Pregabalin-Induced Suicidal Ideations

Pregabalin is a novel compound that is approved for the treatment of anxiety disorders, neuropathic pain and partial-onset seizures. Several studies reported excellent safety and efficacy of pregabalin, most frequent adverse events were dizziness and somnolence [1] [2] [3]. There are recently published reports about the potential of novel antiepileptic drugs to induce suicidal behaviour and self-harm in epilepsy [4] and of antiepileptic dugs generally when used in other disorders [5]. However, pregabalin has been classified as a new antiepileptic drug with very low risk of inducing suicidal behaviour [4]. We present the first case of dose-dependent pregabalin-induced suicidal ideations.

“Ms. L”, a 21-year-old woman, was treated in our psychiatric outpatient department. She reported symptoms such as avoidance of social interactions and social inhibition. During subsequent outpatient treatment, we initiated pharmacotherapy with pregabalin (600 mg/day) because of reported anxiety symptoms and diagnosis of generalized anxiety disorder according to DSM-IV (confirmed with the mini-international neuropsychiatric interview). The patient reported no significant depressive symptoms. The Hamilton anxiety score (HAMA) before initiation of the pharmacotherapy was 31/56 points. She initially tolerated the medication without any side effects (apart from short-term, moderate fatigue), and reported a significant reduction of anxiety symptoms (HAMA at day 16 of treatment: 10/56). However, 25 days after initiation of pregabalin treatment, she reported suicidal ideations, which had been hitherto unknown to her. She therefore stopped the medication immediately by herself, and the suicidal ideations decreased rapidly. However, after discontinuation of pregabalin, anxiety symptoms increased again. So she took 300 mg pregabalin/day again, suicidal thoughts disappeared completely. Nevertheless, we advised at the next visit to discontinue pregabalin treatment and initiated intermittent anxiolytic therapy with lorazepam.

In conclusion, we found that since increasing the treatment with pregabalin at a dosage of 600 mg the patient experienced suicidal ideations. After reducing the dosage to 300 mg/day suicidal thoughts disappeared completely. We propose a dose-dependent effect of pregabalin to induce suicidal ideations.

Newer antiepileptic drugs have been associated with depression and a 3-fold increased risk of self-harm and suicidal behaviour [4]. However, pregabalin, a GABA-analogue that selectively binds to the alpha2 subunit of voltage-gated calcium channels, inhibits the release of excitatory neurotransmitters and has been classified as low-risk antiepileptic drug with respect to inducing suicidal behaviour [4]. This case control study by Andersohn et al. included only patients diagnosed with epilepsy. The number of patients treated with pregabalin was not indicated, but none of them presented suicidal behaviour [4]. There was no discrimination between the different antiepileptic drugs increasing the risk of suicidal behaviour in the study of Arana et al. [5]. It is also important to keep in mind that most psychiatric diagnoses are per se associated with an increased risk of suicidal behaviour.

In fact pregabalin has been associated with reducing anxious syndromes in previous reports (1–3). Here we report that pregabalin may have a potential for inducing suicidal ideations, which was a dose-dependent effect in our case. We therefore recommend being cautious and sensitive to possible suicidal ideations when using pregabalin to treat patients with a psychiatric disease.

References

• 1 Feltner DE, Crockatt JG, Dubovsky SJ. et al . A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder.  J Clin Psychopharmacol. 2003;  23 240-249
• 2 Pande AC, Feltner DE, Jefferson JW. et al . Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.  J Clin Psychopharmacol. 2004;  24 141-149
• 3 Pohl RB, Feltner DE, Fieve RR. et al . Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing.  J Clin Psychopharmacol. 2005;  25 151-158
• 4 Andersohn F, Schade R, Willich SN. et al . Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behaviour.  Neurology. 2010;  75 335-340
• 5 Arana A, Wentworth CE, Ayuso-Mateos JL. Arellano FM. Suicide-related events in patients treated with antiepileptic drugs.  New Engl J Med. 2010;  363 542-451

Correspondence