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Date of release: 24 March, 2014

Safety of low-dose paroxetine


Postmenopausal women aged 40–79 years (mean 54 years) who had moderate to severe vasomotor symptoms (VMS) were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks [1]. Assessments included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale score (ASEX), Hot Flash-Related Daily Interference Scale sexuality subscore, and adverse events related to weight or sexual dysfunction. Pooled efficacy and safety populations comprised 1174 and 1175 participants of two phase-3 studies. Baseline values were similar for median weight (~75 kg), median BMI (~28 kg/m), and the proportion of women with sexual dysfunction (~58%). No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group. Small but statistically significant increases in weight and BMI were observed in the placebo group only at week 4. No significant difference between treatment groups was observed in the proportion of participants who had 7% or higher gain in body weight at weeks 4, 12, or 24. Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups.

Comment

Current recommendations for the treatment of menopause-related VMS, in the case where hormone therapy is not considered for some reason, put selective serotonin receptor inhibitors (SSRIs) as a second best line of therapy. Paroxetine is the first and only US Food and Drug Administration approved non-hormonal option for the treatment of moderate to severe VMS associated with menopause. This indication was approved based on positive phase-3 results, which showed a significant reduction in the number and severity of VMS while using paroxetine [2]. Hormone therapy is the most effective way to treat VMS, yet many women cannot use it (e.g. breast cancer survivors), or prefer not to use it because of potential adverse events. It makes sense that the second in-line therapy, paroxetine, should be evaluated not only for its efficacy against VMS, but also for its safety. SSRIs have a long list of associated side-effects, and some are serious ones. These include increased suicide risk, serotonin syndrome, abnormal bleeding, akathisia, hyponatremia, impaired cognitive and motor performance [3]. In addition, there are many, less severe side-effects, which are associated with SSRIs, among which two deserve special attention in the context of menopause – weight gain and decreased sexual function. Thus, the rationale of the study was to examine the downside of paroxetine therapy rather than its benefits. To note, the dosage of the usual anti-depression therapy ranges up to 40 mg/daily, while paroxetine for VMS was tested and approved in a low dose of 7.5 mg/daily. The phase-3 trials showed that therapy reduced the burden of VMS, on the one hand, and demonstrated a satisfactory safety profile, on the other hand. In regard to the above-mentioned particular adverse effects, body weight and BMI did not change in the paroxetine users. The proportions of participants with a weight gain of 7% or more at week 24 were 4% (paroxetine 7.5 mg) and 3% (placebo; p = 0.47). No significant differences were detected in any of the ASEX symptoms (sex drive, arousal, vaginal lubrication, orgasm, or satisfaction) between the paroxetine 7.5 mg group and the placebo group at any time point during the studies. Thus, women may be reassured that, despite the known gamut of side-effects attributed to SSRIs, the two important unwanted consequences of menopause in general, namely weight gain and sexual dysfunction, are not influenced by low-dose paroxetine prescribed for VMS. Yet the durations of the phase-3 studies were relatively short, up to 24 weeks, and therefore both sides of the benefit–risk balance cannot be extrapolated to longer-term treatment.

Comentario

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    References

  1. Portman DJ, Kaunitz AM, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause. Menopause 2014 Feb 17. Epub ahead of print
    http://www.ncbi.nlm.nih.gov/pubmed/24552977

  2. Simon JA, Portman DJ, Kaunitz AM, et al. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause 2013;20:1027-35
    http://www.ncbi.nlm.nih.gov/pubmed/24045678

  3. Prescribing information of paroxetine
    http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021299s024lbl.pdf

  4. Marks DM, Park MH, Ham BJ, et al. Paroxetine: safety and tolerability issues. Expert Opin Drug Saf 2008;7:783-94
    http://www.ncbi.nlm.nih.gov/pubmed/18983224