Articulating the Unmet Need in the

Diagnosis and Treatment of Pseudobulbar Affect:

Prevalence of the Condition and

Limitations of Existing Therapies

Ursula Hess, PhDTorre Lazur McCann West

Estimated US Patients With PBA: 1.7 Million

1o DisorderPBA

Prevalence

Total US Cases

With 1o Disorder

MS 10% 300,000

ALS 49% 30,000

AD 39% 4,000,000

Stroke 18% 590,000

Severe TBI 5% 230,000

PBA Impact on Quality of Life (QOL)

• No QOL studies

• PBA can be severe, persistent, and deteriorate

• Widely recognized that PBA can be profoundly disabling socially and occupationally

– Embarrassing and distressing

– Can impair ability to communicate

– May be dangerous during eating or drinking

– Related to decreased sexual activity poststroke

– Fear of attacks, secondary phobias and social withdrawal often make symptoms worse

– Interferes with rehabilitation

Poorly Clinically Defined Condition With Unknown Disease Mechanism

• Evidenced by plethora of names for condition

• Lack of agreement on defining features– Episodes are sudden, involuntary, difficult to control,

excessive, disproportionate, and labile

– Mood congruent or incongruent?

– Limited to laughing and crying?

• Etiology unknown – Caused by structural brain damage, but seen after

bilateral, diffuse as well as single, focal lesions

– Possible that lesions within different neural systems result in different manifestations of the syndrome

PBA Is Underrecognized and Sometimes Misdiagnosed

• Validated scales exist to measure PBA but are infrequently and inconsistently used– PLACS, interviewer-rated instrument (Robinson et al, 1993)– CNS-LS, self-report measure (Moore et al, 1997)

• PBA is distinct from, but can coexist with, affective disorders such as depression

• Crying spells in depression and laughing episodes in schizophrenia, hysteria, and mania may mimic PBA symptoms

• Neurological disease as a cause of crying is vastly underestimated by referring physicians (Green et al, 1987)

No Approved Pharmacotherapy With Indication for PBA

• Antidepressants (TCAs, SSRIs) and dopaminergic agents used with varying success– Complete resolution of symptoms or no response– DA agents only ~40%-50% successful

• Available agents do NOT have proven efficacy in large, well-controlled clinical trials using standardized scales– 5 comparative antidepressant trials with N≤28– 2/5 trials did not use objective scales

• TCAs have an unfavorable side effect profile, and their use may be limited in PBA patients

• Even severe cases often remain untreated

NeurodexTM

• Specific indication for PBA

• Proven effective and safe in large (N=140), well-controlled trial using the CNS-LS

• Significantly improved QOL and QOR; not shown for existing therapies

• Offers a potentially more targeted approach to the treatment of PBA than existing agents

Physician and Patient Education Needed

• Raise awareness of PBA

• Facilitate seeking of counseling and treatment– NeurodexTM

• Implement the use of standardized scales for diagnosis and assessment of therapy– CNS-LS