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Abstract
Background: Various nonhormonal agents have been used for the treatment of hot flashes in women
with natural or tamoxifen-induced menopause. Some studies have reported that gabapentin
appears to be an effective and well-tolerated treatment modality.
Objective: To investigate the efficacy and tolerability of gabapentin for the treatment of menopausal
hot flashes, we performed a systematic review of all trials reporting on the efficacy
and tolerability of gabapentin in women with hot flashes and a meta-analysis of the
randomized controlled trials (RCTs) conducted in this patient population.
Methods: For the systematic review, a literature search was conducted through MEDLINE, EMBASE,
and Cochrane Central Register of Controlled Trials for articles published in English
from inception of the databases through November 2008. The reference sections of retrieved
articles were searched, and a manual search of key journals and abstracts from major
meetings in clinical pharmacology was conducted. To be included in the meta-analysis,
RCTs had to compare gabapentin with placebo in the treatment of hot flashes in women
with natural or tamoxifen-induced menopause, regardless of the sample size, dosage
used, duration of treatment, or frequency of the episodes. Uncontrolled and openlabel
trials were reviewed but excluded from the meta-analysis. The percent reduction in
hot flash frequency (relative to baseline) and the composite score (summation of the
number of hot flashes in each severity category multiplied by the severity score)
were used as primary outcome measures. Dropout rates and the incidences of frequently
reported adverse events (eg, dizziness/unsteadiness, fatigue/somnolence) were also
investigated.
Results: The systematic review included 7 trials conducted in 901 patients between 2002 and
2008. Study sizes ranged from 22 to 420 patients, total daily doses of gabapentin
ranged from 900 to 2400 mg, and titration periods lasted 3 to 12 days. All of the
trials were conducted in North America (6 in the United States and 1 in Canada); 4
of the trials enrolled subjects with a history of breast cancer, whereas the remaining
3 trials only enrolled postmenopausal women. Four RCTs were included in the meta-analysis.
Data were expressed as weighted mean difference (WMD) or relative risk (RR), with
the associated 95% CI. Women assigned to gabapentin reported a significantly greater
percent reduction in both the frequency of hot flashes (WMD = 23.72 [95% CI, 16.46–30.97];
P < 0.001) and the composite score (WMD = 27.26 [95% CI, 21.24–33.29]; P < 0.001), with significant between-study heterogeneity (I2 = 97.8% and 95.6%, respectively). Dropouts due to adverse events were more frequent
in women randomized to gabapentin than in controls (RR = 2.09 [95% CI, 1.13–3.85];
P = 0.02; I2 = 0%). The risk of symptom clustering also was significantly higher in the treatment
group than in the controls (dizziness/unsteadiness: RR = 6.94 [95% CI, 3.19–15.13];
P < 0.001; I2 = 63.1%; and fatigue/somnolence: RR = 4.78 [95% CI, 2.23–10.25]; P < 0.001; I2 = 0%).
Conclusions: Comparisons of gabapentin and placebo revealed reductions of 20% to 30% in the frequency
and severity of hot flashes with gabapentin, although data across the studies were
too heterogeneous to provide a reliable summary effect. Clusterings of dizziness/unsteadiness
and fatigue/somnolence were the most frequently reported adverse events associated
with gabapentin and resulted in a higher dropout rate due to adverse events in the
gabapentin-treated patients than in the controls. More studies are needed to consolidate
the outcomes and elucidate useful details regarding this treatment.
Key words:
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Article info
Publication history
Accepted:
December 10,
2008
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
