Pharmacological Interventions to Treat Antipsychotic-Induced Dyslipidemia in Schizophrenia Patients: A Systematic Review and Meta Analysis

Abstract

Introduction: Antipsychotic-induced dyslipidemia represents a common adverse effect faced by patients with schizophrenia that increases risk for developing further metabolic complications and cardiovascular disease. Despite its burden, antipsychotic-induced dyslipidemia is often left untreated, and the effectiveness of pharmacological interventions for mitigating dyslipidemia has not been well-addressed. This review aims to assess the effectiveness of pharmacological interventions in alleviating dyslipidemia in patients with schizophrenia.Methods: Medline, PsychInfo, and EMBASE were searched for all relevant English articles from 1950 to November 2020. Randomized placebo-controlled trials were included. Differences in changes in triglycerides, HDL cholesterol, LDL cholesterol, and VLDL cholesterol levels between treatment and placebo groups were meta-analyzed as primary outcomes.Results: Our review identified 48 randomized controlled trials that comprised a total of 3,128 patients and investigated 29 pharmacological interventions. Overall, pharmacological interventions were effective in lowering LDL cholesterol, triglycerides, and total cholesterol levels while increasing the levels of HDL cholesterol. Within the intervention subgroups, approved lipid-lowering agents did not reduce lipid parameters other than total cholesterol level, while antipsychotic switching and antipsychotic add-on interventions improved multiple lipid parameters, including triglycerides, LDL cholesterol, HDL cholesterol, and total cholesterol. Off label lipid lowering agents improved triglycerides and total cholesterol levels, with statistically significant changes seen with metformin.Conclusion: Currently available lipid lowering agents may not work as well in patients with schizophrenia who are being treated with antipsychotics. Additionally, antipsychotic switching, antipsychotic add-ons, and certain off label interventions might be more effective in improving some but not all associated lipid parameters. Future studies should explore novel interventions for effectively managing antipsychotic-induced dyslipidemia.Registration: PROSPERO 2020 CRD42020219982; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219982.

Metformin for the prevention of clozapine‐induced weight gain: A retrospective naturalistic cohort study

“…Metformin has additionally been associated with adaptive changes in insulin sensitivity 18,[33][34][35][36] and lipid parameters such as triglycerides and total cholesterol, 20 which we also demonstrate in the present naturalistic cohort study. These findings are expected given the known antihyperglycemic properties of metformin and its use as a first-line antidiabetic agent for over five decades.…”

“…In severe mental illness, metformin has been widely studied “off‐label” as a pharmacological intervention for the treatment of AP‐related weight gain, with the most evidence supporting its efficacy and safety 18,19 . Importantly, the reporting literature demonstrates good tolerability with no significant difference in reports of nausea compared with placebo, and no concerns of changes in psychiatric symptomatology 16,20 . As such, metformin is now recommended in several guidelines, including the World Health Organization (WHO) and British Association of Psychopharmacology (BAP) as well as the Mental Health section of the Canadian Obesity Guidelines, for the treatment of AP‐induced weight gain in conjunction with lifestyle modification 21–23 .…”

“…18,19 Importantly, the reporting literature demonstrates good tolerability with no significant difference in reports of nausea compared with placebo, and no concerns of changes in psychiatric symptomatology. 16,20 As such, metformin is now recommended in several guidelines, including the World Health Organization (WHO) and British Association of Psychopharmacology (BAP) as well as the Mental Health section of the Canadian Obesity Guidelines, for the treatment of AP-induced weight gain in conjunction with lifestyle modification. [21][22][23] The role of metformin as a preventative agent has also been previously studied in mitigating AP-induced weight gain, including weight gain associated with higher risk agents such as olanzapine.…”

Acid sphingomyelinase/ceramide system in schizophrenia: implications for therapeutic intervention as a potential novel target

“…Adjunctive rosuvastatin improved the efficacy of olanzapine on behavioral impairment and hippocampal metabolic abnormalities in isolation-reared male rats [63]. Rosuvastatin also improved antipsychotic-induced dyslipidemia in patients with schizophrenia [63,64]. In consideration of the high prevalence of metabolic syndrome that includes overweight, obesity, and hyperlipidemia in schizophrenia patients, rosuvastatin might bring multiple benefits.…”

Antipsychotic‐induced weight gain: Is the weight over? New guidelines needed

“…Meta-analyses showed that metformin was well-tolerated and significantly reduced weight compared to placebo in participants with schizophrenia, schizoaffective disorder and bipolar disorder (À3.27 to À2.01 kg). 12,[29][30][31][32][33][34][35][36] Few studies have examined the role of metformin in the prevention of AiWG. A recent retrospective cohort study included in this current issue showed that metformin was associated with less weight gain compared to the control group after 6 (À0.15 kg vs. 2.99 kg) and 12 months (À0.67 kg vs. 4.72 kg) in 396 participants newly initiated on clozapine, of which 69 were on metformin ≤3 months after clozapine initiation.…”