title: The adverse event profile of pregabalin across different disorders: a meta-analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: U.O. Neurologia, Azienda Sanitaria di Firenze, Florence, Italy. gaetano.zaccara@asf.toscana.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zaccara
authors.forename: Piero
authors.initials: P
authors.lastname: Perucca
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Gangemi
mesh_terms: D000293:Adolescent; D000700:Analgesics / Q000009:adverse effects*; D001008:Anxiety Disorders / Q000188:drug therapy; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy; D005356:Fibromyalgia / Q000188:drug therapy; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy; D000069583:Pregabalin; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid