What are the contraindications of using Desvenlafaxine (Pristiq) and Strattera (Atomoxetine) in combination?

Contraindications for Combining Desvenlafaxine and Strattera (Atomoxetine)

There are no absolute contraindications to combining desvenlafaxine and atomoxetine, but the combination requires careful monitoring for serotonin syndrome and cardiovascular effects, particularly blood pressure and heart rate elevations. 1, 2, 3

Absolute Contraindications to Each Drug Individually

Desvenlafaxine Contraindications:

• Hypersensitivity to desvenlafaxine, venlafaxine, or any formulation excipients (angioedema has been reported) 2
• Concurrent use with MAOIs or within 7 days of stopping desvenlafaxine (increased serotonin syndrome risk) 2
• Use within 14 days of stopping an MAOI intended to treat psychiatric disorders 2
• Concurrent use with linezolid or intravenous methylene blue (MAOI activity increases serotonin syndrome risk) 2

Atomoxetine Contraindications:

• Concurrent use with MAOIs or within 14 days of MAOI discontinuation (serotonin syndrome risk) 1, 3

Critical Safety Concerns When Combining These Medications

Serotonin Syndrome Risk:

• Both desvenlafaxine (an SNRI) and atomoxetine (a selective norepinephrine reuptake inhibitor) affect monoamine neurotransmitter systems 1, 3
• When combining two non-MAOI serotonergic drugs, start the second medication at a low dose, increase slowly, and monitor intensively for symptoms in the first 24-48 hours after dosage changes 1
• Serotonin syndrome symptoms include mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis, vomiting, diarrhea) 1
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness that can be fatal 1

Cardiovascular Monitoring Requirements:

• Desvenlafaxine causes sustained clinical hypertension, increased blood pressure, and increased pulse 1
• Atomoxetine produces statistically significant increases in both heart rate and blood pressure 3
• Monitor height, weight, pulse, and blood pressure at baseline and regularly during treatment with both medications 1

Additional Shared Adverse Effects:

• Both medications can cause behavioral activation/agitation, hypomania, mania, sexual dysfunction, seizures, and abnormal bleeding 1
• Both carry warnings for suicidal thinking and behavior through age 24 years 1
• Atomoxetine has a black-box warning for suicidal ideation based on meta-analysis data 3
• Desvenlafaxine has been associated with overdose fatalities 1

Common Pitfalls to Avoid:

• Do not combine either medication with MAOIs, tramadol, meperidine, methadone, fentanyl, dextromethorphan, amphetamines, or other serotonergic agents without extreme caution 1
• Do not abruptly discontinue either medication - both require slow taper due to discontinuation syndrome risk 1
• Do not ignore cardiovascular parameters - the additive effects on blood pressure and heart rate can be clinically significant even if each drug alone produces only modest changes 1, 3

Drug Interaction Considerations:

• Desvenlafaxine has minimal CYP450 enzyme involvement, reducing pharmacokinetic drug interaction risk 4, 5, 6
• Atomoxetine is extensively metabolized by CYP2D6; poor metabolizers have greater exposure and slower elimination 3
• CYP2D6 inhibitors (like paroxetine) significantly alter atomoxetine pharmacokinetics and should be avoided or require dose adjustment 3