Can I take amitriptyline (Elavil) for interstitial cystitis while on mirtazapine (Remeron), and are there alternative treatments such as hydroxyzine (Vistaril) or hormone level checks due to my polycystic ovary syndrome (PCOS) diagnosis?

Amitriptyline and Mirtazapine Combination: Safety and Alternatives

Can You Take Amitriptyline with Mirtazapine?

Yes, you can safely take amitriptyline with mirtazapine—the risk of serotonin syndrome from this combination is extremely low and should not prevent concurrent use for interstitial cystitis pain management. 1

Why This Combination is Safe

• Amitriptyline is a tricyclic antidepressant (TCA) with minimal serotonergic activity at the doses used for interstitial cystitis (10-75 mg), primarily working through norepinephrine reuptake inhibition and anticholinergic effects 1, 2
• Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that blocks certain serotonin receptors rather than increasing serotonin levels like SSRIs do 1
• The mechanism of action differs fundamentally from the combinations that cause serotonin syndrome (typically SSRIs/SNRIs with MAO inhibitors or multiple serotonergic agents) 1
• Amitriptyline is not being offered as a substitution for mirtazapine—it serves a completely different purpose (bladder pain vs. psychiatric indication) and both can be continued simultaneously 1

Evidence for Amitriptyline in Interstitial Cystitis

• The American Urological Association recommends amitriptyline as a second-line oral medication for IC/BPS with Grade B evidence strength 1
• Amitriptyline has been shown superior to placebo for improving IC/BPS symptoms, though adverse effects like sedation, drowsiness, and nausea are common 1
• Dosing strategy: Start at 10 mg daily and titrate gradually to 50-75 mg as tolerated, with benefit most likely in patients achieving at least 50 mg daily 1, 2
• Response rates: 66% of patients achieving 50+ mg daily showed moderate to marked improvement compared to 47% with placebo 2

Hydroxyzine as an Alternative

Hydroxyzine is a reasonable alternative to consider and may be used instead of or in addition to amitriptyline for IC/BPS. 1

Evidence for Hydroxyzine

• The AUA guidelines list hydroxyzine as a second-line oral medication with Grade C evidence strength 1
• Hydroxyzine has shown clinically significant improvement compared to placebo in IC/BPS symptoms 1
• Patients with systemic allergies may be more likely to respond to hydroxyzine, as it addresses mast cell activation—a key component of IC/BPS pathophysiology 1, 3
• Common adverse effects include short-term sedation and weakness, which are generally not serious 1
• Switching from loratadine (a non-sedating antihistamine) to hydroxyzine (an H1-blocker with additional properties) is mechanistically sound for IC/BPS treatment 3, 4

Multimodal Approach Recommendation

• Combination therapy is most effective for IC/BPS: The evidence supports using amitriptyline plus hydroxyzine together, not as alternatives 3, 4
• A multimodal regimen addressing urothelial dysfunction, mast cell activation, and neural upregulation provides optimal symptom relief 4
• You could take amitriptyline (with mirtazapine) AND hydroxyzine concurrently for maximum benefit 3, 4

Hormone Testing for PCOS

Hormone level testing is reasonable given your PCOS diagnosis, but should be coordinated with your OBGYN as recommended. 1

What to Communicate to Your OBGYN

• Request evaluation of metabolic parameters: fasting glucose, fasting insulin, HOMA-IR, lipid panel (total cholesterol, LDL, HDL, triglycerides) 1
• Androgenicity assessment: free and total testosterone, SHBG, DHEAS, FAI (Free Androgen Index) 1
• Weight management discussion: If weight is a concern, newer GLP-1 receptor agonists (liraglutide, semaglutide) show promise for PCOS management when combined with lifestyle interventions 1
• PCOS can worsen IC/BPS symptoms through inflammatory pathways, so optimizing PCOS management may indirectly benefit bladder symptoms 3

Clinical Action Plan

Immediate Steps

1. Continue mirtazapine without interruption—no psychiatric consultation needed for drug interaction concerns 1
2. Start amitriptyline 10 mg at bedtime, increase by 10-25 mg every 1-2 weeks targeting 50-75 mg as tolerated 1, 2
3. Consider adding hydroxyzine 25-50 mg at bedtime (can be used with amitriptyline) 1, 3, 4
4. Coordinate with OBGYN for comprehensive PCOS hormone evaluation and metabolic screening 1

Monitoring and Follow-up

• Expect 4-12 weeks for amitriptyline to show benefit in IC/BPS symptoms 2
• Common side effects to anticipate: sedation (take at bedtime), dry mouth, constipation—these often improve with continued use 1
• If sedation is excessive with both medications, consider timing doses differently or reducing amitriptyline dose 1

Common Pitfalls to Avoid

• Do not discontinue mirtazapine based on unfounded serotonin syndrome concerns—this combination is used safely in clinical practice 1
• Do not use hydroxyzine alone without addressing other IC/BPS components—behavioral modifications, bladder training, and dietary changes remain essential 1
• Do not delay treatment while waiting for hormone results—IC/BPS management and PCOS evaluation can proceed in parallel 1