A Clinical Overview of Pseudobulbar Affect: Part II of II

Thursday, February 7, 2013 | 0

Today we conclude our two-part series about a distressing complication that may arise following a traumatic brain injury—pseudobulbar affect (PBA). Due to minimal awareness and knowledge of PBA in the medical community, PBA is often misdiagnosed as depression or part of the primary neurological disease when in fact, it’s a separate, treatable condition. In our last article, we described the condition and the complexity involved with distinguishing disorders of affect with disorders of mood.

The Challenge of Diagnosing Pseudobulbar Affect

In 1969, K. Poeck characterized four main features which he hoped would serve as criteria for diagnosing PBA:

(1) Episodes are inappropriate to the situation and can be precipitated by nonspecific stimulation, such as contraction of facial muscles, removal of bed covers, or the approach of someone toward the patient.
(2) There is not a close relationship between the emotional expression and how the patient is feeling.
(3) The episodes are relatively stereotyped, and it is very difficult for the patients to control the extent and duration of the episodes.
(4) There are no episodic mood changes corresponding to the episodes, and there is no sense of relief as the emotions are expressed.

This last criteria tries to capture the fact that the episodes appear to come from nowhere and are out of context. Others have postulated Poeck’s criteria may exaggerate the dissociation and give the impression the evoking stimulus is never appropriate. This may not always be the case, especially in patients with aphasia or other forms of cognitive impairment.

Complications of Depression

Differentiating between PBA with crying episodes and crying due to depression may be difficult. The behavior of depressed individuals (e.g., crying) is congruent with the emotion, whereas this may not be the case in most instances for those with PBA. And when PBA is associated with depression, it makes the diagnosis even more difficult.

Some surveys of patients have found the emotions of labile anger and frustration to be present in more than half of those with underlying neurological disorders. These findings are consistent with previous epidemiological data suggesting episodes of anger and frustration, in addition to laughter and crying, are an important component of the emotional lability in PBA. Recent surveys of PBA report the mean prevalence to be at 10% minimally and up to 38% across the six most common underlying neurological conditions. Based on U.S. estimates for these neurological conditions (i.e., Alzheimer’s disease, ALS, MS, Parkinson’s disease, stroke, and traumatic brain injury), the total prevalence may be between 2-7 million people.

Although the cause and origin of PBA remains unclear, many consider it to be the result of brain lesions interfering with neural circuits and neural transmitters. These neural transmitters are involved in regular, voluntary and perhaps over-learned involuntary emotional expressions. This has led many patients to report their symptoms have not been sufficiently controlled by medications primarily involving tricyclic antidepressants, selective serotonin-uptake inhibitors, other non-tricyclic antidepressants, and antipsychotics. Good news arrived in 2011 when the FDA approved the first treatment for PBA, Nuedexta (Avanir). This oral treatment is a fixed dose combination of the cough suppressant dextromethorphan hydrobromide and the anti-arrhythmic quinidine sulfate.

Seeking Treatment

The studies which support the effectiveness of Nuedexta were performed in patients with underlying ALS or MS. At this time, the drug has not been shown to be safe or effective in other types of emotional lability. The pharmacological action of the combination of this drug is felt to be the dextromethorphan that acts by inhibition of glutamate neurotransmission which has an excitatory effect on neurons, thereby decreasing behaviorals which occur at inappropriate times. The quinidine sulfate increases the bioavailability of dextromethorphan, thereby extending its effectiveness. This medication has not been compared to other drugs used for PBA. The common adverse effects associated with the higher dosages of quinidine sulfate (used to suppress cardiac arrhythmias), including immune-mediated thrombocytopenia, lupus-like syndrome, granulomatous hepatitis, and QT prolongations, have not occurred with the much lower dose used in Nuedexta. The dextromethorphan may increase the risk of the life-threatening serotonin syndrome when used with other antidepressants. The initial dosage is one capsule once daily for seven days followed by one capsule twice daily thereafter. It does appear to be safe when used alone, but a negative could be the monthly cost of more than $500.

The Importance of Differentiation

In conclusion, it is important to differentiate pseudobulbar affect from disorders of mood. This requires clinicians to first define mood and affect on temporal grounds before characterizing the subjective and objective aspects of those domains of emotions. This is especially important in the context of many neurological disorders, as PBA seems to occur more frequently than has been commonly recognized in general medical, neurological, rehabilitation and psychiatric practices.

Assessment scales, including the Pathological Laughing and Crying Scale, Emotional Lability Questionnaire, the Affective Lability Scale, and the Center for Neurologic Study Lability Scale, may help guide clinical evaluations. Not only will these scales assist clinicians with a diagnosis, but they may also help to measure the effects of treatments prescribed for this condition. It is hoped that this new agent, Nuedexta, may serve as a new category of neurotropic agents and lead to further medications being developed for this condition.

Dr. H. Richard Adams is a medical director for Paradigm Outcomes and a practicing physician and brain injury specialist currently serving as staff physical medicine and rehabilitation specialist at Long Beach Memorial Medical Center in California. This column was reprinted with permission from Paradigm's Outlook on Outcomes blog.</i>