Psychotropic medications and mitochondrial toxicity

In a recent Review, Husseini Manji and colleagues summarize the growing body of evidence linking impaired mitochondrial function to the pathophysiology of several major psychiatric illnesses, including mood disorders, autism and schizophrenia (Impaired mitochondrial function in psychiatric disorders. Nature Rev. Neurosci. 13, 293–307 (2012))1.

One of the often-overlooked contributors to mitochondrial dysfunction is the psychotropic medication used to treat these psychiatric conditions. Multiple studies have shown that both typical and atypical antipsychotic medications can inhibit the mitochondrial respiratory chain2,3,4. Similarly, the mood stabilizer valproic acid can inhibit the mitochondrial respiratory chain and result in secondary impairment of mitochondrial function through the induction of carnitine deficiency5,6. Selective serotonin reuptake inhibitor antidepressants inhibit mitochondrial function in animal models of depression and are potentially toxic in high doses, resulting in dysfunction of the mitochondrial respiratory chain and decreased ATP production7,8.

Psychiatric symptomatology can be the initial clinical expression of an underlying mitochondrial disorder9,10. In our experience, the psychiatric symptoms of patients with mitochondrial disorders are often resistant to treatment and may actually worsen with exposure to psychotropic medications, supporting the notion that these agents can compromise mitochondrial function9,10. This under-recognized mitochondrial toxicity may contribute to the limited efficacy and problematic side effects of many psychotropic medications, not only in those with mitochondrial disorders but also in the much wider population of patients receiving treatment with these agents for psychiatric illness.

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Correspondence to Rebecca Anglin.

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Anglin, R., Rosebush, P. & Mazurek, M. Psychotropic medications and mitochondrial toxicity. Nat Rev Neurosci 13, 650 (2012). https://doi.org/10.1038/nrn3229-c1

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