Antidepressants
The results for the selective serotonin reuptake inhibitors (SSRIs) as a class were inconsistent and based on short-term studies only. One RCT (with a low risk of bias) in women after breast cancer found that paroxetine (10 or 20 mg/d for 4 weeks) significantly reduced hot flush frequency and severity during treatment compared with placebo.14 However, three RCTs (with a low to moderate risk of bias) found that neither fluoxetine (20 mg/d for 4 weeks)15 nor sertraline (25 to 100 mg/d for 4-6 weeks)16, 17 had a consistent effect on hot flushes compared with placebo. [ES2]
In a population of peri- and postmenopausal women, two RCTs in a systematic review found that the SSRI escitalopram (10-20 mg/d for 8 weeks) significantly reduced hot flush frequency compared to placebo.18 One of these RCTs (with a low risk of bias) was identified in one pooled analysis (with at least 14 bothersome vasomotor symptoms per week) found that 8 weeks of escitalopram (10 mg/d) significantly reduced vasomotor symptom frequency and bother compared with placebo.19 [ES30]
Venlafaxine was the only serotonin-norepinephrine reuptake inhibitor (SNRI) assessed in the population of women experiencing menopausal symptoms after breast cancer. Two studies showed that venlafaxine significantly reduced hot flush frequency and severity in women after breast cancer compared with placebo: one RCT (with a low risk of bias) found that 12 weeks of venlafaxine at 75 mg/d (slow release) significantly reduced hot flush frequency and severity compared with placebo,20 while a second study (with a moderate risk of bias) found that 14 weeks of venlafaxine at 37.5mg/d significantly reduced hot flush frequency and severity compared with placebo.21 [ES3]
Venlafaxine was also found to have greater efficacy at reducing the frequency and severity of hot flushes than clonidine, and equivalent efficacy at reducing hot flushes compared with gabapentin and acupuncture. Three RCTs (with a low to moderate risk of bias) found that venlafaxine or clonidine reduced hot flush frequency and/or severity from baseline,20, 22, 23 and in one RCT the improvement with venlafaxine was significantly greater than with clonidine.23 One RCT (with a moderate risk of bias) found that 4 weeks of venlafaxine or gabapentin were associated with equivalent reductions in hot flash scores,24 while another RCT (with a moderate risk of bias) found 12 weeks of venlafaxine or a course of acupuncture were associated with similar reductions in hot flash frequency and severity.25 [ES3]
One RCT (with an low risk of bias) identified in a pooled analysis of peri- and postmenopausal women (with at least 14 bothersome vasomotor symptoms per week) found that 8 weeks of low-dose venlafaxine XR (37.5 mg/d for the first week, then 75 mg/d) significantly reduced vasomotor symptom frequency and bother compared with placebo.19 [ES31]
One RCT (with a low risk of bias) in menopause transition and postmenopausal women found a significant reduction in vasomotor symptoms frequency and severity with venlafaxine (37.5mg/d for 1 week, then 75mg/d for 7 weeks) and with low dose oestradiol (0.5mg/d for 8 weeks) compared to placebo. Reduction of vasomotor symptoms frequency was greater in the low estradiol group (53%) compared to the venlafaxine group (48%). Reduction in vasomotor symptoms bother was found to be significant with the low oestradiol group compared to placebo, but not significant with the venlafaxine group compared to placebo.19, 26 [ES35]
In a population of postmenopausal women, six RCTs in a systematic review found the SNRI desvenlafaxine (100 or 150 mg/d for 12 weeks) significantly reduced hot flush frequency compared to placebo27 Seven RCTs (with an unclear risk of bias) identified in one Systematic Review (with a moderate risk of bias) in postmenopausal women (with at least seven moderate to severe hot flushes per day) found that 12 or more weeks of desvenlafaxine (≥100 mg/d) significantly reduced hot flush frequency and severity compared with placebo. Higher daily doses of 150mg and 200mg were associated with more adverse events and drug discontinuation.28 [ES32]
One RCT (with a moderate risk of bias) in women after breast cancer found that 4 weeks of the atypical antidepressant bupropion (300 mg/day) had no statistically significant effect on the severity of hot flushes compared with placebo.29 [ES1]
Sedatives
One RCT (with a moderate risk of bias) in women after breast cancer found that 5 weeks of SSRI/SNRI augmentation with zolpidem (10 mg/d) had no statistically significant additional effect on vasomotor symptoms compared with SSRI/SNRI augmentation with placebo.30 [ES4]
Antihypertensives
One RCT (with a low risk of bias) in women after breast cancer found that the α-2 adrenergic receptor agonist clonidine (0.1 mg/d) significantly reduced the frequency and severity of hot flushes relative to placebo.20 However, two RCTs (with a moderate risk of bias) found the reduction in vasomotor symptoms observed with clonidine was equivalent or less than the reduction observed with 75mg/d slow-release venlafaxine.22, 23 [ES5]
Anticonvulsants
One RCT (with a moderate risk of bias) in women after breast cancer found that 4-8 weeks of the γ-aminobutyric acid analogue gabapentin (900 mg/d) was associated with a reduction in hot flush frequency and severity compared with placebo.31 In addition, three RCTs (two with a moderate risk of bias and one with a high risk of bias) found that 4-12 weeks of gabapentin (900mg/d or 300mg/d) was associated with a significant reduction in hot flush frequency and severity compared to baseline.24, 32, 33 In one of these RCTs, the effect size was equivalent to that observed with venlafaxine,24 while in the other, the effect size was less than that observed with megestrol acetate.32 [ES6]