Can any of the listed medications (vitamin D3 5,000 IU, multivitamin, low‑dose aspirin, hydroxyurea, pexidartinib, atorvastatin, lisinopril, levothyroxine, amlodipine) cause anxiety?

Medications That May Cause Anxiety

Among your medication list, levothyroxine is the most likely culprit for causing anxiety, particularly if your dose is too high or if you have underlying hyperthyroidism. 1 Pexidartinib also carries a notable risk of anxiety as a documented adverse effect. 2

High-Risk Medications

Levothyroxine (25 mcg daily)

• Anxiety is a well-established adverse effect of levothyroxine therapy, particularly when doses exceed what is needed (therapeutic overdosage). 1
• The FDA label explicitly lists anxiety among central nervous system adverse reactions, along with hyperactivity, nervousness, irritability, emotional lability, and insomnia. 1
• Research confirms that hyperthyroidism (whether from disease or excessive thyroid hormone replacement) significantly increases anxiety symptoms, with psychic anxiety being one of the distinguishing features. 3
• Key clinical pitfall: Even a "low" dose like 25 mcg can cause anxiety if it's excessive for your individual needs—this is why TSH monitoring is essential. 1

Pexidartinib (250 mg twice daily)

• Anxiety is listed as a common adverse effect in obesity management guidelines that discuss similar drug classes. 2
• This medication requires monitoring for neuropsychiatric effects given its mechanism of action.

Moderate-Risk Medications

Hydroxyurea (20 mg/kg daily)

• While not primarily known for causing anxiety, hydroxyurea can cause central nervous system effects including headache and dizziness that may be misinterpreted as anxiety.
• No direct evidence links it to anxiety disorders in the provided literature.

Low-Risk Medications

Atorvastatin (20 mg daily)

• Statins are not associated with causing anxiety. 4
• In fact, the combination of atorvastatin with amlodipine showed no psychiatric adverse effects in large trials. 4
• One interaction to note: Vitamin D supplementation (which you're taking at 5,000 IU) can lower atorvastatin concentrations, potentially reducing its effectiveness. 5

Lisinopril (10 mg daily)

• ACE inhibitors are not associated with anxiety as an adverse effect.
• No evidence in the provided literature suggests anxiety risk.

Amlodipine (2.5 mg daily)

• Calcium channel blockers do not cause anxiety. 4
• Well-tolerated in cardiovascular trials without psychiatric adverse effects. 4

Aspirin (81 mg daily)

• Low-dose aspirin has no association with anxiety.
• The perioperative guidelines discussing aspirin make no mention of psychiatric effects. 2

Vitamin D3 (5,000 IU daily)

• Vitamin D supplementation does not cause anxiety.
• Important interaction: Your high-dose vitamin D may be reducing your atorvastatin effectiveness, though this doesn't relate to anxiety. 5

Multivitamin

• Standard multivitamins do not cause anxiety.
• No evidence of psychiatric adverse effects. 2

Clinical Action Plan

If you're experiencing new or worsening anxiety:

1. Check your thyroid function tests (TSH, free T4) immediately. 1 Even small doses of levothyroxine can cause anxiety if they result in subclinical or overt hyperthyroidism.

2. Review the timing of anxiety onset relative to starting pexidartinib, as this is a known adverse effect that may require dose adjustment or discontinuation. 2

3. Monitor for other signs of thyroid hormone excess: heat intolerance, palpitations, tremor, insomnia, weight loss, or increased heart rate. 1 The presence of these symptoms alongside anxiety strongly suggests levothyroxine-induced hyperthyroidism.

4. Do not abruptly stop levothyroxine even if it's causing anxiety—work with your prescriber to adjust the dose based on lab results. 1

5. Consider that anxiety from levothyroxine typically improves within days to weeks after dose reduction, whereas primary anxiety disorders require different management. 3