What is the best course of action for an 18-year-old autistic male patient taking Paxil (paroxetine) 15mg, fluvoxamine 125mg twice a day, and buspirone 10mg, considering potential risks of serotonin syndrome?

Immediate Discontinuation of Paroxetine Required Due to High Risk of Serotonin Syndrome

This patient is at extremely high risk for serotonin syndrome and requires immediate discontinuation of paroxetine (Paxil) 15mg, as he is already taking fluvoxamine 250mg daily—a dangerous combination of two SSRIs that significantly increases serotonergic activity. 1, 2

Critical Safety Concern: Dual SSRI Therapy

• The concurrent use of paroxetine and fluvoxamine constitutes dual SSRI therapy, which dramatically elevates the risk of serotonin syndrome—a potentially life-threatening condition characterized by mental status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (hyperreflexia, incoordination), and gastrointestinal symptoms 1, 2

• Patients with autism spectrum disorder may be at even higher risk for serotonin syndrome due to preexisting hyperserotonemia (elevated whole blood serotonin), which is present in more than 25% of individuals with autism 3

• A case report documented serotonin syndrome in an adult with autism on sertraline 50mg monotherapy after only 4 days, demonstrating heightened susceptibility in this population 3

Pharmacological Interaction Analysis

• Fluvoxamine is a potent inhibitor of multiple cytochrome P450 enzymes (CYP1A2, CYP2C19, CYP2D6, CYP3A4), which can increase plasma concentrations of other medications 4, 5

• Paroxetine is metabolized by CYP2D6 and is itself a potent CYP2D6 inhibitor 5

• The combination creates a bidirectional interaction where fluvoxamine inhibits paroxetine metabolism while both drugs synergistically increase serotonergic activity 5

Immediate Management Algorithm

Step 1: Discontinue Paroxetine Immediately

• Stop paroxetine 15mg immediately—do not taper given the acute safety concern and relatively low dose 1
• Monitor closely for serotonin syndrome symptoms over the next 24-48 hours 1, 2

Step 2: Assess for Current Serotonin Syndrome

Look specifically for:

• Neuromuscular signs: hyperreflexia, clonus (especially ocular and inducible ankle clonus), muscle rigidity, tremor 1, 3
• Autonomic instability: tachycardia, blood pressure fluctuations, hyperthermia, diaphoresis 1
• Mental status changes: agitation, confusion, restlessness beyond baseline autism symptoms 1, 3

Step 3: Monitor for Paroxetine Discontinuation Syndrome

• Paroxetine has the highest risk of discontinuation syndrome among all SSRIs, characterized by dizziness, fatigue, myalgias, nausea, insomnia, paresthesias, anxiety, and agitation 4, 6
• Symptoms typically emerge within 1-4 days after discontinuation and resolve within 1-2 weeks 4
• The ongoing fluvoxamine therapy may partially mitigate withdrawal symptoms due to continued serotonergic activity 6

Step 4: Optimize Fluvoxamine Monotherapy

• Continue fluvoxamine 125mg twice daily (250mg total daily dose) as monotherapy 4, 2
• Fluvoxamine has demonstrated efficacy in adults with autism, reducing repetitive behaviors, maladaptive behavior, and aggression while improving social relatedness 7
• The current dose is within the therapeutic range (maximum 300mg daily) 4

Step 5: Evaluate Buspirone Continuation

• Buspirone 10mg can be continued as it has minimal serotonergic activity and is useful for mild to moderate agitation 4
• However, note that buspirone may take 2-4 weeks to become effective and the current 10mg dose is subtherapeutic (typical range 15-60mg daily in divided doses) 4
• Consider increasing to 15mg twice daily if additional anxiolytic effect is needed after paroxetine discontinuation 4

Critical Pitfalls to Avoid

• Do not attempt to taper paroxetine slowly in this situation—the risk of ongoing serotonin syndrome outweighs discontinuation syndrome concerns given the low dose and continued SSRI coverage from fluvoxamine 1

• Do not add any additional serotonergic agents including triptans, tramadol, tryptophan supplements, or St. John's Wort 1, 2

• Be aware that fluvoxamine can cause specific adverse effects in children and adolescents with autism, including climbing to high places (8/28 cases), sleep disturbance (9/28), hyperactivity (5/28), and gastrointestinal symptoms (6/28) 8

• Monitor for psychosis-like side effects from fluvoxamine, including insomnia, agitation, confusion, and incoherent thoughts, which occur rarely but are documented 9

Follow-Up Monitoring

• Contact patient/family within 24-48 hours after paroxetine discontinuation to assess for withdrawal symptoms and serotonin syndrome 4, 1

• Weekly monitoring for 4 weeks to ensure stabilization on fluvoxamine monotherapy and resolution of any discontinuation symptoms 4

• Parental oversight is paramount given the patient's autism diagnosis and complex medication history 4