Nonhormonal pharmacotherapy for Hot Flashes:
For women with moderate to severe hot flashes who are not
candidates for hormone therapy based upon their breast cancer, CHD or VTE risk
are appropriate candidates for
nonhormonal medication :
nonhormonal medication :
The best studied agents with positive results include SSRIs,
serotonin-norepinephrine reuptake inhibitors (SNRIs), anti-epileptics,
clonidine ,oxybutynin and centrally acting drugs.
SSRIs/SNRIs —
The most effective pharmacologic alternatives to estrogen include
some of the antidepressants in the SSRI and SNRI classes.
●Although no head-to-head trials have been performed, indirect
comparisons suggest that venlafaxine, desvenlafaxine, paroxetine, citalopram
and escitalopram have a similar modest benefit for hot flashes.
●Low dose paroxetine (7.5 mg/day) is often used as the first
choice of SSRIs/SNRIs, since this is the only agent that has received approval
by the US Food and Drug Administration for treatment of Hot flashes.
However, paroxetine should be avoided in women taking tamoxifen .
However, paroxetine should be avoided in women taking tamoxifen .
●Many authors suggests citalopram as the first choice of
SSRI/SNRIs. The optimal dose of this agent appears to be 20 mg, and side
effects are minimal and similar to those of the other SSRI/SNRIs .
●It is preferable to avoid sertraline and fluoxetine, because
neither has a clinically important effect on hot flashes.
●While venlafaxine is well studied, it has more acute toxicity
(nausea and vomiting) and can have significant withdrawal symptoms in
occasional patients .
If it is used, we suggest the sustained-release preparation starting with 37.5 mg/day for one week, increasing to 75 mg/day after the first week, to reduce the incidence of initial nausea .
When patients stop therapy, they should be instructed to decrease to 37.5 mg for one week before stopping altogether.
If it is used, we suggest the sustained-release preparation starting with 37.5 mg/day for one week, increasing to 75 mg/day after the first week, to reduce the incidence of initial nausea .
When patients stop therapy, they should be instructed to decrease to 37.5 mg for one week before stopping altogether.
●Desvenlafaxine, the main active metabolite of venlafaxine, has
similar benefits for hot flashes and a similar side effect profile as
venlafaxine .
●While SSRIs or SNRIs are preferred as first-line therapy for
most women, gabapentin may be a better option in some, for example, women whose
hot flashes are primarily at night .
●As paroxetine blocks the conversion of tamoxifen to active
metabolites through CYP2D6, it should not be used in women on tamoxifen.
Venlafaxine minimally blocks this enzyme and is preferred in women taking this
antiestrogen.
●Since hot flashes gradually subside without therapy in most,
but not all, postmenopausal women, any drug can be gradually tapered after a
reasonable period of time(one to two years would be an appropriate time).
●For women taking nonhormonal pharmacotherapies, it is advisable
to try another pharmacologic agent if one therapy is ineffective or not
tolerated.
If one SSRI/SNRI is tried but does not work, a second one could be tried before moving to another class of drug.
If the SSRI/SNRI class of drugs is ineffective, a trial of gabapentin would be reasonable. Other options would include pregabalin or clonidine.
If one SSRI/SNRI is tried but does not work, a second one could be tried before moving to another class of drug.
If the SSRI/SNRI class of drugs is ineffective, a trial of gabapentin would be reasonable. Other options would include pregabalin or clonidine.
●Gabapentin –
Gabapentin is an anti-epileptic drug , however it is also effective for hot flashes in some women.
In women whose hot flashes occur primarily at night, it is found that a single dose of gabapentin given at bedtime often relieves the hot flashes .
It is suggested to start with 100 mg one hour before bedtime and increasing by 100 mg every three nights until relief of hot flashes, side effects, or a maximum of 900 mg is reached .(Often relief is achieved with a dose of 300 mg)
Gabapentin is an anti-epileptic drug , however it is also effective for hot flashes in some women.
In women whose hot flashes occur primarily at night, it is found that a single dose of gabapentin given at bedtime often relieves the hot flashes .
It is suggested to start with 100 mg one hour before bedtime and increasing by 100 mg every three nights until relief of hot flashes, side effects, or a maximum of 900 mg is reached .(Often relief is achieved with a dose of 300 mg)
●Pregabalin – Pregabalin, like gabapentin, is used for a number
of indications, including seizures, neuropathic pain, and postherpetic
neuralgia and is effective in relieving hot flashes. The drug at the
recommended dose of 150 to 300 mg is reasonably tolerated.
●Clonidine – Clonidine, a centrally active alpha-2 adrenergic
agonist & is now used infrequently, given its side-effect profile (dry
mouth, dizziness, constipation, and sedation) and the availability of other
effective nonhormonal medications for hot flashes.
If used (ie, if all other options are ineffective or not tolerated), the transdermal preparations might be superior to oral tablets because of stable blood levels. We suggest starting with the TTS-1 (transdermal therapeutic system 1) patch, which delivers 0.1 mg per day, and increasing to TTS-2 (0.2 mg/day) and TTS-3 (0.3 mg/day) based on efficacy and side effects. Oral clonidine, at a dose of 0.1 to 1 mg/day in divided doses, may also be used .
If used (ie, if all other options are ineffective or not tolerated), the transdermal preparations might be superior to oral tablets because of stable blood levels. We suggest starting with the TTS-1 (transdermal therapeutic system 1) patch, which delivers 0.1 mg per day, and increasing to TTS-2 (0.2 mg/day) and TTS-3 (0.3 mg/day) based on efficacy and side effects. Oral clonidine, at a dose of 0.1 to 1 mg/day in divided doses, may also be used .
●Oxybutynin – Oxybutynin, an oral anticholinergic agent used
primarily for overactive bladder are more effective than placebo for relief of
hot flashes but are not used .
New Research:
Neurokinin 3 receptor antagonist —
The thermoregulatory center in the hypothalamus is innervated by
kisspeptin/neurokinin B/dynorphin (KNDy) neurons that are stimulated by
neurokinin B (NKB) and inhibited by estrogen .
After menopause, estrogen declines and NKB signaling is increased. It has been proposed that this results in unregulated KNDy neuron activation and vasomotor symptoms .
Antagonism of NKB signaling at its receptor (neurokinin 3 receptor [NK3R]) has been studied as an alternative to MHT for management of hot flashes, an approach that appears to be promising.
After menopause, estrogen declines and NKB signaling is increased. It has been proposed that this results in unregulated KNDy neuron activation and vasomotor symptoms .
Antagonism of NKB signaling at its receptor (neurokinin 3 receptor [NK3R]) has been studied as an alternative to MHT for management of hot flashes, an approach that appears to be promising.
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