What Pro Re Nata (PRN) medications for anxiety are safe to use with Monoamine Oxidase Inhibitors (MAOIs)?

PRN Medications for Anxiety Safe with MAOIs

Benzodiazepines are the only PRN medications for anxiety that can be safely used with MAOIs, while buspirone and all serotonergic agents are contraindicated or require extreme caution. 1

Safe PRN Options

Benzodiazepines (SAFE)

• Benzodiazepines remain the only truly safe PRN option for acute anxiety when taking MAOIs, as they work through GABA mechanisms rather than serotonergic pathways and have no interaction risk with MAOIs. 2, 3
• These can be used as needed without washout periods or dose adjustments when combined with MAOI therapy. 2
• Common options include lorazepam, clonazepam, or alprazolam for breakthrough anxiety symptoms. 2

Contraindicated PRN Options

Buspirone (CONTRAINDICATED)

• The FDA explicitly contraindicates buspirone with MAOIs due to reports of elevated blood pressure and risk of serotonin syndrome. 1
• Buspirone must be discontinued before initiating MAOI treatment, and at least 14 days should elapse between stopping an MAOI and starting buspirone. 1
• If buspirone is being used, it should be stopped promptly if urgent MAOI treatment is needed. 1

Hydroxyzine (USE WITH EXTREME CAUTION)

• First-generation antihistamines like hydroxyzine may cause additive sedation and cognitive effects, particularly problematic in elderly patients, though they lack the hypertensive crisis risk of other agents. 3
• While not absolutely contraindicated like serotonergic agents, the sedation profile makes this a poor choice for PRN use with MAOIs. 3

Critical Safety Considerations

Serotonin Syndrome Risk

• Any serotonergic PRN medication (SSRIs, SNRIs, or serotonin precursors like tryptophan) is absolutely contraindicated with MAOIs due to life-threatening serotonin syndrome risk. 2, 4, 1
• Serotonin syndrome presents with mental status changes, autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular changes (tremor, rigidity, hyperreflexia), and can be fatal. 1

Sympathomimetic Agents (ABSOLUTELY AVOID)

• All over-the-counter cold medications containing pseudoephedrine, phenylephrine, or dextromethorphan must be avoided as they can trigger hypertensive crisis. 3
• Patients must be explicitly warned to avoid energy drinks, weight loss products, and any stimulant-containing supplements. 3

Common Pitfalls to Avoid

• The most dangerous error is prescribing buspirone as a "safe" anxiolytic without recognizing the FDA black box contraindication with MAOIs. 1
• Failure to educate patients about avoiding all over-the-counter medications without consultation leads to preventable hypertensive crises. 3
• Assuming antihistamines are universally safe—while second-generation antihistamines like loratadine are safer for allergies, first-generation sedating antihistamines add unnecessary cognitive burden. 3

Clinical Algorithm for PRN Anxiety with MAOIs

1. First-line: Prescribe short-acting benzodiazepines (lorazepam 0.5-1mg PRN or alprazolam 0.25-0.5mg PRN) as the only safe PRN option. 2, 3

2. Absolutely avoid: Buspirone, any SSRI/SNRI, hydroxyzine (unless benefits clearly outweigh sedation risks), and all sympathomimetic agents. 1, 3

3. Patient education is mandatory: Provide written instructions listing all contraindicated medications, signs of hypertensive crisis (thunderclap headache, chest pain, severe blood pressure elevation), and requirement to inform all providers about MAOI use. 3, 4

4. If anxiety is not controlled with PRN benzodiazepines alone, consider whether the MAOI itself is providing adequate continuous anxiolytic effect, as MAOIs have proven efficacy for continuous treatment of anxiety disorders, particularly panic disorder and agoraphobia. 5, 6, 7