Suicide is a major public heath concern. The estimated global burden of suicide is a million deaths per year. Self-inflicted death accounts for 1.5% of all deaths and is the tenth leading cause of death worldwide.
Compiling evidence on suicidality is fraught with problems. E.g. suicide deaths are generally perceived as underreported or prone to misclassification during cause-of-death ascertainment procedures. The suicide rates may be underestimated by 10% to 22%.
The reliability of suicidality recording in electronic databases has recently been studied. Arana et al investigated data from the United Kingdom database THIN and found that the codes and the algorithm used to identify suicidality had a very high predictive value (97%). The positive predictive values for completed suicide was lower (88%) and 14% of 'true', completed suicides were not identified as having died. Hall who did a validation study of death and suicide recording in the same databases identified seven cases of suicide out of 1394 'true deaths' (0.5%). One had a record of 'suicide' as a Read code, a second case was identified by 'hanging' in the comments section, a third probable suicide case by the Read term 'overdose of drug' plus an additional comment 'paracetamol/propaxyphene', and the four remaining cases were identified by external documents such as death certificates. Hall excluded patients with 'major emotional events' and a history of cancer. This may be one of the reasons why the percentage of suicide deaths was lower than expected (0.5% versus 1.5%) as mentioned above.
Antiepileptic medications are a heterogeneous pharmacologic class characterized by various chemical structures and postulated mechanisms of actions. The main therapeutic applications of antiepileptics include epilepsy, bipolar disorder, depression, neuralgia, and migraine. AEDs are among the most commonly prescribed centrally active agents. In a survey, carried out in a Danish County, 1.1% of the studied people received AEDs. The use of these drugs increased with increasing age.
Patients with the above mentioned indication such as epilepsy, major depression, and bipolar disorders have a higher risk for suicide compared with the general population.
A possible association between antiepileptic drugs and suicidality has been studied using different data sources such as the UK GPRD, the UK THIN, the US HealthCore Integrated Research Database (HIRD), Danish patient registries, Swedish patient registries, and data from clinical trials. The investigators applied different study designs such as cohort, matched case-control, case-crossover studies as well as a meta-analysis.
The published effects of antiepileptic drugs on suicidality covered a range between odds ratio (OR) 0.24 (95% CI: 0.03-2.17) for pregabalin and OR 6.42 (95% CI: 1.24-33.36) for levetiracetam. The effects of individual AEDs differed considerably within studies and between studies. The same holds for different indications. Arana et al found the lowest OR in patients with epilepsy only (OR 0.59; 95% CI: 0.35 - 0.98) and the highest OR in patients with depression only (OR 1.65; 95% CI: 1.24 - 2.19). The authors compared current use of AEDs with no use of AEDs in different indications.
Due to the complexity of the present issue, adequate adjustment for the numerous potential confounders such as socioeconomic aspects, various comorbidities, and concomitantly prescribed medication, is an analytic challenge. Further to this, the availability of a sufficiently large number of patients for investigation is another issue.
