Can withdrawal from Caplyta (lumateperone) cause cardiovascular issues, such as orthostatic hypotension, in a patient who has stopped taking the medication and is now experiencing symptoms including projectile vomiting and hypothermia?

Caplyta Withdrawal and Cardiovascular Effects

Your symptoms of projectile vomiting and hypothermia are not typical cardiovascular manifestations of Caplyta withdrawal, but orthostatic hypotension is a known risk with this medication that could contribute to your presentation.

Understanding Caplyta's Cardiovascular Profile

Caplyta (lumateperone) can cause orthostatic hypotension and syncope, particularly during initial dosing or dose changes. 1 The FDA label specifically warns that atypical antipsychotics like Caplyta cause orthostatic hypotension through disruption of autonomic blood pressure regulation. 1

Key Cardiovascular Risks with Caplyta:

• Orthostatic hypotension occurs when blood pressure drops upon standing, causing dizziness, lightheadedness, and potential syncope 1
• In clinical trials, orthostatic hypotension occurred in 0.7% of schizophrenia patients and 0% of bipolar depression patients on Caplyta 1
• Syncope rates were 0.2-0.3% across trials 1
• The risk is highest in elderly patients, those with dehydration, hypovolemia, concurrent antihypertensive medications, or known cardiovascular disease 1

Your Specific Symptoms

Projectile vomiting and hypothermia are NOT typical cardiovascular withdrawal effects. However, these symptoms warrant immediate medical evaluation for several reasons:

Critical Considerations:

• Temperature dysregulation can occur with atypical antipsychotics, as they disrupt the body's ability to regulate core body temperature 1
• Severe vomiting leading to dehydration could precipitate or worsen orthostatic hypotension 2, 3
• Hypovolemia from vomiting is a recognized cause of orthostatic hypotension that requires fluid resuscitation 2
• Your symptoms could represent a medical emergency unrelated to Caplyta withdrawal (infection, metabolic disturbance, etc.)

Orthostatic Hypotension: What You Need to Know

Orthostatic hypotension is defined as a sustained decrease in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg within 3 minutes of standing. 2, 4, 3

Common Symptoms Include:

• Dizziness, lightheadedness, weakness, and fatigue 2, 3
• Visual disturbances (blurring, tunnel vision, loss of vision) 2
• Nausea and pallor 2
• Syncope (fainting) 2, 3
• Less commonly: chest pain, neck/shoulder pain ("coat hanger pain") 2, 3

Cardiovascular Consequences:

Orthostatic hypotension is associated with serious cardiovascular outcomes including increased risk of coronary events, stroke, atrial fibrillation, heart failure, and cardiovascular mortality. 5 It also independently predicts falls, fractures, and overall mortality. 5, 6

Immediate Actions Required

You need urgent medical evaluation today for:

1. Assessment of orthostatic vital signs - blood pressure should be measured after 5 minutes lying down, then at 1 and 3 minutes after standing 2, 7
2. Evaluation of volume status - severe vomiting causes dehydration which worsens orthostatic hypotension 2, 8
3. Temperature monitoring - hypothermia with vomiting suggests possible serious illness 1
4. Fluid resuscitation - oral or intravenous fluids with sodium supplementation for dehydration-related orthostatic hypotension 2

Management If Orthostatic Hypotension Confirmed

Non-Pharmacological First-Line Measures:

• Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams daily (unless contraindicated by heart failure) 2, 7, 6
• Physical counter-maneuvers including leg crossing, squatting, and muscle tensing during symptomatic episodes 2, 7, 6
• Gradual positional changes - avoid rapid standing 8, 7
• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria 7, 6
• Compression garments (waist-high stockings 30-40 mmHg) to reduce venous pooling 7, 6

Pharmacological Options If Symptoms Persist:

Midodrine is the first-line medication with the strongest evidence base, starting at 2.5-5 mg three times daily, with the last dose at least 4 hours before bedtime to prevent supine hypertension. 7, 9, 6 Three randomized controlled trials demonstrate efficacy. 7

Fludrocortisone can be added if midodrine alone is insufficient, starting at 0.05-0.1 mg daily, titrated to 0.1-0.3 mg daily. 8, 7, 3 Monitor for supine hypertension, hypokalemia, heart failure, and peripheral edema. 8, 7

Droxidopa is FDA-approved specifically for neurogenic orthostatic hypotension and may reduce falls. 7, 9

Pyridostigmine (60 mg three times daily) is beneficial for refractory cases, particularly when supine hypertension is a concern, as it does not worsen supine blood pressure. 2, 7, 6

Critical Warnings

Do not assume your symptoms are simply from Caplyta withdrawal. Projectile vomiting with hypothermia requires immediate medical evaluation to rule out:

• Infection or sepsis
• Metabolic emergencies
• Gastrointestinal pathology
• Neuroleptic malignant syndrome (rare but serious)
• Other acute medical conditions

Seek emergency care immediately if you experience:

• Continued vomiting preventing oral intake
• Persistent hypothermia
• Syncope or near-syncope
• Chest pain or palpitations
• Confusion or altered mental status
• Inability to maintain adequate hydration

Treatment Goals

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normal blood pressure readings. 8, 7 Treatment must balance improving standing blood pressure against the risk of worsening supine hypertension. 8, 7