From the Guidelines
It is not recommended to take both amitriptyline and Paxil (paroxetine) together without close medical supervision due to the increased risk of serotonin syndrome and other adverse effects. These medications belong to different classes of antidepressants - amitriptyline is a tricyclic antidepressant while Paxil is a selective serotonin reuptake inhibitor (SSRI). When combined, they can increase the risk of developing 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, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.
Some key considerations 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, as recommended in the guideline 1
- Being aware of the potential for drug-drug interactions, particularly with paroxetine, which may interact with drugs metabolized by CYP2D6 1
- Monitoring for discontinuation syndrome, which has been associated with paroxetine, characterized by dizziness, fatigue, lethargy, general malaise, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, sensory disturbances, paresthesias, anxiety, irritability, and agitation 1
If your doctor has prescribed both medications, they have likely weighed the benefits against the risks for your specific situation. Never adjust your medication regimen without consulting your healthcare provider first. If you're concerned about taking these medications together, discuss alternative treatment options with your doctor rather than stopping either medication abruptly.
From the Research
Combination of Amitriptyline and Paxil
- The combination of amitriptyline and Paxil (paroxetine) can lead to serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as confusion, psychomotor agitation, hyperreflexia, and spontaneous myoclonus 2.
- Studies have compared the efficacy and tolerability of paroxetine and amitriptyline in the treatment of recurrent depression, with paroxetine showing better tolerability and fewer side effects 3, 4.
- Amitriptyline has been found to be effective in preventing migraine, with a sedating effect that can be beneficial for patients with comorbid insomnia 5.
- Serotonin plays a complex role in regulating pain sensation, cognition, and emotions, and its receptors may be a promising target for the treatment of chronic pain and injury-related anxiety 6.
Safety Considerations
- The use of amitriptyline and Paxil together requires careful monitoring due to the risk of serotonin syndrome 2.
- Patients should be counseled about the possibility of a withdrawal effect from selective serotonin reuptake inhibitors (SSRIs) like Paxil 5.
- The side effect burden of antidepressants can be substantial, and patients should be carefully evaluated for potential interactions and contraindications 3, 4, 5.