Behavioral and emotional adverse events of drugs frequently used in the treatment of bipolar disorders: clinical and theoretical implications

Alejandro Szmulewicz, Cecilia Samamé, Pablo Caravotta, Diego J. Martino, Ana Igoa, Diego Hidalgo-Mazzei, Francesc Colom, Sergio A. Strejilevich

Behavioral and emotional adverse events induced by drugs commonly prescribed to patients with bipolar disorders are of paramount importance to clinical practice and research. However, no reviews on the topic have been published so far. An extensive search was performed. Reports were reviewed if they described behavioral side effects related to pharmacological treatments for bipolar disorders in healthy subjects or patients with different neuropsychiatric disorders. For this review, lithium, antipsychotics, anticonvulsants and selective serotonin reuptake inhibitors were included. Apathy or emotional blunting, diminished sexual desire, and inability to cry were reported to be associated with exposure to selective serotonin reuptake inhibitors. Neuroleptic-induced deficit syndrome/emotional detachment and obsessive-compulsive symptomatology and decision-making modifications. A lithium-related amotivational syndrome was also reported in the literature. Furthermore, hypersexuality and obsessive-compulsive symptoms have been noted in subjects treated with lamotrigine. Primary studies on drug-related adverse events are scant so far and most of the data currently available derive from case reports. Moreover, most of the evidence reviewed is based on studies performed on healthy subjects and patients with neuropsychiatric conditions other than bipolar disorders. There is a remarkable dearth of data on behavioral adverse events of pharmacological treatment for bipolar disorders. However, the pieces of evidence available at present, though scant and scattered, suggest that different behavioral adverse events may be related to pharmacological treatment for these disorders. The implications of these findings for research and management of patients with mood disorders are discussed.