Gabapentin is an anticonvulsant and is commonly used to treat neuropathic pain [15]. While not FDA approved for the management of VMS, it has been shown to be more effective than placebo in reducing the frequency of menopausal VMS. Gabapentin 900 mg per day was found to have a 45 % reduction in hot flash frequency and a 54 % reduction in composite score (frequency and severity) of VMS in a small RCT [54]. Both treatment effects were statistically significant when compared to placebo with 29 % and 31 % reductions, respectively [54]. In another small RCT, gabapentin 600 mg was shown to reduce severe-intensity and severe-frequency VMS by 60.6 % and 58.9 %, respectively [55].

Potential side effects include dizziness and drowsiness, which may resolve after 2 weeks of therapy. In addition, weight gain may be seen, and any anticonvulsant may increase suicidal thoughts or behavior [6]. It is recommended to avoid antacid use within two hours of dosing, due to decreased absorption, and to taper the dose on discontinuation [1]. Risks and benefits of treatment and therapy options should be reevaluated every 6–12 months due to limited data on long-term use [7].

Pregabalin is a newer compound that works similarly to gabapentin and may be effective in the treatment of VMS. A randomized controlled trial using pregabalin 75 mg twice a day showed a 65 % decrease in VMS score compared to 50 % with placebo, which may be similar to the efficacies of gabapentin and other SSRI/SNRIs in the treatment of VMS [56].

There are no concerns regarding use of gabapentin in the setting of breast cancer or tamoxifen use, and gabapentin may therefore be considered as an effective option when hormone therapy is not desirable. A trial of gabapentin can safely be considered for the patient above and holds promise of reducing the magnitude of symptom burden to an appreciable degree.

Clonidine is an antihypertensive agent that may have a mild effect on VMS. It is thought that clonidine may decrease VMS by reducing peripheral vascular reactivity, though evidence is contradictory regarding its efficacy [6]. A small RCT showed clonidine and venlafaxine have similar efficacy in the reduction of VMS, although a more immediate reduction of hot flash scores was seen in the venlafaxine group [57]. A meta-analysis of ten RCTs demonstrated no improvement in the severity of VMS in 6 of the 10 RCTs, though improvement was seen in the remaining four RCTs [58].

Potential side effects may include hypotension, difficulty sleeping, dry mouth, constipation, itchiness (with use of patch), and drowsiness [6]. Nonetheless, it is generally well tolerated at low doses. Dosing formulations include 0.05 mg twice daily to 0.1 mg twice daily or the clonidine patch, which delivers 0.1 mg daily. Weaning the dose on discontinuation is recommended to avoid rebound hypertension and other side effects [1].

Clonidine is a potential option for the patient above because it is a non-hormonal therapy and there are no concerns for use with a history of breast cancer or being on tamoxifen therapy. However, the efficacy of clonidine is less than that of other non-hormonal options, including SSRIs/SNRIs and gabapentin. Therefore, it would likely not be the most effective selection for the patient above. It should be considered a second-line approach, in the event that trial of gabapentin or a non-paroxetine SSRI is contraindicated or fails to offer significant benefit.

Many alternative and complementary therapies have been investigated for the treatment of VMS of menopause with inconsistent results [6]. On review of evidence in the English literature, there has been no difference between placebo and any of the herbal remedies such as black cohosh, dong quai root, evening primrose oil, kava kava, ginseng root, vitamin E, or omega-3 fatty acids [1]. There is a high placebo effect observed when studying the efficacy of therapies for VMS, which may obscure the interpretation of results.

In some studies, phytoestrogens, which are plant-derived substances with estrogenic biologic activity, such as soybean isoflavones, have shown a statistically significant decrease in VMS compared to placebo. A systematic literature review from Eden et al. in 2012 concluded isoflavones are slightly superior than placebo, but the degree of effect was small and not clinically significant [59]. Dang gui bu xue tang, a Chinese herb, was found to be more effective than placebo in one study in the treatment of mild VMS [60]. Notably, caution is advised when considering use of CAM agents in the setting of hormone-sensitive cancers, as implications for tumor recurrence and risk for metastases are entirely unclear [1].

In summary, CAM strategies would not be recommended for our patient due to lack of evidence displaying efficacy, possibility for estrogenic effects with some agents such as phytoestrogens, and unquantifiable implications for her personal risk for breast cancer recurrence.

Eszopiclone is a hypnotic medicine that has been shown to decrease nocturnal VMS [1] as well as improve symptoms of depression and anxiety, therefore improving overall quality of life in peri- and postmenopausal women [61]. Eszopiclone 1–3 mg/day is commonly used in breast cancer survivors and is especially ideal for patients with sleep initiation difficulties due to short half-life of ~1 h [62].

Stellate ganglion block (SGB), a minimally invasive intervention, was shown to decrease VMS by 45–90 % in four uncontrolled, open-label studies [63–66]. It involves an injection of a local anesthetic into the stellate ganglion at the level of the sixth cervical vertebra. SGB shows great potential as a means of reducing the number of hot flushes and night awakenings in breast cancer survivors [67, 68]. In addition, SGB may be an effective treatment for breast cancer-related lymphedema [69]. Overall, efficacy data are variable, and more clinical trials need to be performed to further determine the efficacy and safety profile of this novel technique in the treatment of VMS [70].

An ideal treatment strategy for a woman with moderate or severe VMS should decrease VMS without detriment to breast tissue and the endometrium and additionally have favorable effects on the vaginal mucosa, increase bone mass density, and decrease the risks of coronary heart disease (CHD), venous thromboembolism (VTE), and stroke. There are many special considerations and risks involved in the management approach for treating VMS in breast cancer survivors. Treatment strategies should be targeted to best treat the patient based on their unique risk profile.

After detailed discussion of the available options and review of individualized risks versus benefits for each strategy, the patient opted for a trial of gabapentin while initiating lifestyle modifications. If gabapentin therapy had failed, a trial on a specific SSRI/SNRI (a weak inhibitor of the CYP2D6 pathway such as venlafaxine or citalopram) was planned as an appropriate next step with trial of MHT as a last resort in the event that all non-hormonal options failed to provide relief. The patient verbalized being comfortable with the outlined systematic approach and was initiated on gabapentin 300 mg daily with significant relief of VMS and improvement in nocturnal sleep. She likewise found it easier to focus during the day, and her work performance was restored. She continued with tamoxifen treatment for breast cancer without complications or undue adverse effects. She continued gabapentin therapy for one and a half years, at which time she was weaned off without difficulty or side effects.