Notable Side Effects

✽ Probably increases risk for diabetes mellitus and dyslipidemia

• Dizziness, sedation

• Dry mouth, constipation, dyspepsia, weight gain

• Peripheral edema

• Joint pain, back pain, chest pain, extremity pain, abnormal gait, ecchymosis

• Tachycardia

• Orthostatic hypotension, usually during initial dose titration

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

• Rare rash on exposure to sunlight

Life-Threatening or Dangerous Side Effects

• Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking atypical antipsychotics

• 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

• Frequent and can be significant in amount

• Can become a health problem in some

• More than for some other antipsychotics, but never say always as not a problem in everyone

Sedation

• Many patients experience and/or can be significant in amount

• Usually transient

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

What to Do About Side Effects

• Wait

• Wait

• Wait

• Take at bedtime to help reduce daytime sedation

• Anticholinergics may reduce motor side effects such as akathisia when present, but rarely necessary

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

• 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

OLANZAPINE: DOSING AND USE

Usual Dosage Range

• 10–20 mg/day (oral or intramuscular)

• 6–12 mg olanzapine/25–50 mg fluoxetine (olanzapine-fluoxetine combination)

• 210–300 mg/2 weeks (depot)

Dosage Forms

• Tablets 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg

• Orally disintegrating tablets 5 mg, 10 mg, 15 mg, 20 mg

• Intramuscular formulation 5 mg/mL, each vial contains 10 mg (available in some countries)

• Depot 210 mg, 300 mg, 405 mg

• Olanzapine-fluoxetine combination capsule (mg equivalent olanzapine/mg equivalent fluoxetine) 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, 12 mg/50 mg

How to Dose

• Initial 5–10 mg once daily orally; increase by 5 mg/day once a week until desired efficacy is reached; maximum approved dose is 20 mg/day

• For intramuscular formulation, recommended initial dose 10 mg; second injection of 5–10 mg may be administered 2 hours after first injection; maximum daily dose of olanzapine is 20 mg, with no more than 3 injections per 24 hours

• For olanzapine-fluoxetine combination, recommended initial dose 6 mg/25 mg once daily in evening; increase dose based on efficacy and tolerability; maximum generally 18 mg/75 mg

Dosing Tips – Oral

✽ More may be more: raising usual dose above 15 mg/day can be useful for acutely ill and agitated patients and some treatment-resistant patients, gaining efficacy without many more side effects

✽ Some heroic uses for patients who do not respond to other antipsychotics can occasionally justify dosing over 30 mg/day and short-term up to 90 mg/day

• For high doses in treatment-resistant or violent patients, monitor therapeutic drug levels and target generally higher than the usual range of 5–75 mg/mL (i.e., greater than 125 mg/mL), but keep below the toxic range associated with QTc prolongation (700–800 mg/mL)

• See also the Switching section below, after Pearls, for initiating both oral and long-acting injectable

• Rather than raise the dose above these levels in acutely agitated patients requiring acute antipsychotic actions, consider augmentation with a benzodiazepine or conventional antipsychotic, either orally or intramuscularly

• Rather than raise the dose above these levels in partial responders, consider augmentation with a mood-stabilizing anticonvulsant, such as valproate or lamotrigine

• Clearance of olanzapine is slightly reduced in women compared to men, so women may need lower doses than men

• Children and elderly should generally be dosed at the lower end of the dosage spectrum

✽ Olanzapine intramuscularly can be given short-term, both to initiate dosing with oral olanzapine or another oral antipsychotic and to treat breakthrough agitation in patients maintained on oral antipsychotics

• Treatment should be suspended if absolute neutrophil count falls below 1,000/mm³