Should amphetamines be taken with Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

From the Guidelines

Taking amphetamines with SSRIs or SNRIs is not recommended without close medical supervision due to the risk of serotonin syndrome and other serious drug interactions. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, concomitant administration of any of the SSRIs or SNRIs with any of the monoamine oxidase inhibitors (MAOIs) is contraindicated because of increased risk of serotonin syndrome. Similarly, the guideline notes that SSRIs and SNRIs can interact with other drugs, including those that prolong the QT interval, and that caution is necessary when starting or changing doses of these medications.

Some key points to consider when taking amphetamines with SSRIs or SNRIs include:

• The risk of serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as agitation, confusion, rapid heart rate, and high blood pressure 1
• The potential for increased cardiovascular risks, including elevated blood pressure and heart rate
• The need for careful monitoring of dosages and regular check-ups to assess for side effects
• The importance of starting with lower doses and gradually increasing as needed and tolerated

It is essential to note that medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications, including SSRIs and SNRIs 1. If you are prescribed both types of medications, your doctor should provide clear guidance on timing of medication intake and monitor you closely for any potential interactions or side effects.

From the FDA Drug Label

The concomitant use of amphetamine sulfate and serotonergic drugs increase the risk of serotonin syndrome Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during amphetamine sulfate initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate and the concomitant serotonergic drug(s) (see WARNINGS and PRECAUTIONS) Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort. The concomitant use of amphetamine sulfate and CYP2D6 inhibitors may increase the exposure of amphetamine sulfate compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during amphetamine sulfate initiation and after a dosage increase If serotonin syndrome occurs, discontinue amphetamine sulfate and the CYP2D6 inhibitor (see WARNINGS , OVERDOSAGE). Examples of CYP2D6 inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Amphetamines and SSRIs/SNRIs: Amphetamines should be used with caution when taken with SSRIs or SNRIs due to the increased risk of serotonin syndrome.

• Key considerations:
  • Initiate with lower doses
  • Monitor patients for signs and symptoms of serotonin syndrome
  • Discontinue amphetamine sulfate and the concomitant serotonergic drug(s) if serotonin syndrome occurs 2

From the Research

Amphetamines and SSRIs or SNRIs

• There is no direct evidence in the provided studies to suggest that amphetamines should be taken with SSRIs or SNRIs 3, 4, 5, 6, 7.
• However, it is known that combining certain medications can increase the risk of serotonin syndrome, a potentially life-threatening condition 3.
• The studies provided focus on the use of SSRIs and SNRIs in treating depression, anxiety, and other disorders, but do not specifically address the use of amphetamines with these medications 3, 4, 5, 6, 7.

Potential Interactions

• SSRIs and SNRIs can interact with other medications, including those that affect the CYP450 enzyme system, which can lead to increased levels of certain medications in the body 3, 6.
• Amphetamines can also interact with other medications, including those that affect the cardiovascular system, which can increase the risk of adverse effects 4.
• Therefore, it is essential to exercise caution when combining amphetamines with SSRIs or SNRIs, and to carefully monitor patients for potential interactions and adverse effects 3, 4, 5, 6, 7.

Clinical Considerations

• The decision to use amphetamines with SSRIs or SNRIs should be made on a case-by-case basis, taking into account the individual patient's medical history, current medications, and potential risks and benefits 3, 4, 5, 6, 7.
• Clinicians should carefully monitor patients for potential interactions and adverse effects, and adjust treatment plans as needed to minimize risks and optimize benefits 3, 4, 5, 6, 7.