Can certain medications exacerbate symptoms?

Can Certain Medications Make Symptoms Worse?

Yes, numerous medications can directly worsen or exacerbate existing symptoms through multiple mechanisms, and this is a critical consideration in clinical practice that requires immediate medication review when patients experience symptom deterioration.

Cardiovascular Conditions

In patients with hypertrophic cardiomyopathy (HCM), diuretics and vasodilators can worsen symptoms related to left ventricular outflow tract obstruction (LVOTO). 1

• These medications decrease preload, which augments LVOTO and can precipitate dangerous hypotension 1
• While these agents may be used in asymptomatic HCM patients, their introduction in symptomatic patients requires either uptitration of medications treating the obstructive HCM or consideration of alternative therapies for comorbid conditions 1
• Acute hypotension in obstructive HCM is a medical urgency requiring maximization of preload and afterload while avoiding increases in contractility or heart rate 1

Neurological and Psychiatric Conditions

Benzodiazepines, anticholinergics, and certain other medications significantly worsen balance disturbances, cognitive function, and fall risk in older adults. 1, 2

• Anticholinergic medications (cyclobenzaprine, oxybutynin, prochlorperazine, promethazine, tricyclic antidepressants, paroxetine) increase postoperative delirium risk 1
• Diphenhydramine, meperidine, midazolam, and histamine-2 receptor antagonists are strongly associated with increased delirium 1
• Antipsychotics in older adults cause balance disturbances, increase mortality risk, and carry strong recommendations against use due to anticholinergic burden 2
• Benzodiazepines are a significant independent risk factor for falls and should be avoided entirely in elderly patients 2

Opioids exacerbate obstructive sleep apnea (OSA) through multiple mechanisms. 1

• 75-85% of patients treated with opioids develop at least mild sleep apnea, with 36-41% experiencing severe cases 1
• Opioids cause relaxation of tongue and upper airway muscles leading to airway obstruction, and increase central apneas while decreasing obstructive apneas 1
• When combined with benzodiazepines, opioids cause dangerous respiratory depression and increase overdose risk 1

Metabolic and Weight-Related Conditions

Multiple medication classes induce weight gain, which can precipitate or worsen obstructive sleep apnea. 1

• Atypical antipsychotics, certain antidepressants (particularly paroxetine), anticonvulsants, antidiabetic drugs, antihistamines, and beta/alpha-adrenergic blockers are associated with weight gain 1
• Since 70% of OSA patients are obese and obesity is the principal risk factor for OSA, medications causing weight gain can create a vicious cycle 1
• Alternative medications should be considered—for example, fluoxetine or sertraline cause less weight gain than paroxetine 1

Pain and Headache Conditions

Overuse of acute headache medications can worsen chronic migraine through medication overuse headache. 1

• Simple analgesics should be limited to fewer than 15 days per month 1
• Triptans should be limited to fewer than 10 days per month 1
• Beta-blockers and flunarizine may exacerbate depression in patients with comorbid mood disorders 1

Mental Health Conditions

Antidepressants can precipitate manic episodes in patients with undiagnosed bipolar disorder. 3

• Treating a major depressive episode with an antidepressant alone may increase the likelihood of precipitating a mixed/manic episode in at-risk patients 3
• Patients with depressive symptoms should be adequately screened for bipolar disorder risk before initiating antidepressant treatment 3
• Screening should include detailed psychiatric history and family history of suicide, bipolar disorder, and depression 3

Combining serotonergic medications increases the risk of potentially life-threatening serotonin syndrome. 4, 3

• The combination of SSRIs with other serotonergic drugs (triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort) increases serotonin syndrome risk 3
• Monitor for mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity within the first 24-48 hours after starting or changing doses 4
• Symptoms include agitation, hallucinations, tachycardia, labile blood pressure, tremor, rigidity, myoclonus, hyperreflexia, and gastrointestinal symptoms 3

Respiratory Conditions

Testosterone and baclofen worsen obstructive sleep apnea. 1

• Testosterone increases apnea-hypopnea index (AHI) and prolongs hypoxemia time in men 1
• Baclofen provokes upper airway collapse during sleep, worsening OSA and affecting central apneas or hypoventilation by depressing respiratory drive 1
• It is prudent to avoid baclofen in OSA patients 1

Common Pitfalls and How to Avoid Them

Do not assume that medications are safe simply because they are commonly prescribed. 5

• The higher the number of medications patients take, the higher their risk of adverse drug reactions 5
• Understanding pharmacokinetics and pharmacodynamics can help anticipate and avoid adverse reactions 5

Do not continue potentially harmful medications without reassessing the indication. 2

• When patients experience symptom worsening, immediately review all medications for potential causative agents 2
• Discontinue or reduce to the lowest effective dose any medication that may be contributing to symptoms 2

Do not overlook drug-drug interactions that can exacerbate symptoms. 1

• Older adults are more likely to receive multiple medications that may interact, such as opioids with benzodiazepines 1
• Patients with mental health conditions are more likely to receive benzodiazepines, which exacerbate opioid-induced respiratory depression 1

Do not prescribe vestibular suppressants (meclizine, antihistamines, benzodiazepines) for chronic balance problems. 2

• These medications interfere with central compensation, cause drowsiness and cognitive deficits, and significantly increase fall risk 2
• They should not be used for benign paroxysmal positional vertigo (BPPV) as they delay recovery 2