Intermittent Explosive Disorder Tied to Multiple Comorbidities

Intermittent explosive disorder (IED), characterized by impulsive aggression and poorly regulated emotional control, was associated with multiple classes of comorbidities, an analysis of 117.7 million healthcare records showed.

Of 30,000 individuals with an IED diagnosis during their lifetime, 95.7% had at least one other psychiatric diagnosis, reported Yanli Zhang-James, MD, PhD, of SUNY Upstate Medical University in Syracuse, and co-authors in JAMA Psychiatry.

All psychiatric subcategories and 92% of psychiatric diagnoses were significantly associated with IED, with hazard ratios (HRs) ranging from 2.1 for substance use disorder to 76.6 for disorders of adult personality and behavior.

Neurodegenerative diseases (HR 5.0), epilepsy (HR 4.9), movement disorders (HR 3.1), cerebral palsy (HR 2.6), and sleep disorders (HR 2.2) were the primary neurologic conditions associated with IED. Obesity (HR 1.6), hyperlipidemia (HR 1.5), hypertension (HR 1.6), and gastroesophageal reflux disease (HR 1.7) were among the main somatic disorders.

Only 0.03% of the total patient population had an IED diagnosis. “Our findings shed unique light on how IED is diagnosed in clinical practice, distinct from research settings,” Zhang-James and colleagues wrote.

Because the analysis relied on diagnostic codes in medical records, the prevalence of IED was “very low in this study compared with community studies, which have the prevalence closer to about 2.5% to 3%,” observed Emil Coccaro, MD, of the Ohio State University College of Medicine in Columbus, who was not involved with the research.

This is likely because clinicians don’t screen for aggression and “rarely use the IED diagnosis; a diagnosis of IED is rarely ‘top of mind,'” he wrote in an email to MedPage Today. “Also, people with aggression issues mostly don’t seek evaluation and treatment for aggression or IED.”

IED usually predates comorbid diagnoses, suggesting that IED or aggression is a risk factor for other, later-appearing, diagnoses, Coccaro pointed out.

“The age of onset of IED is in the pre-teen years — around 11 years in age — as reported in epidemiologic studies of adolescents,” he noted. “The age of onset for other diagnoses is typically later than that.”

Zhang-James and co-authors investigated IED prevalence and comorbidities in matched groups of patients with and without IED in the TriNetX Research Network, which included records from 87 healthcare organizations.

The researchers evaluated 30,357 people with at least one recorded IED diagnosis based on ICD-10 codes and 30,357 matched controls. In both groups, 70% were male and the mean age at the first visit was 26.

Among people with IED, the prevalence of mood disorders was 60.3%, anxiety disorders was 59%, and developmental disorders were 44.5%. More than a third of people with IED also had neurotic, personality, or other non-psychotic disorders; attention-deficit hyperactivity disorder (ADHD); or substance use disorders.

“A striking finding was that IED without psychiatric comorbidity, or so-called pure IED, was rare: only 4.3% of those with IED did not have another psychiatric diagnosis,” Zhang-James and co-authors wrote.

The findings raise provocative hypotheses for clinical practice, they noted. Clinicians should consider using the diagnosis of IED more frequently when warranted, they suggested. “Highlighting aggression as a separate diagnosis may focus more attention on aggressive behavior and facilitate the development of targeted treatments,” they wrote. “Otherwise, aggressive behavior remains somewhat hidden as a feature within other disorders.”

The association of IED with falls or accidents suggests that impulsivity may bring people to medical attention, the researchers noted. “The fact that 34% of ICD codes were significantly associated with IED suggests that impulsivity may be an underestimated risk factor in health care,” they wrote. “Ideally, IED treatment may include teaching thinking-before-acting skills,” and not just target aggression.

The relationship between IED and ADHD, which also is centered on impulsivity, suggests that early effective treatment for ADHD may reduce IED prevalence, they added.

The findings also raise questions about how diagnostic systems are constructed, Zhang-James and co-authors said, noting that “it is impossible to know how often IED is overlooked vs not given due to clinicians’ judgment that aggression is better explained by another diagnosis.”

Limitations included the study’s reliance on medical records. Low diagnostic rates of IED may affect the generalizability of findings.

The researchers recommended validation in prospective studies, and acknowledged that the data did not provide clues about why diagnosis in clinical practice was rare.