What are the potential side effects of Vraylar (cariprazine) when starting treatment, particularly in patients with a history of psychiatric conditions such as schizophrenia or bipolar disorder?

Vraylar Side Effects When Starting Treatment

When initiating Vraylar (cariprazine), expect akathisia and extrapyramidal symptoms as the most common early adverse effects, occurring in a substantial proportion of patients across all indications, with movement disorders being dose-dependent and typically emerging within the first weeks of treatment. 1

Most Common Early Side Effects by Indication

Schizophrenia

• Extrapyramidal symptoms (EPS) and akathisia are the predominant early adverse reactions, occurring at rates significantly higher than placebo 1
• These movement-related side effects are dose-dependent and more likely at higher doses 1

Bipolar Mania

• EPS, akathisia, dyspepsia, vomiting, somnolence, and restlessness represent the most frequent early adverse effects (incidence ≥5% and at least twice placebo rate) 1
• Movement disorders remain the primary concern during initiation 1

Bipolar Depression

• Nausea, akathisia, restlessness, and EPS are the most common early side effects 1
• Treatment response rates of 46.3% vs 35.9% for placebo come with akathisia as a prominent tolerability concern 2

Adjunctive Treatment for Major Depressive Disorder

• Akathisia, restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness, and EPS are the most frequently reported early adverse effects 1

Movement Disorder Spectrum

Akathisia (Motor Restlessness)

• This represents the single most common adverse effect across all indications when starting Vraylar 1, 3
• Characterized by severe inner restlessness and inability to sit still 4
• Occurs early in treatment and is dose-related 1

Extrapyramidal Symptoms

• Include acute dystonia (sudden muscle spasms), parkinsonism (tremor, rigidity, bradykinesia), and akathisia 4, 1
• Young patients, particularly males, are at higher risk for acute dystonic reactions 5
• These symptoms can be distressing and may require anticholinergic medications for management 6

Critical Early Monitoring Considerations

Late-Occurring Adverse Reactions

Because Vraylar has an extremely long half-life (1-3 weeks for the active metabolite didesmethyl-cariprazine), adverse reactions may emerge or persist for several weeks after starting treatment or changing doses 1, 7

• This unique pharmacokinetic profile means side effects can appear delayed and persist longer than with other antipsychotics 1
• Monitor patients for adverse reactions and response for several weeks after initiation and with each dosage adjustment 1

Metabolic Effects (Early Baseline Required)

• Obtain baseline weight, BMI, waist circumference, blood pressure, fasting glucose, and lipid panel before starting 1
• Real-world data shows estimated weight gain of +0.91 kg/year during treatment, which is relatively modest 8
• Metabolic changes are generally not clinically significant compared to other atypicals 9, 7

Cardiovascular Monitoring

• Monitor orthostatic vital signs, especially in elderly patients, those with dehydration, or cardiovascular disease 1
• Assess for orthostatic hypotension during initial dose titration 1

Serious but Less Common Early Risks

Neuroleptic Malignant Syndrome (NMS)

• Rare but potentially lethal syndrome consisting of mental status changes, fever, muscle rigidity, and autonomic dysfunction 1
• Requires immediate discontinuation and emergency management if suspected 1
• Risk factors include dehydration, physical exhaustion, and concomitant psychotropic medications 5

Hematologic Effects

• In patients with pre-existing low white blood cell count or history of drug-induced leukopenia/neutropenia, perform complete blood count frequently during the first few months 1
• Consider discontinuation if clinically significant decline in WBC occurs without other causative factors 1

Cognitive and Motor Impairment

• Somnolence occurs in 6-11% of patients depending on indication 1
• Warn patients about operating hazardous machinery until they know how Vraylar affects them 1

Practical Early Management Algorithm

Week 1-2 After Initiation:

• Assess for akathisia and EPS at every contact 1
• Monitor for nausea, vomiting, and gastrointestinal symptoms 1
• Check orthostatic vital signs if patient reports dizziness 1

Week 2-4:

• Continue monitoring movement disorders, as they may emerge or worsen 1
• Assess for somnolence and cognitive effects 1
• Evaluate tolerability to determine if dose adjustment needed 1

Week 4-8:

• Remember that adverse effects may still be emerging due to long half-life 1
• Reassess metabolic parameters (weight, blood pressure) 1
• Monitor for any delayed-onset side effects 1

Important Caveats

Discontinuation Rates

• Overall discontinuation due to adverse events is relatively low: 6.7% for cariprazine vs 4.8% for placebo (NNH 51, not significant) 2
• This suggests most side effects are tolerable despite their frequency 2

Dose-Dependent Effects

• Higher doses (particularly 3 mg vs 1.5 mg) are associated with increased adverse events and discontinuation rates 2
• Start at 1.5 mg daily and titrate slowly to minimize side effects 1

Drug Interactions

• Reduce Vraylar dosage when co-administered with strong or moderate CYP3A4 inhibitors 1
• Concomitant use with CYP3A4 inducers is not recommended 1

Boxed Warnings to Discuss

• Increased mortality in elderly patients with dementia-related psychosis (Vraylar is not approved for this use) 1
• Suicidal thoughts and behaviors in pediatric and young adult patients when used as antidepressant (close monitoring required) 1

The likelihood to experience therapeutic benefit substantially outweighs the likelihood of discontinuation due to adverse events, with akathisia and EPS being manageable in most cases through dose adjustment or adjunctive medications 2.