Antiepileptic drugs and risk of suicide attempts: a case-control study exploring the impact of underlying medical conditions.

PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level. Copyright © 2017 John Wiley & Sons, Ltd.

Relationship between posttrauma GABA plasma levels and PTSD at 1-year follow-up.

OBJECTIVE: Gamma-aminobutyric acid (GABA) exerts a prominent effect on central adrenergic stress responses in times of high stress and has been associated with acute posttraumatic stress disorder (PTSD). The authors examined the association between low posttrauma plasma GABA levels and long-term PTSD. METHOD: Plasma GABA levels were measured in 78 victims of road traffic accidents who met criteria for trauma exposure on arrival at a trauma department and were admitted for at least 3 days. Patients were assessed for PTSD and major depressive disorder at 6-week and 1-year follow-ups. RESULTS: At 6 weeks and at 1 year, mean posttrauma GABA levels were significantly lower among subjects who met all or nearly all criteria for PTSD than among those who did not. Among patients who met all or nearly all criteria for PTSD at 6 weeks, 75% of those with posttrauma GABA levels above 0.20 mmol/ml no longer met criteria at 1 year. By contrast, among patients whose GABA levels were below 0.20 mmol/ml, 80% met all or nearly all criteria for PTSD at 1 year. Two-thirds of patients who met all or nearly all criteria for PTSD at 1 year also met criteria for major depressive disorder. CONCLUSIONS: A plasma GABA level above 0.20 mmol/ml may protect against chronic PTSD and may represent a marker of recovery from trauma.

Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder.

BACKGROUND: Gamma amino-butyric acid (GABA) regulates the intensity and the duration of the central hyperadrenergic response in times of high stress and has been negatively associated with anxiety, depression, and sleep problems. We hypothesized that individuals with low plasma GABA levels may be more prone to develop posttraumatic stress disorder (PTSD) in the aftermath of trauma exposure. METHODS: To test this hypothesis, we measured plasma GABA levels in a population of 108 road traffic accident victims on arrival at a traumatology department and assessed them for PTSD 6 weeks later. RESULTS: The mean GABA level (nmol/mL) in the PTSD group (n = 55; M =.20; SD =.08) was significantly lower compared with members of the trauma-exposed group who did not develop PTSD [n = 17; M =.30; SD =.09), t(70) = 3.94, p =.0002]. CONCLUSIONS: Provided that GABA levels in the brain are genetically predetermined, our results would suggest that individuals with low plasma GABA levels are premorbidly more vulnerable to stress-related disorders such as acute PTSD. If replicated, plasma GABA levels measured in the aftermath of trauma exposure might help to identify individuals at high risk for developing PTSD.

Fright (effroi) and other peritraumatic responses after a serious motor vehicle accident: prospective influence on acute PTSD development.

OBJECTIVE: We prospectively examined the relation between various peritraumatic responses (that is, fear, helplessness, horror, amnesia, and fright) and the development of posttraumatic stress disorder (PTSD) 2 months after a trauma. METHOD: Participants included 123 motor vehicle accident (MVA) victims consecutively hospitalized in a traumatology department for over 72 hours during a 16-month period. Between day 2 and day 5 of their hospitalization, a psychiatrist assessed the patients' peritraumatic responses and acute stress disorder (ASD). Two months after the accident, an experienced psychiatrist contacted the patients by telephone, and the PTSD symptoms and the diagnosis were assessed with a modified version of the Clinician-Administered PTSD Scale (CAPS). RESULTS: Of the participants, 48 reported an immediate fright reaction when faced with the prospect of their own death. Participants who reported a fright experience had a 17 times greater risk of subsequently meeting the diagnostic criteria for PTSD (odds ratio 16.75). A fright reaction predicted PTSD development with a specificity of 0.93 and a sensitivity of 0.60 CONCLUSION: The immediate reactions described in criterion A2 of the DSM-IV (that is, fear, helplessness, and horror) did not seem to be equally relevant. An initial feeling of fright seems to be an essential qualitative factor in the clinical description of psychological trauma.