Abstract
Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect patients’ compliance. Sexual and erectile dysfunction has been reported in several studies by patients who take lithium as monotherapy or combined with other psychotherapeutic agents. The exact mechanisms underlying such side effects of lithium are not completely understood. It seems that both central and peripheral mechanisms are involved in the lithium-related sexual dysfunction. Here, we had an overview of the epidemiology of lithium-related sexual and erectile dysfunction in previous clinical studies as well as possible pathologic pathways that could be involved in this adverse effect of lithium based on the previous preclinical studies. Understanding such mechanisms could potentially open a new avenue for therapies that can overcome lithium-related sexual dysfunction and improve patients’ adherence to the medication intake.
Highlights
Academic Editor: Aditi BhargavaLithium is a monovalent cation (Li+ ) when it loses the only electron of the second orbital
IV-TR bipolar I/II disorder and on long-term lithium monotherapy found significantly less sexual intercourses, sexual fantasies, sexual desires, as well as less pleasure and satisfaction during intercourse in these patients compared to 176 age-matched healthy control subjects, and 30% of patients described their sexual problems in association with the introduction of lithium intake [43]
A more recent multicenter, cross-sectional study on 114 outpatients with bipolar disorder found that lithium in monotherapy or combined with benzodiazepines is related to more sexual dysfunction, as assessed by the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14), and worse sexual desire compared to anticonvulsants monotherapy [44]
Summary
Lithium is a monovalent cation (Li+ ) when it loses the only electron of the second orbital. Lithium inhibits the glycogen synthase kinase 3 β (GSK3β) that phosphorylates Rev-Erbα (an intracellular transcription factor protein), and as a result, inhibits the circadian clock This will disturb many biological functions governed by the brain, such as metabolism, sleep (diurnal rhythm), and body temperature [10,11]. This enzyme dephosphorylates inositol monophosphate to free inositol, and as a result, the inositol pool is attenuated This could clarify the therapeutic function of lithium with slight effects on physiological behavior [16,17]. The exact mechanisms underlying such adverse effects of lithium have not been completely understood This is an important consideration, as medications’ adverse effects (e.g., sexual dysfunction) is one of the major reasons for medication’s non-compliance as well as the negative impact on the quality of life of psychiatric patients. We will discuss the epidemiology of sexual and erectile dysfunction related to lithium intake, possible both central and peripheral mechanisms underlying such effects of lithium, and therapeutic approaches to potentially overcome these adverse effects of lithium
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