brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Atypical antipsychotic (serotonin– dopamine antagonist)

Zoleptil commonly prescribed for

(Bold for FDA approved)

How Zoleptil works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

• Interactions at a myriad of other neurotransmitter receptors may contribute to zotepine’s efficacy

• Specifically inhibits norepinephrine uptake

How long until Zoleptil works

• Psychotic and manic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on cognitive symptoms

Notable Side Effects

• Atypical antipsychotics may increase the risk for diabetes and dyslipidemia, although the specific risks associated with zotepine are unknown

• Agitation, anxiety, depression, asthenia, headache, insomnia, sedation, hypo/ hyperthermia

• Constipation, dry mouth, dyspepsia, weight gain

• Tachycardia, hypotension, sweating, blurred vision

• Tardive dyskinesia

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

• Dose-related hyperprolactinemia

Life Threatening Side Effects

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare seizures (risk increases with dose, especially over 300 mg/day)

• Blood dyscrasias

• Dose-dependent QTc prolongation

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

weight gain

common

sedation

common

What to do about Zoleptil side effects

• Wait

• Wait

• Wait

• For drug-induced parkinsonism, add an anticholinergic agent

• Beta blockers, benzodiazepines, or serotonin 2A antagonists (e.g., mirtazapine, cyproheptadine) may reduce akathisia

• Take more of the dose at bedtime to help reduce daytime sedation

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

• Reduce the dose

• Switch to a first-line atypical antipsychotic

usual dosage range

• 75–300 mg/day in 3 divided doses

Dosage Forms

• Tablet 25 mg, 50 mg, 100 mg

long term use

• Can be used to delay relapse in long-term treatment of schizophrenia

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Recommended starting dose 25 mg twice a day; recommended maximum dose generally 75 mg twice a day

Hepatic Impairment

• Recommended starting dose 25 mg twice a day; recommended maximum dose generally 75 mg twice a day

• May require weekly monitoring of liver function during the first few months of treatment

Cardiac Impairment

• Drug should be used with caution

• Zotepine produces a dose-dependent prolongation of QTc interval, which may be enhanced by the existence of bradycardia, hypokalemia, congenital or acquired long QTc interval, which should be evaluated prior to administering zotepine

• Use with caution if treating concomitantly with a medication likely to produce prolonged bradycardia, hypokalemia, slowing of intracardiac conduction, or prolongation of the QTc interval

• Avoid zotepine in patients with a known history of QTc prolongation, recent acute myocardial infarction, and uncompensated heart failure

Elderly

• Recommended starting dose 25 mg twice a day; recommended maximum dose generally 75 mg twice a day

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Not recommended for use in children under age 18

Pregnancy

• Insufficient data in humans to determine risk

• There is a risk of abnormal muscle movements and withdrawal symptomsin newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Zotepine is not recommended during pregnancy

Breast Feeding

• Zotepine is not recommended during breast feeding

• Immediate postpartum period is a highrisk time for relapse of psychosis, so may consider treatment with another antipsychotic