Caplyta (Lumateperone) Side Effects
Caplyta is generally well-tolerated with the most common side effects being sleepiness, dizziness, nausea, and dry mouth, while serious but rare risks include increased mortality in elderly patients with dementia-related psychosis and suicidal thoughts in young adults. 1
Most Common Side Effects
The most frequently reported side effects with Caplyta 42 mg include:
- Sleepiness/somnolence (occurring in approximately 24% of patients vs 10% with placebo) 1, 2
- Dizziness 1, 3
- Nausea 1, 3
- Dry mouth (5-10.8% vs 2% with placebo) 1, 3, 4
- Sedation and fatigue (9.5% vs 2.1% with placebo) 2, 4
- Constipation 2, 5
- Diarrhea 2, 3
Serious Side Effects Requiring Immediate Medical Attention
Black Box Warnings
Increased mortality risk in elderly patients with dementia-related psychosis - antipsychotics like Caplyta raise the risk of death in this population, and Caplyta is not approved for dementia-related psychosis 1
Increased suicidal thoughts and actions - particularly in children, adolescents, and young adults under 24 years, especially within the first few months of treatment or with dose changes 1
Other Serious Risks
- Neuroleptic Malignant Syndrome (NMS) - presents with high fever, confusion, stiff muscles, changes in breathing/heart rate/blood pressure, and increased sweating 1
- Stroke risk in elderly patients with dementia-related psychosis 1
- Tardive dyskinesia - uncontrolled movements of face, tongue, or body parts that may not resolve even after stopping the medication 1
Metabolic and Laboratory Abnormalities
Caplyta demonstrates a favorable metabolic profile compared to other antipsychotics:
- Minimal weight gain - studies show weight decrease rather than gain in many patients 2, 3
- Low risk of metabolic syndrome - blood sugar, cholesterol, and triglyceride changes are minimal and similar to placebo 3, 4
- Decreased prolactin levels compared to standard antipsychotics like risperidone 2
- Low white blood cell count may occur, requiring monitoring during the first few months 1
However, patients should still be monitored for:
- High blood sugar (hyperglycemia) - symptoms include excessive thirst, frequent urination, hunger, weakness, confusion, or fruity breath odor 1
- Cholesterol and triglyceride levels should be checked before starting and periodically during treatment 1
Cardiovascular and Neurological Effects
- Orthostatic hypotension - feeling lightheaded or faint when rising from sitting/lying position 1
- Elevated heart rate 1
- Seizures (convulsions) may occur 1
- Falls - due to sleepiness, dizziness, or blood pressure changes, potentially causing fractures or injuries 1
Extrapyramidal Symptoms (EPS)
Caplyta has minimal risk for movement disorders compared to other antipsychotics:
- EPS-related adverse events occur less frequently with lumateperone 42 mg than with risperidone 2
- Tremor occurs in approximately 5% of patients 4
- Risk of dystonia and parkinsonism is significantly lower than first-generation antipsychotics 2, 6
Other Notable Side Effects
- Difficulty swallowing - may cause food or liquid to enter the lungs 1
- Problems controlling body temperature - may feel too warm 1
- Fertility problems in both males and females 1
- Headache 2, 4
Discontinuation Rates
Treatment discontinuation due to adverse events is relatively low at 12.4% with lumateperone plus antidepressant therapy versus 0.8% with placebo, indicating good overall tolerability 3
Critical Safety Monitoring
Patients should immediately contact their healthcare provider if experiencing:
- New or worsening depression, anxiety, or agitation 1
- Thoughts about suicide or dying 1
- Panic attacks or trouble sleeping 1
- Acting aggressive, angry, or violent 1
- Extreme increase in activity and talking (mania) 1
- Signs of high blood sugar (excessive thirst, urination, hunger, weakness) 1
- Signs of NMS (high fever, confusion, muscle stiffness) 1