Are there any interactions between doxepin and escitalopram (Lexapro)?

From the Guidelines

Doxepin and Lexapro (escitalopram) should not be taken together without medical supervision due to potential serious interactions, as both medications can increase serotonin levels in the brain and prolong the QT interval of the heart, potentially causing serotonin syndrome and dangerous heart rhythm disturbances. These medications can interact to cause 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 1. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders, concomitant administration of any of the SSRIs with any of the monoamine oxidase inhibitors (MAOIs) is contraindicated because of increased risk of serotonin syndrome, and SSRIs may also interact with drugs that prolong the QT interval 1.

Some key points to consider when taking these medications together include:

• Starting the second non-MAOI serotonergic drug at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1
• Informing your doctor immediately about all medications you're taking, and never adjusting dosages or stopping taking either medication without medical guidance, as abrupt discontinuation can cause withdrawal symptoms
• The potential for drug-drug interactions, particularly with fluvoxamine, which may have greater potential for drug-drug interactions due to its effects on CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6 1
• The recommended therapeutic ranges for antidepressant drugs, including doxepin and escitalopram, which can help guide dosage adjustments and monitoring 1.

It's essential to work closely with your doctor to weigh the benefits and risks of taking doxepin and Lexapro together, and to carefully monitor your condition to minimize the risk of adverse interactions 1.

From the Research

Interaction between Doxepin and Lexapro

• There is no direct evidence of an interaction between doxepin and Lexapro (escitalopram) in the provided studies.
• However, it is known that both doxepin and Lexapro can increase the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive levels of serotonin in the body 2.
• The study on serotonin syndrome associated with the use of escitalopram suggests that combining escitalopram with other medications that increase serotonin levels can increase the risk of serotonin syndrome 2.
• Another study on drug-drug interactions notes that combinations of drugs that increase the risk of serotonin syndrome are a common type of drug-drug interaction 3.
• While there is no specific evidence on the interaction between doxepin and Lexapro, it is possible that combining these two medications could increase the risk of serotonin syndrome or other adverse effects.
• A study on the efficacy and tolerability of antidepressants in individuals with comorbid physical conditions and depressive disorders found that selective serotonin reuptake inhibitors (SSRIs) like escitalopram have a relatively good benefit-risk profile, but tricyclic antidepressants like doxepin are less tolerated 4.
• The study on esketamine combined with SSRI or SNRI for treatment-resistant depression found that the combination of esketamine with an SNRI had a lower incidence of mortality, hospitalizations, and depressive relapses compared to the combination with an SSRI, but the study did not specifically examine the combination of doxepin and Lexapro 5.