Question 1

When should I consider an MAOI for anxiety, and is it worth the burden?

Accepted Answer

Phenelzine produces the largest effect size of any anxiolytic in the published literature, with unique dual monoaminergic + GABAergic mechanism (MAO-A/B inhibition + GABA transaminase inhibition). Blanco 2003 meta-analysis (social anxiety disorder): phenelzine ES 1.02 vs. clonazepam 0.97, gabapentin 0.78, SSRIs 0.65. Liebowitz 1992 RCT: 64% improvement vs. 30% atenolol, 23% placebo. SSRI washout required (14 days most agents, 35 days fluoxetine). Dietary restrictions modernized: Shulman & Walker — approximately 50mg tyramine threshold for dangerous pressor response; fresh meats/commercial cheeses/pasteurized beer safe; aged cheeses/cured meats/draft beer/fermented soy unsafe. Tranylcypromine offers activating profile with less sexual dysfunction. Selegiline patch 6mg: NO dietary restrictions, but weak anxiolytic effect. MAOIs reserved for SSRI-failed SAD or atypical depression + anxiety.

Question 2

How do MAOI effect sizes compare to SSRIs for anxiety?

Accepted Answer

Phenelzine produces the largest effect size of any anxiolytic in the published literature, with unique dual monoaminergic + GABAergic mechanism (MAO-A/B inhibition + GABA transaminase inhibition). Blanco 2003 meta-analysis (social anxiety disorder): phenelzine ES 1.02 vs. clonazepam 0.97, gabapentin 0.78, SSRIs 0.65. Liebowitz 1992 RCT: 64% improvement vs. 30% atenolol, 23% placebo. SSRI washout required (14 days most agents, 35 days fluoxetine). Dietary restrictions modernized: Shulman & Walker — approximately 50mg tyramine threshold for dangerous pressor response; fresh meats/commercial cheeses/pasteurized beer safe; aged cheeses/cured meats/draft beer/fermented soy unsafe. Tranylcypromine offers activating profile with less sexual dysfunction. Selegiline patch 6mg: NO dietary restrictions, but weak anxiolytic effect. MAOIs reserved for SSRI-failed SAD or atypical depression + anxiety.

Question 3

Why is phenelzine especially effective for social anxiety disorder?

Accepted Answer

Phenelzine produces the largest effect size of any anxiolytic in the published literature, with unique dual monoaminergic + GABAergic mechanism (MAO-A/B inhibition + GABA transaminase inhibition). Blanco 2003 meta-analysis (social anxiety disorder): phenelzine ES 1.02 vs. clonazepam 0.97, gabapentin 0.78, SSRIs 0.65. Liebowitz 1992 RCT: 64% improvement vs. 30% atenolol, 23% placebo. SSRI washout required (14 days most agents, 35 days fluoxetine). Dietary restrictions modernized: Shulman & Walker — approximately 50mg tyramine threshold for dangerous pressor response; fresh meats/commercial cheeses/pasteurized beer safe; aged cheeses/cured meats/draft beer/fermented soy unsafe. Tranylcypromine offers activating profile with less sexual dysfunction. Selegiline patch 6mg: NO dietary restrictions, but weak anxiolytic effect. MAOIs reserved for SSRI-failed SAD or atypical depression + anxiety.

Question 4

What dietary restrictions make MAOIs difficult?

Accepted Answer

Phenelzine produces the largest effect size of any anxiolytic in the published literature, with unique dual monoaminergic + GABAergic mechanism (MAO-A/B inhibition + GABA transaminase inhibition). Blanco 2003 meta-analysis (social anxiety disorder): phenelzine ES 1.02 vs. clonazepam 0.97, gabapentin 0.78, SSRIs 0.65. Liebowitz 1992 RCT: 64% improvement vs. 30% atenolol, 23% placebo. SSRI washout required (14 days most agents, 35 days fluoxetine). Dietary restrictions modernized: Shulman & Walker — approximately 50mg tyramine threshold for dangerous pressor response; fresh meats/commercial cheeses/pasteurized beer safe; aged cheeses/cured meats/draft beer/fermented soy unsafe. Tranylcypromine offers activating profile with less sexual dysfunction. Selegiline patch 6mg: NO dietary restrictions, but weak anxiolytic effect. MAOIs reserved for SSRI-failed SAD or atypical depression + anxiety.

Question 5

What's the required washout period between an SSRI and an MAOI?

Accepted Answer

Phenelzine produces the largest effect size of any anxiolytic in the published literature, with unique dual monoaminergic + GABAergic mechanism (MAO-A/B inhibition + GABA transaminase inhibition). Blanco 2003 meta-analysis (social anxiety disorder): phenelzine ES 1.02 vs. clonazepam 0.97, gabapentin 0.78, SSRIs 0.65. Liebowitz 1992 RCT: 64% improvement vs. 30% atenolol, 23% placebo. SSRI washout required (14 days most agents, 35 days fluoxetine). Dietary restrictions modernized: Shulman & Walker — approximately 50mg tyramine threshold for dangerous pressor response; fresh meats/commercial cheeses/pasteurized beer safe; aged cheeses/cured meats/draft beer/fermented soy unsafe. Tranylcypromine offers activating profile with less sexual dysfunction. Selegiline patch 6mg: NO dietary restrictions, but weak anxiolytic effect. MAOIs reserved for SSRI-failed SAD or atypical depression + anxiety.

PsychHQ

Monoamine Oxidase Inhibitors for Anxiety: The Case for Phenelzine in Social Anxiety Disorder