1. Antihistamines (for Allergies and Colds)

Antihistamines, especially first-generation types like diphenhydramine (Benadryl), are well-known for their sedative effects. They work by blocking histamine receptors — which, aside from controlling allergy symptoms, also play a role in wakefulness.

Even “non-drowsy” formulas, such as cetirizine (Zyrtec) or loratadine (Claritin), can sometimes cause mild fatigue in sensitive individuals.

What you can do:

Try taking antihistamines in the evening or talk to your doctor about switching to a newer, less sedating version. Always check labels, as combination cold medicines often include antihistamines by default.

2. Blood Pressure Medications (Beta-Blockers and ACE Inhibitors)

Drugs like metoprolol, atenolol, and lisinopril are widely prescribed for managing blood pressure — but they can slow your heart rate and reduce circulation to muscles, sometimes leading to tiredness or even depression-like symptoms.

Why it happens:

Beta-blockers lower adrenaline activity, which helps your heart but can also decrease your natural “energy drive.” ACE inhibitors may alter potassium and fluid balance, subtly affecting how your body feels day to day.

Tip:

Discuss dosage timing with your physician. Taking certain blood pressure medications at night may lessen daytime fatigue.

3. Antidepressants (SSRIs and Tricyclics)

While antidepressants are designed to improve mood, some — especially tricyclic antidepressants (TCAs) like amitriptyline — are strongly sedating. Even SSRIs such as sertraline (Zoloft) or fluoxetine (Prozac) can, for some people, flatten energy or motivation levels.

Insight:

Energy changes usually appear within the first few weeks of treatment. Adjusting timing, dosage, or switching to a different class can often resolve fatigue without losing therapeutic benefit.

4. Pain Relievers (Opioids and Some Muscle Relaxants)

Prescription painkillers such as hydrocodone, codeine, and morphine are central nervous system depressants — meaning they slow brain activity and reaction times. Similarly, muscle relaxants like cyclobenzaprine (Flexeril) can produce pronounced drowsiness.

The challenge:

Fatigue here is both a side effect and a safety mechanism — your body is trying to slow you down while the drug is active. Never combine these with alcohol or other sedatives, and consult a doctor before making adjustments.

5. Diabetes Medications

Some medications that control blood sugar, like insulin or sulfonylureas, can cause dips in glucose levels that lead to tiredness or mental fog. Others, such as metformin, may reduce vitamin B12 absorption over time — which can also contribute to fatigue.

Action step:

Ask your doctor about monitoring your B12 levels and timing meals or snacks to stabilize your energy. Fatigue could be an early sign that your dosage or diet needs fine-tuning.

6. Statins (Cholesterol-Lowering Drugs)

Statins like atorvastatin (Lipitor) and simvastatin (Zocor) help reduce cholesterol — but for some, they can affect muscle metabolism and energy production. Research has shown a small subset of users experience muscle weakness or fatigue even without pain.

What experts suggest:

Don’t stop statins suddenly. Instead, discuss alternatives like dose adjustment or trying a different statin with a lower side-effect profile.

7. Sleep Aids and Anti-Anxiety Medications

Ironically, the very drugs designed to help with rest or anxiety can cause next-day drowsiness. Benzodiazepines (like lorazepam or alprazolam) and sleep medications such as zolpidem (Ambien) can linger in your system, affecting coordination and alertness the following day.

Pro tip:

Consider behavioral alternatives like cognitive-behavioral therapy for insomnia (CBT-I) or mindfulness-based anxiety management — both of which can improve rest without residual fatigue.