Second-generation (atypical) antipsychotic
Antagonist at dopamine D₂ and serotonin 5-HT₂A receptors, with additional antagonism at multiple other serotonergic (5-HT₂C, 5-HT₇), adrenergic (α₁, α₂), and histaminergic (H₁) receptors; minimal anticholinergic activity
Schizophrenia; bipolar I disorder (acute manic or mixed episodes as monotherapy or adjunct)
Psychosis in dementia, acute agitation, augmentation in treatment-resistant mood disorders
Sublingual tablet (Saphris); transdermal patch (Secuado)
For schizophrenia, typically start at 5 mg sublingually BID; titrate to 10 mg BID if tolerated. For bipolar disorder, initial dose is 5 mg BID, may increase to 10 mg BID.
10–20 mg/day divided BID (sublingual); transdermal patch is once daily (3.8–7.6 mg/24 hours)
Bioavailability ~35% (sublingual); extensive hepatic metabolism via UGT1A4, CYP1A2, and CYP3A4; half-life ~24 hours; avoid food or water for 10 minutes post-dose (sublingual)
Somnolence, dizziness, oral hypoesthesia, akathisia, extrapyramidal symptoms, weight gain
QT prolongation (dose-dependent), hypersensitivity reactions (including anaphylaxis), neuroleptic malignant syndrome (NMS), tardive dyskinesia
Monitor weight, fasting glucose, and lipids at baseline and periodically. Periodic ECG may be considered in high-risk patients. Assess for EPS, sedation, and adherence challenges due to route of administration.
Increased mortality in elderly patients with dementia-related psychosis
Use caution in individuals with cognitive impairment, dementia, or Parkinson’s disease (PD) due to risk of sedation and extrapyramidal symptoms. The sublingual formulation may pose adherence challenges in patients with dysphagia, poor cooperation, or intellectual disability. The transdermal patch may be better tolerated in some cases but carries similar metabolic and extrapyramidal risks.