Drug, Country |
Study Design |
Patient Characteristics |
Treatment, Dosage, and Duration |
Outcome Measures |
Findings and Comments |
Clonidine |
United Kingdom[27] |
MC, R, DB, PC, CO |
86 postmenopausal women with hot flashes severe enough to warrant treatment |
Clonidine 0.025 mg b.i.d. vs placebo; dosage could be titrated to a maximum of 0.075 mg b.i.d. as needed; 4 wks for each arm |
Hot-flash frequency, severity, duration; adverse effects; heart rate; blood pressure |
Placebo effect was seen. Compared with placebo, clonidine significantly decreased hot-flash frequency, severity, and duration. |
New Zealand[34] |
R, DB, PC, CO |
12 hypertensive, postmenopausal women with hot flashes for 116 mo |
Clonidine 0.0375 mg b.i.d. and 0.075 mg b.i.d. vs placebo; 2 wks for each arm |
Hot-flash frequency, severity, duration; severity of perspiration; blood pressure; adverse effects |
Placebo effect was seen. Hot-flash frequency, severity, duration were significantly decreased with higher dosage clonidine compared with placebo. No significant benefit with the low dosage. |
United Kingdom[30] |
R, DB, PC, CO |
41 postmenopausal women with severe hot flashes |
Clonidine 0.05 mg b.i.d. vs placebo; dosage could be increased to t.i.d. after 1 wk if needed; 6 wks for each arm |
Menopausal symptoms and severity |
Placebo effect was seen. No statistically significant difference between clonidine and placebo. |
Finland[32] |
R, DB, PC, CO |
40 postmenopausal women with menopausal symptoms |
Clonidine 0.025 mg b.i.d. vs placebo; dosage could be increased every 2 wks to 0.075 mg b.i.d.; 6 wks for each arm |
Hot-flash frequency, blood pressure, adverse effects |
Placebo effect was seen. No statistically significant difference between clonidine and placebo. |
Canada[28] |
MC, R, DB, PC, CO |
66 postmenopausal women with symptoms for 312 mo |
Clonidine 0.05 mg b.i.d. vs placebo; 4 wks for each arm |
Hot-flash frequency, severity, duration; adverse effects |
Placebo effect was seen. Compared with placebo group, the clonidine group had significant improvements in hot-flash frequency, severity, and duration. |
United States[29] |
SB, PC, DR |
10 postmenopausal women with frequent severe hot flashes |
Clonidine 0.05, 0.1, and 0.2 mg b.i.d. vs placebo; each dosage for 2 wks |
Subjective and objective measures of hot-flash occurrence; adverse effects. |
Small placebo effect. Compared with placebo, clonidine significantly decreased average hot-flash occurrence, with a 46% reduction from baseline in the 0.2-mg b.i.d. group. |
Australia[31] |
DB, PC, CO |
14 postmenopausal women experiencing hot flashes for 312 mo |
Clonidine 0.05 mg b.i.d. vs placebo; 4 wks for each arm |
Hot-flash and menopausal symptom frequency, blood pressure, adverse effects |
No significant differences between clonidine and placebo. |
United States[33] |
R, DB, PC |
30 postmenopausal women |
Clonidine transdermal system 0.1 mg/24 hrs vs placebo; 8-wk treatment period |
Hot-flash frequency, severity, duration; blood pressure; adverse effects |
Placebo effect was seen. Clonidine significantly decreased hot-flash frequency, severity, and duration. At 8 wks, hot flashes resolved in 4 of 12 clonidine patients who experienced a reduction in hot flashes. |
United States[24] |
R, DB, PC, CO |
110 women receiving tamoxifen for breast cancer who requested treatment for hot flashes; women experiencing ≥ 7 hot flashes/day for at least 1 mo |
Clonidine transdermal system 0.1 mg/24 hrs vs placebo; 4 wks for each arm |
Hot-flash frequency and severity; adverse effects |
Placebo effect on hot-flash frequency only. Compared with placebo, clonidine significantly decreased hot-flash frequency by about 20%, severity by about 10%. |
United States[36] |
R, DB, PC |
194 postmenopausal women receiving tamoxifen for breast cancer for at least 1 mo who reported > 1 hot flash/day |
Clonidine 0.1 mg/night vs placebo; 8-wk treatment period |
Hot-flash frequency, severity, duration; adverse effects; QOL scores |
Placebo effect seen. Compared with placebo, clonidine significantly reduced hot-flash frequency at wks 4 and 8, which is about 2.2 fewer hot flashes/day. Hot-flash duration and severity were not significantly different at wks 4, 8, or 12. |
Venlafaxine |
United States[38] |
Phase II |
28 women with history of breast cancer or men after androgen-deprivation therapy, who had ≥ 14 bothersome hot flashes/wk. Tamoxifen was allowed; 68% taking tamoxifen (25 completed study). |
Venlafaxine 12.5 mg b.i.d.; 1-wk run-in, 4-wk treatment period |
Frequency of hot flashes; hot-flash score; percentage reporting ≥ 50% reduction in hot-flash score; percentage wishing to continue venlafaxine after study |
Median hot-flash score reducedby 55%; 54% with ≥ 50% decrease in hot flashes; 64% wished to continue venlafaxine. |
United States[25] |
R, DB, PC |
191 women with history or fear of breast cancer, with ≥ 14 bothersome hot flashes/wk. Tamoxifen was allowed. |
Venlafaxine XR 37.5, 75, or 150 mg/day vs placebo. All venlafaxine groups started at 37.5 mg/day, doubling dose every 7 days in the 75- and 150-mg groups; 1-wk run-in, 4-wk treatment period. |
Average daily hot-flash activity; global QOL score; Beck Depression Inventory |
Median decrease in hot-flash scores was significantly greater in all three venlafaxine groups vs placebo (p<0.0001). No significant benefit when dose increased to 150 mg. Baseline depression unrelated to reduction in hot flashes; significant improvement in QOL score (p=0.02) with all venlafaxine doses. |
United States[41] |
Open-label, continuation phase of above trial.[25] |
102 women from above trial[25] who wanted to continue venlafaxine XR treatment |
Participants could self-titrate dosage up to 150 mg/day for optimal efficacy |
Hot-flash frequency and score |
Reduction in hot flashes in randomized trial was maintained. No further benefit in hot flashes when dose increased from 75 to 150 mg. |
SSRIs |
United States[42] |
Pilot study |
30 women with prior breast cancer, with ≥ 14 hot flashes/wk. Tamoxifen was allowed. |
Paroxetine 10 mg/day x 1 wk, then 20 mg/day x 4 wks; 1-wk run-in, 5-wk treatment period |
Hot-flash frequency and severity, depression, sleep disruption, anxiety, QOL |
67% reduction in hot-flash frequency; 75% reduction in hot-flash severity; significant improvements in depression, sleep, anxiety, and QOL. |
United States[43] |
Pilot study |
13 women with breast cancer having hot flashes of moderate severity. Tamoxifen was allowed. |
Paroxetine 10 mg/night x 3 days, then 20 mg/night; 5-wk treatment period |
Hot-flash frequency and severity, sleep quality index, depression scale, fatigue inventory |
Significant improvements in hot-flash severity. Percentage with severe hot flashes decreased from 100% to 38% (p=0.008). Improvements in fatigue, sleep quality, and depressive symptoms. |
United States[44] |
DB, R, PC, parallel group |
165 women with > 23 menopausal hot flashes/day. Patients with active cancer or receiving chemotherapy or radiation therapy were excluded; 7 and 5 patients taking concurrent tamoxifen and raloxifene, respectively. |
Paroxetine CR 12.5 mg/day vs 25 mg/day vs placebo; 1-wk run-in, 6-wk treatment period |
Hot-flash composite score |
Median reductions in hot-flash scores decreased by 37.8%, 62.2%, and 64.6% in the placebo, paroxetine CR 12.5-mg, and 25-mg groups, respectively. |
United States[45] |
DB, R, 2-period, CO |
81 women with prior breast cancer or perceived increased risk of breast cancer,with ≥ 14 bothersome hot flashes/wk. Tamoxifen and raloxifene were allowed. |
Fluoxetine 20 mg/day vs placebo; 1-wk run-in, 4 wks for each arm |
Hot-flash frequency and score |
After first treatment period, hot flashes decreased by 42% with fluoxetine vs 31% with placebo (p=0.54). Hot-flash scores decreased by 50% with fluoxetine vs 36% with placebo (p=0.35). Crossover analysis indicated reduction of 19% in daily hot flashes and 24% in hot-flash scores (p=0.01 and 0.02). |
Gabapentin |
United States[47] |
Open-label pilot study |
24 women with history of breast cancer or not wishing to take estrogen, with ≥ 14 bothersome hot flashes/wk (16 completed study). Tamoxifen was allowed; 70% taking tamoxifen. |
Gabapentin dosage titrated to 300 mg t.i.d. over 3 wks; 1-wk run-in, 4-wk treatment period |
Hot-flash frequency and score |
66% reduction in hot-flash frequency; 70% reduction in hot-flash score. |
United States[48] |
Open-label pilot study |
19 women with breast cancer receiving tamoxifen, with ≥ 1 hot flash/day (16 completed study; data available for 14) |
Gabapentin 300 mg t.i.d. for 4 wks |
Hot-flash number, duration, severity; QOL |
70% reduction in hot-flash duration (p=0.58); 42% reduction in frequency (p=0.000); 50% reduction in severity (p=0.000); 10 women reported a 21% improvement in QOL (p=0.013). |
United States[49] |
Two phases: R, DB, PC, then 5-wk open-label phase |
59 postmenopausal women with ≥ 7 hot flashes/day. Concurrent tamoxifen treatment excluded. |
Gabapentin dosage titrated to 300 mg t.i.d. over 1 wk; 2-wk run-in, 12-wk treatment followed by 5-wk open-label study in which all subjects received gabapentin dosage that could be titrated to 2700 mg/day |
Hot-flash frequency and composite score; patient global impression-of-change score, profile of mood states, sleep quality index, Short Form-36 Health Survey score |
45% reduction in hot-flash frequency and 54% reduction in hot-flash composite score were significantly greater than with placebo after 12 wks. Higher open-label gabapentin dosing was associated with 54% and 67% reductions in hot-flash frequency and score. |
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