Which medications could cause this?

Medications That Can Cause Obstructive Sleep Apnea (OSA)

Direct OSA-Worsening Medications

Benzodiazepines, opioids, testosterone, and muscle relaxants directly worsen sleep apnea through respiratory depression and should be avoided or used with extreme caution in patients with OSA. 1

Central Nervous System Depressants

• Benzodiazepines cause mixed apnea (both obstructive and central) by depressing respiratory drive, with studies showing decreased minimum oxygen saturation and increased apnea-hypopnea index (AHI) 1
• Opioids and opiates produce respiratory depression with documented cases of sudden respiratory arrests and severe respiratory depression episodes, particularly with morphine and remifentanil 1
• Muscle relaxants (myorelaxants) such as baclofen worsen OSA through combined respiratory depression and upper airway muscle relaxation 1

Sedative-Hypnotics

• Zolpidem (20-30 mg) increases AHI in OSA patients despite being marketed as a sleep aid 1
• Flurazepam worsens respiratory parameters when compared to placebo 1
• Notably, ramelteon (a melatonin receptor agonist) does NOT worsen OSA and can be used safely 1

Hormonal Agents

• Testosterone replacement therapy significantly worsens OSA, with studies showing increased AHI and decreased minimum oxygen saturation in hypogonadal men receiving testosterone injections 1
• The mechanism involves both central respiratory drive suppression and increased upper airway collapsibility 1

Indirect OSA-Worsening Medications (Through Weight Gain)

Multiple medication classes promote weight gain, which independently worsens OSA severity—these should be avoided when alternatives exist. 1

Antipsychotics (Highest Risk)

• Olanzapine, clozapine, quetiapine, risperidone, thioridazine, and haloperidol cause substantial weight gain 1
• Consider switching to ziprasidone or aripiprazole as weight-neutral alternatives 1

Antidepressants

• Paroxetine has the highest weight gain risk among all SSRIs 1, 2
• Amitriptyline, nortriptyline, imipramine, doxepin (tricyclics) and mirtazapine cause significant weight gain 1, 2
• Phenelzine (MAO inhibitor) promotes weight gain 1
• Preferred alternatives: protriptyline, bupropion, nefazodone, fluoxetine, or sertraline 1, 2

Anticonvulsants

• Valproate, carbamazepine, and gabapentin consistently cause weight gain 1
• Consider topiramate, lamotrigine, or zonisamide as alternatives that may actually improve OSA through weight loss 1

Antidiabetic Drugs

• Insulin, sulfonylureas, and thiazolidinediones promote weight gain 1
• Preferred alternatives: metformin, SGLT2 inhibitors (canagliflozin, dapagliflozin), GLP-1 agonists (exenatide, liraglutide), DPP-4 inhibitors (sitagliptin, saxagliptin) 1

Antihistamines

• Cyproheptadine causes weight gain through central H1 receptor blockade 1, 3
• First-generation sedating antihistamines that cross the blood-brain barrier promote more weight gain than second/third-generation agents 3
• Use inhalers or decongestants as alternatives 1

Cardiovascular Medications

• Propranolol (beta-blocker) and doxazosin (alpha-blocker) cause weight gain 1, 3
• Consider ACE inhibitors or calcium channel blockers as alternatives 1

Hormonal Contraceptives and Steroids

• Oral contraceptives, glucocorticoids, and progestational steroids promote weight gain 1
• Consider barrier methods or nonsteroidal anti-inflammatory agents as alternatives 1

Anesthetic Considerations

• Propofol with isoflurane may decrease oxygen desaturation index in the immediate postoperative period, though the overall impact of anesthesia on OSA is probably marginal 1
• Standard anesthetics require careful monitoring in known OSA patients undergoing elective surgery 1

Critical Clinical Algorithm

1. Screen all OSA patients for the medications listed above 1
2. Prioritize discontinuation or dose reduction of benzodiazepines, opioids, and testosterone first (direct respiratory effects) 1
3. Switch weight-promoting medications to alternatives listed above when clinically feasible 1
4. Monitor weight at 3-month intervals during continued treatment with any weight-promoting medication 3
5. If weight gain exceeds 5% of baseline, strongly consider medication switch 3

Common Pitfalls to Avoid

• Do not assume all SSRIs behave identically—paroxetine causes significant weight gain while fluoxetine and sertraline are weight-neutral 2
• Do not overlook testosterone replacement therapy as a reversible cause of OSA worsening 1
• Do not combine multiple CNS depressants without extreme caution and close monitoring 1
• Do not dismiss antihistamines as benign—sedating first-generation agents can promote weight gain through central mechanisms 3