Although most people with epilepsy lead normal lives, neurobehavioral problems are found in a large proportion of patients. Higher rates of psychopathology are observed in people with epilepsy relative to the general population, to other neurological control groups, and to people with chronic non-neurological disorders. This largely reflects the effect of uncontrolled epilepsy and the underlying brain injury, which predispose patients to depression, anxiety, and other psychiatric symptoms. In particular, increased psychopathology is common in patients with refractory temporal lobe epilepsy (TLE). Depression is the most frequent type of psychiatric disorder identified in patients with epilepsy, with prevalence of up to 50% in some studies (Mendez et al., 1986). Epidemiological studies have identified a variety of psychoses in up to 9% of epilepsy patients. Likewise, patients with epilepsy commonly report anxiety and, finally, the risk of suicide in patients with epilepsy is estimated to be 4 to 5 times greater than that of the general population, and a higher risk is found in TLE (Kanner & Palac, 2002). The causes of psychopathology in epilepsy are multifactorial and include genetic predisposition, biological risk factors, iatrogenic causes (e.g., antiepileptic drugs), and other causes. A bidirectional relationship between psychosis or depression and epilepsy has been suggested in the literature. For example, similar neurotransmitter alterations may underlie both depression and epilepsy (Yan et al., 1998). Although the clinical manifestations of psychiatric disorders in epilepsy are often indistinguishable from those of nonepileptic patients, certain types of depression and psychotic disorders may present with clinical characteristics that are particular to those of patients with epilepsy. These include postictal psychosis, alternate psychosis (or forced normalization), and certain forms of interictal depressive disorders.
Some antiepileptic drugs (AEDs) are also psychotropic agents with positive or negative effects. The psychotropic effects of AEDs in people with epilepsy are, however, variable and unpredictable. Unfortunately, a history of psychiatric illness may be a risk factor for a negative psychotropic effect by an AED. Thus, the beneficial psychotropic effects seen with AEDs in the general nonepileptic population may be less apparent in epilepsy patients. However, for example, it would be reasonable to prescribe an appropriate AED with anxiolytic potential in a patient with preexisting anxiety disorder. For instance, pregabalin, and to a lesser extent gabapentin, are effective in anxiety disorders and pregabalin is in fact licensed for the treatment of generalized anxiety disorder (Box 22.1). On the other hand, the treating physician should be aware of the possibility of aggravating anxiety symptomatology when prescribing certain AEDs to patients with epilepsy (Box 22.2). Besides, use of sedating doses and combinations of AEDs that can impair cognitive and behavioral functions should be avoided in all patients (Nadkarni & Devinsky, 2005; Schmitz, 2006; Kaufman, 2011; Bialer, 2012; Kimiskidis & Valeta, 2012). When prescribing an AED for a patient with epilepsy, preexisting psychiatric problems or learning disabilities, drug-drug interactions and adverse effects of the AED should be considered (Boxes 22.2, 22.3, and 22.4). The treating physician should consider which AED might best help the patient in maximizing seizure control and minimizing psychiatric symptoms.
Adapted from: Kaufman KR. Antiepileptic drugs in the treatment of psychiatric disorders. Epilepsy Behav 2011; 21(1): 1–11.
Last, all AEDs have the potential to cause adverse psychiatric effects. Antiepileptic drugs increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. The increased risk of suicidal thoughts or behavior with AEDs is observed as early as 1 week after starting treatment with AEDs and persists for the duration of treatment. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. However, in the authors’ experience, some agents are more apt to do so than others. We have observed the greatest incidence of psychiatric side effects with phenobarbital, primidone, levetiracetam, topiramate, and zonisamide. Patients and their families should be cautioned about potential psychiatric adverse effects when these agents are used, so that problems can be promptly addressed should they occur. (Box 22.3 and Box 22.4)
From Nadkarni and Devinsky (2005), Brodtkorb and Mula (2006), Schubert (2005), Schmitz (2006), Mula et al. (2007), Tassone et al. (2007), Kaufman (2011), Bialer (2012), and Kimiskidis and Valeta (2012).
All antiepileptic drugs may increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.
Note: Sexual dysfunction due to AEDs is common and may have psychiatric consequences:
1. Enzyme-inducing AEDs, such as carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine and topiramate in high doses, can increase sex hormone−binding globulin, reduce free (bioactive) testosterone, and thereby reduce libido and impair sexual function (Harden, 2006).
2. Other AEDs, including acetazolamide, benzodiazepines, pregabalin, and topiramate, may cause sexual dysfunction as well.
3. Sexual dysfunction is not common with ethosuximide, gabapentin, lamotrigine, levetiracetam, tiagabine, valproate, and zonisamide (Drug Facts and Comparisons, 2007). However, study of sexual function with these drugs is limited.
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