Efficacy and tolerability of pharmacological interventions on metabolic disturbance induced by atypical antipsychotics in adults: A systematic review and network meta-analysis

Abstract

Background: There have been a few systematic reviews and conventional meta-analyses reporting effect of drugs on metabolic disturbance induced by atypical antipsychotics (AAPs). However, few of them provided sufficient and comprehensive comparisons between pharmacological interventions. Aims: We aimed to qualitatively compare drugs’ effect on AAPs-induced metabolic abnormalities by using network meta-analysis (NMA). Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and PsycINFO on March 26, 2019. Of 5889 records identified, 61 randomized clinical trials including 3467 participants were included. We estimated weighted mean difference (WMD) and odds ratio (OR) using NMA. We assessed the risk of bias of individual studies with the Review Manager 5.3. Primary outcomes included change of body weight and body mass index (BMI). Secondary outcomes included change of other cardiometabolic risk factors, acceptability, and tolerability. Results: For body weight, topiramate (WMD −5.4, 95% CI −7.12 to −3.68), zonisamide (−3.44, 95% CI −6.57 to −0.36), metformin (−3.01, 95% CI −4.22 to −1.83), glucagon-like peptide-1 receptor agonists (GLP-1RAs) (−3.23, 95% CI −5.47 to −0.96), and nizatidine (−2.14, 95% CI −4.01 to −0.27) were significantly superior to placebo. Results regarding to BMI were similar to that of body weight. With respect to tolerability, only topiramate (OR 24, 95% CI 3.15 to 648) was inferior to placebo. Conclusions: Considering both efficacy and tolerability, evidence from this NMA indicates zonisamide, metformin, GLP-1RAs, and nizatidine in adults should be the first-line treatment for alleviating AAPs-induced weight gain or elevated BMI.

Antipsychotics, the heartland of clinical psychopharmacology?

“…Their results suggest roflumilast has dose-dependent cognitive enhancing effects on cognitive flexibility and they conclude that this study may provide preliminary support for the ability of roflumilast to improve cognitive flexibility deficits in patients with schizophrenia (Livingston et al, 2021). Wang et al (2021) conducted a network meta-analysis to compare drugs' effect on atypical antipsychotics (AAPs)-induced metabolic abnormalities. Sixty-one randomised clinical trials including 3467 participants were included.…”

“…Sixty-one randomised clinical trials including 3467 participants were included. Their findings indicate that zonisamide, metformin, GLP-1RAs and nizatidine in adults should be considered as the first-line treatment to mitigate body weight gain or increased body mass index (BMI) induced by AAPs (Wang et al, 2021).…”

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.…”

“…Meta-analyses showed that the addition of topiramate was also effective to reduce weight (À5.4 to À2.75 kg) and psychopathology (SMD À0.57 to À0.40) in people with SMI. 33,34,36,[41][42][43][44] Meanwhile, meta-analyses demonstrated that topiramate was less well-tolerated than placebo or metformin (OR = 24) and associated with a higher incidence of concentration difficulties (RR = 8.97) and paresthesia (RR = 2.03-2.67). 12,36,41,42,44 Topiramate can be considered as adjunctive medication for treatment of AiWG, but the risk of paresthesia and cognitive adverse effects needs to be taken into account and examined in future studies.…”

“…However, the current literature indicates that offlabel addition of metformin or switching antipsychotics to aripiprazole in the treatment of AiWG should be considered when lifestyle interventions are not feasible or insufficiently effective. 17,[30][31][32][33][34][35][36] Additionally, clinicians can consider topiramate as treatment for AiWG if metformin is not tolerated or contra-indicated. However, topiramate is associated with cognitive adverse effects, aggression and paresthesia which limits clinical applicability.…”