Management of Hot Flashes

Medications for Hot Flash Reduction

The National Comprehensive Cancer Network recommends gabapentin to reduce hot flashes by 46% at 900 mg/day 1, 2
The National Comprehensive Cancer Network suggests venlafaxine reduces hot flashes by 61% at 75 mg/day 1, 2
Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and citalopram, reduce hot flashes by 50-65% 1, 3, 4
Clonidine reduces hot flashes by up to 46% 5, 6

Hot flashes are primarily associated with menopausal status due to hormonal changes 1
Breast cancer treatments, particularly tamoxifen use, cause hot flashes in 81% of patients 1

If a patient on lamotrigine is experiencing hot flashes, investigate other causes, including concurrent medications such as tamoxifen or aromatase inhibitors 3
Other medical conditions affecting thermoregulation should also be considered as potential causes of hot flashes 2

The National Comprehensive Cancer Network recommends avoiding paroxetine and fluoxetine in patients taking tamoxifen concurrently, as they interfere with tamoxifen metabolism through CYP2D6 inhibition 7, 8
The National Comprehensive Cancer Network suggests that venlafaxine and citalopram have minimal effects on tamoxifen metabolism and are preferred in this population 7, 8

Endoxifen, the active metabolite of tamoxifen, causes hot flushes due to its anti-estrogenic effects, as established by the National Comprehensive Cancer Network 9

The American College of Clinical Pharmacology notes that certain antidepressants, such as paroxetine and fluoxetine, which inhibit CYP2D6, can interact with tamoxifen, but clozapine does not contribute to hot flushes 10, 9

Potent CYP2D6 inhibitors, such as paroxetine and fluoxetine, decrease plasma endoxifen levels by interfering with the enzymatic conversion of tamoxifen to endoxifen, as reported by the National Comprehensive Cancer Network 10, 9

The National Comprehensive Cancer Network suggests that if a patient on tamoxifen experiences hot flushes, this may indicate adequate drug metabolism and therapeutic effect 9

The National Comprehensive Cancer Network recommends starting with gabapentin 900 mg/day as the first-line alternative, which reduces hot flash severity by 46% and has no drug interactions, no sexual dysfunction, and no withdrawal syndrome 11, 12
Gabapentin dosing should start at 300 mg/day and titrate up to 900 mg/day over 1-2 weeks, reducing hot flash severity by 46-49% at 900 mg/day compared to 15-21% with placebo 11, 13
Venlafaxine is a second choice, with dosing starting at 37.5 mg daily and increasing to 75 mg daily after 1 week, reducing hot flashes by 61% at 75 mg/day compared to 27% with placebo 12, 14
The American Society of Clinical Oncology suggests that if a patient is on tamoxifen, venlafaxine is preferred over paroxetine because it has minimal effects on CYP2D6 and doesn't interfere with tamoxifen metabolism 12, 14
Gabapentin has advantages over other options, including no drug interactions, no sexual dysfunction, and no withdrawal syndrome, making it particularly useful when given at bedtime for patients with sleep disturbance from hot flashes 11, 12

The National Comprehensive Cancer Network recommends assessing if a patient is on tamoxifen or other medications, and choosing gabapentin first, or venlafaxine/citalopram as alternatives, and never using paroxetine or fluoxetine if on tamoxifen 12, 14
If a patient has sleep disturbance, gabapentin at bedtime is ideal due to its somnolence side effect 11
If a patient has bipolar disorder/manic depression, SSRIs/SNRIs should be avoided due to the risk of inducing mania 14

The Journal of the National Comprehensive Cancer Network suggests considering adding weight loss if overweight/obese, cognitive behavioral therapy, or acupuncture, which has been shown equivalent to or better than venlafaxine or gabapentin in some studies 11