From:  Psychotropic medications and metabolic side effects

 Potential benefits and metabolic risks associated with selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) [2, 7, 17–24].

Medication/ClassPotential benefitsMetabolic risk
SSRIsMetabolic risk is lower with antidepressants than with antipsychotics. Acute SSRI administration improves glucose-dependent insulin release. LDL levels decrease while HDL levels increase.Chronic use induces mild to moderate mitochondrial dysfunction and is associated with persistent elevation in CRP, IL-6, and TNF-α.
Contribute to insulin resistance, leptin resistance, and weight gain.
Increase type 2 diabetes risk.
Clozapine, olanzapine (SGAs)Clozapine: Superior efficacy in treatment-resistant schizophrenia, reduces risk of suicide and tardive dyskinesia, decreases the rate of relapse, and improves the quality of life.
Olanzapine: May help with treatment-resistant depression and is less likely to cause tardive dyskinesia.		Greatest antagonism to H1 and 5-HT2C.
Greatest risk of weight gain, dyslipidemia, and glucose dysregulation among SGAs.
Induce inflammation and ROS generation.
Reduce hepatic mitochondrial complex activity.
Induce gut dysbiosis.
Quetiapine (SGA)In CNS, they suppress TNF-α and nitric oxide production in microglia.Intermediate mitochondrial toxicity.
Marked increase in serum CRP.
Doubles MPO activity.
Reduced hepatic mitochondrial activity (less than clozapine and olanzapine).
Risperidone (SGA)Lower H1 and 5-HT2C affinity corresponds to modest weight gain.Reduces complex I activity and inhibits ATP production.
Increases depolarization of mitochondrial membrane and accumulation of ROS (milder than clozapine and olanzapine).
Aripiprazole (SGA)Minimal activity at H1 and 5-HT2C.
Most metabolically favorable among SGAs.
Safest profile due to minimal impacts on mitochondrial function and appetite.		Increased risk of weight gain, hyperglycemia, and diabetes.
Associated with increased levels of cholesterol and triglycerides.
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LDL: low-density lipoprotein; HDL: high-density lipoprotein; CRP: C-reactive protein; IL-6: interleukin-6; TNF-α: tumor necrosis factor alpha; 5-HT2C: 5-hydroxytryptamine 2C; ROS: reactive oxygen species; CNS: central nervous system; MPO: myeloperoxidase.