Experts Search for Meds to Help Youth With DMDD

Five years since DMDD first appeared in DSM-5, there has been little follow-up research on DMDD, and there is no consensus pharmacological option for treating this disorder. Most clinicians rely on medications that are known to reduce symptoms of irritability and temper tantrums in children with other conditions, including attention-deficit/hyperactivity disorder (ADHD) and autism.

Argyris Stringaris, M.D., Ph.D., the chief of the Mood Brain & Development Unit at the National Institute of Mental Health, noted that there appears to be a relationship between patients with ADHD and DMDD. Studies have shown that up to 85 percent of children with DMDD also have ADHD. Therefore, stimulants such as Ritalin are a commonly prescribed medication for this disorder. Children with DMDD appear to respond to stimulants, Stringaris told Psychiatric News, though he said this may be due to improvements in the co-occurring ADHD symptoms, which, in turn, may reduce irritability.

The antipsychotics risperidone and aripiprazole, which are approved by the Food and Drug Administration to treat irritability in autism, are also commonly prescribed to patients with DMDD. While antipsychotics may offer what Stringaris termed “a short-term fix” to reduce symptoms of DMDD, he said that he worries about the long-term effects the medications might have on children. “I think a combination of stimulants plus a parenting intervention is a more benign approach.”

The antidepressant citalopram might offer yet another treatment option for children with DMDD, according to Stringaris. Citalopram is the preferred treatment for premenstrual dysphoric disorder (PMDD)—another less well-understood psychiatric illness that shares similarities with DMDD, he noted. Like DMDD, PMDD is marked by extended irritability and is a known risk factor for major depression (both disorders are also categorized as depressive disorders in the DSM-5).

Stringaris is currently conducting a randomized clinical trial of citalopram as an add-on therapy for children with DMDD receiving stimulant medications.

Matthews said he has also found success treating patients with DMDD with a different combination of medications: anticonvulsants and the dopamine agonist amantadine. He developed this regimen when he was running an inpatient unit for children with aggression problems while he was at Duke University.

Matthews said he noticed that many patients failed to recall their outbursts shortly after they took place. “It was almost seizure-like,” he said. “That led me to think an anticonvulsant like oxcarbazepine might work.”

Brain scans of youth with aggression problems suggested that they had heightened activity in the amygdala (the brain’s emotional center) due to a deficiency of dopamine, which resulted in a state of hypervigilance and poor impulse control. These findings may help to explain why stimulants appear to help children with DMDD (stimulants can block dopamine transporters to reduce dopamine reuptake). The findings also suggested to Matthews that a stronger dopamine activator like amantadine—which can both trigger more dopamine release and block dopamine reuptake—might be even more effective in reducing symptoms in these patients.

In some clinical studies, Matthews has shown that the oxcarbazepine–amantadine combination can dramatically lower the risk of rehospitalization in children who had been admitted for severe irritability and recurrent outbursts.

Even more encouraging, he has tracked some children treated with this combination into their adolescence and found that in about 50 percent of cases, the children show normalized amygdala activity in addition to improved symptoms. According to Matthews, some of these children have been able to reduce or even discontinue the oxcarbazepine–amantadine combination.

While finding a good medication to treat children with DMDD is important, Matthews said he recognizes the importance of psychotherapy in rehabilitating these patients as well.

“Many of these youth have dealt with these temper problems for almost their whole lives,” he said. “Once the medication restores their chemical balance, they need behavioral rehabilitation.” ■