THERAPEUTICS

Brands

• Clozaril, Clopine, Fazaclo ODT, Versacloz, Denzapine, Zaponex, Leponex Generic?

• Yes

Class

• Antipsychotic

Commonly Prescribed for

(FDA approved in bold)

• Treatment-resistant schizophrenia

• Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder

• Dyskinesia

• Psychosis in patients with Parkinson’s disease (PD) or dementia with Lewy bodies (DLB)

• Bipolar disorder (treatment resistant)

• Severe psychosis

• Post-traumatic stress disorder

How the Drug Works

• It is a dibenzodiazepine derivative of high affinity for 5-HT2, α1/2, M1–5, and H1 receptors and moderate affinity for D2/4 receptors. The effect is likely from antagonizing D2 receptors (for positive symptoms) and 5-HT2A receptors (for negative symptoms)

How Long Until It Works

• Psychosis: may be effective in days, more commonly takes weeks or months to determine best dose and achieve best clinical effect

If It Works

• Continue to use at lowest required dose with appropriate monitoring. Patients with PD and DLB may improve more than patients with schizophrenia

If It Doesn't Work

• Increase dose

• In psychosis related to PD or DLB, eliminate or reduce dose of offending medications, such as dopamine agonists or amantadine

Best Augmenting Combos for Partial Response or Treatment-Resistance

• PD and DLB: cholinesterase inhibitors may reduce psychotic symptoms

• In dementia, SSRIs may improve behavioral symptoms

Tests

• Obligatory. Prior to starting treatment, obtain CBC, including white count and absolute neutrophil count. Repeat weekly for 6 weeks, then every other week as long as patient is on medication and for 4 weeks after stopping. Also monitor blood sugar periodically

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Motor AEs: blocking of D2 receptors

• Sedation, weight gain: blocking of H1 receptors

• Hypotension: blocking of α1/2-adrenergic receptors

• Dry mouth, constipation: blocking of muscarinic receptors (anticholinergic)

Notable AEs

• Most common: CNS (sedation, dizziness/vertigo, headache, tremor); cardiovascular (tachycardia, orthostatic hypotension, syncope); autonomic (hypersalivation, sweating, dry mouth, visual disturbance, urinary retention); GI reaction (GI hypomotility, constipation, nausea); and fever