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Hot Flashes in Palliative Care Part 2
Authors: Carolyn Lefkowits, MD and Robert Arnold MD
Background: Hot flashes (‘flushes’) are a common anddisabling symptom, particularlywhen caused by cancer treatment. Assessment of hotflashes was reviewed in April’s newsletter. This month’snewsletter will cover procedural and pharmacologicaltreatment of hot flashes.
Pharmacologic Treatments: The most well studiedpopulations with cancer treatment – related hot flashesare patients with breast and prostate cancer. Efficacyof pharmacologic treatments seems to be independent ofthe patient’s sex. The average improvement in hot flashesassociated with placebo is around 25%, so improvementsassociated with pharmacologic therapies are typicallycompared to placebo.
• Hormonal Therapies: In general, hormonaltherapies are more effective than non-hormonaltherapies. Estrogen and progestins are effective inboth men and women. Estrogen and progestins arecontraindicated in women with a history of breastcancer because of increased risk of recurrence. Inmen, estrogen therapy is associated with breasttenderness and gynecomastia. Common sideeffects of progestins include weight gain, nausea,and edema. Both estrogen and progestins areassociated with some risk of thromboembolicand cardiovascular disease. Cyproterone, andantiandrogen (not available in US), also works withmen, but may interfere with androgen deprivationtherapy for prostate cancer.
• Antidepressants: The mechanism of by whichselective serotonin reuptake inhibitors (SNRIs)reduce hot flashes is thought to be relatedto the role of serotonin and norepinephrinein thermoregulation. Randomized controlledtrials have supported the efficacy of fluoxetine,paroxetine, sertraline, citalopram, escitalopram,venlafaxine, and desvenlafazine. Many (SSRIs)can interfere with the effectiveness of tamoxifenas they inhibit cytochrome P450 enzyme CYP2D6which is involved in tamoxifen metabolism.
Paroxetine and fluoxetine are the strongestCYP2D6 inhibitors, followed, in order of decreasingpotency of inhibition, by seratraline, Citalopram,and venlaxifine. Al SSRIs have similar side effectprofiles, including sexual dysfunction, drowsiness,weight gain, insomnia, anxiety, dizziness, andheadache.
• Gabapentin: A pooled analysis of 3 trials showedreduction in hot flashes of 35-38% over placeboat doses of 900-2400 mg/day (2). The mechanismby which gabapentin reduces hot flashes is clear.
Adding an SSRI to gabapentin has not been shownto be additionally effective.
• Clonidine: Appears to be marginally, butstatistical y significantly, better than placebo, withside effects including dry mouth, drowsiness, andconstipation.
Procedural: Pilot data suggest that a stellate-ganglion block(once or twice) showed a decrease in the total number ofhot flashes per week, as well as number of very severe hotflashes per week over a three month period (5). Thoughstandard procedural risks apply, there were no reportedadverse effects from the block in this smal series.
Summary: It is reasonable to use either gabapentin or anSSRI/SNRI as first line treatment. Of the SSRI/SNRI group,venlafaxine and citalopram are among the most effective andhave a low risk of interfering with tamoxifen. Paroxetine andfluoxetine should be avoided in patients on tamoxifen.
References: 1. Sloan JA, Loprinzi CL, Novotny PJ, Methodologic Lessons Learned from Hot Flashes2. Loprinzi CL, Sloan J, Stearns V, Newer antidepressants and gabapentin for hot flashes; an . individual patient pooled analysis.
3. Loprinzi CL, Barton DL, Qin R, Nonestrogenic management of hot flashes.
4. Goldberg RM, Loprinzi CL, O’Fal on JR, Transdermal clonidinefor ameliorating tamoxifen induced hot flashes. 5. Lipov EG, Joshi JR, Sanders S, Effects of stellate-ganglion block on hot flashes and night awakenings in survivors of breast cancer: a pilot study6. Fisk J, managing hot flashes in men after prostate cancer – a systematic review.
7. Loibl S, Lintermans A, Dieudonne AS, Neven P, Management of menopausal symptoms in breast cancer patients.
8. Rada g, Capurro D, Pantoja T, Non hormonal interventions for hot flushes in women with a history of breast cancer.
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