The Matthews Protocol for DMDD: A Comprehensive Guide to an Integrative Approach

Disruptive Mood Dysregulation Disorder (DMDD) is a serious mood disorder marked by chronic irritability and frequent temper outbursts, often causing significant distress in children, adolescents, and their families. At Alpine Psychiatry, we recognize the urgent need for effective, low-burden treatments that restore emotional regulation and support long-term wellness.

One such emerging approach is the Matthews Protocol, which utilizes a phased, integrative medication strategy—primarily using amantadine and oxcarbazepine (Trileptal)—to stabilize mood and reduce the functional impairments caused by DMDD. While the medications used in this protocol are FDA-approved for other conditions, their off-label use in DMDD has shown promising results, especially for patients who do not respond well to traditional neuroleptics.

What Is the Matthews Protocol?

The Matthews Protocol is a treatment framework that applies two well-tolerated medications—amantadine, a dopaminergic agent, and oxcarbazepine, an anti-epileptic mood stabilizer—to reduce the neurological drivers of dysregulated mood and behavior. By carefully titrating these medications in sequence, clinicians can better isolate therapeutic effects and manage potential side effects.

Why It’s Gaining Attention

Clinical observations report a 75%+ success rate in improving DMDD symptoms using this method. This effectiveness, combined with a relatively lower side effect profile, makes the protocol an attractive alternative to antipsychotic or heavy sedating regimens. It offers:

• Improved mood stability

• Reduced irritability and aggression

• Decreased hospitalization needs

• Greater treatment adherence due to fewer side effects

How the Protocol Works

Phase 1: Starting with Amantadine

Amantadine (Symmetrel) is introduced first to support dopamine regulation and reduce emotional reactivity.

• Initial dosing: 25–50 mg in the morning for children under 100 lbs

• Titration: Increase by 25 mg every 5–7 days

• Common side effects: Mild dizziness, nausea, insomnia

Close monitoring is essential during this phase to detect side effects early and adjust accordingly.

Phase 2: Introducing Oxcarbazepine (Trileptal)

Oxcarbazepine is added next to stabilize mood and prevent extreme shifts in behavior.

• Primary benefits: Anticonvulsant mood stabilization for both DMDD and bipolar presentations

• Notable risks: Dizziness, fatigue, and rare but serious rash (especially in individuals of Asian descent due to HLA-B*1502 allele)

Read more about oxcarbazepine and mood disorders here.

Alternatives for Sensitive or Non-Responsive Patients

At Alpine Psychiatry, we believe in adapting treatment to the individual. When amantadine or Trileptal are not tolerated:

• Memantine may be considered as an alternative to amantadine.

• Lamotrigine can be used in place of oxcarbazepine for its mood-stabilizing benefits with a different side effect profile.

We tailor each medication plan using functional testing and careful clinical monitoring. Learn more about our integrative psychiatry services.

Off-Label Use and Clinical Backing

Though these medications are not FDA-approved specifically for DMDD, their off-label use is supported by:

• Research in mood stabilization

• Anti-inflammatory and neuroregulatory effects

• Practical success in outpatient psychiatric care

We integrate emerging treatments supported by both evidence and clinical outcomes to bring families effective, compassionate care.

Getting Started with Treatment

Alpine Psychiatry specializes in treating complex mood disorders like DMDD through an integrative, whole-person approach—combining psychotherapy, evidence-based medication, biomedical interventions, and lifestyle support.

If your child is struggling with emotional dysregulation or has not responded to traditional treatments, the Matthews Protocol may offer a new path forward.

Reach out to us today to schedule a consultation and explore how we can support your family.