Can trazodone be added to a regimen of amitriptyline (tricyclic antidepressant) and buspirone (anxiolytic)?

From the Guidelines

I do not recommend adding trazodone to a regimen that already includes amitriptyline and buspirone without medical supervision due to potential serious drug interactions. These three medications can interact to increase the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness. Additionally, the combination of amitriptyline and trazodone may increase the risk of QT interval prolongation, which can lead to dangerous heart rhythm problems.

According to the evidence from 1, sedating low-dose antidepressants, such as trazodone, may be considered when accompanied by comorbid depression or in the case of other treatment failures. However, the evidence for their efficacy when used alone is relatively weak, and no specific agent within this group is recommended as preferable to the others.

The most recent and highest quality study, 1, provides a clinical practice guideline from the American College of Physicians, which emphasizes the importance of evaluating the benefits and harms of nonpharmacologic treatments and selective serotonin reuptake inhibitors (SGAs), alone or in combination, for major depressive disorder (MDD).

If you're experiencing symptoms that make you consider adding another medication, please consult your healthcare provider who can evaluate your current medication effectiveness, adjust dosages if needed, or suggest appropriate alternatives. They can also monitor for side effects and interactions if multiple medications are deemed necessary for your condition. Self-adjusting psychiatric medications can be dangerous and may worsen your condition rather than improve it.

Some key points to consider:

• The risk of serotonin syndrome and QT interval prolongation when combining trazodone with amitriptyline and buspirone
• The importance of medical supervision when adding new medications to a regimen
• The need to evaluate the benefits and harms of nonpharmacologic treatments and SGAs for MDD
• The potential for self-adjusting psychiatric medications to worsen your condition rather than improve it.

From the FDA Drug Label

After addition of buspirone to the amitriptyline dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) of amitriptyline or its metabolite nortriptyline were observed Trazodone There is one report suggesting that the concomitant use of Desyrel (trazodone hydrochloride) and buspirone may have caused 3- to 6-fold elevations on SGPT (ALT) in a few patients. Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of Trazodone Hydrochloride Tablets with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, 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)

The combination of trazodone, amitriptyline, and buspirone may increase the risk of serotonin syndrome, a potentially life-threatening condition.

• Trazodone and buspirone may have interactive effects on hepatic transaminases.
• Amitriptyline is a tricyclic antidepressant that can increase the risk of serotonin syndrome when used with other serotonergic drugs like trazodone and buspirone. It is recommended to exercise caution when combining these medications and to closely monitor patients for signs of serotonin syndrome 2 3.

From the Research

Combination Therapy with Trazodone, Amitriptyline, and Buspirone

• The provided studies do not directly address the combination of trazodone with amitriptyline and buspirone 4, 5, 6, 7, 8.
• However, it is known that trazodone can be used in combination with other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), to augment their antidepressant effect 8.
• Trazodone has a unique mechanism of action and a favorable side effect profile, with a low risk of anticholinergic side effects, weight gain, and sexual side effects 6, 8.
• Amitriptyline is a tricyclic antidepressant (TCA) with a different mechanism of action and side effect profile compared to trazodone 5, 6.
• Buspirone is an anxiolytic medication that can be used in combination with antidepressants to treat anxiety symptoms 5.
• When combining multiple medications, it is essential to consider their potential interactions and side effects, as well as the patient's individual response to each medication.
• The decision to add trazodone to a regimen of amitriptyline and buspirone should be made on a case-by-case basis, taking into account the patient's specific needs and medical history, and under the guidance of a qualified healthcare professional.

Key Considerations

• Trazodone's efficacy and safety profile make it a potential option for combination therapy 4, 5, 7, 8.
• The dosage of trazodone used in combination therapy may be lower than the dosage used as a monotherapy 8.
• Close monitoring of the patient's response to the combination therapy and adjustment of the medication regimen as needed is crucial.
• The potential benefits and risks of combining trazodone with amitriptyline and buspirone should be carefully weighed, and the patient should be informed of the possible outcomes.