title: Adverse effects of non-hormonal pharmacological interventions in breast cancer survivors, suffering from hot flashes: A systematic review and meta-analysis.
abstract: To access frequency and severity of adverse effects (AE) of non-hormonal drugs (NHD) for hot flashes in breast cancer survivors compared to controls and analyze adverse-effect risk by reviewing published randomized trials.
  
  
  
  Cochrane Central Register for Controlled Trials, Embase, Medline, PsycINFO and PubMed databases were searched. Trials were included where participants were survivors of breast cancer suffering from hot flashes, treatment included self-administered venlafaxine, gabapentin or clonidine, and AE were reported. AE frequency and severity were graded. A meta-analysis of ten trials with sub-group analyses was conducted.
  
  
  
  Forty-nine studies were identified, and 12 were included. A total of 1467 participants experienced 772 adverse effects, 81 % (n = 627) in the treatment group and 19 % (n = 145) in the control group. Sixty-seven percent of AE was graded as mild and 33 % as moderate. The frequency of AE for NHD was overall significant compared to placebo. Sub-group analysis indicated that AE frequency and severity increased at higher doses of venlafaxine and gabapentin compared to placebo.
  
  
  
  The odds for experiencing AE was significantly higher in patients randomized to high-dose NHD than those randomized to controls, including placebo, low-dose medication and acupuncture. These therapies should be considered as a potential treatment alternative.
authors.affiliation: Department of Anesthesia, Pain Clinic, Vestfold Hospital Trust, 3116, Tonsberg, Norway. jill.hervik@siv.no.
authors.forename: Jill Brook
authors.identifier: 0000-0001-6647-8072
authors.initials: JB
authors.lastname: Hervik
authors.affiliation: The National Research Center in Complementary and Alternative Medicine (NAFKAM) Department of Community Medicine, Faculty of Health Science, UiT The Arctic University of Norway, 9037, Tromso, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Stub
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy*; D000073116:Cancer Survivors; D003131:Combined Modality Therapy; D005260:Female; D019584:Hot Flashes / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Adverse effects; Breast cancer; Hot flashes; Non-hormonal drugs