Gabapentin Improves Menopausal Hot Flashes, Insomnia

Extended-release (ER) gabapentin (Serada, Depomed), an investigational nonhormonal drug, improves sleep and reduces hot flashes in menopausal women, according to a phase 3 clinical trial known as BREEZE 3.

The results were presented here at the North American Menopause Society (NAMS) 23rd Annual Meeting.

“Right now, if women don’t want to take hormones, and if over-the-counter products, acupuncture, and lifestyle changes do not work, we don’t have any FDA [US Food and Drug Administration] approved therapies,” said lead researcher JoAnn Pinkerton, MD, who is professor of obstetrics and gynecology at the University of Virginia in Charlottesville and past president of NAMS.

A New Drug Application was submitted for gabapentin ER in July. If approved, the drug will be the first nonhormonal, nonantidepressant treatment for the bothersome symptoms of menopause, Dr. Pinkerton explained.

BREEZE 3 looked at the effect of gabapentin ER on hot flashes and on sleep. Data were presented in 2 different abstracts by 2 different investigators.

Gabapentin is used to control epileptic seizures and restless leg syndrome, and recently was approved by the FDA for the treatment of postherpetic neuralgia.

The ER formulation was developed to be taken twice a day instead of 3 times a day, which significantly decreases the adverse-effect profile, Dr. Pinkerton said.

“With the short-acting version, 20% of patients were somnolent or dizzy. In this trial, with the extended-release formulation, the rate of somnolence or dizziness started at 11% and went down to 3% very quickly. It was very well tolerated and very few people discontinued treatment because of those symptoms,” she said. At the end of 6 months, people felt significantly better, she added.

 

Gabapentin Improves Insomnia

In the sleep part of BREEZE 3, gabapentin was found to have a positive impact on sleep disturbance. Researchers assessed the impact of gabapentin using 2 measures of sleep: the Insomnia Severity Index (ISI) score and the daily sleep interference (S/I) score.

At baseline, the mean ISI scores were 17.54 in the gabapentin group and 17.33 in the placebo group, indicating moderate insomnia, and the mean S/I scores were 7.3 and 7.4, respectively, indicating a moderate to severe sleep disturbance.

After 12 weeks, there was a clinically meaningful reduction in ISI score in the gabapentin group, compared with the placebo group (8.7 vs 6.3; = .0044), and in S/I score (3.6 vs 2.8; P = .0056). Reductions out to week 24 were maintained in the ISI score (8.6 vs 6.2; P = .0068) and in the S/I score (3.9 vs 3.0; P = .0084).

“I was happy that sleep was looked at in an objective way. If you ask many women, their hot flushes at night really bother them. If they can’t sleep because of hot flushes, they basically cannot function during the day, so we need to look at sleep separately,” said Risa Kagan, MD, from East Bay Physicians Medical Group, Alta Bates Summit Medical Center, in Berkeley, and clinical professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco, who led the sleep part of BREEZE 3.

Dr. Kagan added that, although it is fine to look at all of the data objectively, in the end, the aim is to help women transition through the menopause. “This was not just a placebo effect, this was actually a statistically significant improvement in sleep over placebo,” she explained.

http://www.medscape.com/viewarticle/772249

Treatment effects of gabapentin for primary insomnia

OBJECTIVES:

The prevalence of insomnia is very high in our society. Although pharmacological treatment of insomnia is available, most hypnotics have been shown to alter sleep architecture and have many adverse effects. Gabapentin was originally designed for antiepileptic therapy; however, some studies reported that its use increases slow-wave sleep in healthy volunteers or patients. Our goal was to evaluate the benefits of gabapentin in the treatment of primary insomnia in patients.

METHODS:

Eighteen patients with primary insomnia participated in the study. They received gabapentin treatment for at least 4 weeks. All patients received polysomnography, a biochemical blood test, and neuropsychological tests before and after the treatment period. All measures were analyzed with Student t test to examine the treatment effects of gabapentin, except that the measures of heart rate variability were analyzed with analysis of variance.

RESULTS:

Polysomnographic study revealed increased sleep efficiency and slow-wave sleep, decreased wake after sleep onset, and spontaneous arousal index after gabapentin treatment. The biochemical blood test revealed decreased prolactin levels in the morning after treatment. Electroencephalographic power spectral analysis showed increased delta-2 and theta power in sleep stage 1 and decreased sigma activity power in sleep stages N2 and N3 after gabapentin treatment. Heart rate variability analyses also showed a significant increase in normalized high frequency percentage in sleep stages N2 and N3 and low frequency-high frequency ratio in sleep stage N2 after treatment. In addition, neuropsychological tests revealed the elevation of visual motor processing speed after gabapentin treatment.

insomnia

CONCLUSIONS:

Gabapentin enhances slow-wave sleep in patients with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal. The results suggest that gabapentin may be beneficial in the treatment of primary insomnia.

Author information

  • Department of Neurology and Sleep Center, Chung Shan Medical University and University Hospital, Tai-Chung, Taiwan.

Gabapentin FDA approval

Gabapentin was originally approved by the U.S. Food and Drug Administration (FDA) in December 1993, for use as an adjuvant (effective when added to other antiseizure drugs) medication to control partial seizuresin adults; that indication was extended to children in 2000. In 2004, its use for treating postherpetic neuralgia (neuropathic pain following shingles) was approved.

Gabapentin 800 mg Tab-IVA