Is there evidence to support the use of the Matthews protocol in a child with Disruptive Mood Dysregulation Disorder (DMDD), anxiety, and attentional issues, currently taking Lexapro (escitalopram)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 8, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

No Evidence Supports the "Matthews Protocol" for DMDD

There is no published evidence, guideline recommendation, or established clinical protocol known as the "Matthews Protocol" for treating Disruptive Mood Dysregulation Disorder (DMDD). This term does not appear in any major psychiatric guidelines, FDA-approved treatment algorithms, or peer-reviewed literature for DMDD management.

Evidence-Based Treatment Approach for DMDD

Since no "Matthews Protocol" exists, here is the evidence-based approach for a child with DMDD, anxiety, and attentional issues currently on escitalopram:

First-Line: Optimize Stimulant Therapy for ADHD Component

  • Start with methylphenidate as first-line treatment for the attentional issues, as stimulants have 70-80% response rates and the largest effect sizes from over 161 randomized controlled trials 1, 2.

  • The only published trial specifically examining DMDD treatment used methylphenidate first, followed by citalopram (an SSRI similar to escitalopram) in children ages 7-17 3.

  • Methylphenidate dosing for children ranges from 5-20 mg three times daily, with various extended-release formulations available for once-daily dosing 1, 2.

Role of SSRIs in DMDD

  • Escitalopram (Lexapro) is FDA-approved for major depressive disorder in adolescents aged 12-17 years, not specifically for DMDD 1.

  • The evidence for SSRIs in DMDD is extremely limited and complicated by lack of specific measures of irritable mood and severity of outbursts 3.

  • One trial found citalopram added to methylphenidate showed some benefit, but the response was complicated by inadequate outcome measures and the study was conducted on inpatient units, limiting generalizability 3.

  • Escitalopram has demonstrated efficacy for generalized anxiety disorder in children ages 7-17, with significant reductions in anxiety symptoms (PARS severity score difference of -1.42, p=0.028) 4.

Critical Monitoring Requirements

  • Monitor closely for suicidality and unusual behavioral changes when using SSRIs in children and adolescents, as required by FDA boxed warning 1.

  • Obtain baseline blood pressure and heart rate before starting any ADHD medication, then monitor at each dose adjustment 1, 5.

  • Track height and weight regularly, as stimulants commonly cause appetite suppression 1, 2.

Treatment Algorithm for This Specific Case

  1. Continue escitalopram for the anxiety component, as it has established efficacy for pediatric generalized anxiety disorder 4, 6.

  2. Add methylphenidate (starting at 5 mg and titrating by 5-10 mg weekly) to address attentional issues 1, 2.

  3. If irritability persists after optimizing both medications, consider adding guanfacine (starting at 1 mg daily, titrating to 0.05-0.12 mg/kg/day) specifically for irritability and emotional dysregulation 5, 2.

  4. Guanfacine requires 2-4 weeks for full effect and should be dosed in the evening to minimize daytime somnolence 5, 2.

Common Pitfalls to Avoid

  • Do not assume escitalopram alone will treat DMDD, as there is insufficient evidence for SSRIs as monotherapy for this condition 3.

  • Do not use the term "Matthews Protocol" with families or in documentation, as it has no established meaning in psychiatric literature and may cause confusion.

  • Do not abruptly discontinue guanfacine if added—it must be tapered by 1 mg every 3-7 days to avoid rebound hypertension 5, 2.

  • Future studies need standardized measures of irritability, outburst severity, and longer follow-up beyond 8 weeks to determine optimal DMDD treatment 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Medication Options for Managing Both Mood Symptoms and ADHD

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Editorial: Antidepressants to the Rescue in Severe Mood Dysregulation and Disruptive Mood Dysregulation Disorder?

Journal of the American Academy of Child and Adolescent Psychiatry, 2020

Guideline

Guanfacine for ADHD Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.