Endocrine and metabolic effects of medications used for bipolar disorder [Effetti endocrini e metabolici dei farmaci utilizzati nel disturbo bipolare]

Objective: Patients with bipolar disorder suffer a disproportionate burden of cardiovascular and endocrine illness compared to the general population. While the exact pathogenesis of this excess morbidity is not completely known, biologic, behavioral, and sociodemographic factors have been implicated. Among biologic factors, a growing body of evidence suggests that several of the medications that are commonly used to treat bipolar disorder can contribute to several of the illnesses above. While the balance between risks and benefits of medication treatment in bipolar disorder is usually favorable, an increased knowledge of these risks is imperative, in order to avoid the impression that a disruption in physical health is an inevitable token for the patient to pay in order to achieve and maintain his or her mental health. The goal of this paper is to review the endocrine and metabolic effects of medications used for the treatment of bipolar disorder. Methods: This paper selectively reviews the literature on the endocrine risks of the medications used to treat patients with bipolar disorder. The manuscript focuses on the most practical and clinically relevant data and describes the possible strategies to prevent, monitor and treat the common endocrine illnesses that patients with bipolar disorder frequently develop during the course of treatment. Results: Most of the medications that are used to treat bipolar disorder can affect the endocrine system. However, differences exist from one medication to another. The potential endocrine and metabolic risks of olanzapine, clozapin risperidone, quetiapine, aripiprazole, ziprasidone, lithium, valproate, carbamazepine, lamotrigine, and topiramate are reviewed and discussed. A particular attention is given to the risks of weight gain, obesity, dyslipidemia, diabetes mellitus, hyperprolactinemia, thyroid and parathyroid illness, diabetes insipidus, and sexual and reproductive dysfunctions. Medications such as clozapine and olanzapine carry a high risk of weight gain and metabolic problems but most of the other drugs are not completely free from these risks. For instance, lithium, which remains one of the mainstay of treatment of bipolar disorder is associated with a considerable risk of weight gain and other metabolic and endocrine disturbances such as hypothyroidism, hyperparathyroidism and diabetes insipidus. Carbamazepine, which is not associated to a high risk of weight gain, carries a significant risk for dyslipidemia and electrolytic disturbances. Valproate is frequently associated with significant weight gain and may increase the risk of polycystic ovary syndrome. Conclusions: Almost all medications used to treat bipolar disorder carry a risk to cause or worsen endocrine or metabolic syndromes. However, the degree of risk is different for different agents and may be different from one patient to another. Particular attention in selecting the medication with the best risk/benefit ratio for each particular case is warranted. There is a general agreement that all patients identified as having, or developing, severe endocrine problems, such as the metabolic syndrome, should be referred to appropriate services such as a general practitioner, diabetologist, dietologist and other specialist service. The possibility switching medication should be considered even in the early stages of the development of endocrine/metabolic problems (e.g. in a patient whose weight increases more than 5% from initial weight) and balanced against the risk of losing efficacy.