Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Srisurapanont, Manit; Suttajit, Sirijit; Maneeton, Narong; Maneeton, Benchalak

doi:10.1016/j.jpsychires.2015.01.004

Cited by 52 publications

(49 citation statements)

References 44 publications

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“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

“…There were meta‐analytic data for 17 different pharmacological interventions: aripiprazole augmentation, fluoxetine, metformin, nizatidine, NMDA receptor antagonists including amantadine and memantine, ranitidine, topiramate, dextroamphetamine, d‐fenfluramine, famotidine, metformin in combination with sibutramine, orlistat, rosiglitazone, fluvoxamine, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), and switching from olanzapine to quetiapine or aripiprazole.…”

Section: Resultsmentioning

confidence: 99%

“…In 16 meta‐analyses (59%), the total pooled sample was less than 500 cases, while only five meta‐analyses (18%) had a total sample of more than 1,000 participants. Only two meta‐analyses (7%) had one included trial with at least 200 participants. Finally, following the AMSTAR‐Plus Content criteria, a significant heterogeneity was found for 12 meta‐analyses (44%), and 18 (67%) could not disprove the presence of a publication bias.…”

Section: Resultsmentioning

confidence: 99%

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The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 metaanalyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=-0.98) and exercise interventions (SMD=-0.96), followed by psychoeducation (SMD=-0.77), aripiprazole augmentation (SMD=-0.73), topiramate (SMD=-0.72), d-fenfluramine (SMD=-0.54) and metformin . Regarding waist circumference reduction, aripiprazole augmentation (SMD=-1.10) and topiramate (SMD=-0.69) demonstrated the best evidence, followed by dietary interventions . Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=-0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=-0.71) and metformin (SMD=-0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=-0.39), dietary interventions (SMD=-0.37) and aripiprazole augmentation (SMD=-0.34), whereas insulin resistance improved the most with metformin (SMD=-0.75) and rosiglitazone . Topiramate had the greatest efficacy for triglycerides (SMD=-0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=-0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=-0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=-0.35 to -0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.People with schizophrenia have substantially poorer physi cal health than the general population 14 , which is often attrib uted to an interaction between social circumstances, lifestyle factors and treatment effects 5 . For instance, behavioral re search has demonstrated that people with schizophrenia are less physically active and exhibit more sedentary behavior than the general population 6 , have a higher quantity but lower qual ity of dietary food intake 7 , and increased adverse health behav iors, such as smoking 8 . Additionally, psychiatric treatment with antipsychotics and other commonly prescribed agents, such as mood stabilizers and antidepressants, further increases the risk of physical health conditions 9,10 . Consequently, people with schizophrenia more frequently have cardiometabolic diseases 1113 , respiratory d...

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“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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“…They report that there is consistent emerging data supporting aripiprazole for reregulate lipid profiles.Canadian Agency for Drugs and Technologies in Health 2012 [35]30June 16, 2010NRRCTschizophrenia /schizoaffective disorder inadequately managed with one or more AAPs at recommended dosesHigh dose AP/ APPAP Low dose /monotherapyAE (endocrine / metabolic markers for glucose, prolactin,Modified SIGN checklist assigned a rating (very good, good, or poor); 27/30 rated poor. Low quality tested in sensitivity analysesProbably yes but results NRTotal cholesterol and LDL were statistically significantly lower with Clozapine +AP.Zheng 2016 [24]55June 2015NRRCTPatients using antipsychotic drugsAripiprazole + APPlacebo + AP or AP aloneNo outcome of interestCochrane Risk of bias tool: 2 trials at low riskYesNo effect estimate on metabolic outcomes.Mizuno 2014 [29]50November 5, 2013NRRCTschizophrenia or related psychotic disordersNR; likely any APPAP plus placebo or AP monotherapyHbA1C, LDL, total cholesterolCochrane Risk of bias tool: results NRYesAdd-on aripiprazole compared to monotherapy led to l better HbA1C control, and better lipid profile.Lerner 2004 [31]292003BothAlltreatment-resistant t schizophrenic /schizoaffective patients on combinations atypical antipsychoticsTypical AP+ Atypical APAPAENRNoNo synthesis; No effect reported for metabolic outcomes.Srisurapanont 2015 [28]5July, 2014NRRCTSchizophrenia patients with unsatisfactory response to clozapineAripiprazole + clozapineClozapine alone (AP)AE (LDL)Cochrane Risk of bias tool: 1 trial at low risk in all domainsYesLDL reduction effects favoured APP with aripiprazole addition compared to monotherapy.Gallego 2012 [33]16NRNRAllNRAPP in general; specificAPP combinationsNRAE (glucose and lipid metabolism effect/ metabolic syndrome)(not defined)NRNoNo synthesis; expert opinion presented: APP carries an increased side effect burden compared to monotherapy; Aripiprazole augmentation was associated with a decrease in dyslipidaemia.Lochmann van Bennekom 2013 [30]46…”

Section: Resultsmentioning

confidence: 99%

“…It is possible that APP is only harmful relative to monotherapy when the final equivalent dose is excessive and not when it is kept within established therapeutic ranges [13]. Some reviews [28, 31–33, 35] addressed APP which included clozapine. Clozapine can cause leukopenia [39] and should only be used after an ineffective trial with two other antipsychotics [8].…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: a review of systematic reviews

et al. 2018

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BackgroundThere is conflicting evidence on the association between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. We conducted a review of published systematic reviews to evaluate evidence on the association between metabolic syndrome (diabetes, hypertension, and hyperlipidaemia) and exposure to antipsychotic polypharmacy in schizophrenia.MethodsWe searched five electronic databases, complemented by reference screening, to find systematic reviews that investigated the association of antipsychotic polypharmacy in schizophrenia with hypertension, diabetes, or hyperlipidaemia. Selection of reviews, data extraction and review quality were conducted independently by two people and disagreements resolved by discussion. Results were synthesised narratively.ResultsWe included 12 systematic reviews, which reported heterogeneous results, mostly with narrative syntheses and without pooled data. The evidence was rated as low quality. There was some indication of a possible protective effect of drug combinations including aripiprazole for diabetes and hyperlipidaemias, compared to other combinations and/or monotherapy. Only one review reported the association between APP and hypertension. The most frequently reported combinations of medication included clozapine, possibly representing a sample of patients with treatment resistant illness. No included review reported results separately by setting (primary or secondary care).ConclusionsFurther robust studies are needed to elucidate the possible protective effect of aripiprazole. Long-term prospective studies are required for accurate appraisal of diabetes risk, hypertension and hyperlipidaemia in patients exposed to antipsychotic polypharmacy.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1848-y) contains supplementary material, which is available to authorized users.

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Schizophrenia and Related Psychoses

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenialike symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuroimaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with agematched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

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Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Cited by 52 publications

References 44 publications

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: a review of systematic reviews

Schizophrenia and Related Psychoses

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