Table 3. Main studies performed on gabapentin for HFs treatment.

Type of patients	Author, year of publication and type of study, number of patients (N)	Type of treatment	Type of measurement	Main results	Adverse events (AEs)
Healthy women	Guttuso et al [29] Randomised, double-blind, placebo-controlled trial N = 59	1) 900 mg oral gabapentin for 12 weeks versus placebo 2) Extension phase: gabapentin up to 2,700 mg/day	Diary for HFs severity and frequency, composite score including both	1) 45% HFs frequency and 54% HFs score reduction from baseline, compared with 29% (p < 0.02) and 31% (p < 0.01), respectively, for placebo 2) With the higher dose, further reduction of HFs (54% in HF frequency and 67% in the score)	- Somnolence, dizziness, rash - In 50% of gabapentin patients, at least one AE (versus 27.6% for placebo) - 13% withdrawal rate in the gabapentin group for AEs (versus 3% for placebo)
	Butt et al [30] Randomised, double-blind, placebo-controlled trial N = 200	900 mg gabapentin for 4 weeks	Diary for HFs severity and frequency, score including both	51% HFs score and 45.7% frequency reduction versus placebo (26.5% and 24.7%, respectively, p < 0.001)	More dizziness, unsteadiness and drowsiness in the gabapentin group versus placebo in the first treatment week, with later AEs reduction
Breast cancer survivors	Pandya et al [31] Randomised, double-blind, placebo-controlled, multi-institutional trial N = 420 BCSs	300 mg/d or 900 mg/d gabapentin versus placebo over 8 weeks	Diary for HFs severity, frequency and duration	44% HFs frequency and 46% severity reduction in the 900 mg gabapentin group versus placebo (15% for both, p < 0.0001) → gabapentin is effective in HFs control at a dose of 900 mg/day	- Withdrawal rate of 12% at 4 weeks and 17% at 8 weeks for AEs - Significant worsening of appetite
	Biglia et al [32] RCT N = 115 BCSs	Oral gabapentin 900 mg/day (N = 60) versus vitamin E 800 IU/day (N = 55) for 12 weeks	1) For HFs: daily HFs diary 2) For sleep quality: PSQI 3) For other menopausal Symptoms: MRS 4) For QoL: SF-36 Health Survey	1) HFs frequency and score decreased by 57% and 67%, respectively, (p < 0.05) in the gabapentin group 2) Improvement in quality of sleep (PSQI score reduction: 21.33%, p < 0.05).	The prescribed treatment with gabapentin was never started by 28.3% of BCSs and was interrupted by 28% of BCSs for AEs (dizziness and somnolence)

HFs = hot flushes; AEs: adverse events; BCSs = breast cancer survivors; PSQI = Pittsburgh Sleep Quality Index; MRS = Menopause Rating Scale; QoL = quality of life