Table 1 Characteristics of included systematic reviews on effects of APP
From: Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: a review of systematic reviews
Study | Studies (N) included | Date of latest search | Study Settings (Primary/ Secondary care) | Included Study Designs | Participants | Intervention/Exposures | Comparison | Outcomes | Quality assessment in the review | Meta-analysis | Findings/ effect aon metabolic markers/ conditions |
|---|---|---|---|---|---|---|---|---|---|---|---|
Galling 2016 [32] | 67 | 05/25/2015 | Both | RCTs | Schizophrenia /schizoaffective disorder | Any APP; APP with D2 antagonists; APP with partial D2 agonists | AP monotherapy | Total cholesterol; LDL cholesterol; | No formal assessment; all studies considered at high risk; sensitivity analysis done for blinding. | Yes | APP was associated with lower total cholesterol and LDL-cholesterol |
Young 2015 [25] | 53 | June 2013 | NR | Case control; cohort; cross-sectional | All diagnostic groups. Children and adults | Any AP | AP monotherapy | Prevalence of: Metabolic disorder; diabetes mellitus; hypertension; | Author defined criteria used to give scores and only highest scoring studies summarised. | No | APP was associated with increased prevalence of AE: metabolic syndrome, dyslipidaemia, diabetes. A longer duration of treatment was associated with greater severity; Clozapine strongly associated with metabolic disturbance |
Tranulis 2008 [26] | 51 | 23 Aug 2006 | NR | All | Schizophrenia | APP specific combinations | NR | Safety | NR | No | No synthesisb/effect estimate on metabolic outcomes. |
Tracy 2013 [27] | 72 | 6 January 2013 | NR | All | Schizophrenia/schizoaffective disorder or related diagnoses | APP | NR | Any functional outcome or adverse effect | NR | No | No synthesis/effect estimate on metabolic outcomes. They report that there is consistent emerging data supporting aripiprazole for reregulate lipid profiles. |
Canadian Agency for Drugs and Technologies in Health 2012 [35] | 30 | June 16, 2010 | NR | RCT | schizophrenia /schizoaffective disorder inadequately managed with one or more AAPs at recommended doses | High dose AP/ APP | AP Low dose /monotherapy | AE (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 analyses | Probably yes but results NR | Total cholesterol and LDL were statistically significantly lower with Clozapine +AP. |
Zheng 2016 [24] | 55 | June 2015 | NR | RCT | Patients using antipsychotic drugs | Aripiprazole + AP | Placebo + AP or AP alone | No outcome of interest | Cochrane Risk of bias tool: 2 trials at low risk | Yes | No effect estimate on metabolic outcomes. |
Mizuno 2014 [29] | 50 | November 5, 2013 | NR | RCT | schizophrenia or related psychotic disorders | NR; likely any APP | AP plus placebo or AP monotherapy | HbA1C, LDL, total cholesterol | Cochrane Risk of bias tool: results NR | Yes | Add-on aripiprazole compared to monotherapy led to l better HbA1C control, and better lipid profile. |
Lerner 2004 [31] | 29 | 2003 | Both | All | treatment-resistant t schizophrenic /schizoaffective patients on combinations atypical antipsychotics | Typical AP+ Atypical AP | AP | AE | NR | No | No synthesis; No effect reported for metabolic outcomes. |
Srisurapanont 2015 [28] | 5 | July, 2014 | NR | RCT | Schizophrenia patients with unsatisfactory response to clozapine | Aripiprazole + clozapine | Clozapine alone (AP) | AE (LDL) | Cochrane Risk of bias tool: 1 trial at low risk in all domains | Yes | LDL reduction effects favoured APP with aripiprazole addition compared to monotherapy. |
Gallego 2012 [33] | 16 | NR | NR | All | NR | APP in general; specific APP combinations | NR | AE (glucose and lipid metabolism effect/ metabolic syndrome)(not defined) | NR | No | No 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 | April 2012 | NR | RCT; SR | Schizophrenia | APP | NR | AE | NR | No | No synthesis; no effect on metabolic outcomes. |
Correll 2013 [34] | 8 | NR | NR | RCT | schizophrenia | APP | Placebo | glucose and lipid metabolism; cardio metabolic outcomes (not defined) | NR | Yes | Aripiprazole+ clozapine/ olanzapine led to: Significant reduction in total and LDL cholesterol and triglycerides, but not in HDL-cholesterol or glucose. No significant cardio metabolic effects were found with risperidone/ fluphenazine + clozapine, aripiprazole + quetiapine/ risperidone, or aripiprazole + haloperidol. |