Transcript Psych case presentation Final

PISA SYNDROME: HOW DO
I STAY UPRIGHT?
Case Presentation: Psychiatry
Rotation
Rajwant Minhas
Outline
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Learning Objectives
Patient Case: PC
Drug Related Problems
Goals of Therapy
Background: Pisa Syndrome & treatment
Clinical Question
Literature Evaluation
Recommendation
Monitoring Plan
Learning Objectives
• Gain understanding of Pisa Syndrome
– Pathophysiology
– Prevalence
– Drug Causes
• Learn about strategies that can be used to
manage Pisa Syndrome
Patient: PC
• ID: 20 yo Korean Male, Wt: 67 kg Height: 1.76 m
• Allergies: Amoxicillin (rash, patient denies)
• C/C: Sedation, drooling, Pisa syndrome
• Diagnosis: Refractory Schizoaffective Disorder manifested by:
– Paranoid and grandiose delusions
– Sexual preoccupation
– Disinhibition
– Impaired insight & judgement
• Hx of extreme sensitivity to antipsychotics resulting in EPS, catatonic
and Parkinsonian symptoms
History of psychiatric illness
• Spring 2010: Disorganized thinking, grandiose, religious &
paranoid delusions, bizarre behaviour
• June 2010: RCH: Stabbed himself superficially in the
chest with scissors as he felt “stronger than God.”
• Dec 2010: SMH, 2 admissions at MSA, Abbotsford
• May 13, 2011: Abbotsford ICU  RCH
• May 26, 2011: RCH (5 month stay)  RVH
• August 15, 2011: RVH (E4) D3 (Refractory Psychosis Unit)
Patient PC
• FH: Negative for any neuropsychiatric disorders
– Hx of diabetes and hypertension
• Psychosocial History: Immigrated to Canada at 10
months of age
– Excellent student until grade 11
– Ambition to become a gay rapper, caged dancer
in bars
• No hx of substance abuse
Meds Prior to Admission
Lithium Citrate liquid
1050 mg HS
Paliperidone
6 mg HS
Loxapine
25 mg TID
Lorazepam
1 mg HS
Procyclidine
5 mg daily
Past Medical History
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Catatonic: stopped eating and drinking
– July-Nov 2010: 12 ECT treatments, unclear response
– March 2011: Carbamazepine substituted for Lithium
• poor results, increased agitation
– Spring 2011- ECT course, mildly effective
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Sept 2010: Episodic unresponsiveness, mutism & intermittent incontinence
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EEG found to be normal, found more “withdrawn” than catatonic
At least 5 CT scans
July 19, 2010: CT scan within normal limits
August 2010: MRI & EEG normal
April 2011: Advanced global atrophy for age
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Drooling & dysarthria present prior to clozapine institution
Medications tried so far…
Started
Medication/ Maximum
dose
Response
Jul 2010
Fluoxetine 20 mg/day
Disinhibited
June 2010
Olanzapine 20 mg/day
Partial response, led to Catatonia
Nov 2010
Lithium 1050 mg/day
Moderate mood stabilizing
Nov 2010
Benztropine 4 mg/day
Marginal improvement on 2 mg BID
Nov 2010
Risperidone 4.5 mg/day
Pisa syndrome & drooling
Dec 2010
Quetiapine 500 mg/day
Tolerated well. Helped with insomnia but no strong
antipsychotic effect. So switched to clozapine & loxapine
May 2011
Paliperidone 6 mg/day +
loxapine 125 mg/day
Dysphagia & sialorrhea
May 2011
Clozapine 350 mg/day
Sialorrhea & Pisa Syndrome
Some improvement in grandiosity, hyperthermia on 350 mg
daily
Current Medications
Regular
PRN Medications
Clozapine 350 mg qHS
Lorazepam 1-2 mg PO/IM Q4H PRN
Tetrabenazine:12.5 mg po
QAM started on Jan 19
Loxapine multi-route 10-25 mg PO/IM
Q4H PRN
Ipratropium 0.03% 2 Puffs Q6H PRN
Benztropine 1-2 mg PO/IM Q6H PRN
Bowel regime
Al & Mg hydroxide 30 mL po Q4H
PRN
Review of Systems
CNS
Drowsy
HEENT
Teeth malocclusion resulting in open mouth
Excessive drooling
Liver/Spleen/Endo
Dec 20/2011
ALT=17 (<50), AST=23 (<36), GGT=51 (<49)
CK=62 (<165), Ammonia= 50 (11-35)
Ceruloplasmin = 23 (220-495)
Serum copper = 5.7 (10.1-18.4)
Fluid/Lytes/Heme
Jan 24/2012
WBC=3.8 (4.2-10.8), Neutrophils = 2.10 Platelet = 115 (160-390)
Dec 20/2011
Clozapine = 1200 nmol/L
Norclozapine = 575 nmol/L
MSK/Skin/Extrem
Leaning to the right
WBC Trend
Wilson’s Disease
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Wilson disease first attacks the liver, the central nervous system, or both.
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Most patients develop signs and symptoms that accompany chronic liver disease
– swelling of the liver or spleen
– jaundice, or yellowing of the skin and whites of the eyes
– Fluid buildup in the legs or abdomen
– A tendency to bruise easily
– Fatigue
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A build up of copper in the CNS result in neurologic symptoms, including
– problems with speech, swallowing, or physical coordination
– tremors or uncontrolled movements
– muscle stiffness
– behavioural changes
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Other symptoms:
– anemia
– low platelet or white blood cell count
– slower blood clotting,high levels of amino acids, protein, uric acid, and carbohydrates in
urine
– premature osteoporosis and arthritis
Pisa Syndrome or Pleurothotonus
• Reported with use of:
antipsychotics,
antidepressants, lithium,
benzodiazepines,
antiemetics,
cholinesterase inhibitors
• Occurs mostly after dose
changes in antipsychotic
therapy
Clinical Characteristics
Pisa Syndrome: Pathophysiology
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Organic changes in the brain
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Dopaminergic-cholingeric imbalances induced by antipsychotic drugs
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Norepinephrine, Serotonin and dopamine interaction in patients on TCAs and
SSRIs
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Does not always reappear when rechallenged with antipsychotic
– May be far more neurochemical changes involved
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Uncertain if it is a subtype of acute or chronic dystonia
– May develop not only as a subtype of acute dystonia, but also as atypical
subtype of tardive dystonia
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Clinical evidence suggests that from a pharmacological viewpoint drug-induced
Pisa syndrome is similar to tardive dystonia
– Develops insidiously during prolonged treatment and benefits little from
anticholinergic therapy
Pisa Syndrome: Prevalence
• Documented in young and elderly patients
• Predominantly in female and elderly patients
• Young males more susceptible to both acute and
tardive dystonia
• In contrast:
– Pisa syndrome more prevalent in young and elderly females with
organic brain changes.
• Also appeared in patients on anticholinergics
Pisa Syndrome: Treatment
• Therapy not established
• Generally disappears after discontinuing antipsychotics or
decreasing dose
• Effects of anticholinergics not systematically studied
Neurology Consult Dec 2011
• Dysarthria and drooling
• Denied dysphagia, rigidity, epsiodes of freezing
• Felt a bit “slowed down” and body felt heavy
• Tardive dystonia possibility as first observed during
tx with risperidone
– Although usually associated with retrocollis (absent here)
• Absence of benefit from benztropine 4 mg/day
– Does not preclude diagnosis of TD
Neurology Consult Suggestions
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Trihexiphenidyl 1 mg tid, titrate to 2 mg tid over several
weeks
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Tetrabenazine but quite prone to induce drug-induced
parkinsonism, might worsen symptoms
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Restart quetiapine, titrate dose up above 500 mg/day
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If clozapine should be continued add aripiprazole:
One case report: Clozapine-induced Pisa syndrome
improved with the combination
Drug Related Problems
• PC is experiencing Pisa syndrome secondary to clozapine and/or
wilson’s disease and would benefit from reassessment of his
schizoaffective therapy.
• PC is at risk of acquiring infections secondary to low WBC count due
to clozapine and or wilson’s disease and would benefit from
reassessment of his schizoaffective therapy.
PC is experiencing continued drooling secondary to receiving
clozapine and would benefit from reassessment of his
schizoaffective therapy.
• PC is experiencing sedation secondary to receiving clozapine and
would benefit from reassessment of his schizoaffective therapy.
Goals of Therapy
• Control symptoms of schizoaffective
disorder
• Treat Wilson’s disease
• Relieve symptoms of Pisa Syndrome
• Minimize side effects from medications:
drooling, sedation
Clinical Question
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P: In a 20 year old Asian male
I: is tetrabenazine better than
C: trihexiphenidyl
O: to treat symptoms of Pisa syndrome?
Tetrabenazine & Pisa Syndrome
• No studies found
• Approved by FDA for treatment of hyperkinetic
movement disorders: Huntington's chorea,
hemiballismus, senile chorea, Tourette syndrome,
and tardive dyskinesia
• Depletes monoamine neurotransmitters (dopamine,
serotonin, norepinephrine) in presynaptic vesicles.
– Inhibits presynaptic dopamine release
– Blocks CNS dopamine receptors.
Effectiveness of anticholinergics and neuroleptic dose reduction
on neuroleptic-induced pleurothotonus (Suzuki et al.)
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Most previous reports failed to show results with anticholinergics
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Benztropine in 5 cases
Trihexyphenidyl in 1 case
Amantadine slightly beneficial in 2 cases; failed in 2 other cases
2 cases among 20 patients (10%)
• Suzuki et al study:
– N = 21, 13 diagnosed with schizophrenia
– 20 patients: >2 of the following antipsychotic drugs:
• Phenothiazines (chlorpromazine, levomepromazine etc.)
• butyrophenones (haloperidol) & zotepine
– 1 patient: TCAs combination
– Trihexiphenidyl 6 mg/day to prevent EPS
Suzuki et al
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Pleurothotonus treatment:
Trihexiphenidyl 4 mg tid
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Biperiden HCl IM 5mg/dose
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Pleurothotonus disappeared within 3 weeks after dose increase in 9 patients
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40% response
Higher dose & ethnic homogeneity
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No definitive toxic side effects (delirium, confusion, urinary retention)
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Recurred in 2 cases within 1-year of follow-up
– Improved after dose reduction
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Use high-dose anticholinergics if dose reduction may worsen psychotic symptoms
Suzuki et al.
• Remaining cases improved by a reduction or withdrawal
– Efficacy consistent with previous reports.
• Although not always appearing insidiously, pleurothotonus may
be neurochemically similar to tardive dystonia.
• Striking difference between drug-induced pleurothotonus and
tardive dystonia:
– Benefit from withdrawal or reduction of antipsychotics vs. tardive
dystonia
– Thus, clinical evidence suggests that distinct pathophysiologic
mechanisms may underlie drug-induced acute and tardive dystonia.
• Garcia and Diez-Martin: Clozapine effective in treating Pisa
syndrome induced by antipsychotics
– Rarely develops in patients on clozapine, worthwhile to use clozapine to
treat
Quetiapine
• Hepatic impairment (30%): lower clearance
– May result in higher concentrations. Dosage adjustment
– IR tablet: Oral: Initial: 25 mg/day, increase dose by 25-50
mg/day to effective dose
– Extended release tablet Oral: Initial: 50 mg/day; increase dose
by 50 mg/day to effective dose, based on clinical response and
tolerability to patient.
• Hematologic side effects: Neutropenia (≤2%), leukopenia (≥1%),
hemorrhage (1%)
• Hepatic: Transaminases increased (1% to 6%), GGT increased
(1%)
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Overall Summary
Option
Pros
Cons
Trihexiphenidyl
Some evidence might be
effective
Anticholinergic side effects: sedation,
constipation
Tetrabenazine
No evidence found. Contraindicated in
hepatic impairment
EPS (15% to 33%), sedation (31%), fatigue
(22%), insomnia (22%), akathisia (19%),
depression (19%), anxiety (15%)
Parkinsonism (3% to 10%)
Clozapine
Effective for his psychosis Pisa syndrome, sedation, risk of
(grandiosity)
agranulocytosis. Contraindicated in active
hepatic disease associated with nausea,
anorexia, or jaundice; progressive hepatic
disease or hepatic failure
Quetiapine
Tolerated well in the past
Side effects: neutropenia(2%),
Adjustment in hepatic impairment
Recommendations
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Initiate treatment of Wilson’s disease
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Continue trial of tetrabenazine
– Titrate to max 25 mg TID
– Usual maximum tolerated dosage: 25 mg 3 times/day; maximum
recommended dose: 200 mg/day
– If no improvement at the maximum tolerated dose after 7 days,
improvement is unlikely; consider discontinuation
• If no improvement with tetrabenazine:
– Consider decreasing clozapine dose to 300 mg
• If no improvement in CBC consider discontinuing clozapine
– Consider switching to quetiapine and titrate up to >500 mg/day
• Consider monitoring CBC every week vs. biweekly
Monitoring
Parameter
When
Who
Efficacy:
Improvement in Pisa syndrome
Delusions/Hallucinations
Ongoing
Ongoing
Doctor, RN, Pharmacist
Doctor, RN, Pharmacist
Safety:
CBC
Sedation
Depression
Every week Doctor, Pharmacist
Ongoing
Doctor, Patient, RN,
Pharmacist
Ongoing
Doctor, Patient, RN,
Pharmacist
References
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Toshihito Suzuki, Hisashi Matsuzaka. Drug-Induced Pisa Syndrome
(Pleurothotonus) Epidemiology and Management. CNS Drugs 2002; 16
(3): 165-174.
The Pisa Syndrome [cited 2012 Jan 19]. Available from:
http://mirecc.stanford.edu/pdf/Pisa%20Syndrome.pdf
Toshihito Suzuki et al. Effectiveness of anticholinergics and neuroleptic
dose reduction on neuroleptic-induced pleurothotonus (the Pisa
syndrome). J Clin Psychopharmacol. 1999 Jun;19(3):277-80.
Yassa R, Nastase C, Cvejic J et al. The Pisa syndrome (or pleurothotonus): prevalence in a psychogeriatric population. Biol.
Psychiatry 1991; 29: 942–5.
National Institute of Diabetes and Digestive and Kidney Diseases.
Wilson’s disease. Available from:
http://digestive.niddk.nih.gov/ddiseases/pubs/wilson/WilsonDisease.pdf