Is it safe to use Ingrezza (valbenazine) and Prozac (fluoxetine) together?

Ingrezza and Prozac Can Be Used Together Safely

Yes, Ingrezza (valbenazine) and Prozac (fluoxetine) can be used together safely, as there are no significant drug-drug interactions between these medications, and clinical trial data specifically demonstrates efficacy and tolerability of valbenazine in patients with mood disorders who were maintained on their antidepressant regimens. 1

Evidence Supporting Concurrent Use

Clinical Trial Data

• Valbenazine was specifically studied in patients with mood disorders who were receiving concurrent psychotropic medications, including antidepressants, with stable medication regimens allowed throughout the trial. 1
• In the KINECT 3 study, 77 subjects with mood disorders received valbenazine while continuing their baseline psychiatric medications, demonstrating both efficacy for tardive dyskinesia and tolerability over 48 weeks of treatment. 1
• The combination showed sustained improvement in abnormal involuntary movements without safety concerns related to drug interactions. 1

Mechanism and Interaction Profile

• Valbenazine is a VMAT2 inhibitor that works by reducing dopamine release at synaptic terminals, while fluoxetine is an SSRI that increases serotonin availability—these are distinct, non-overlapping mechanisms. 2, 3
• Unlike some SSRIs (particularly fluvoxamine), fluoxetine has moderate effects on CYP450 enzymes, primarily CYP2D6, but valbenazine metabolism does not create clinically significant interactions with this pathway. 4

Important Monitoring Considerations

Serotonin Syndrome Vigilance

• While valbenazine itself does not increase serotonin, monitor for serotonin syndrome if other serotonergic agents are added to the regimen. 4
• Serotonin syndrome symptoms include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis). 4
• Symptoms typically arise within 24-48 hours after combining serotonergic medications. 4

Movement Disorder Assessment

• Valbenazine is specifically indicated for tardive dyskinesia, so ensure the movement disorder diagnosis is appropriate before initiating treatment. 2, 3
• The drug showed clinically significant improvement in TD with an effect size of d=0.90 at 80 mg/day dosing. 3
• Monitor for parkinsonism or excessive sedation, though these were not prominent adverse effects in clinical trials. 2

Psychiatric Stability

• No worsening of suicidal ideation or suicidal behavior was reported in participants treated with valbenazine in the Huntington's disease trial, and no treatment-emergent mania was observed in mood disorder populations. 2, 1
• Continue routine psychiatric monitoring as you would for any patient on fluoxetine, watching for behavioral activation, particularly in the first month of SSRI treatment or with dose increases. 4

Common Pitfalls to Avoid

Do Not Confuse with Other VMAT2 Inhibitors

• Valbenazine has a superior tolerability profile compared to tetrabenazine, with once-daily dosing and better short-term side effects. 3
• Unlike tetrabenazine, valbenazine did not show clinically important changes in vital signs, electrocardiograms, or laboratory tests in phase 3 trials. 2

QT Prolongation Considerations

• While fluoxetine (particularly citalopram among SSRIs) can prolong QT interval, valbenazine did not demonstrate clinically significant QT prolongation in clinical trials. 2, 4
• The concern about QT prolongation with antipsychotics listed in pediatric guidelines does not apply to valbenazine, which is not an antipsychotic. 4

Avoid Unnecessary Discontinuation

• If valbenazine is discontinued, tardive dyskinesia symptoms will re-emerge, as demonstrated by AIMS scores returning toward baseline within 4 weeks of washout. 1
• Plan for long-term treatment if TD improvement is achieved, as sustained benefits were demonstrated over 48 weeks of continuous therapy. 1

Dosing Approach

• Start valbenazine at 40 mg once daily, with option to increase to 80 mg daily after one week based on tolerability and efficacy. 3
• The 80 mg dose showed superior efficacy (effect size d=0.90) compared to 40 mg (effect size d=0.52). 3
• Maintain stable fluoxetine dosing during valbenazine initiation to avoid confounding psychiatric symptom changes. 1