nausea; Epilepsies, Partial
PubMed: 38078494
DOI: 10.1002/14651858.CD001909.pub4 -
Journal of Psychiatric Research Jun 2024Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and... (Review)
Review
Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3-8) for risperidone literature and 5 for aripiprazole (range: 4-6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested.
Topics: Humans; Aripiprazole; Cytochrome P-450 CYP2D6; Risperidone; Cytochrome P-450 CYP2C19; Antipsychotic Agents
PubMed: 38631139
DOI: 10.1016/j.jpsychires.2024.04.001