From the FDA Drug Label
5 mg and fluoxetine 20 to 50 mg. Antidepressant efficacy was demonstrated with ZYPREXA and fluoxetine in combination in adult patients with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Oral olanzapine should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine Dosage adjustments, if indicated, can be made according to efficacy and tolerability within dose ranges of oral olanzapine 5 to 20 mg and fluoxetine 20 to 50 mg.
Olanzapine can be taken with antidepressants (Selective Serotonin Reuptake Inhibitors (SSRIs) / Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)) and anti-anxiety medications (anxiolytics), specifically fluoxetine, as demonstrated in clinical trials.
- The recommended dose range for olanzapine is 5 to 20 mg and for fluoxetine is 20 to 50 mg.
- Dosage adjustments should be made according to efficacy and tolerability.
- However, safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies 1.
From the Research
Olanzapine can be taken with antidepressants and anti-anxiety medications, but this combination should only be used under close medical supervision. The most recent and highest quality study, 2, published in 2018, found that the combination of olanzapine and venlafaxine was effective in reducing anxiety and depressive symptoms in patients with severe major depressive disorder. This study suggests that olanzapine can be used in combination with antidepressants, such as SSRIs and SNRIs, to achieve better symptom control in conditions like treatment-resistant depression or psychotic depression.
Some common SSRI medications that may be combined with olanzapine include:
- Fluoxetine
- Sertraline
- Escitalopram While SNRIs like venlafaxine or duloxetine may also be prescribed alongside olanzapine. In fact, there is even a combination medication called Symbyax that contains olanzapine and fluoxetine together, as noted in 3.
When combining olanzapine with benzodiazepines like lorazepam or clonazepam, caution is needed as the sedative effects may be enhanced. Dosing should always be individualized, typically starting with lower doses of each medication and gradually adjusting based on response and side effects. Patients should be aware that these combinations may increase the risk of certain side effects, including:
- Sedation
- Weight gain
- Metabolic changes
- In rare cases, serotonin syndrome (particularly with SSRIs/SNRIs)
Regular monitoring of vital signs, weight, blood glucose, and lipid levels is important when taking these medication combinations, as noted in 4. The rationale for combining these medications is that they work on different neurotransmitter systems - olanzapine primarily affects dopamine and serotonin receptors, while antidepressants target serotonin and/or norepinephrine reuptake, allowing for potentially better symptom control in conditions like bipolar disorder, treatment-resistant depression, or psychotic depression.