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Richard C. Josiassen Ph.D. Hyponatremia and Schizophrenia. Are Vaptans a Treatment Option?. Is Hyponatremia an Important Clinical Issue in the Overall Care of Individuals with Schizophrenia ? .

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Hyponatremia and schizophrenia l.jpg

Hyponatremiaand Schizophrenia

Are Vaptans

a Treatment Option?


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Is Hyponatremia an Important Clinical Issue in the Overall Care of Individuals with Schizophrenia?


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  • Case Study J.C Care of Individuals with .64 years oldChronic schizophreniaHospitalized 37 yearsFirst hyponatremiadiagnosis ???Hx of multiple seizuresMuteSodium 118 – 125TremorsAggressive


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  • Targowla R (1923): Des troubles fonctionnel du rein dans les maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion). Bull Soc Med Hop Paris 47:1711-1715.

  • Hoskins RG (1933): Schizophrenia from the physiological point of view. Ann Intern Med 7:445-456.

  • Barahal HS (1938): Water intoxication in a mental case. Psychiat Quart 12:767-771.


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Three-Month Prevalence Rate maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

  • NSH Population(n = 328) 233 males 105 femalesMean Serum Sodium X = 139.3 SD = 2.87.9% HyponatremiaNo association with dose or class of anti-psychotic medication


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Symptoms of Hyponatremia maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

Depend on:

• Degree

• Rapidity

• Susceptibility

age (young and old), CNS

trauma, respiratory reserve,

female gender


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Symptoms of Hyponatremia maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

In the Context of Schizophrenia

Normal 140 (mmol/L) 

??? 135 

Lethargy, Apathy 130 

Confusion 

Agitation 

Muscle Cramps 

Hallucinations 120 

Seizures 

Coma 

Pseudobulbar palsy 110 

Hypothermia 

Death 


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Symptoms of Hyponatremia maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

Mostly CNS in nature:

• Acute

• Chronic


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Day 1 maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion). 104 mmol/LSeizuresComatoseDay 2121 mmol/LDay 3140 mmol/L Kurokawa et al (2004)


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Other morbidities include: maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

•impaired cognition

•impaired gait and balance leading to falls

•pathologic fractures and

osteoporosis

(Siegel, 2008)


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Available Treatments for Hyponatremia maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion).

Correct underlying disorder

Diuretics

Fluid Restriction

Hypertonic Saline

Off-label

• Demeclocycline

• Lithium carbonate

• Urea

• Clozapine


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A recent review identified more than 30 pharmacologic studies of agents thought to:

reduce fluid intake (e.g. beta blockers, alpha adrenergic antagonists, angiotensin converting enzyme inhibitors)

reduce stereotypic behaviors (e.g. opiod antagonists)

increase water excretion (lithium, demeclocycline)

directly increase plasma tonicity (e.g. salt, electrolyte containing beverages).


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“…the trials offer little useful data studies of agents thought to:to the clinician” to guide effective management of polydipsia or hyponatremia.

(Brooks & Ahmed, 2006)


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Vasopressin Antagonists studies of agents thought to:

V2 SpecificV1b/V2 non-specific

OPC-41061 OPC-31260

- Otsuka (tolvaptan) - Otsuka

VPA-985 YM-087

- Cardiokine (lixivaptan) - Yamanouchi (conivaptan)

SR-121463

- Sanofi (satavaptan)


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“Double-Blind, Placebo-Controlled, Multicenter Trial of a Vasopressin V2-Receptor Antagonist in Patients With Schizophrenia and Hyponatremia”

Richard C. Josiassen, PhD, Morris Goldman, MD, Meera Jessani, MD, Rita A. Shaughnessy, MD, PhD, Ala Albazzaz, MD, Jennifer Lee, John Ouyang, PhD, Cesare Orlandi, MD and Frank Czerwiec, MD, PhD

Biological Psychiatry (in press)


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Demographic & Baseline Vasopressin V2-Receptor Antagonist in Patients With Schizophrenia and Hyponatremia”Characteristics

Characteristic TolvaptanPlacebo p-value

(n = 7) (n = 12)

______________________________________________________

n (%) n (%)

Male 4 (57%) 11 (92%) ns

Smoker 6 (86%) 10 (83%) ns

Atypical neuroleptic 5(71%) 11(92%) ns

Diagnosis

Schizophrenia 5 (71%) 9 (75%)

Schizoaffective 2 (28.6%) 2 (16.7%)

Psychosis NOS -- 1 (8%)



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  • Case Study J.C of Individuals with .64 years oldChronic schizophreniaNormal Na for four years

    Living in the communityClinically stable and socially engaged


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ARTHUR P. NOYES of Individuals with RESEARCH FOUNDATION

Richard C. Josiassen, PhD

Rita A. Shaughnessy, MD, PhD

Nina Skuban, MD

Dawn M. Filmyer

Margit Kacso

Jessica L. Curtis

Marice J. Davis

Maurice D. Cornelius

Naomi Finkel, RN

Ann Marie Donohue, PhD

Bruce McNeel

Affiliated with the University of Pennsylvania


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