Common Medications That Cause Fatigue

Feeling exhausted all the time? The culprit may be lurking in your medicine cabinet. Many common prescription and over-the-counter medications can cause fatigue, especially in older adults who take several drugs.

A 2025 research review published in Scientific Reports found that approximately 43% of adults ages 60 and older experience fatigue. Although tiredness is common with aging, it should not automatically be dismissed as a normal part of getting older.

"Many medications, whether over the counter or prescribed, can cause sedation, tiredness and low energy and concentration," says Dr. Mohammed Issa, medical director of the Pain Management Center at Brigham and Women's Faulkner Hospital and an assistant professor at Harvard Medical School.

According to AARP, four common categories of medications can contribute to fatigue, sometimes increasing the risk of falls, accidents and impaired driving. The effects depend on the specific drug, dosage, timing and a person's overall health.

1. Antihistamines. Older allergy medications, including diphenhydramine (Benadryl) and chlorpheniramine commonly cause drowsiness because they affect the central nervous system.

Newer antihistamines, such as loratadine (Claritin) and fexofenadine (Allegra), are generally less sedating. Cetirizine (Zyrtec) is another option, although it can still cause drowsiness in some people. Ask your doctor or pharmacist which medication is most appropriate.

2. Blood pressure medications. Several types of medications used to control hypertension can contribute to fatigue.

Beta blockers, including metoprolol (Lopressor, Toprol-XL), atenolol (Tenormin) and propranolol (Inderal), slow the heart rate and may cause tiredness.

Diuretics, such as hydrochlorothiazide, furosemide (Lasix) and chlorthalidone, can cause fatigue if they lead to dehydration or electrolyte imbalances.

Other medications, including ACE inhibitors such as lisinopril (Zestril) and calcium channel blockers such as amlodipine (Norvasc), may also cause fatigue in some patients.

If tiredness develops after starting or increasing a blood pressure medication, ask your healthcare provider whether an adjustment is appropriate. Never stop taking these drugs without medical guidance.

3. Antidepressants and anti-anxiety medications. Some medications used to treat depression and anxiety can cause drowsiness, particularly when treatment begins or the dose increases.

These include selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft), paroxetine (Paxil) and fluoxetine (Prozac), as well as serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine (Effexor XR) and duloxetine (Cymbalta).

"They elevate serotonin levels, which elevates mood, but can cause drowsiness, fatigue and low energy," Issa says.

Other potentially sedating antidepressants include trazodone, mirtazapine (Remeron) and amitriptyline.

Benzodiazepines, such as alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium) and clonazepam (Klonopin), can also cause significant drowsiness and impair coordination.

If fatigue becomes troublesome, your doctor may recommend changing the dose, timing or medication. Benzodiazepines and antidepressants should not be stopped abruptly without medical supervision.

4. Pain medications. Several drugs prescribed for pain can slow activity in the central nervous system, causing sleepiness, dizziness and fatigue.

Opioids, including oxycodone, hydrocodone, morphine, tramadol and codeine, are particularly likely to cause sedation.

Muscle relaxants such as cyclobenzaprine (Flexeril), baclofen, tizanidine (Zanaflex) and methocarbamol (Robaxin) can have similar effects.

Medications used for nerve pain, including gabapentin (Neurontin) and pregabalin (Lyrica), may also cause drowsiness and dizziness.

Combining these medications with alcohol or other sedating drugs can increase the risk of dangerous side effects, including slowed breathing.

If you suspect a medication is causing fatigue, review your prescriptions, supplements and over-the-counter products with your doctor or pharmacist.

In some cases, adjusting the dosage or taking a medication at a different time may help. However, not all medications should be taken at bedtime, and changes should be made only with professional guidance.

Avoid driving or operating machinery whenever a medication makes you sleepy or affects your alertness.

"You also shouldn't drive for a few weeks until the adjustment happens, although there are some medications, such as benzodiazepines and opioids, which may cause persistent side effects of sedation, drowsiness and fatigue," he adds. "And therefore, patients are recommended to avoid driving or using heavy machinery during the entire time that they take these medications."

Persistent fatigue can also signal other medical conditions, including anemia, thyroid disorders and sleep apnea. If exhaustion continues despite medication adjustments, ask your doctor about other possible causes.