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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

Hyponatremiaand Schizophrenia

Are Vaptans

a Treatment Option?

slide3
Is Hyponatremia an Important Clinical Issue in the Overall Care of Individuals with Schizophrenia?
slide4
Case Study J.C.64 years oldChronic schizophreniaHospitalized 37 yearsFirst hyponatremiadiagnosis ???Hx of multiple seizuresMuteSodium 118 – 125TremorsAggressive
slide5
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.
three month prevalence rate
Three-Month Prevalence Rate
  • 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
slide7
Symptoms of Hyponatremia

Depend on:

• Degree

• Rapidity

• Susceptibility

age (young and old), CNS

trauma, respiratory reserve,

female gender

slide8
Symptoms of Hyponatremia

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 

slide9
Symptoms of Hyponatremia

Mostly CNS in nature:

• Acute

• Chronic

slide11
Other morbidities include:

•impaired cognition

•impaired gait and balance leading to falls

•pathologic fractures and

osteoporosis

(Siegel, 2008)

slide12
Available Treatments for Hyponatremia

Correct underlying disorder

Diuretics

Fluid Restriction

Hypertonic Saline

Off-label

• Demeclocycline

• Lithium carbonate

• Urea

• Clozapine

slide13
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).

slide14
“…the trials offer little useful datato the clinician” to guide effective management of polydipsia or hyponatremia.

(Brooks & Ahmed, 2006)

vasopressin antagonists

Vasopressin Antagonists

V2 SpecificV1b/V2 non-specific

OPC-41061 OPC-31260

- Otsuka (tolvaptan) - Otsuka

VPA-985 YM-087

- Cardiokine (lixivaptan) - Yamanouchi (conivaptan)

SR-121463

- Sanofi (satavaptan)

slide16
“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)

slide17
Demographic & BaselineCharacteristics

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%)

slide20
Case Study J.C.64 years oldChronic schizophreniaNormal Na for four years

Living in the communityClinically stable and socially engaged

arthur p noyes research foundation
ARTHUR P. NOYESRESEARCH 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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