Levetiracetam-induced sexual disorders

We read with great interest the article by Metin et al. dealing with the possible correlation between hypersexuality and levetiracetam (LEV). Indeed, the authors reported a female patient with epilepsy who experienced increased sexual drive after the addition of LEV (2000 mg/day) to her ongoing carbamazepine (CBZ) therapy. Although the association between epilepsy and sexual-dysfunction (SD) has often been described, to date, the aetiology of SDrelated epilepsy remains uncertain, but likely to be multifactorial involving neurological (type of epilepsy, age of onset, seizure frequency), endocrine (effect of epileptiform activity on the hypothalamic–pituitary–gonadal axis), iatrogenic (antiepileptic drugs, antidepressant) psychiatric (anxiety and depression), cognitive and psychosocial factors. In particular, liver enzyme-inducing antiepileptic drugs (AEDs), i.e. phenobarbital, phenytoin, and carbamazepine, can cause SD by decreasing bioactive testosterone, accelerating sexual hormone metabolism, and stimulating binding hormone proteins production. Conversely, new AEDs, including topiramate, zonisamide, oxcarbazepine, lamotrigine and pregabalin, are thought to cause SD through complex and poorly understood mechanisms. Although Svalheim et al. have demonstrated that LEV treatment apparently has no drug-specific sexual or endocrine side effects in men or women aged 45 years, a few case reports are emerging from the literature showing a possible correlation between SD and LEV ingestion. Indeed, alongside the interesting case of LEV-induced hypersexuality by Metin et al., we have recently reported two young men with epilepsy who experienced severe loss of libido and anhedonia after LEV intake. Levetiracetam is a new AED exerting its antiepileptic effect through multiple and poorly understood mechanisms of action. Synaptic vesicle glycoprotein 2A vesicular membrane protein appears to be the main pharmacological target, but several effects on ion channels have been described, including blockade of highvoltage-activated Ca channels, modulation of K+ channels, and enhancement of GABAand glycine-gated currents. In particular, LEV-induced inhibition of presynaptic P/Q-type calcium channels has been demonstrated to increase brainstem serotonin concentration