Usual Adult Dose for Depression

Initial Dose: Fluoxetine 25 mg-olanzapine 6 mg orally once a day
Maintenance dose: Adjust as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally once a day
• Olanzapine: 3 to 12 mg orally once a day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally once a day
Duration: It is generally accepted that treatment-resistant depression and Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, are chronic illnesses requiring chronic treatment.

Comments:

• Dose adjustments may be made according to efficacy and tolerability.
• The safety of doses above fluoxetine 75 mg and olanzapine 18 mg per day has not been evaluated in clinical studies.

Use: Acute treatment of treatment-resistant depression and depressive episodes associated with Bipolar I Disorder

Usual Adult Dose for Bipolar Disorder

Initial Dose: Fluoxetine 25 mg-olanzapine 6 mg orally once a day
Maintenance dose: Adjust as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally once a day
• Olanzapine: 3 to 12 mg orally once a day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally once a day
Duration: It is generally accepted that treatment-resistant depression and Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, are chronic illnesses requiring chronic treatment.

Comments:

• Dose adjustments may be made according to efficacy and tolerability.
• The safety of doses above fluoxetine 75 mg and olanzapine 18 mg per day has not been evaluated in clinical studies.

Use: Acute treatment of treatment-resistant depression and depressive episodes associated with Bipolar I Disorder

Usual Geriatric Dose for Depression

Initial Dose: Fluoxetine 25 mg-olanzapine 3 mg to fluoxetine 25 mg-olanzapine 6 mg orally once a day
Maintenance dose: Adjust with caution as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally once a day
• Olanzapine: 6 to 12 mg orally once a day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally once a day
Duration: It is generally accepted that treatment-resistant depression and Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, are chronic illnesses requiring chronic treatment.

Comments:

• Dose adjustments may be made according to efficacy and tolerability.
• This drug combination has not been systematically studied in patients over 65 years of age.

Use: Acute treatment of treatment-resistant depression and depressive episodes associated with Bipolar I Disorder

Usual Geriatric Dose for Bipolar Disorder

Initial Dose: Fluoxetine 25 mg-olanzapine 3 mg to fluoxetine 25 mg-olanzapine 6 mg orally once a day
Maintenance dose: Adjust with caution as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally once a day
• Olanzapine: 6 to 12 mg orally once a day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally once a day
Duration: It is generally accepted that treatment-resistant depression and Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, are chronic illnesses requiring chronic treatment.

Comments:

• Dose adjustments may be made according to efficacy and tolerability.
• This drug combination has not been systematically studied in patients over 65 years of age.

Use: Acute treatment of treatment-resistant depression and depressive episodes associated with Bipolar I Disorder

Usual Pediatric Dose for Depression

10 to 17 years of age:
Initial Dose: Fluoxetine 25 mg-olanzapine 3 mg orally once a day
Maintenance dose: Adjust as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally per day
• Olanzapine: 6 to 12 mg orally per day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally per day
Duration: It is generally accepted that Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, is a chronic illness requiring chronic treatment.

Comment: The safety of doses above fluoxetine 50 mg and olanzapine 12 mg per day has not been evaluated in pediatric clinical studies

Use: Acute treatment of depressive episodes associated with Bipolar I Disorder

Usual Pediatric Dose for Bipolar Disorder

10 to 17 years of age:
Initial Dose: Fluoxetine 25 mg-olanzapine 3 mg orally once a day
Maintenance dose: Adjust as clinically necessary to within a range of:

• Fluoxetine: 25 to 50 mg orally per day
• Olanzapine: 6 to 12 mg orally per day

Maximum dose: Fluoxetine 50 mg-olanzapine 12 mg orally per day
Duration: It is generally accepted that Bipolar I disorder, including the depressive episodes associated with Bipolar I disorder, is a chronic illness requiring chronic treatment.

Comment: The safety of doses above fluoxetine 50 mg and olanzapine 12 mg per day has not been evaluated in pediatric clinical studies

Use: Acute treatment of depressive episodes associated with Bipolar I Disorder

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

Liver dysfunction:
Initial dose: Fluoxetine 25 mg-olanzapine 3 mg to fluoxetine 25 mg-olanzapine 6 mg orally once a day

• A lower or less frequent dose of the fluoxetine component should be used in patients with cirrhosis; dose adjustments, if clinically indicated, should be done with caution.

Dose Adjustments

An initial dose of fluoxetine 25 mg-olanzapine 3 mg to fluoxetine 25 mg-olanzapine 6 mg orally once a day should be considered in patients:

• With a predisposition to hypotensive reactions
• Who exhibit a combination of factors that may slow the metabolism of fluoxetine-olanzapine (e.g., female gender, geriatric age, nonsmokers)
• Who may be pharmacodynamically sensitive to olanzapine

Comments:

• Dose increases, if clinically indicated, should be performed with caution in these patients.
• Caution is advised when using fluoxetine-olanzapine in patients with diseases or conditions that could affect its metabolism

Switching from:
MAOI to fluoxetine-olanzapine therapy: At least 14 days should elapse
Fluoxetine-olanzapine to MAOI therapy: At least 5 weeks should elapse

Treatment withdrawal:

• A gradual dose reduction is recommended instead of abrupt cessation where possible.
• If intolerable symptoms occur, it is recommended to consider resuming the previously prescribed dose and to decrease the dose at a more gradual rate.

Precautions

US BOXED WARNINGS:
SUICIDAL THOUGHTS AND BEHAVIORS:

• Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.
• In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and emergence of suicidal thoughts and behaviors.
• Advise families and caregivers of the need for close observation and communication with the prescriber.
• Fluoxetine-olanzapine is not approved for use in children less than 10 years of age.

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS:

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
• Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
• Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
• Fluoxetine-olanzapine is not approved for the treatment of patients with dementia-related psychosis.

Safety and efficacy have not been established in patients younger than 10 years for the treatment of Bipolar I depression.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: No adjustment recommended
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• Doses should be taken in the evening without regard to meals.

General:

• Changes in dose will not be fully reflected in plasma for several weeks due to the long elimination half-lives of fluoxetine and its major active metabolite.
• The need for ongoing treatment should be regularly reviewed.
• Antidepressant efficacy was seen in a daily dose range of fluoxetine 25 to 50 mg and olanzapine 6 mg to 12 mg.

Monitoring:

• Cardiovascular: ECG monitoring (in patients with risk factors for QT-interval prolongation)
• Hepatic: Liver function
• Metabolic: Hyponatremia, hyperglycemia, hyperlipidemia, weight gain
• Nervous system: Serotonin syndrome
• Psychiatric: Emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior

Patient advice:

• Tell your healthcare provider about all of the medicines that you take, including prescription and non-prescription medicines.
• This medicine may increase the risk of suicidal thoughts and behavior. Be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report any behavior of concern to your healthcare provider as soon as possible.
• This medicine may cause drowsiness and dizziness; do not drive a car or operate dangerous machinery until you know how this drug affects you.
• Patients should be advised to speak to a healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.
• Do not drink alcohol or take other medicines that may cause sleepiness or dizziness while taking this medicine until you talk to your healthcare provider.