Does cyclobenzaprine (Flexeril) interact with sertraline (Zoloft)?

From the Guidelines

Yes, Flexeril (cyclobenzaprine) and Zoloft (sertraline) can interact with each other, potentially increasing the risk of serotonin syndrome, as noted in the most recent study 1. This interaction is considered moderate in severity. When taken together, these medications may cause excessive serotonin levels in the brain, leading to symptoms such as confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, high fever, and in severe cases, seizures or unconsciousness. The risk increases with higher doses of either medication. If you must take both medications, your doctor should monitor you closely for signs of serotonin syndrome, especially when starting treatment or changing doses, as recommended by the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. Report any unusual symptoms promptly, including agitation, hallucinations, rapid heartbeat, fever, excessive sweating, shivering, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea. Your healthcare provider may need to adjust dosages or consider alternative medications if the interaction risk is too high for your specific situation, taking into account the potential for drug-drug interactions and the need for careful monitoring, as discussed in the study on preoperative management of opioid and nonopioid analgesics 1. Key considerations include:

• Starting with a low dose and increasing slowly to minimize the risk of adverse effects
• Monitoring for symptoms of serotonin syndrome, especially in the first 24 to 48 hours after dosage changes
• Being aware of the potential for withdrawal symptoms when discontinuing cyclobenzaprine, and tapering the medication over 2 to 3 weeks to prevent these symptoms, as noted in the study 1.

From the FDA Drug Label

The development of a potentially life-threatening serotonin syndrome has been reported with Cyclobenzaprine Hydrochloride when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or monoamine oxidase (MAO) inhibitors. Postmarketing cases of serotonin syndrome have been reported during combined use of Cyclobenzaprine Hydrochloride and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or monoamine oxidase (MAO) inhibitors Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Cyclobenzaprine Hydrochloride and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or monoamine oxidase (MAO) inhibitors

Cyclobenzaprine (Flexeril) interacts with sertraline (Zoloft), as sertraline is an SSRI. The interaction may increase the risk of serotonin syndrome, a potentially life-threatening condition.

• Key points:
  • Concomitant use of cyclobenzaprine and sertraline may increase the risk of serotonin syndrome
  • Patients should be cautioned about the risk of serotonin syndrome
  • Careful observation is advised if concomitant treatment is clinically warranted 2 2

From the Research

Interaction between Cyclobenzaprine and Sertraline

• Cyclobenzaprine (Flexeril) is a muscle relaxant that can interact with sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI) 3, 4.
• The interaction between cyclobenzaprine and sertraline can increase the risk of serotonin syndrome, a potentially life-threatening condition caused by an excess of serotonin in the body 3, 4.
• Serotonin syndrome can cause symptoms such as neuromuscular excitation, autonomic instability, and altered mental status 5, 3, 4.
• The use of cyclobenzaprine with other serotonin-enhancing drugs, including SSRIs like sertraline, should be done with caution and close monitoring for signs of serotonin syndrome 3, 4.

Case Reports and Studies

• A case report published in The American Journal of Emergency Medicine described a patient who developed serotonin syndrome while taking Lexapro (an SSRI) and Flexeril (cyclobenzaprine) 3.
• Another study published in Anesthesia and Analgesia reported two cases of severe serotonin syndrome induced by the administration of cyclobenzaprine in postoperative patients already receiving another proserotoninergic drug 4.
• While the study published in the Journal of Clinical Psychopharmacology found no significant difference in the incidence of serotonin syndrome when linezolid was used alone or in combination with an SSRI or SNRI, it highlights the importance of monitoring for serotonin syndrome when combining proserotoninergic medications 6.