He suggests that physicians look for emotions that are expressed very suddenly and usually stop very quickly, as well as crying in the absence of thoughts of helplessness, hopelessness, and guilt, or disturbances in sleep or appetite.

Scientists investigating the possible causes of IEED have devised several different theories. Hillel Panitch, MD, of the University of Vermont College of Medicine in Burlington, explains, “Because it occurs in so many different disease states, it is hard to say what areas of the brain are affected and which neurotransmitters are involved. But there is probably some kind of a disconnection between the frontal lobes, which normally keep emotions under control, and the brain stem and cerebellum, where these reflexes are mediated.”

In treating the condition, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are both at least partially effective. This indicates that receptors on the surface of the cerebellum and brain stem may play an important role. The widely-used cough suppressant dextromethorphan, which is also beneficial for IEED, works in a similar way.

Tricyclic antidepressants including amitriptyline and nortriptyline have been used for many years to treat IEED, but they are not fully effective. SSRIs such as citalopram may be better, but Panitch believes, “nothing really appears to be as effective as the new compound Zenvia (or dextromethorphan/quinidine), which is currently being developed by Avanir Pharmaceuticals.”

This combination is thought to “help regulate excitatory neurotransmission.” In a 2006 trial of 150 multiple sclerosis patients with IEED, it led to significantly greater reductions in symptoms than placebo, was deemed to be safe, and improved quality of life and quality of relationships.

Panitch reports that, unlike the older antidepressants prescribed for IEED, this drug combination is associated with few significant side effects and rapid efficacy. It was considered to have the most therapeutic benefit, in terms of the mechanism of action in the brain, in a 2007 review.

Symptoms were reduced or eliminated by the drug combination in a recent trial presented at the 134th annual meeting of the American Neurological Association. The 12 week randomized trial of 326 patients with amyotrophic lateral sclerosis or multiple sclerosis found that IEED episodes reduced in frequency by nearly 50 percent.

Lead researcher, Benjamin Rix Brooks, MD, of the Carolinas Medical Center in Charlotte, North Carolina, said, “The impact of pseudobulbar affect on social function is severe and may result in social withdrawal. We observed that dextromethorphan/quinidine at 30mg/10mg significantly improved quality of life as related to mental health.”

But the US Food and Drug Administration is delaying approval for the combination to treat IEED due to safety concerns.

References

http://www.psychiatrictimes.com/display/article/10168/57621?verify=0

Brooks, B. R. et al. Presentation title: Double-Blind, Placebo-Controlled Study of AVP-923 for Pseudobulbar Affect. Abstract WIP-24. Findings presented at the American Neurological Association 134th Annual Meeting held in Baltimore, Maryland from October 11-14, 2009.

Cummings, J. L. Involuntary emotional expression disorder: definition, diagnosis, and measurement scales. CNS Spectrums, Vol. 12, April 2007, pp. 11-16.

Werling, L. L. et al. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Experimental Neurology, Vol. 207, October 2007, pp. 248-57.

Involuntary Emotional Expression Disorder