Monitoring after starting an atypical antipsychotic

✽ BMI monthly for 3 months, then quarterly

✽ Consider monitoring fasting triglycerides monthly for several months in patients at high risk for metabolic complications and when initiating or switching antipsychotics

✽ Blood pressure, fasting plasma glucose, fasting lipids within 3 months and then annually, but earlier and more frequently for patients with diabetes or who have gained >5% of initial weight

• Treat or refer for treatment and consider switching to another atypical antipsychotic for patients who become overweight, obese, pre-diabetic, diabetic, hypertensive, or dyslipidemic while receiving an atypical antipsychotic

✽ Even in patients without known diabetes, be vigilant for the rare but life-threatening onset of diabetic ketoacidosis, which always requires immediate treatment, by monitoring for the rapid onset of polyuria, polydipsia, weight loss, nausea, vomiting, dehydration, rapid respiration, weakness, and clouding of sensorium, even coma

• Routine EKGs for screening or monitoring of dubious clinical value

• EKGs may be useful for selected patients (e.g., those with personal or family history of QTc prolongation; cardiac arrhythmia; recent myocardial infarction; uncompensated heart failure; or those taking agents that prolong QTc interval such as pimozide, thioridazine, selected antiarrhythmics, moxifloxacin, sparfloxacin, etc.)

• Patients at risk for electrolyte disturbances (e.g., patients on diuretic therapy) should have baseline and periodic serum potassium and magnesium measurements

• Patients with low white blood cell count (WBC) or history of drug-induced leucopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months and ziprasidone should be discontinued at the first sign of decline of WBC in the absence of other causative factors

Ziprasidone: side effects How Drug Causes Side Effects

• By blocking alpha 1 adrenergic receptors, it can cause dizziness, sedation, and hypotension, especially at high doses

• By blocking dopamine 2 receptors in the striatum, it can cause motor side effects (unusual)

✽ Mechanism of any possible weight gain is unknown; weight gain is not common with ziprasidone and may thus have a different mechanism from atypical antipsychotics for which weight gain is common or problematic

✽ Mechanism of any possible increased incidence of diabetes or dyslipidemia is unknown; early experience suggests these complications are not clearly associated with ziprasidone and if present may therefore have a different mechanism from that of atypical antipsychotics associated with an increased incidence of diabetes and dyslipidemia

Notable Side Effects

✽ Some patients may experience activating side effects at very low to low doses

• Dizziness, extrapyramidal symptoms, sedation, dystonia at high doses

• Nausea, dry mouth

• Asthenia, skin rash

• Rare tardive dyskinesia (much reduced risk compared to conventional antipsychotics)

• Orthostatic hypotension

Life-Threatening or Dangerous Side Effects

• Rare neuroleptic malignant syndrome (much reduced risk compared to conventional antipsychotics)

• Rare seizures

• Increased risk of death and cerebrovascular events in elderly patients with dementia-related psychosis

Weight Gain

• Reported in a few patients, especially those with low BMIs, but not expected

• Less frequent and less severe than for most other antipsychotics

Sedation

• Some patients experience, especially at high doses

• May be less than for some antipsychotics, more than for others

• Usually transient and at higher doses

• Can be activating at low doses

What to Do About 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 motor side effects when present

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

✽ 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

Best Augmenting Agents for Side Effects

• Benztropine or trihexyphenidyl for motor side effects

• Many side effects cannot be improved with an augmenting agent

ZIPRASIDONE: DOSING AND USE

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

• Capsules 20 mg, 40 mg, 60 mg, 80 mg

• Injection 20 mg/mL

How to Dose

• Schizophrenia (according to manufacturer): initial oral dose 20 mg twice a day; however, 40 mg twice a day or 60 mg twice a day may be better tolerated in many patients (less activation); maximum approved dose 100 mg twice a day

• Bipolar disorder (according to manufacturer): initial oral dose 40 mg twice a day; on day 2 increase to 60 or 80 mg twice a day

• For intramuscular formulation, recommended dose is 10–20 mg given as required; doses of 10 mg may be administered every 2 hours; doses of 20 mg may be administered every 4 hours; maximum daily dose 40 mg intramuscularly; should not be administered for more than 3 consecutive days

• See also the Switching section below, after Pearls