The adverse event profile of pregabalin across different disorders: a
Author(s): Zaccara G, Perucca P, Gangemi PF.
Affiliation(s): U.O. Neurologia, Azienda Sanitaria di Firenze, Florence, Italy.
Publication date & source: 2012, Eur J Clin Pharmacol. , 68(6):903-12
PURPOSE: In a recent meta-analysis of 38 double-blind randomized controlled
trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events
(AEs) to be significantly associated with PGB treatment. In the present study, we
evaluated whether the incidence of these 20 AEs differs across distinct disorders
in which PGB was investigated.
METHODS: Among the 38 previously identified RCTs of PGB, we selected only those
including a PGB 600 mg/day arm and subsequently classified them into four
distinct groups according to the disorder in which PGB was investigated: (1)
drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and
(4) neuropathic pain. We used risk differences (RDs) to quantify the
placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs
and to determine the placebo-corrected incidence of each of the 20 PGB AEs across
the four disorders.
RESULTS: Twenty-two RCTs were included in this study. Neither the proportion of
subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs
(with the exception of ataxia) differed significantly across the four disorders.
Ataxia was more common in drug-resistant partial epilepsy compared to
fibromyalgia. When limiting analyses to subjects on placebo, most
vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be
more common in drug-resistant partial epilepsy compared to all other disorders.
Diplopia and blurred vision were more common in epilepsy than in neuropathic
pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and
fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy
compared to neuropathic pain and in anxiety disorders alone compared to
neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than
in neuropathic pain and fibromyalgia.
CONCLUSIONS: Although drug-resistant partial epilepsy is associated with a higher
probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity
does not differ across distinct disorders.