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

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• 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

Breast Feeding

• Unknown if ziprasidone is secreted in human breast milk, but all psychotropics 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

Ziprasidone: the art of psychopharmacology Potential Advantages

• Some cases of psychosis and bipolar disorder refractory to treatment with other antipsychotics

✽ Patients concerned about gaining weight and patients who are already obese or overweight

✽ Patients with diabetes

✽ Patients with dyslipidemia (especially elevated triglycerides)

• Patients requiring rapid relief of symptoms (intramuscular injection)

• Patients switching from intramuscular ziprasidone to an oral preparation

Potential Disadvantages

• Patients noncompliant with twice daily dosing

✽ Patients noncompliant with dosing with food

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Cognitive symptoms

• Unstable mood (both depression and mania)

• Aggressive symptoms

Pearls

• Recent landmark head-to-head study in schizophrenia suggests lower metabolic side effects and comparable efficacy compared to some other atypical and conventional antipsychotics

✽ When given to patients with obesity and dyslipidemia associated with prior treatment with another atypical antipsychotic, many experience weight loss and decrease in fasting triglycerides

✽ QTc prolongation fears are often exaggerated and not justified since QTc prolongation with ziprasidone is not dose-related and few drugs have any potential to increase ziprasidone’s plasma levels

✽ Efficacy may be underestimated since ziprasidone is mostly under-dosed (<120 mg/day) in clinical practice

✽ Well accepted in clinical practice when wanting to avoid weight gain because less weight gain than most other atypical antipsychotics

✽ May not have diabetes or dyslipidemia risk, but monitoring is still indicated

• Less sedation than some antipsychotics, more than others (at moderate to high doses)

✽ More activating than some other antipsychotics at low doses

• Anecdotal reports of utility in treatment-resistant cases, especially when adequately dosed

✽ A short-acting intramuscular dosage formulation is available

• Approved for mania in children ages 10–17

• Patients with inadequate responses to atypical antipsychotics may benefit from determination of plasma drug levels and, if low, a dosage increase even beyond the usual prescribing limits

• For treatment-resistant patients, especially those with impulsivity, aggression, violence, and self-harm, long-term polypharmacy with 2 atypical antipsychotics or with 1 atypical antipsychotic and 1 conventional antipsychotic may be useful or even necessary while closely monitoring

• In such cases, it may be beneficial to combine 1 depot antipsychotic with 1 oral antipsychotic

THE ART OF SWITCHING