The clinical spectrum of bipolar symptoms in epilepsy: a critical reappraisal

Mood disorders are a frequent psychiatric comorbidity in patients with epilepsy, affecting quality of life and prognosis. Classic neuropsychiatric literature focused on major depression with data on bipolar disorder (BD) remains limited. However, emerging evidence suggests that mood instability, mixed irritability, or even mania is not uncommon in patients with epilepsy. Theoretically, epilepsy and BD share a number of clinical and neurobiological features. Both are episodic conditions that can become chronic. Moreover, the kindling phenomenon, changes in neurotransmitters, modifications in voltage-opened ion channels, and second-messenger systems have been reported in both cases. This article reviews the available evidence regarding this intriguing comorbidity to discuss valuable clinical issues. In fact, recent data suggest that in most cases, bipolar symptoms are related to phenotype copies of BD such as peri-ictal manifestations (eg, preictal dysphoria or postictal mania), the so-called interictal dysphoric disorder, or the forced normalization phenomenon. In a minority of subjects, these symptoms represent treatment-emergent adverse effects of medications or surgery complications. Epileptologists need to be aware of the large and complex spectrum of bipolar symptoms in epilepsy to inform patients and their families, as well as to develop appropriate treatment strategies.