Pharmacoresistant epilepsy is estimated to affect about 30% of patients with
epilepsy and predisposes to a higher risk for psychiatric comorbidities and depression.
This is one of the most common complications in epilepsy but the mechanisms
underlying its development are still unclear. Periclinical studies have shown that
selective serotonin reuptake inhibitors (SSRIs) are ineffective against comorbid
depression. Dysfunction in circadian rhythms which are driven by the suprachiasmatic
nucleus (SCN), is a hallmark of depression. The activity of this circadian pacemaker is
under the fine-tuning control of the endogenous hormone melatonin. Over the past
decade, there has been extensive research on the therapeutic potential of melatonin and
its analogues in the management of both epilepsy and depressive disorders. Melatonin
and its analogues targeting the melatonin MT1 and MT2 receptors are considered as
potential adjuvants for the treatment of epilepsy associated with moderate-to-strong
antioxidant, anti-inflammatory, and neuroprotective activity at non-toxic doses. One of
the main advantages of the melatonin system is associated with its chronobiotic
properties and pivotal role in the resynchronization of disturbed circadian rhythms of
different parameters. This chapter summarizes the available experimental and clinical
data on melatonin and drugs acting on the MT receptors, which are currently of
therapeutic interest in the treatment of epilepsy and depression. Despite the fact that
melatonin and drugs based on MT receptors have been used for many purposes over
the last three decades, the available data on the potential implementation of melatonin
compounds in epilepsy and comorbid depression are scarce. The many unanswered
questions regarding the use of melatonin to treat epileptic seizures and complications
associated with epilepsy are briefly summarized.
Keywords: Epilepsy, Comorbid depression, Circadian rhythms, Melatonin,
Antioxidant, Anti-inflammatory, Neuroprotection, Chronobiotic properties,
Treatment.
