Can I use Anafranil (clomipramine) with moclobemide?

Combining Anafranil (Clomipramine) with Moclobemide is Contraindicated Due to Risk of Fatal Serotonin Syndrome

The combination of Anafranil (clomipramine) with moclobemide is strongly contraindicated due to the high risk of potentially fatal serotonin syndrome. 1, 2, 3

Mechanism of Dangerous Interaction

This dangerous drug interaction occurs because:

• Clomipramine is a tricyclic antidepressant (TCA) with strong serotonergic effects
• Moclobemide is a reversible inhibitor of monoamine oxidase-A (RIMA)
• When combined, these medications can cause excessive serotonin accumulation in the central nervous system 4

Documented Risks

The evidence clearly demonstrates serious risks:

• Multiple case reports document fatal outcomes from this specific combination 2, 3
• Clinical guidelines explicitly warn against combining MAOIs (including moclobemide) with serotonergic drugs like TCAs 1
• A study specifically examining moclobemide interactions identified the combination with clomipramine as "potentially fatal" due to serotonin syndrome risk 4

Signs of Serotonin Syndrome

If these medications were accidentally combined, watch for these symptoms developing within 24-48 hours:

• Mental status changes: confusion, agitation, anxiety
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity
• Autonomic hyperactivity: hypertension, tachycardia, hyperthermia, diaphoresis
• Advanced symptoms: fever, seizures, arrhythmias, unconsciousness 1

Alternative Options

If you require treatment for depression or anxiety:

1. Sequential use with washout period: If transitioning between these medications:

   • Allow 14 days after stopping moclobemide before starting clomipramine
   • Allow 14 days after stopping clomipramine before starting moclobemide

2. Alternative medication combinations:

   • SSRIs alone (e.g., paroxetine, sertraline, fluoxetine) 1, 5
   • SNRIs (e.g., duloxetine, milnacipran) 1
   • Clomipramine alone (without moclobemide) 1
   • Moclobemide alone (without clomipramine) 6

Clinical Implications

This combination poses an unacceptable risk:

• The serotonin syndrome from this combination can progress rapidly to life-threatening complications
• Even at therapeutic doses, this combination can trigger serotonin syndrome
• In overdose situations, this combination is particularly lethal 2
• Emergency treatment requires immediate discontinuation of both medications and supportive care with continuous cardiac monitoring 1

Conclusion

The evidence is unequivocal that combining Anafranil (clomipramine) with moclobemide creates an unacceptable risk of potentially fatal serotonin syndrome. This combination should be strictly avoided in all clinical scenarios.