What is the interaction between antidepressants and Plaquenil (hydroxychloroquine)?

Interactions Between Antidepressants and Hydroxychloroquine (Plaquenil)

There are no major contraindicated interactions between most antidepressants and hydroxychloroquine (Plaquenil), but caution should be exercised due to potential additive effects on QT interval prolongation and risk of serotonin syndrome with certain combinations.

Key Interaction Concerns

• QT interval prolongation: Both hydroxychloroquine and certain antidepressants (particularly tricyclic antidepressants and some SSRIs) can prolong the QT interval, potentially increasing the risk of cardiac arrhythmias when used together 1, 2

• CYP2D6 interactions: Hydroxychloroquine may be partially metabolized through CYP2D6 pathways, and strong CYP2D6 inhibitors like fluoxetine and paroxetine could theoretically increase hydroxychloroquine levels 3, 4

• Serotonergic effects: While not as concerning as MAOI interactions, there is a theoretical risk of enhanced serotonergic effects when combining hydroxychloroquine with SSRIs or SNRIs 1, 3

Specific Antidepressant Classes and Their Interactions

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Most SSRIs can be used with hydroxychloroquine with appropriate monitoring 1, 3
• Fluoxetine and paroxetine (strong CYP2D6 inhibitors) may require more careful monitoring due to potential for increased hydroxychloroquine levels 3, 5
• Monitor for enhanced sedation, dizziness, or cognitive impairment, particularly during the first 24-48 hours after starting the combination 3

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Generally can be used with hydroxychloroquine with appropriate monitoring 1, 4
• Duloxetine (moderate CYP2D6 inhibitor) may require more careful monitoring 5
• Watch for potential additive effects on blood pressure and heart rate 2

TCAs (Tricyclic Antidepressants)

• Use with caution due to increased risk of QT prolongation when combined with hydroxychloroquine 1, 2
• Consider ECG monitoring when combining TCAs with hydroxychloroquine, especially in patients with pre-existing cardiac conditions 2
• Clomipramine has particularly strong serotonergic effects and should be used with extra caution 1

MAOIs (Monoamine Oxidase Inhibitors)

• While there is no specific contraindication listed, MAOIs have the highest potential for serious drug interactions among antidepressants and should be used with extreme caution 6, 2
• Consider alternative antidepressant classes when hydroxychloroquine is needed 6

Monitoring Recommendations

• Baseline ECG: Consider obtaining a baseline ECG before starting the combination, particularly in patients with cardiac risk factors or when using TCAs 2

• Regular monitoring: Monitor for symptoms of excessive sedation, dizziness, or cognitive impairment, especially during the first few weeks of treatment 3

• Cardiac symptoms: Watch for palpitations, syncope, or other cardiac symptoms that might indicate arrhythmias 2

• Serotonergic symptoms: Monitor for signs of serotonin syndrome (agitation, tremor, hyperthermia, hyperreflexia, incoordination) 1, 6

Risk Factors for Increased Interaction Severity

• Hepatic impairment: Patients with liver disease may be at higher risk for interaction effects due to reduced drug metabolism 3, 4

• Elderly patients: More sensitive to CNS depressant effects of both medications and at higher risk for QT prolongation 3, 2

• Polypharmacy: Patients taking multiple medications that affect serotonin levels or prolong QT interval are at increased risk 6, 2

• Pre-existing cardiac conditions: Patients with heart disease are at higher risk for cardiac complications 2

Clinical Management Approach

1. Select the safest antidepressant: Consider using antidepressants with minimal CYP2D6 inhibition (e.g., sertraline, citalopram, escitalopram) when hydroxychloroquine is needed 3, 5

2. Start with standard dosing of both medications, but monitor closely for adverse effects 3

3. Consider dose adjustments if side effects occur, typically reducing the antidepressant dose first 4

4. Avoid adding other medications that prolong QT interval or have serotonergic effects when possible 3, 2

5. Educate patients about potential symptoms that should prompt medical attention (dizziness, palpitations, syncope) 3