Bipolar I Acute Manic or Mixed Episodes Tolerability & Safety

Metabolics, prolactin, and weight change (bipolar I manic or mixed episodes studies)

Shifts from baseline to endpoint in pivotal studies1,2*

Fasting glucose Proportion of patients with metabolic shifts was similar to placebo
Total cholesterol
Fasting triglycerides
Prolactin (ng/mL) No meaningful
increase in mean levels

Weight change from baseline to endpoint in pivotal 3-week studies1†‡

at endpoint
Proportion of patients with
weight increase ≥7%
Placebo (n=439) +0.4 lb 2%
VRAYLAR 3-6 mg/day (n=259) +1.1 lb 1%

*Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high; total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL)1,2

Data shown from baseline to endpoint (Week 3 for mania or mixed studies) by modal daily dose, defined as most frequently administered dose per patient1

Recommended dose range of VRAYLAR is 3–6 mg/day for manic and mixed episodes and 1.5–3 mg/day for depressive episodes associated with bipolar I. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed.1

Observed adverse reactions and discontinuation (bipolar I manic or mixed episodes)

Most common adverse reactions (≥5% and at least twice that of placebo)1

dose range
3-6 mg/day (n=263)§
9-12 mg/day (n=360)§
EPSII 12% 26% 29%
Akathisia 5% 20% 21%
Vomiting 4% 10% 8%
Dyspepsia 4% 7% 9%
Somnolence 4% 7% 8%
Restlessness 2% 7% 7%

>92% of EPS and akathisia events in bipolar I acute manic studies were mild or moderate2

§Data shown from baseline to endpoint (Week 3) by modal daily dose, defined as most frequently administered dose per patient1

IIEPS included bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, oromandibular dystonia, parkinsonism, salivary hypersecretion, and tremor.1

Somnolence included hypersomnia, sedation, and somnolence.1


EPS=extrapyramidal symptoms.

Discontinuation rates1

Overall, 12% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 7% of placebo-treated patients in these trials.

  Placebo VRAYLAR
3-6 mg/day
EPS (excluding akathisia/restlessness) 0.2% 1%
Akathisia 0% 2%

Monitor patients when initiating or changing the dose of VRAYLAR1

EPS and akathisia are among the most common adverse reactions and are most frequently observed following initiation or up-titration1,18