In modern care, mental and physical health are inseparable. Medications used to treat psychiatric conditions—from antidepressants to antipsychotics—can exert profound effects not just in the brain, but across the body. As clinicians and patients, we must strive for a treatment approach that supports both mind and body, minimizing side effects while maximizing therapeutic benefit.

A striking example of this interplay comes from a recent systematic review and meta-analysis published in JAMA Psychiatry, titled Antipsychotic Drugs and Dysregulated Glucose Homeostasis. Researchers pooled data from 127 randomized controlled trials assessing changes in key metabolic markers. The results are eye-opening: compared to placebo, antipsychotic (AP) drug exposure was associated with significant increases in fasting glucose, fasting insulin, and hemoglobin A₁c—and a higher risk of hyperglycemia. Crucially, these changes were largely independent of weight gain, diagnosis, antipsychotic type, dose, treatment duration, age, or previous AP exposure. JAMA Network+2JAMA Network+2

In other words: even in patients who don’t gain much weight on these medications, glucose regulation can still be disrupted. That insight matters deeply for clinical practice. Many of us have long assumed that metabolic side effects of antipsychotics were mediated primarily through weight gain and adiposity. But this analysis underscores that direct effects on insulin signaling, beta-cell function, or peripheral glucose regulation may also play a role. JAMA Network+2PMC+2

Given these risks, what is the responsible way forward? For most patients, a one-size-fits-all approach is not enough. Instead, a personalized, holistic treatment paradigm becomes imperative—especially when you're offering integrative or naturopathic modalities, as at Aureo.

Here’s how that kind of care model can be structured:

Baseline and ongoing individualized laboratory testing and metabolic monitoring.
Before initiating psychiatric medications, patients should undergo a panel including fasting glucose, insulin, HbA₁c, lipid panel, liver enzymes, inflammatory markers, micronutrient levels, and possibly more advanced metabolic testing (e.g. insulin resistance indices). These labs then guide both medication choice and adjunctive metabolic support. Over time, regular monitoring can detect early dysglycemia or insulin resistance before it becomes overt diabetes.
Nutritional support and metabolic optimization.
Dietary interventions (e.g. low glycemic load, anti-inflammatory diets, individualized macronutrient balancing), targeted supplementation (e.g. magnesium, chromium, inositols, alpha-lipoic acid), and support of the gut microbiome may help buffer metabolic stress and optimize insulin sensitivity.
Somatic and lifestyle interventions.
Incorporating structured physical exercise, sleep optimization, stress reduction (e.g. mindfulness, biofeedback, yoga), and neuromodulation can support both mental health and metabolic resilience. Regular movement, for example, improves insulin sensitivity and counters mood dysregulation.
Judicious psychopharmacology with metabolic awareness.
When choosing or adjusting psychiatric medications, clinicians should weigh both neuropsychiatric efficacy and metabolic risk. Some antipsychotics carry higher diabetogenic potential (e.g. olanzapine has a known strong association with weight gain and metabolic derangements) Wikipedia+1. In such cases, lower-risk alternatives, dose minimization, and early metabolic interventions are essential.
Novel and adjunctive therapies (e.g. ketamine, neurostimulation, somatic treatments).
For appropriate patients, ketamine therapy (whether IV, intranasal, or another modality) can offer robust antidepressant or mood-stabilizing effects with a different side effect profile, potentially reducing dependence on medications with higher metabolic liabilities. Paired with somatic approaches (e.g. TMS, ECT, vagal stimulation, neurofeedback), such integration allows for therapeutic synergy while potentially lowering cumulative drug burden.

At Aureo, we aim to deliver a precision, integrative model: early and repeated lab monitoring, metabolic support, lifestyle and somatic therapies, and thoughtful medication use—tuned to each patient’s physiology, genetics, and metabolic risks.

The bottom line: mental health medications are powerful tools, but they do not act in isolation. As the JAMA meta-analysis demonstrates, antipsychotics can perturb glucose homeostasis even apart from weight gain. We must, therefore, adopt a holistic lens: treat the brain without ignoring the body. In doing so, we can uphold not just psychiatric wellness, but whole-person thriving.

References:

Smith ECC, Agarwal SM, Panganiban KJ, et al. Antipsychotic drugs and dysregulated glucose homeostasis: a systematic review and meta-analysis. JAMA Psychiatry. 2024;81(5):467-478. doi:10.1001/jamapsychiatry.2024.0301
De Hert M, Detraux J, van Winkel R, Yu W, Correll CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2012;8(2):114-126. doi:10.1038/nrendo.2011.156
Vancampfort D, Stubbs B, Mitchell AJ, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder, and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14(3):339-347. doi:10.1002/wps.20252
Sarris J, Logan AC, Akbaraly TN, et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015;2(3):271-274. doi:10.1016/S2215-0366(14)00051-0
Dore J, Turnipseed B, Dwyer S, et al. Ketamine-assisted psychotherapy (KAP): patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. J Psychoactive Drugs. 2019;51(2):189-198. doi:10.1080/02791072.2019.1587556

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