Overview of nonhormonal drug therapy for vasomotor symptoms

Nonhormonal drugs used to treat vasomotor symptoms of menopause (hot flushes and night sweats) are listed in Examples of nonhormonal medications for managing vasomotor symptoms.

Evidence for efficacy of nonhormonal drug therapy for menopausal symptoms is limited, and usually derived from short-term studies. The efficacy of nonhormonal drugs in treating hot flushes is modest; the most effective nonhormonal drug is only as effective as low-dose oral estradiol. Clonidine is the only nonhormonal drug approved by the Australian Therapeutic Goods Administration (TGA) for treatment of hot flushes, but it is less effective than other drugs.

Note: Choice of nonhormonal menopausal therapy requires individualised assessment.

Choice of nonhormonal therapy primarily depends on concurrent symptoms (eg mood disorder, disrupted sleep, pain, urinary symptoms); see Examples of nonhormonal medications for managing vasomotor symptoms for a summary of symptoms improved by various nonhormonal therapies. Also consider pattern of vasomotor symptoms, comorbidities, concurrent medications, adverse effect profile and patient preference.

For all nonhormonal drug therapies, start with a low dose and increase according to response. Onset of action is usually within 4 weeks at an effective dose but may take 8 weeks to have full effect.

Review the use of nonhormonal drugs for menopausal vasomotor symptoms every 6 to12 months. Data on long -term use are limited. Switching to another drug or using more than one drug (eg an SSRI or SNRI with gabapentin) may be necessary. If stopping any nonhormonal therapy, taper dosage gradually to avoid withdrawal symptoms. See here for advice on stopping SSRIs and SNRIs.

Table 1. Examples of nonhormonal medications for managing vasomotor symptoms
[NB1]
Drug	Reduction in hot flushes [NB2]	Other symptoms improved
Serotonin and noradrenaline reuptake inhibitors (SNRIs)
desvenlafaxine [NB3]	64%	sleep quality of life mood
venlafaxine	60%	sleep quality of life mood
Selective serotonin reuptake inhibitors (SSRIs)
escitalopram [NB3]	50 to 60%	sleep quality of life mood
citalopram [NB3]	43 to 50%	mood
paroxetine [NB4]	40 to 56%	mood sleep (with low dosages)
fluoxetine [NB3] [NB4]	36 to 50%	quality of life mood
Gabapentinoids
gabapentin	50 to 80%	sleep neuropathic pain
pregabalin	65 to 71%	sleep neuropathic pain
Other drugs
clonidine [NB5]	40%	migraine (prophylaxis)
oxybutynin	50 to 60%	overactive bladder and urge urinary incontinence
Note: NB1: Evidence for efficacy of nonhormonal drug therapy for menopausal symptoms is limited, and usually derived from short-term studies. NB2: Figures are taken from studies of each drug versus placebo; studies were not head-to-head, so efficacy of drugs is not directly comparable. NB3: These drugs are not associated with adverse effects on libido or orgasm, unlike others in their class. NB4: These drugs inhibit cytochrome P450 and may reduce the active metabolite of tamoxifen; coadministration is contraindicated. NB5: Clonidine is the only nonhormonal drug available on the Pharmaceutical Benefits Scheme (PBS) for hot flushes; see the PBS website for current information.