Can Prozac (fluoxetine) cause chest pain?

Can Prozac (Fluoxetine) Cause Chest Pain?

Prozac (fluoxetine) does not directly cause chest pain as a primary adverse effect, but it can be associated with chest pain indirectly through rare cardiovascular effects including bradycardia and syncope, or as part of serotonin syndrome when combined with other serotonergic medications.

Direct Cardiovascular Effects

Fluoxetine has a favorable cardiovascular safety profile compared to older antidepressants:

• Fluoxetine does not cause the anticholinergic, hypotensive, sedative, or particular cardiovascular effects seen with tricyclic antidepressants 1
• Therapeutic doses do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease 2
• Chronic treatment with fluoxetine does not affect the electrocardiogram (ECG), with no clinical evidence of conduction delay and very little evidence of orthostatic hypotension 3

Rare But Documented Cardiovascular Complications

While uncommon, fluoxetine can cause potentially hazardous cardiac effects:

• Bradycardia accompanied by faintness or syncope has been reported, likely representing a direct central nervous system effect of increased serotonin on medullary cardiovascular regulation 4
• Dysrhythmias including atrial fibrillation have been documented in association with fluoxetine treatment and overdose 3
• These cardiac symptoms, though not common, do raise clinical concerns 3

Serotonin Syndrome Risk

Chest pain can occur as part of serotonin syndrome, which is triggered when fluoxetine is combined with other serotonergic medications:

• Symptoms arise within 24-48 hours after combining medications and include autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis) 5
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness 5
• MAOIs are contraindicated with fluoxetine and play a role in most cases of serotonin syndrome 5
• Caution is required when combining fluoxetine with other serotonergic drugs including other antidepressants, opioids, tramadol, dextromethorphan, and stimulants 5

Clinical Context: Chest Pain in Depression

Importantly, chest pain itself may be the presenting complaint in patients with depression:

• In patients with suspected angina and negative coronary angiography who have comorbid depression, fluoxetine 20 mg daily significantly improved both depression symptoms AND chest pain over 4 weeks 6
• The improvement in chest pain correlated significantly with improvement in depression and anxiety scores (r = 0.867, P < 0.001) 6
• This suggests that in many cases, chest pain may be a manifestation of the underlying psychiatric condition rather than a medication side effect 6

Differential Diagnosis Algorithm

When a patient on fluoxetine presents with chest pain:

1. First, exclude acute coronary syndrome and other cardiac causes - the 2021 AHA/ACC guidelines recommend systematic evaluation for cardiac causes before attributing symptoms to psychiatric or medication effects 5

2. Assess for serotonin syndrome - check for recent addition of serotonergic medications, mental status changes, neuromuscular hyperactivity, and autonomic instability 5

3. Check heart rate and rhythm - bradycardia <45 bpm or new arrhythmias warrant fluoxetine discontinuation and cardiac monitoring 4

4. Consider non-cardiac causes - gastroesophageal reflux disease, musculoskeletal pain (costochondritis), and anxiety/panic disorder are more common causes of chest pain in patients on SSRIs 5

5. Evaluate for underlying psychiatric symptoms - persistent chest pain with negative cardiac workup may represent inadequately treated depression or anxiety requiring cognitive-behavioral therapy referral 5

Key Clinical Pitfalls

• Do not automatically attribute chest pain to fluoxetine without excluding cardiac causes - the medication's cardiovascular safety profile makes direct causation unlikely 1, 2
• Monitor for drug-drug interactions - fluoxetine interacts with drugs metabolized by CYP2D6, and combining with other serotonergic agents increases serotonin syndrome risk 5
• Recognize that chest pain may improve with fluoxetine - in patients with depression and functional chest pain, the SSRI may be therapeutic rather than causative 6