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Restless legs syndrome (RLS) and nausea and vomiting of pregnancy (NVP) are both common maternal conditions affecting quality of life. Gabapentin is currently FDA-approved for treating RLS and preliminary results have shown it may be effective for treating the most severe form of NVP, hyperemesis gravidarum (HG). Because NVP and HG symptoms peak early in pregnancy, the potential teratogenicity of gabapentin needs to be considered. We reviewed published pregnancy registries and cohorts for pregnancy outcomes associated with maternal gabapentin use. Gabapentin exposures from 5 pregnancy registries, 1 HG pilot study and 2 additional cases were reviewed. Among 294 first trimester gabapentin-monotherapy exposures, there were 5 major congenital malformations (MCMs) reported (1.7%), which favorably compares to the MCM rate in the general population (1.6-2.2%). Two of the registries reported maternal gabapentin use among 261 singleton pregnancies to be associated with roughly equivalent rates of premature birth, birth weight after correction for gestational age at delivery and maternal hypertension/eclampsia as those that have been reported in the general population. These data support the safety of gabapentin use in pregnancy; however, the number of exposures to date is still small. If future pregnancy registry data confirm this positive safety profile, gabapentin therapy would likely be a safe and effective treatment for RLS during pregnancy. Controlled, clinical trials are needed to assess gabapentin's effectiveness for HG., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Gabapentin's main clinical use is in the treatment of neuropathic pain where its binding to neuronal alpha-2/delta subunits of voltage-gated calcium channels (VGCCs) is critical to its mechanism of action. Over the past 10 years, there have been several reports of gabapentin also having anti-nausea and anti-emetic effects in conditions including postoperative nausea and vomiting (PONV), chemotherapy-induced nausea and vomiting (CINV), and hyperemesis gravidarum (HG). In this report, a MEDLINE electronic search was performed, and relevant citations were reviewed and classified by level of evidence; a grade of recommendation was then assigned for gabapentin's use for each studied indication. Out of 33 clinical trials reviewed, 12 assessed nausea and/or vomiting (N/V) associated with gabapentin therapy as primary outcome measures. These 12 studies provided a Grade A recommendation for gabapentin use in treating PONV, a Grade B recommendation for use in treating CINV, and a Grade C recommendation for use in treating HG. Further research is needed to confirm these initial promising results, which implicate the alpha-2/delta VGCC subunit as a novel therapeutic target in the treatment of several N/V-associated clinical conditions.

Although many non-hormonal compounds have shown statistically significant benefit over placebo in hot flash randomized controlled trials (RCTs), these studies have varied considerably in basic methodology making it challenging to deduce which compounds have the greatest potential to provide clinically meaningful benefit. This review used evidence-based methodology closely mirroring the FDA and EMEA guidelines as a template to identify "well-designed" RCTs from which effective and clinically meaningful non-hormonal hot flash therapies could be identified. In addition, pertinent safety information was reviewed. Out of 3548 MEDLINE citations and abstracts, 51 well-designed hot flash RCTs were identified. From these trials, gabapentin, oxybutynin ER, desvenlafaxine, soy-derived isoflavones and black cohosh each showed a clinically meaningful treatment effect in at least 1 RCT. Among these 5 compounds, only gabapentin demonstrated consistent and statistically significant benefit over placebo in all of its well-designed RCTs. Desvenlafaxine, soy-derived isoflavones, and black cohosh demonstrated statistically significant benefit over placebo in 75%, 21%, and 17% of the well-designed RCTs for each compound, respectively. There was only 1 well-designed RCT using oxybutynin ER, which showed it to have a robust and clinically meaningful benefit. In terms of safety, there have been cardiovascular risks associated with desvenlafaxine use in postmenopausal women with hot flashes. The use of anticonvulsants, in general, has been associated with an absolute 0.21% increase in suicidal thoughts and behavior. Further research is needed with several of these nonhormonal compounds to replicate these findings and to also directly compare their efficacy and tolerability with those of hormone replacement therapy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Insomnia related to nighttime awakenings is known to be more prevalent in women than men. Three cases are presented here of late premenopausal women experiencing frequent nighttime awakenings that responded well to bedtime treatment with gabapentin. In one case, what started as isolated nighttime awakenings slowly progressed to awakenings accompanied by typical menopausal night sweats. This led to the theory that the initial isolated nighttime awakenings in this patient may have been secondary to a menopausal etiology related to low serum estradiol levels. In the subsequent 2 cases, early follicular phase serum estradiol was confirmed to be low. It is theorized that isolated nighttime awakenings in some premenopausal women may be caused by low serum estradiol, triggering events physiologically related to menopausal night sweats. Further research is needed to determine if low early follicular phase serum estradiol is associated with nighttime awakenings in premenopausal women not experiencing night sweats.

Among 7 subjects with hyperemesis gravidarum (HG), we found gabapentin therapy to be associated with mean reductions in nausea and emesis from Baseline to Days 12-14 of 80% and 94%, respectively. There have been 2 congenital defects among 7 exposed infants. Gabapentin may be effective in the treatment of HG.

Objective: The aim of this research was to analyze gabapentin's effect on Pittsburgh Sleep Quality Index (PSQI) scores in menopausal women., Methods: Secondary analysis of data from a cohort of menopausal women participating in a randomized, double-blind, placebo-controlled trial of gabapentin 300 mg three times daily (TID) for hot flashes. The outcomes of interest were PSQI global and factor scores at weeks 4 and 12., Results: Subjects randomized to gabapentin demonstrated improvement in the sleep quality factor score, compared to placebo-treated subjects, at 4 and 12 weeks (p < 0.03). There was also gabapentin-associated improvement in the global PSQI score (p = 0.004) and the sleep efficiency factor score (p = 0.05) at 4 weeks. There was no significant effect of gabapentin on the daily disturbance factor score., Conclusions: Gabapentin may improve sleep quality in menopausal women with hot flashes. These results warrant further prospective investigation, with an emphasis on measuring subjective sleep quality and maintenance.

Purpose: Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials., Patients and Methods: Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via chi2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved., Results: This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms., Conclusion: Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

Objective: To compare the efficacy of gabapentin, estrogen, and placebo in the treatment of hot flushes., Methods: We performed a randomized, double-blind, placebo-controlled trial of 60 postmenopausal women to assess the efficacy of estrogen and gabapentin in the treatment of moderate-to-severe hot flushes. Participants were randomly assigned to receive either 0.625 mg/d of conjugated estrogens (n = 20), placebo (n = 20), or gabapentin titrated to 2,400 mg/d (n = 20) for 12 weeks. Participants recorded frequency and severity of baseline hot flushes on a hot flush diary for 2 weeks before randomization and for 12 weeks after randomization. The primary outcome measure was the weekly hot flush composite score, which takes into account both severity and frequency of hot flushes. Secondary outcome measures were differences in pre- and posttreatment scores pertaining to depression (Zung Depression Scale) and other climacteric symptoms (Greene Climacteric Scale)., Results: Intention-to-treat analysis showed that the reduction in the hot flush composite score for both estrogen (72%, P = .016) and gabapentin (71%, P = .004) was greater than the reduction associated with placebo (54%) at the conclusion of the 12th week. The extent of reduction in hot flush composite score, however, was not significantly different between estrogen and gabapentin (P = .63). No differences were seen between groups in the Zung Depression Scale, or in any of the Greene Climacteric subscales except for the Somatic Symptom cluster, which was significantly greater in the gabapentin arm than in the placebo arm. Despite a lack of group differences in adverse events, the Headache, Dizziness, and Disorientation cluster appeared with greater frequency in the gabapentin group. Estimation of the number needed to harm in this cluster suggests that these symptoms may occur with every fourth patient treated with gabapentin., Conclusion: Despite the small scale of this study, gabapentin appears to be as effective as estrogen in the treatment of postmenopausal hot flushes., Clinical Trial Registration: Clinicaltrials.gov, NCT 00276081., Level of Evidence: I.

Craniotomy-associated chronic emesis can be refractory to currently approved antiemetic therapy. The authors describe a man who suffered 4 weeks of severe refractory emesis, failure to thrive, and a 40-lb weight loss after he underwent resection of a posterior fossa cholesteatoma. The patient experienced complete resolution of emesis and anorexia in response to combined gabapentin-scopolamine therapy. This case provides anecdotal evidence for the use of gabapentin-scopolamine therapy in patients with chronic, refractory nausea and emesis, particularly following posterior fossa surgery, during which medullary nausea and emesis centers may be affected.

There is a need for alternative therapies for hot flashes, as hormone replacement therapy (HRT) is associated with increased rates of breast cancer and heart disease, and some women fail to respond to HRT. A 32-year-old woman with surgically-induced menopause experienced 20-30 severe hot flashes per day and failed to respond to various formulations of HRT and selective serotonin reuptake inhibitor (SSRI) therapy for 17 years. She markedly responded to gabapentin therapy. Gabapentin, SSRIs, and estrogen may act at different cellular targets in the treatment of hot flashes.

In an anecdotal report, complete resolution of chemotherapy-induced nausea was seen in a patient with breast cancer, after she was placed on the anticonvulsant gabapentin. On this basis, we did an open-label study in which oral gabapentin 300 mg thrice daily was given for every other chemotherapy treatment in nine patients with breast cancer. Six of the nine reported at least a three-point improvement in peak delayed nausea (on an eight-point nausea scale), and three patients had complete resolution of nausea when taking gabapentin. This preliminary evidence shows that gabapentin might have a role in treatment of chemotherapy-induced nausea.

Objective: To evaluate whether treatment with the anticonvulsant gabapentin may be effective in reducing hot flash frequency and severity., Methods: A randomized, double-blind, placebo-controlled trial was conducted in 59 postmenopausal women with seven or more hot flashes per day examining the effects of gabapentin 900 mg per day on hot flash frequency after 12 weeks of treatment. Subsequently, study patients were enrolled in a 5-week, open-label treatment phase, during which patients could increase the dose of gabapentin to 2,700 mg per day, if needed., Results: After 12 weeks of double-blind treatment, intention-to-treat analysis showed that gabapentin 900 mg per day was associated with a 45% reduction in hot flash frequency and a 54% reduction in hot flash composite score (frequency and severity combined into one score) from baseline, compared with 29% (P =.02) and 31% (P =.01) reductions, respectively, for placebo. Four patients (13%) in the gabapentin group and one (3%) in the placebo group withdrew from the double-blind study because of adverse events. Fifteen patients (50.0%) in the gabapentin group reported at least one adverse event, compared with eight patients (27.6%) in the placebo group. Higher, open-label gabapentin dosing was associated with 54% and 67% reductions in hot flash frequency and composite score from baseline, respectively., Conclusion: Gabapentin is effective in reducing hot flash frequency and severity in postmenopausal women.