How the Drug 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 olanzapine’s efficacy

✽ Specifically, antagonist actions at 5HT2C receptors may contribute to efficacy for cognitive and affective symptoms in some patients

✽ 5HT2C antagonist actions plus serotonin reuptake blockade of fluoxetine add to the actions of olanzapine when given as Symbyax (olanzapine-fluoxetine combination)

How Long Until It 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 cognitive symptoms

• IM formulation can reduce agitation in 15–30 minutes

If It Works

• Most often reduces positive symptoms in schizophrenia but does not eliminate them

• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia

• Most schizophrenic patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third

• Perhaps 5–15% of schizophrenic patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year

• Such patients are considered super-responders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships

• Many bipolar patients may experience a reduction of symptoms by half or more

• Continue treatment until reaching a plateau of improvement

• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis

• For second and subsequent episodes of psychosis, treatment may need to be indefinite

• Even for first episodes of psychosis, it may be preferable to continue treatment indefinitely to avoid subsequent episodes

• Treatment may not only reduce mania but also prevent recurrences of mania in bipolar disorder

If It Doesn’t Work

• Try one of the other atypical antipsychotics (risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride, asenapine, iloperidone, lurasidone)

• If 2 or more antipsychotic monotherapies do not work, consider clozapine

• Some patients may require treatment with a conventional antipsychotic

• If no first-line atypical antipsychotic is effective, consider higher doses or augmentation with valproate or lamotrigine

• Consider noncompliance and switch to another antipsychotic with fewer side effects or to an antipsychotic that can be given by depot injection

• Consider initiating rehabilitation and psychotherapy such as cognitive remediation

• Consider presence of concomitant drug abuse