Management of Paresthesias on Latuda, Trazodone, and Citalopram
The most likely cause of paresthesias in this patient is SSRI discontinuation syndrome from citalopram, and management should focus on ensuring medication adherence, gradual dose adjustments if changes are needed, and ruling out serotonin syndrome given the combination of serotonergic agents.
Primary Differential: SSRI Discontinuation Syndrome
The combination of citalopram (an SSRI), trazodone (a serotonergic antidepressant), and lurasidone creates a polypharmacy situation with multiple serotonergic effects. Paresthesias are a hallmark symptom of SSRI discontinuation syndrome, which occurs with missed doses or abrupt discontinuation of shorter-acting SSRIs 1.
Key Clinical Features to Assess:
- Medication adherence: Verify if the patient has missed any doses of citalopram, as discontinuation syndrome can occur even with missed doses 1
- Timing of symptoms: Paresthesias typically arise within 24-48 hours of missed doses or dose changes 1
- Associated symptoms: Look for dizziness, vertigo, sensory disturbances, anxiety, irritability, headaches, nausea, or imbalance—all components of discontinuation syndrome 1
Critical Safety Concern: Rule Out Serotonin Syndrome
This patient is on three medications with serotonergic activity (citalopram, trazodone, and potentially lurasidone), creating risk for serotonin syndrome 1. While paresthesias alone are more consistent with discontinuation syndrome, you must actively exclude serotonin syndrome.
Immediate Assessment Required:
- Mental status changes: confusion, agitation, anxiety 1
- Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity 1
- Autonomic hyperactivity: hypertension, tachycardia, diaphoresis, shivering, vomiting, diarrhea 1
- Advanced symptoms: fever, seizures, arrhythmias (medical emergency requiring hospitalization) 1
If serotonin syndrome is present, immediately discontinue all serotonergic agents and provide supportive care with continuous cardiac monitoring 1.
Management Algorithm
Step 1: Verify Medication Adherence
- Confirm the patient is taking citalopram consistently without missed doses 1
- Review timing of all three medications and any recent dose changes 1
Step 2: If Discontinuation Syndrome is Confirmed
Restart or continue citalopram at the previous effective dose 1. The paresthesias should resolve within 24-48 hours of resuming consistent dosing 1.
- If dose reduction is clinically necessary, taper slowly over 1-2 week intervals using the smallest available increments 1
- Never abruptly discontinue citalopram, as it is associated with discontinuation syndrome 1
Step 3: Evaluate the Polypharmacy Regimen
The combination of citalopram, trazodone, and lurasidone requires caution 1. While lurasidone itself has minimal direct serotonergic effects and is generally well-tolerated with low rates of extrapyramidal symptoms 2, 3, 4, the combination with two serotonergic antidepressants increases risk.
- Citalopram considerations: Monitor for QT prolongation, especially if dose exceeds 40 mg/day; avoid in patients with long QT syndrome 1
- Trazodone considerations: Use with caution in patients with cardiac conduction abnormalities 1; can contribute to serotonin syndrome when combined with other serotonergic agents 5
- Drug interactions: Citalopram has the least effect on CYP450 enzymes compared to other SSRIs, reducing interaction potential 1
Step 4: If Symptoms Persist Despite Adherence
- Consider switching from citalopram to a longer half-life SSRI (e.g., fluoxetine) which has lower discontinuation syndrome risk 1
- Alternatively, simplify the regimen by discontinuing trazodone if it was added primarily for sedation, as lurasidone can cause mild sedation 2, 4
- Taper any medication changes slowly over 1-2 weeks to minimize withdrawal symptoms 1
Common Pitfalls to Avoid
- Do not assume paresthesias are benign without ruling out serotonin syndrome, especially with multiple serotonergic agents 1, 5
- Do not abruptly discontinue citalopram even if you suspect it is causing side effects; taper gradually 1
- Do not add anticholinergic agents to treat symptoms, as this can worsen cognitive function and does not address the underlying cause 1
- Monitor for akathisia from lurasidone, which can be mistaken for anxiety or agitation and may prompt inappropriate dose escalation of other medications 2, 4
Monitoring Parameters
- Short-term (24-48 hours): Resolution of paresthesias after ensuring medication adherence 1
- Ongoing: Vital signs, mental status, neuromuscular examination for signs of serotonin syndrome 1
- ECG monitoring: If citalopram dose is >40 mg/day or if patient has cardiac risk factors 1
- Metabolic parameters: Lurasidone has minimal metabolic effects, but baseline and periodic monitoring is reasonable with long-term use 2, 3, 4