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Antipsychotic (AP) medications are associated with weight gain, dyslipidemia, and altered blood glucose regulation, which can increase risk of obesity, cardiovascular disease, and type 2 diabetes. Several mental illnesses are associated with compromised metabolic health, so if medications are causing iatrogenic glucose dysregulation, then as noted by the authors of a recent systematic review and meta-analysis published in JAMA Psychiatry, “AP-induced glycemic dysregulation puts an already metabolically vulnerable population at even greater risk for substantial short- and long-term health consequences.”
It has long been known that APs may cause weight gain, and it was believed that disruptions in glucose regulation were secondary to increased weight. The new publication presented evidence that some of the glycemic effects may be independent of weight gain.
The analysis included 163 studies (127 RCTs) that encompassed 15 unique APs and included mostly adult subjects, with 16 studies including children or adolescents (ages 10 to 17). Most studies involved patients with either schizophrenia spectrum disorder or bipolar disorder I and II, with the remaining studies covering patients with major depressive disorder and healthy controls.
In total, the analysis included nearly 29,000 AP-treated subjects and 15,000 placebo-treated subjects. Compared to placebo-treated subjects, AP-treated subjects were found to have significantly higher fasting glucose, fasting insulin, HbA1c, and hyperglycemia (defined as fasting glucose ≥126mg/dL).
The researchers found that AP treatment is associated with “significantly dysregulated
glucose homeostasis,” and that this was largely independent of diagnosis, age, study length, mean AP dose, and concomitant use of psychotropic medications. They acknowledged that “there is undeniably a contributory effect of weight gain” (on worsening glucose control), but noted that “even minimal AP exposure may contribute to glucose homeostasis disruptions,” with minimal exposure being unlikely to significantly alter weight.
The authors wrote, “…the current findings should motivate development of new APs with fewer cardiometabolic adverse effects and/or more effective metabolic interventions.” They mentioned coadministration of GLP-1 receptor agonists and dopamine receptor agonists as avenues for future research to potentially “outcompete APs’ peripheral metabolic actions” and therefore mitigate the adverse effects of these drugs on gluco-regulation and risk for cardiometabolic disease.
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