The adverse event profile of pregabalin: a systematic review and meta-analysis of
randomized controlled trials.
Author(s): Zaccara G, Gangemi P, Perucca P, Specchio L.
Affiliation(s): U.O. Neurologia, Azienda Sanitaria di Firenze, Firenze, Italy.
Publication date & source: 2011, Epilepsia. , 52(4):826-36
PURPOSE: Despite the widespread use of antiepileptic drugs (AEDs) across
different neurologic and psychiatric disorders, no study has systematically
reviewed all available randomized controlled trials (RCTs) of a given AED to
fully uncover its tolerability profile. We aimed at identifying treatment
emergent adverse events (AEs) associated with pregabalin through a systematic
review and meta-analysis of all available RCTs. We also assessed the association
between serious AEs and pregabalin, and investigated whether pregabalin AEs
display a dose-response relationship.
METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for
RCTs. Additional studies were identified from reference lists of retrieved papers
and from online clinical databases. We selected placebo-controlled, double-blind
RCTs investigating the therapeutic effects of pregabalin in adults with any
condition. Studies had to include at least 20 subjects per arm and have a
duration of at least 4 weeks. AEs were assessed for their association with
pregabalin after identification/exclusion of synonyms, rare AEs, and
nonassessable AEs due to methodologic limitations. We used relative risks (RRs)
to assess the association of any [99% confidence intervals (CIs)] or serious AEs
(95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate
dose-response relationships of pregabalin AEs.
KEY FINDINGS: Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%)
were significantly associated with pregabalin (dizziness, vertigo,
incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia,
tremor, somnolence, confusional state, disturbance in attention, thinking
abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth,
constipation). The highest RRs were found for cognition/coordination AEs. There
was no significant association between serious AEs and pregabalin. There was a
selective dose-response pattern in the onset of pregabalin AEs, with certain AEs
appearing at lower doses than others.
SIGNIFICANCE: Individuals starting treatment with pregabalin are at increased
risk for several AEs, particularly those affecting cognition/coordination.
Pregabalin AEs appear according to a selective dose-response pattern, possibly
reflecting the severity of dysfunction of distinct anatomic structures. These
findings may aid clinicians in providing better patient management, and support
the value of including in meta-analyses of AED tolerability profiles RCTs
performed in different conditions.