For a 58‑year‑old male with normal labs who discontinued paroxetine (Paxil) 40 mg daily and now has worsening depression, how should his antidepressant therapy be managed?

Restart Paroxetine 40 mg Daily Immediately

This patient should restart paroxetine 40 mg daily without delay, as he discontinued an effective antidepressant and is now experiencing worsening depression—a predictable consequence of stopping treatment prematurely. 1

Why Restart the Same Medication

• Prior response to paroxetine is the strongest predictor of future response, making it the optimal choice to restart rather than switching to a different agent 1
• Discontinuation of effective antidepressant treatment commonly leads to relapse, with studies showing 26–52% of patients relapse when medication is stopped 1
• The American Family Physician guidelines recommend paroxetine as a first-line SSRI for depression, though it should generally be avoided in older adults due to higher adverse effect rates 1

Critical Safety Monitoring After Restarting

• Monitor for suicidal ideation closely during the first 1–2 weeks after restarting, as SSRIs carry FDA black-box warnings for treatment-emergent suicidality, particularly in adults under age 65 2
• Watch for activation symptoms (agitation, anxiety, panic attacks, insomnia, irritability, hostility, impulsivity) especially during the first few weeks, as these may represent precursors to emerging suicidality 2
• Assess treatment response at 4 weeks and 8 weeks using standardized depression rating scales 1

Treatment Duration to Prevent Future Relapse

• Continue paroxetine for a minimum of 4–9 months after satisfactory response for what appears to be recurrent depression 1
• Given that this patient had been taking paroxetine 40 mg daily (suggesting prior treatment), he likely has recurrent depression and should consider longer duration of ≥1 year or indefinite maintenance therapy 1
• After a first episode, recurrence probability is 50%; after two episodes it increases to 70%; after three episodes it reaches 90% 1

Why Paroxetine Was Likely Discontinued Abruptly

• Paroxetine has the highest risk of severe discontinuation syndrome among all SSRIs due to its short half-life and lack of active metabolites 3, 4
• Withdrawal symptoms typically begin within 24–48 hours after stopping and include dizziness, vertigo, headache, nausea, flu-like symptoms, anxiety, confusion, irritability, excessive dreaming, and insomnia 4
• The intensity of withdrawal symptoms depends on the daily dose (40 mg is relatively high) and duration of treatment 4

Important Counseling Points

• Never stop paroxetine abruptly again—if discontinuation is needed in the future, taper by 10 mg/day at weekly intervals down to 20 mg/day, then continue 20 mg for 1 week before stopping 2
• Educate the patient that stopping antidepressants prematurely is a common cause of relapse and that maintenance therapy is essential 1
• If intolerable symptoms occur during future tapering, resume the previous dose and decrease more gradually 2

Alternative Consideration Only If Paroxetine Is Refused

• If the patient refuses to restart paroxetine due to concerns about withdrawal risk, switch to sertraline 50–100 mg daily or escitalopram 10–20 mg daily, which have lower discontinuation syndrome risk 1
• However, switching to a different SSRI yields remission in only approximately 21–25% of cases after failure of the first SSRI, whereas restarting a previously effective medication has much higher success rates 1

Common Pitfall to Avoid

• Do not start a new antidepressant without first attempting to restart paroxetine, as this patient had a known response to paroxetine 40 mg and stopping it was the clear precipitant of worsening depression 1
• The American College of Physicians found no evidence that one SSRI is superior to another for efficacy, but prior individual response is the most important factor 1