What is the recommended use and dosage of Moclobemide (monoamine oxidase inhibitor) for treating depression and social anxiety?

Moclobemide for Depression and Social Anxiety Disorder

Moclobemide is recommended as a second-line treatment for social anxiety disorder at doses of 300-600 mg/day for depression and 600-900 mg/day for social anxiety disorder, with higher doses showing greater efficacy for social anxiety. 1, 2

Mechanism of Action and Advantages

• Moclobemide is a reversible inhibitor of monoamine oxidase-A (RIMA), which makes it safer than traditional irreversible MAOIs 2
• Unlike older MAOIs, moclobemide has a negligible risk of hypertensive crisis ("cheese reaction") with tyramine-rich foods, requiring less strict dietary restrictions 2
• The drug has minimal anticholinergic, sedative, and cardiovascular effects, making it particularly suitable for elderly patients or those with cardiac disease 3

Dosage Recommendations

For Depression:

• Initial therapeutic dose range: 300-600 mg/day, divided in 2-3 doses 2
• Steady-state plasma levels are reached approximately one week after dose adjustment 2
• Therapeutic doses can often be reached rapidly due to good tolerability 2

For Social Anxiety Disorder:

• Higher doses (600-900 mg/day) tend to be more efficacious for social anxiety disorder 2
• In long-term treatment studies for social phobia, mean doses of approximately 723 mg/day were used 4

Efficacy

Depression:

• Meta-analyses and comparative studies indicate moclobemide is more efficacious than placebo and as effective as tricyclic antidepressants and SSRIs in treating depression 2
• Effective for various subtypes of depression including dysthymia, endogenous (unipolar and bipolar), reactive, atypical, agitated, and retarded depression 2

Social Anxiety Disorder:

• Evidence for social anxiety is mixed - one controlled trial and one long-term open-label study found moclobemide efficacious, while three subsequent controlled trials showed either no effect or less robust effects 2
• German S3 guidelines recommend moclobemide for social anxiety disorder based on expert consensus 1
• Long-term treatment studies showed 58.4% of patients with social phobia were rated as not ill (45.5%) or minimally ill (11.9%) after 2 years of treatment 4

Side Effects and Tolerability

• Most common side effects: dizziness, nausea, and insomnia 2
• Gastrointestinal side effects and sexual dysfunction are much less frequent with moclobemide than with SSRIs 2
• Side effects are typically mild and occur mainly in the first 2 months of treatment 4
• The drug is relatively safe even in overdose 2

Special Considerations

• No dose adjustment required for patients with renal dysfunction 2
• Dose reduction needed for patients with severe hepatic impairment 2
• Moclobemide is a substrate of CYP2C19 and inhibits CYP1A2, CYP2C19, and CYP2D6, though relatively few clinically important drug interactions have been reported 2
• Combination with other serotonergic agents or opioids should be undertaken with caution due to risk of serotonin syndrome 2
• The combined use with pethidine or dextropropoxyphene should be avoided 2

Treatment Algorithm

1. For depression:

   • Start with 300 mg/day divided in 2-3 doses
   • Titrate up to 600 mg/day based on response and tolerability 2

2. For social anxiety disorder:

   • Start with 300 mg/day
   • Titrate up to 600-900 mg/day for optimal efficacy 2, 4
   • Monitor for response for at least 8 weeks before determining efficacy 5

3. For treatment-resistant cases:

   • Consider combination with other antidepressants such as clomipramine or SSRIs
   • Use lower entry doses, slower titration, and careful monitoring due to risk of serotonin syndrome 2

Monitoring Parameters

• Assess clinical response using standardized scales (Hamilton Anxiety Scale, Liebowitz Scale for Social Phobia) 4
• Monitor for side effects, particularly in the first 2 months of treatment 4
• No specific laboratory monitoring required, unlike with traditional MAOIs 3