Transcript No Slide Title - Calef Biomedical Consulting

Articulating the Unmet Need in the
Diagnosis and Treatment of Pseudobulbar Affect:
Prevalence of the Condition and
Limitations of Existing Therapies
Ursula Hess, PhD
Torre Lazur McCann West
Estimated US Patients With PBA:
1.7 Million
PBA
1o Disorder Prevalence
MS
10%
Total US Cases
With 1o Disorder
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