Verrotti et al overall average of about 11.5%. This wide range could be due to the different populations studied. However, Nilsson and colleagues’ experience of a large cohort of adults with epilepsy (N = 9061) is interesting. The authors identiﬁed 26 individuals with epilepsy who committed suicide and compared their case histories with those of 171 individuals with epilepsy (controls). They reported a 9-fold increase in the risk of suicide in the context of a mental illness and a 10-fold increase in relative risk with the use of antipsychotic drugs (Nilsson et al 2002). Many studies have reported elevated rates of suicide among individuals with epilepsy. In a population-based study, Hauser and colleagues (980) reported only 3 suicides, which was not above the expected number. Cockerell and colleagues (1994), in a population study (N = 1091), reported only 1 suicide during a follow-up of 6.9 (median) years. A group in Iceland (Rafnsson et al 2001) reported 4 suicides among 224 individuals with epilepsy, who were followed up for more than 30 years; this suicide rate was higher than would have been predicted. Recently, two large meta- analyses (Pompili et al 2005, 2006) of 30 studies comprising 51,216 people with epilepsy concluded that suicide in patients with epilepsy is more frequent than in the general population (Pompili et al 2005). Finally, we should note the methodological issues dis- cussed in a recently published study of mortality among epi- leptics (Logroscino and Hesdorffer 2005): this study suggests that the gold standard for studies on mortality should be a population-based cohort of incident cases. Only this type of study permits a complete collection of data and the observa- tion of the clinical phase of the disease from the diagnosis of epilepsy to the outcome of the study, death. Risk factors Predicting death caused by suicide is a nearly impossible task. Yet assessing suicide risk requires identiﬁcation of the factors that make individuals susceptible, and quantifying the individual’s level of risk. Psychiatric comorbidity Psychiatric comorbidity is the primary risk factor. Individuals with epilepsy appear to have elevated rates of Axis I disorders according to the DSM, ranging from 19% to 62% (Shukla et al 1979; Fiordelli et al 1993; Manchanda et al 1996), with rates of major depressive episodes from 32% to 48% (Blumer et al 1997; Robertson 1997; Kanner 1999; Gilliam et al 2002). Nilsson and colleagues (2002) have shown a ninefold increase in related risk of suicide associated with 366 psychiatric illness and a 10-fold increase in related risk suicide with the intake of antipsychotic drugs. Among epileptic patients, the most frequent diagnoses include affective disorders, schizophrenia, and substance abuse. Psychosis in particular may contribute to increased suicide risk: postictal psychotic episodes may increase the risk of suicide in individuals with epilepsy and, more speciﬁcally, individuals with temporal lobe epilepsy (TLE) (Mendez et al 1992; Fukuchi et al 2002). Fukuchi and colleagues (2002) showed that three of six individuals with complex partial seizures who committed suicide did so during postictal psychotic episodes, so that the presence of psychotic symptoms may increase the risk of death by suicide among individuals with epilepsy. Psychiatric disorders in epilepsy may result from the inhibitory activity that develops as a reaction to the excessive excitatory activity of the chronic seizure disorder (Pompili et al 2005, 2006). Blumer and colleagues (2002) suggested that successful inhibition of psychiatric disorders could result in persistent suppression of seizures in chronic epilepsy, although some people are at risk of developing many different types of psychiatric complications. The relationship between epilepsy and psychiatric disorders is based on: (1) delay in the devel- opment of interictal dysphoric and even more of psychotic disorders after onset of epilepsy, as inhibitory mechanisms become increasingly established; (2) as seizures decrease and are controlled, dysphoric symptoms and psychosis tend to be exacerbated or to emerge de novo (Hill 1953; Blumer 1984; Blumer et al 2000); (3) the same psychiatric changes also appear at times when acute worsening of the seizures causes an enhanced inhibitory response, commonly in the prodromal and postictal phases; (4) a delay of 6–18 months has been noted before psychiatric changes after optimal surgical elimination of the epileptogenetic zone. The acute engagement of inhibitory mechanisms by the seizure event tends to result in peri-ictal dysphoric symptoms that may include postictal depressive mood with consequent possible suicide. Reports vary on the prevalence of interictal psychosis, but it is considered higher than the prevalence of psychosis in the general population (Nilsson et al 2002). Kanemoto and colleagues (1999) showed suicide attempts to be more closely associated with postictal psychosis than with inter- ictal psychosis. Risks for depression in epilepsy include genetic, neuro- logic, and iatrogenic factors. A family history of depression is quite common among depressed patients with epilepsy. Neuropsychiatric Disease and Treatment 2008:4(2)