Published online by Cambridge University Press: 06 October 2020
• Clozaril, Clopine, Fazaclo ODT, Versacloz, Denzapine, Zaponex, Leponex Generic?
Commonly Prescribed for
(FDA approved in bold)
• Treatment-resistant schizophrenia
• Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
• 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
• 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)
• 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
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