Which of my current medications—methylphenidate hydrochloride extended‑release 27 mg, naltrexone (DEPADE) 50 mg, norethindrone acetate/ethinyl estradiol (JUNEL) tablet, albuterol HFA 90 µg per actuation inhaler, fluticasone propionate (FLOVENT) 44 µg per actuation inhaler, fluoxetine 60 mg, bupropion sustained‑release (WELLBUTRIN SR) 150 mg, and fluticasone nasal spray (FLONASE) 50 µg—are causing my hot flashes and night sweats?

Which Medications Are Causing Your Hot Flashes and Night Sweats

The most likely culprits are fluoxetine and bupropion SR—both antidepressants in your regimen can paradoxically cause hot flashes and sweating as side effects, despite being used to treat these symptoms in other contexts. 1, 2

Primary Offenders

Fluoxetine (60 mg)

• SSRIs like fluoxetine commonly cause sweating, hot flashes, and thermoregulatory disturbances as documented side effects 1
• The mechanism involves alterations in serotonin neurotransmission affecting central temperature regulation centers 2
• Your dose of 60 mg is relatively high, which increases the likelihood of these side effects 1
• SSRIs can cause "sweating, tremors, nervousness, insomnia or somnolence, dizziness" as typical adverse effects 1

Bupropion SR (150 mg)

• Bupropion has been specifically studied and shown NOT to reduce hot flashes—in fact, it may worsen them 3, 4
• A randomized controlled trial in breast cancer survivors showed bupropion reduced hot flashes by only 6.31% compared to placebo's 30.47% reduction 4
• The mechanism relates to norepinephrine reuptake inhibition without serotonergic effects, which increases noradrenergic activity—the opposite of what helps hot flashes 3
• Bupropion is described as "activating" and should not be used in agitated patients 1

Secondary Considerations

Methylphenidate HCl ER (27 mg)

• Stimulants like methylphenidate can cause sympathomimetic effects including sweating and thermoregulatory changes 5
• The FDA label specifically mentions "sweating" as an adverse effect of methylphenidate 5
• CNS stimulants increase sympathetic nervous system activity, which can trigger hot flashes and sweating 5

Naltrexone (50 mg)

• While less commonly associated with hot flashes, opioid antagonists can affect thermoregulation
• This is a less likely contributor compared to your antidepressants

Medications Unlikely to Be Causing Symptoms

Norethindrone/Ethinyl Estradiol (Junel 1/20)

• This combined hormonal contraceptive should actually REDUCE hot flashes, not cause them 1
• Estrogens are the most effective treatment for vasomotor symptoms 6
• If anything, this medication is protecting you from worse symptoms

Inhaled Medications (Albuterol, Fluticasone)

• Inhaled bronchodilators and corticosteroids have minimal systemic absorption at therapeutic doses
• These are not associated with hot flashes or night sweats

Clinical Action Plan

Immediate steps to consider with your prescriber:

1. Evaluate whether both antidepressants are necessary—the combination of fluoxetine + bupropion may be synergistically worsening your symptoms 1, 2

2. Consider switching to a different antidepressant strategy:

   • If treating depression: Mirtazapine (7.5-30 mg at bedtime) may help both depression AND hot flashes while promoting sleep 1
   • If one antidepressant suffices: Consider discontinuing bupropion first, as it has been proven ineffective for hot flashes 3, 4

3. If hot flashes persist after medication adjustment, proven treatments include:

   • Gabapentin 900 mg/day (46% reduction in hot flash severity) 1, 2
   • Venlafaxine 75 mg/day (61% reduction) 1, 2
   • Fezolinetant (newer non-hormonal option without SSRI/SNRI side effects) 6

4. Assess your methylphenidate timing:

   • Taking it later in the day may worsen nighttime sweating 5
   • Ensure you're taking it early in the morning only 1

Important Caveat

Never abruptly discontinue fluoxetine or bupropion—both require gradual tapering over 10-14 days to prevent withdrawal symptoms including worsening hot flashes, mood changes, and physical discomfort 1, 7