Transcript A 54-year-old woman with PTSD and neurologic symptoms

A 54-year-old woman with PTSD
and neurologic symptoms
Julie Fagan, M.D.
Primary Care
Conference
8 February 2006
Learning Objectives
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Generate a differential diagnosis for recurrent
focal neurologic symptoms
Question your assumptions!
Understand the importance of and
mechanism for FDA reporting
Financial Conflicts of Interest
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None
Case
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54 y/o WF seen for 1st time since 1999
Suffered traumatic sexual and head injury in
1989—comatose for several days
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Recovered with PTSD, mild cognitive deficits
Worked for 10 years (as an RN), then retired on
disability
In 2002, hospitalized for LOC and dysarthria
Case
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PMH:
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PTSD with flashbacks, major depression with
psychotic features
Migraines without aura
Obesity
Type II DM, on insulin
Hypothyroidism
Dyslipidemia
HTN
Case
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FHx: grandmother with DM, several family
members with hypothyroidism
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No depression or alcoholism
PP: Single, never married. Trained as NP
until assault in 1989; was able to work as RN
and very physically active until health
declined—gained weight after retirement
Medications
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Citalopram 40 mg daily.
Clonazepam 2 mg p.r.n.
Diazepam 20 mg p.r.n
Dicyclomine 10 mg q.i.d.
Diphenoxylate/atropine prn
Depakote 1500 mg daily
Gemfibrozil 600 mg b.i.d
Glimepiride 4 mg daily
Glargine 25 units at h.s.
Lispro 8 units at breakfast, 5
units at lunch, 10 units at
supper
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Levothyroxine 0.1 mg daily
Mirtazapine 60 mg daily
Nitroglycerin p.r.n
Olanzapine 15 mg at h.s
Percocet p.r.n
Propanolol 40 mg b.i.d.
Clothiapine 200 mg AM, 600
mg PM
Simvastatin 40 mg daily
Allergies/ADRs
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NKDA
Family History
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Positive for strokes, MIs in older adults (>70
y/o); HTN, DM, dyslipidemia
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Possible protein S deficiency in a cousin
Negative for depression, psychosis
Social Hx
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Single, never married, G0
Trained as NP, never able to go back after
brutal sexual and physical assault in 1989
due to “minimal brain injury”
Worked as RN until 2000, when depression
worsened and she began having CNS sx
ROS
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Over a 5-year period, weight increased from
130 to 210, requiring metformin, and
eventually insulin
Otherwise, went through uneventful
menopause, denies increased frequency of
migraines or other neuro sx
What Her “Spells” Were Like
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Admitted 7/00 to Meriter with disorientation, ataxia,
dysarthria, R arm weakness
Workup: neuro consult, head CT, MRI, MRA, LP,
EEG, echo, carotid dopplers, VEPs, CBC, TSH,
electrolytes, creat, LFTs, ammonia, ABGs, tox
screen, Ca/Mg/PO4 , thrombophilia panel, ANA all
NORMAL
Psych consult: psychotic depression: rx “continue
meds”
Discharged 1 week later on ASA; back to baseline
after 26 hours
Diagnosis/Differential
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TIA/stroke
Migraine with neurologic effects
Tumor
Encephalitis
Atypical seizures
Hysteria/conversion reaction
Vasculitis/SLE
Clinical Course
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Admitted 2 more times, repeated MRIs,
MRAs, carotid dopplers, consideration of
angiogram
Her course was nearly identical each time—
fairly rapid resolution of sx
Meds increased from
ASAclopidogrelwarfarin without change
in pattern of episodes
The Answer: Serendipity Strikes Again
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Her psychiatrist felt she needed an
adjustment of her regimen, therefore
switched from olanzapine to quetiapine for
psychosis control
She has not had a single “spell” since!
She has also been able to lose 80 lbs, start
modest exercise, stop warfarin, insulin
Olanzapine and TIAs
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Listed as “rare” (<1%): personality change,
dizziness, stroke, weakness in PDR
Epocrates lists TIAs as serious, does not
give frequency
The literature contains analysis of
relationship to strokes, not TIAS
Atypical Psychotics and Stroke
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Conflicting reports
Most studies in elderly demented pts
Some large, but retrospective, case control,
cohort based
Conclusion: atypical antipsychotics should be
used cautiously in elderly pts with dementia
due to increased stroke risk (FDA warning)
2005 BMJ Study Shows No Increased
Stroke Risk
Main analysis (full cohorts)
Atypical
antipsychotic cohort
(n=17 845)
Typical
antipsychotic cohort
(n=14 865)
No (%) of new admissions for
ischaemic stroke
284 (1.6)
227 (1.5)
Mean (SD) duration of follow
up (days)
227.2 (264.0)
250.1 (335.4)
Crude event rate (No of
events per 1000 person
years)*
25.5
22.3
Unadjusted hazard ratio
(95% CI)
1.06 (0.89 to 1.27)
1.00
Adjusted hazard ratio (95%
CI)†
1.01 (0.81 to 1.26)
1.00
Other Studies:
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Conclusion from Bandolier 2005:
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“Evidence from randomised trials shows a small
increased risk of stroke in patients with dementia
and agitation treated with atypical antipsychotics
risperidone and olanzapine, but based on a small
number of events. A large observational study
failed to find any increased risk, and probably
limits the size of the effect to no more than two
extra strokes per 1000 person years of
treatment.”
Applicable to My Patient?
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Not elderly
Not demented (though has minimal brain
injury)
No permanent stroke and no evidence of
vascular disease despite extensive testing
Though not rechallenged with olanzapine,
taking quetiapine (another atypical) without
problems
Conclusion: ADR (Adverse Drug
Reaction
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Many drugs have significant ADRs that show
up after FDA approval
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Occasionally sufficient to cause recall
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Rofecoxib, valdecoxib
Fenfluramine, dexfenfluramine
Zomepirac
Troglitazone
If ADR is rare, can be amplified by multiple
reports
How to Report: MedWatch
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www.fda.gov/medwatch
FDA Center for Drug Evaluation and Research
(CDER): mission is to ensure safety and efficacy of
drugs
Download voluntary reporting form, fill out, fax or
mail
FDA, pharmaceutical companies review, collate data
periodically
When events are significant (death or severe
morbidity) or above expected frequency, they issue
warning and ultimately recall
Conclusions
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Adverse drug reactions common
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“Anything can do anything”
Do not dismiss as preposterous even if no
plausible mechanism, patient is suggestible
When in doubt, hold drug and see if
symptoms resolve
Have a low threshold for reporting to
MedWatch