In the JournalsPerspective

Weight, libido unchanged with low-dose paroxetine to treat vasomotor symptoms

Paroxetine administered in low doses to treat vasomotor symptoms associated with menopause did not yield significant changes in body weight or sexual function, according to pooled phase 3 results published in Menopause.

The findings came from two randomized, placebo-controlled trials looking at the effects of paroxetine 7.5 mg (Brisdelle, Noven Therapeutics), a selective serotonin reuptake inhibitor (SSRI), on postmenopausal women with moderate to severe vasomotor systems during 4, 12 and 24 weeks.

“Compared with baseline, no clinically relevant differences in body weight and BMI, or in reports of decreased libido or altered sexual functioning, were observed between treatment arms over time,” the researchers wrote.

The analysis by David J. Portman, MD, of the Columbus Center for Women’s Health Research, Ohio, and colleagues included assessments of changes in BMI and body weight, Arizona Sexual Experiences Scale score, Hot Flash-Related Daily Interference Scale sexuality subscore and adverse events related to weight or sexual dysfunction.

David J. Portman

David J. Portman

The women recruited were experiencing more than seven to eight hot flashes per day, or 50 to 60 per week, in the month preceding screening. After a 12-day, single blind, placebo-controlled run-in period, those compliant with electronic diary entry and still meeting hot flash eligibility criteria were assigned 1:1 to paroxetine 7.5 mg or placebo once daily at bedtime.

The efficacy population (n=1,174) and safety population (n=1,175) had similar baseline values for median weight (approximately 75 kg) and median BMI (approximately 28 kg/m2); the proportion of women with sexual dysfunction was approximately 58%.

No clinically meaningful or statistically significant changes in weight or sexual function assessments were observed with paroxetine from baseline. Small but statistically significant increases in weight and BMI were demonstrated by the placebo group, but only at 4 weeks. No significant between-group differences were seen in the proportion of women with ≥7% gain in body weight on week 4, 12 or 24. Rates for adverse events suggestive of sexual dysfunction were similarly low with paroxetine and placebo.

The researchers noted limitations of the study, including short treatment duration and follow-up period.

“Several studies of SSRIs and [serotonin-norepinephrine reuptake inhibitors] have reported stable weight or even small weight losses during short-term treatment (4-6 months) and increases in weight across a longer trial duration (≥12 months),” the researchers wrote. “The impact of paroxetine 7.5 mg on body weight and sexual function for a treatment duration longer than 24 weeks is unknown.”

Disclosure: Portman reports various financial ties to Noven. See the study for a full list of researchers’ financial disclosures.

Paroxetine administered in low doses to treat vasomotor symptoms associated with menopause did not yield significant changes in body weight or sexual function, according to pooled phase 3 results published in Menopause.

The findings came from two randomized, placebo-controlled trials looking at the effects of paroxetine 7.5 mg (Brisdelle, Noven Therapeutics), a selective serotonin reuptake inhibitor (SSRI), on postmenopausal women with moderate to severe vasomotor systems during 4, 12 and 24 weeks.

“Compared with baseline, no clinically relevant differences in body weight and BMI, or in reports of decreased libido or altered sexual functioning, were observed between treatment arms over time,” the researchers wrote.

The analysis by David J. Portman, MD, of the Columbus Center for Women’s Health Research, Ohio, and colleagues included assessments of changes in BMI and body weight, Arizona Sexual Experiences Scale score, Hot Flash-Related Daily Interference Scale sexuality subscore and adverse events related to weight or sexual dysfunction.

David J. Portman

David J. Portman

The women recruited were experiencing more than seven to eight hot flashes per day, or 50 to 60 per week, in the month preceding screening. After a 12-day, single blind, placebo-controlled run-in period, those compliant with electronic diary entry and still meeting hot flash eligibility criteria were assigned 1:1 to paroxetine 7.5 mg or placebo once daily at bedtime.

The efficacy population (n=1,174) and safety population (n=1,175) had similar baseline values for median weight (approximately 75 kg) and median BMI (approximately 28 kg/m2); the proportion of women with sexual dysfunction was approximately 58%.

No clinically meaningful or statistically significant changes in weight or sexual function assessments were observed with paroxetine from baseline. Small but statistically significant increases in weight and BMI were demonstrated by the placebo group, but only at 4 weeks. No significant between-group differences were seen in the proportion of women with ≥7% gain in body weight on week 4, 12 or 24. Rates for adverse events suggestive of sexual dysfunction were similarly low with paroxetine and placebo.

The researchers noted limitations of the study, including short treatment duration and follow-up period.

“Several studies of SSRIs and [serotonin-norepinephrine reuptake inhibitors] have reported stable weight or even small weight losses during short-term treatment (4-6 months) and increases in weight across a longer trial duration (≥12 months),” the researchers wrote. “The impact of paroxetine 7.5 mg on body weight and sexual function for a treatment duration longer than 24 weeks is unknown.”

Disclosure: Portman reports various financial ties to Noven. See the study for a full list of researchers’ financial disclosures.

    Perspective
    R. Jane Lau

    R. Jane Lau

    This study was part of the phase 3 studies submitted to the FDA to get paroxetine approved as a product, although clinicians have been successfully using selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) off-label for a while now for the treatment of hot flashes — often based on studies that have been presented at The North American Menopause Society annual meeting. There have been posters and presentations, but all of those were off-label indications. This is the first product that now has an FDA indication for use for hot flash treatment.

    Based on background research, Portman highlighted that clinicians have been using doses that were higher than necessary because there was no consensus out there about what dose to use. The doses you would use to treat depression would be 20 or 40 mg. Typically, when you use an SSRI to treat hot flashes, a lesser dose would be effective. But it’s been at 20 mg tablet; 7.5 mg has never been an available dose, until now.

    Portman’s data shows that paroxetine does indeed work to treat hot flashes, and the onset of action is certainly quick. It is faster than the effect of these drugs in treating depression. Typically you don’t see an anti-depressant effect until at least 1 month, whereas Portman was seeing an effect on hot flashes in 2 weeks. This may even be faster than you would see with using estrogen, though the effect is not as robust.

    Another important point that Portman made is no extra relief from hot flashes occurs with higher doses, and then when you get into the potential adverse side effects, particularly the sexual side effects. He stressed in the data that the adverse sexual side effects were not significantly different when compared with placebo.

    • R. Jane Lau, MD
    • Associate Clinical Professor Department of Obstetrics and Gynecology School of Medicine, Indiana University

    Disclosures: Lau has no relevant financial disclosures.