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Centrally active nonhormonal hot flash therapies.

Abstract

Given the problems associated with hormonal therapy, and the prominent problem of hot flashes in menopausal women, there is a need for nonhormonal agents to alleviate hot flashes. Several compounds that appear to act on the central nervous system have been investigated. Potential mechanisms for their effects on hot flashes have been described. Bellergal (no longer available on the US market, where it was known as Bellergal-S), a combination preparation sedative that consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory alkaloids of belladonna, is an old agent that was popular approximately 20 years ago; however, there is limited suggestion of efficacy for this agent. Clonidine, an older antihypertensive drug, is another centrally active agent that has been studied. Randomized trials have demonstrated that it clearly works for reducing hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from this agent limits its utility in the clinic. Methyldopa is another centrally active agent that has been studied but to a more limited degree. It appears to have minimal efficacy and too much toxicity to make it clinically useful. Anecdotal observations from a number of sources suggested that newer antidepressants can alleviate hot flashes. This led to pilot trials of venlafaxine and paroxetine, with results suggesting benefit from both drugs. Subsequently, randomized, placebo-controlled, double-blind clinical trials of venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical trials demonstrated statistically significant reductions in hot flashes with these newer antidepressants compared with placebo. Pilot trials of citalopram and mirtazapine, 2 other newer antidepressants, have also suggested efficacy. Toxicity evaluations have suggested that these agents are, again, well tolerated by the majority of patients. A recent trial, however, was unable to demonstrate any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations also suggested that gabapentin was helpful for alleviating hot flashes. This led to pilot trials that again suggested efficacy. Subsequently, 2 large placebo-controlled, randomized, double-blind clinical trials were conducted. Both of these demonstrated statistically significant efficacy for gabapentin compared with a placebo. This drug is relatively well tolerated by most patients. Thus, centrally active nonhormonal agents clearly do decrease hot flashes in women. The most efficacious and clinically appropriate agents for use are newer antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity of these agents is ongoing.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. loprinzi.charles@mayo.edu

    ,

    Source

    The American journal of medicine 118 Suppl 12B: 2005 Dec 19 pg 118-23

    MeSH

    Amines
    Antidepressive Agents
    Antihypertensive Agents
    Belladonna Alkaloids
    Clonidine
    Cyclohexanecarboxylic Acids
    Drug Combinations
    Ergotamines
    Female
    Gabapentin
    Hot Flashes
    Humans
    Menopause
    Methyldopa
    Methysergide
    Phenobarbital
    gamma-Aminobutyric Acid

    Pub Type(s)

    Consensus Development Conference, NIH
    Journal Article

    Language

    eng

    PubMed ID

    16414336

    Citation

    Loprinzi, Charles L., et al. "Centrally Active Nonhormonal Hot Flash Therapies." The American Journal of Medicine, vol. 118 Suppl 12B, 2005, pp. 118-23.
    Loprinzi CL, Stearns V, Barton D. Centrally active nonhormonal hot flash therapies. Am J Med. 2005;118 Suppl 12B:118-23.
    Loprinzi, C. L., Stearns, V., & Barton, D. (2005). Centrally active nonhormonal hot flash therapies. The American Journal of Medicine, 118 Suppl 12B, pp. 118-23.
    Loprinzi CL, Stearns V, Barton D. Centrally Active Nonhormonal Hot Flash Therapies. Am J Med. 2005 Dec 19;118 Suppl 12B:118-23. PubMed PMID: 16414336.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Centrally active nonhormonal hot flash therapies. AU - Loprinzi,Charles L, AU - Stearns,Vered, AU - Barton,Debra, PY - 2006/1/18/pubmed PY - 2006/1/24/medline PY - 2006/1/18/entrez SP - 118 EP - 23 JF - The American journal of medicine JO - Am. J. Med. VL - 118 Suppl 12B N2 - Given the problems associated with hormonal therapy, and the prominent problem of hot flashes in menopausal women, there is a need for nonhormonal agents to alleviate hot flashes. Several compounds that appear to act on the central nervous system have been investigated. Potential mechanisms for their effects on hot flashes have been described. Bellergal (no longer available on the US market, where it was known as Bellergal-S), a combination preparation sedative that consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory alkaloids of belladonna, is an old agent that was popular approximately 20 years ago; however, there is limited suggestion of efficacy for this agent. Clonidine, an older antihypertensive drug, is another centrally active agent that has been studied. Randomized trials have demonstrated that it clearly works for reducing hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from this agent limits its utility in the clinic. Methyldopa is another centrally active agent that has been studied but to a more limited degree. It appears to have minimal efficacy and too much toxicity to make it clinically useful. Anecdotal observations from a number of sources suggested that newer antidepressants can alleviate hot flashes. This led to pilot trials of venlafaxine and paroxetine, with results suggesting benefit from both drugs. Subsequently, randomized, placebo-controlled, double-blind clinical trials of venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical trials demonstrated statistically significant reductions in hot flashes with these newer antidepressants compared with placebo. Pilot trials of citalopram and mirtazapine, 2 other newer antidepressants, have also suggested efficacy. Toxicity evaluations have suggested that these agents are, again, well tolerated by the majority of patients. A recent trial, however, was unable to demonstrate any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations also suggested that gabapentin was helpful for alleviating hot flashes. This led to pilot trials that again suggested efficacy. Subsequently, 2 large placebo-controlled, randomized, double-blind clinical trials were conducted. Both of these demonstrated statistically significant efficacy for gabapentin compared with a placebo. This drug is relatively well tolerated by most patients. Thus, centrally active nonhormonal agents clearly do decrease hot flashes in women. The most efficacious and clinically appropriate agents for use are newer antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity of these agents is ongoing. SN - 1555-7162 UR - https://www.unboundmedicine.com/medline/citation/16414336/Centrally_active_nonhormonal_hot_flash_therapies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9343(05)00903-4 DB - PRIME DP - Unbound Medicine ER -