Could the new excessive sweating in my adult female patient, who is on atomoxetine, buspirone, propranolol, tizanidine, prazosin, aripiprazole, quetiapine and recently started buprenorphine/naloxone (Suboxone), be caused by the Suboxone?

Suboxone is a Likely Cause of the Excessive Sweating

Yes, the buprenorphine/naloxone (Suboxone) is very likely causing your patient's excessive sweating, though several other medications in her regimen can also contribute to hyperhidrosis and should be considered as potential culprits or exacerbating factors.

Primary Suspect: Suboxone (Buprenorphine/Naloxone)

The temporal relationship between Suboxone initiation and symptom onset strongly suggests causality 1. Opioids, including buprenorphine, are well-documented causes of drug-induced hyperhidrosis 2. The mechanism involves action at the hypothalamus, spinal thermoregulatory centers, sympathetic ganglia, or the eccrine-neuroeffector junction 2.

• Opioid withdrawal can cause sweating, but this patient is receiving Suboxone (an opioid agonist), making withdrawal unlikely unless she was previously on higher-dose full opioid agonists 1
• Opioid-induced sweating is a recognized adverse effect distinct from withdrawal, occurring during active opioid therapy 1, 2

Contributing Medications to Consider

Your patient is on multiple medications known to cause hyperhidrosis, creating a polypharmacy situation that compounds risk:

Atomoxetine (Norepinephrine Reuptake Inhibitor)

• Atomoxetine commonly causes sweating as an adverse effect through noradrenergic mechanisms 1
• This medication may be synergistically contributing to the sweating burden

Aripiprazole

• Aripiprazole has been specifically reported to cause hyperhidrosis in case reports 3
• The mechanism likely involves dopaminergic and serotonergic modulation affecting thermoregulatory centers 3

Quetiapine

• Antipsychotic medications can cause sweating through central thermoregulatory effects 1
• Combined with aripiprazole, the antipsychotic burden may amplify sweating symptoms

Buspirone (Serotonergic Agent)

• As a partial serotonin agonist, buspirone can contribute to serotonergic-mediated sweating 1

Critical Safety Consideration: Serotonin Syndrome Risk

This patient is at significant risk for serotonin syndrome given the combination of atomoxetine (noradrenergic), buspirone (serotonergic), aripiprazole (partial serotonin agonist), and quetiapine (serotonergic properties). 1, 4

• Serotonin syndrome presents with sweating, tremor, diarrhea, delirium, neuromuscular rigidity, and hyperthermia 1
• The American Gastroenterological Association emphasizes that polypharmacy with multiple serotonergic agents substantially increases this risk 4
• Evaluate for other signs of serotonin syndrome: tremor (she's on propranolol which may mask this), agitation, hyperreflexia, myoclonus, or confusion 1

Diagnostic Approach

Rule out secondary causes before attributing sweating solely to medications:

1. Assess for drug withdrawal: Given the complex medication regimen, ensure no recent discontinuations of benzodiazepines, alcohol, or other sedatives that could cause withdrawal-related diaphoresis 1

2. Evaluate for serotonin syndrome: Check for tremor, hyperreflexia, agitation, confusion, or fever 1

3. Consider neuroleptic malignant syndrome: Though rare, the combination of aripiprazole and quetiapine warrants vigilance for muscle rigidity, fever, and elevated creatinine phosphokinase 1

4. Exclude medical causes: Thyroid dysfunction, infection, malignancy, or autonomic dysfunction 5

Management Algorithm

Step 1: Confirm Temporal Relationship

• Document precisely when sweating began relative to Suboxone initiation 1
• The lag time between drug initiation and symptom onset averages 21 days (median 8 days) for drug-induced effects 1

Step 2: Trial Suboxone Dose Reduction

• Reduce the Suboxone dose by 25-50% as the first intervention 2
• Monitor for 1-2 weeks; sweating may take 1-7 days to improve after dose adjustment 1
• Ensure adequate opioid coverage to prevent withdrawal symptoms 1

Step 3: If Dose Reduction Fails or Is Inappropriate

Consider medication substitution or discontinuation:

• Switch to methadone if opioid maintenance therapy must continue, as individual responses to different opioids vary 1
• Discontinue aripiprazole given case reports of aripiprazole-induced hyperhidrosis 3
• Evaluate necessity of atomoxetine, as noradrenergic agents commonly cause sweating 1

Step 4: Pharmacological Management of Sweating

If medications cannot be adjusted and sweating persists:

• Benztropine (anticholinergic): Blocks muscarinic receptors at sweat glands 6, 2

  • Start 0.5-1 mg daily
  • Caution: May worsen cognitive effects in combination with quetiapine and other anticholinergics

• Cyproheptadine (antihistamine with antiserotonergic properties): 4 mg 2-3 times daily 6

  • Dual benefit if serotonergic excess is contributing
  • May cause sedation

• Topical glycopyrrolate for craniofacial sweating if localized 5

Step 5: Non-Pharmacological Options

• Topical aluminum chloride solution for axillary or palmar sweating 5
• Cooling strategies: External water application, air conditioning, moisture-wicking clothing 2

Common Pitfalls to Avoid

1. Do not abruptly discontinue Suboxone without a taper plan, as this will precipitate opioid withdrawal with severe sweating, tachycardia, hypertension, and anxiety 1

2. Do not add anticholinergics without considering polypharmacy burden: This patient is already on multiple CNS-active medications; adding benztropine increases fall risk, confusion, and urinary retention 2

3. Do not overlook the possibility of serotonergic excess: The combination of atomoxetine, buspirone, aripiprazole, and quetiapine creates substantial serotonergic activity 4

4. Do not assume sweating is benign: Progressive sweating with altered mental status, rigidity, or fever requires immediate evaluation for serotonin syndrome or neuroleptic malignant syndrome 1

Recommended Action Plan

Immediate steps:

1. Reduce Suboxone dose by 25-50% 2
2. Comprehensive medication review to identify deprescribing opportunities, particularly aripiprazole 4, 3
3. Monitor for serotonin syndrome symptoms over the next 2 weeks 1

If sweating persists after 2 weeks:

1. Consider switching from Suboxone to methadone 1
2. Trial cyproheptadine 4 mg three times daily (addresses both sweating and potential serotonergic excess) 6
3. Reassess need for atomoxetine and aripiprazole 1, 3

The patient's quality of life is significantly impacted by this distressing symptom 5, and the temporal relationship to Suboxone initiation makes it the most likely culprit, though the polypharmacy burden substantially complicates management 4.