Children and Adolescents

• Approved for use in schizophrenia and manic/mixed episodes (ages 13 and older for both)

• Clinical experience and early data suggest olanzapine is probably safe and effective for behavioral disturbances in children and adolescents

• Children and adolescents using olanzapine may need to be monitored more often than adults

• Intramuscular formulation has not been studied in patients under 18 and is not recommended for use in this population

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

• Early findings of infants exposed to olanzapine in utero currently do not show adverse consequences

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

Breast Feeding

• Unknown if olanzapine 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 olanzapine should be monitored for possible adverse effects

OLANZAPINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

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

✽ Often a preferred augmenting agent in bipolar depression or treatment-resistant unipolar depression

✽ Patients needing rapid onset of antipsychotic action without drug titration

• Patients switching from intramuscular olanzapine to an oral preparation

Potential Disadvantages

• Patients concerned about gaining weight

✽ Patients with diabetes mellitus, obesity, and/or dyslipidemia

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Cognitive symptoms

• Unstable mood (both depressed mood and mania)

• Aggressive symptoms

Pearls

• Recent landmark head-to-head study in schizophrenia suggests greater effectiveness (i.e., lower dropouts of all causes) at moderately high doses compared to some other atypical and conventional antipsychotics at moderate doses

• Same recent head to head study in schizophrenia suggests greater efficacy but greater metabolic side effects compared to some other atypical and conventional antipsychotics

• Well accepted for use in schizophrenia and bipolar disorder, including difficult cases

✽ Documented utility in treatment-refractory cases, especially at higher doses

✽ Documented efficacy as augmenting agent to SSRIs (fluoxetine) in nonpsychotic treatment-resistant major depressive disorder

✽ Documented efficacy in bipolar depression, especially in combination with fluoxetine

• More weight gain than many other antipsychotics —does not mean every patient gains weight

• Motor side effects unusual at low- to mid-doses

• Less sedation than for some other antipsychotics, more than for others

✽ Controversial as to whether olanzapine has more risk of diabetes and dyslipidemia than other antipsychotics

• Cigarette smoke can decrease olanzapine levels and patients may require a dose increase if they begin or increase smoking

✽ A short-acting intramuscular dosage formulation is available

• Long-acting intramuscular dosage formulation is also approved

• 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

• Patients with inadequate responses to atypical antipsychotics may also benefit from a trial of augmentation with a conventional antipsychotic or switching to a conventional antipsychotic

• However, long-term polypharmacy with a combination of a conventional antipsychotic with an atypical antipsychotic may combine their side effects without clearly augmenting the efficacy of either

• 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

• Although a frequent practice by some prescribers, adding 2 conventional antipsychotics together has little rationale and may reduce tolerability without clearly enhancing efficacy

THE ART OF SWITCHING