Can amitriptyline be added to sertraline (Zoloft) 150 milligrams?

From the Guidelines

Amitriptyline can be added to sertraline 150mg, but this combination requires cautious management due to the potential risk of serotonin syndrome and other adverse effects, as highlighted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. When considering the addition of amitriptyline to sertraline, it is essential to start with a low dose of amitriptyline, typically 10-25mg at bedtime, and gradually increase as needed while closely monitoring for side effects, especially in the first 24 to 48 hours after dosage changes 1. Some key considerations for this combination include:

• Increased risk of serotonin syndrome, characterized by symptoms such as confusion, rapid heart rate, dilated pupils, muscle rigidity, and high blood pressure
• Potential for QT interval prolongation, which may require ECG monitoring
• Common side effects like increased drowsiness, dry mouth, constipation, blurred vision, and dizziness
• Importance of informing all healthcare providers about all medications being taken to avoid dangerous interactions It is crucial to weigh the potential benefits of combination therapy against the risks and to closely monitor patients for any adverse effects, as emphasized in the guideline 1.

From the FDA Drug Label

Drugs Metabolized by P450 2D6 Many drugs effective in the treatment of major depressive disorder, e. g., the SSRls, including sertraline, and most tricyclic antidepressant drugs effective in the treatment of major depressive disorder inhibit the biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by P450 2D6 The drugs for which this potential interaction is of greatest concern are those metabolized primarily by 2D6 and which have a narrow therapeutic index, e.g., the tricyclic antidepressant drugs effective in the treatment of major depressive disorder and the Type 1C antiarrhythmics propafenone and flecainide. In a study comparing the disposition of intravenously administered diazepam before and after 21 days of dosing with either sertraline (50 to 200 mg/day escalating dose) or placebo, there was a 32% decrease relative to baseline in diazepam clearance for the sertraline group compared to a 19% decrease relative to baseline for the placebo group (p<0. 03). The concomitant use of sertraline with MAOIs intended to treat psychiatric disorders is contraindicated. Sertraline should also not be started in a patient who is being treated with MAOIs such as linezolid or 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

• Amitriptyline is a tricyclic antidepressant that is metabolized by P450 2D6.
• The use of sertraline with amitriptyline may increase the plasma concentrations of amitriptyline due to the inhibition of P450 2D6 by sertraline.
• Additionally, the concomitant use of sertraline with tricyclic antidepressants such as amitriptyline may increase the risk of serotonin syndrome.
• Therefore, the addition of amitriptyline to sertraline 150mg should be done with caution and close monitoring for signs of serotonin syndrome and increased amitriptyline levels 2 2.

From the Research

Combination of Amitriptyline and Sertraline

• The combination of amitriptyline and sertraline is not directly addressed in the provided studies, but we can look at the properties of each medication to understand potential interactions.
• Amitriptyline is a tricyclic antidepressant (TCA) that has similar in vitro reuptake inhibitory potencies for 5-HT and NA, and is also a 5-HT2 receptor antagonist 3.
• Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is a potent 5-HT reuptake inhibitor, and has been shown to be effective in the treatment of depression 4.
• The combination of SSRIs and TCAs can increase the risk of serotonin syndrome, a potentially life-threatening adverse event 5.
• A study comparing the efficacy and acceptability of SSRIs and TCAs in the treatment of chronic depression found that both types of antidepressants are efficacious, but SSRIs showed better acceptability in terms of dropout rates than TCAs 6.

Potential Risks and Considerations

• The combination of amitriptyline and sertraline may increase the risk of serotonin syndrome, particularly if the patient is also taking other medications with serotonergic properties 5.
• Close monitoring for symptoms of serotonin syndrome should be considered in patients taking this combination, particularly if the patient is also taking other medications that may increase the risk of serotonin syndrome 5.
• The pharmacokinetics and effects on CYP450 enzymes of SSRIs, including sertraline, and TCAs, including amitriptyline, should be considered when combining these medications 7.