ZIPRASIDONE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Atypical antipsychotic (serotonin– dopamine, serotonin; second-generation antipsychotic; also a mood stabilizer)

ZIPRASIDONE commonly prescribed for

(Bold for FDA approved)

How ZIPRASIDONE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• 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 ziprasidone’s efficacy

• Specifically, interactions at serotonin 2C and 1A receptors may contribute to efficacy for cognitive and affective symptoms in some patients

• Specifically, interactions at serotonin 1D and 7 receptors and at serotonin and norepinephrine transporters (especially at high doses) may contribute to efficacy for affective symptoms in some patients

How long until ZIPRASIDONE 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 negative or cognitive symptoms

• Intramuscular formulation can reduce agitation in 15 minutes

Notable Side Effects

• Activation (at very low to low doses)

• Dizziness, drug-induced parkinsonism, sedation (dose-dependent), dystonia at high doses

• Nausea, dry mouth (dose-dependent)

• Asthenia, skin rash

• Orthostatic hypotension (dose-dependent)

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

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

Life Threatening Side Effects

• Rare but serious skin condition known as drug reaction with eosinophilia and systemic symptoms (DRESS)

• 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

• 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

unusual

sedation

not usual

What to do about ZIPRASIDONE side effects

• Wait

• Wait

• Wait

• Usually dosed twice daily, so take more of the total daily dose at bedtime to help reduce daytime sedation

• Anticholinergics may reduce drug-induced parkinsonism when present

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

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

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

• For activating side effects at low doses, raise the dose

• For sedating side effects at high doses, lower the dose

• Switch to another atypical antipsychotic

usual dosage range

• Schizophrenia: 40–200 mg/day (in divided doses) orally

• Bipolar disorder: 80–160 mg/day (in divided doses) orally

• 10–20 mg intramuscularly

Dosage Forms

• Capsule 20 mg, 40 mg, 60 mg, 80 mg

• Injection 20 mg/mL

long term use

• Approved to delay relapse in long-term treatment of schizophrenia

• Often used for long-term maintenance in bipolar disorder and various behavioral disorders

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

habit forming

• No

Renal Impairment

• No dose adjustment necessary

• Not removed by hemodialysis

• Intramuscular formulation should be used with caution

Hepatic Impairment

• No dose adjustment necessary

Cardiac Impairment

• Ziprasidone is contraindicated in patients with a known history of QTc prolongation, recent acute myocardial infarction, and uncompensated heart failure

• Should be used with caution in other cases of cardiac impairment because of risk of orthostatic hypotension

Elderly

• Some patients may tolerate lower doses better

• 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

• Consider pimavanserin for dementia-related psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Not officially recommended for patients under age 18

• Clinical experience and early data suggest ziprasidone may be safe and effective for behavioral disturbances in children and adolescents

• Children and adolescents using ziprasidone may need to be monitored more often than adults and may tolerate lower doses better

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in 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

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Ziprasidone may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

• National Pregnancy Registry for Atypical Antipsychotics: 1-866-961-2388, https://womensmentalhealth.org/research/ pregnancyregistry/atypicalantipsychotic

Breast Feeding

• Unknown if ziprasidone is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed

• Infants of women who choose to breast feed while on ziprasidone should be monitored for possible adverse effects