From the Guidelines
Taking Prozac (fluoxetine) with Pristiq (desvenlafaxine) is not recommended due to the risk of serotonin syndrome, and any such combination should be made under close medical supervision. Both Prozac and Pristiq are antidepressants that increase serotonin levels in the brain, with Prozac being a selective serotonin reuptake inhibitor (SSRI) and Pristiq being a serotonin-norepinephrine reuptake inhibitor (SNRI) 1. The combination of these medications can lead to excessive serotonin accumulation, potentially causing serotonin syndrome, a serious condition characterized by symptoms such as confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness.
Key Considerations
- The risk of serotonin syndrome is a significant concern when combining SSRIs and SNRIs, as noted in the context of potential drug-drug interactions with ozanimod treatment 1.
- Close medical supervision is essential if a healthcare provider decides to prescribe this combination, typically starting with lower doses and gradually adjusting them while monitoring for side effects.
- Patients should never stop taking either medication abruptly, as this can cause withdrawal symptoms.
- The decision to combine these medications should be made cautiously, considering the potential benefits against the risks of adverse reactions, including hypertensive crisis due to potential MAO inhibition by certain drug metabolites 1.
Recommendations for Use
- Consult a healthcare provider before making any changes to your medication regimen.
- If prescribed together, follow the healthcare provider's instructions carefully, and attend all scheduled follow-up appointments to monitor for potential side effects.
- Be aware of the symptoms of serotonin syndrome and seek immediate medical attention if they occur.
From the FDA Drug Label
Other Serotonergic Drugs Clinical Impact Concomitant use of desvenlafaxine with other serotonergic drugs increases the risk of serotonin syndrome Intervention Monitor for symptoms of serotonin syndrome when desvenlafaxine is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of desvenlafaxine and/or concomitant serotonergic drugs [see Warnings and Precautions (5. 2)]. Examples other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, amphetamines, tryptophan, and St. John’s Wort
Prozac (fluoxetine) is an SSRI. Taking Prozac with Pristiq (desvenlafaxine) may increase the risk of serotonin syndrome. Monitoring for symptoms of serotonin syndrome is recommended when using these medications concomitantly. If serotonin syndrome occurs, consideration of discontinuation of one or both medications may be necessary 2.
From the Research
Combination of Prozac and Pristiq
- The combination of Prozac (fluoxetine) and Pristiq (desvenlafaxine) has not been directly studied in the provided evidence.
- However, both medications are serotonergic agents, and their concomitant use may increase the risk of serotonin syndrome, a potentially life-threatening condition 3, 4, 5, 6.
- A case report describes a patient who developed serotonin syndrome while taking venlafaxine, which is the parent compound of desvenlafaxine, and an MAOI 6.
- Another study reports a case of serotonin syndrome in a patient taking bupropion and an SSRI, highlighting the potential risk of combining serotonergic agents 5.
- Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has been reported to cause serotonin syndrome alone in some cases, particularly in adolescents 7.
- The risk of serotonin syndrome may be increased when combining fluoxetine with other serotonergic agents, such as desvenlafaxine, due to pharmacodynamic and pharmacokinetic interactions 4.
Precautions and Monitoring
- Clinicians should be aware of the potential risk of serotonin syndrome when prescribing Prozac and Pristiq together 3, 4, 5, 6.
- Patients taking this combination should be closely monitored for signs and symptoms of serotonin syndrome, such as restlessness, tremor, shivering, diarrhea, vomiting, ataxia, tachycardia, and myoclonus 3.
- The use of concomitant potent cytochrome P450 2D6 inhibitors may increase the risk of serotonin syndrome, and patients should be cautioned about this potential interaction 4.