Are sertraline and amitriptyline (tricyclic antidepressant) compatible?

From the Guidelines

Sertraline and amitriptyline can be prescribed together, but this combination should only be used under careful medical supervision due to potential interactions. Both medications affect serotonin levels in the brain, which creates a risk of serotonin syndrome, a potentially serious condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness 1. The combination may also increase side effects like drowsiness, dry mouth, blurred vision, constipation, and urinary retention.

Key Considerations

• The use of selective serotonin reuptake inhibitors (SSRIs) like sertraline is preferred over tricyclic antidepressants (TCAs) like amitriptyline due to their lower side effect profiles and better safety, especially in patients with comorbid psychiatric disorders 1.
• However, amitriptyline has pain-modulating properties, which can be beneficial for patients with certain types of chronic pain, making the combination sometimes necessary 1.
• A study from 2015 noted that older adults are at a greater risk of adverse drug reactions, and lower starting doses are often recommended, approximately 50% of the adult starting dose 1.
• Tertiary-amine TCAs like amitriptyline are associated with significant adverse anticholinergic effects and are considered potentially inappropriate medications in older adults, according to the American Geriatric Society’s Beers Criteria 1.

Clinical Implications

• If prescribed together, doctors typically start with lower doses and gradually increase while monitoring for adverse effects.
• Patients taking both medications should report any unusual symptoms promptly to their healthcare provider.
• This combination is sometimes used when a single antidepressant hasn't provided adequate relief, particularly in patients with both depression and certain types of chronic pain.

From the FDA Drug Label

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including sertraline, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If concomitant use of sertraline with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases Tricyclic Antidepressant Drugs Effective in the Treatment of Major Depressive Disorder (TCAs) The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved Nevertheless, caution is indicated in the co-administration of TCAs with sertraline, because sertraline may inhibit TCA metabolism. Plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced, if a TCA is co-administered with sertraline

Sertraline and tricyclic antidepressants (such as amitriptyline) are not compatible due to the risk of serotonin syndrome and potential inhibition of TCA metabolism by sertraline. Caution is advised when considering concomitant use, and patients should be monitored for signs of serotonin syndrome. Plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced if co-administered with sertraline 2 2.

From the Research

Compatibility of Sertraline and Amitriptyline

• The compatibility of sertraline and amitriptyline can be assessed based on their pharmacological properties and clinical studies.
• A study published in 1998 3 compared the efficacy and safety of sertraline and amitriptyline in hospitalized patients with major depression, and found no statistically significant differences in efficacy between the two groups.
• However, the study noted that amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline.
• Another study published in 2001 4 reviewed the clinical applications of sertraline in psychiatric disorders and noted that sertraline has a low potential for pharmacokinetic drug interactions, which suggests that it may be compatible with other medications, including tricyclic antidepressants like amitriptyline.
• A study published in 1995 5 compared the efficacy of sertraline with other antidepressants, including tricyclic antidepressants like amitriptyline, and found that sertraline had a similar efficacy profile to these medications.
• However, it is worth noting that the study published in 2018 6 discussed the potential interaction between monoamine oxidase B inhibitors and selective serotonin reuptake inhibitors, and suggested that SSRIs like sertraline can be coadministered with other medications, provided that their recommended doses are not exceeded.
• Additionally, a review published in 2009 7 summarized the clinical use of sertraline in mood and anxiety disorders and noted that sertraline is safe and well-tolerated in numerous patient populations, including those with psychiatric and/or medical comorbidities.

Pharmacological Properties

• Sertraline is a selective serotonin reuptake inhibitor (SSRI) with a low potential for pharmacokinetic drug interactions 4.
• Amitriptyline is a tricyclic antidepressant with a different pharmacological profile than sertraline.
• The combination of sertraline and amitriptyline may be associated with an increased risk of side effects, such as autonomic and circulatory effects 3.

Clinical Implications

• The compatibility of sertraline and amitriptyline should be assessed on a case-by-case basis, taking into account the individual patient's medical history and current medications.
• Clinicians should be aware of the potential risks and benefits of combining these medications and monitor patients closely for any adverse effects 3, 4, 6.