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a medline search revealed a report of olanzapine - induced hyponatremia , and three such cases have been reported at a dutch pharmacovigilance centre .
hyponatremia has also been reported with other typical and atypical antipsychotics . a systemic review by meulendijks et al .
included four studies and 91 publications containing case reports and case series of antipsychotic - induced hyponatremia .
they found that the number of case reports of hyponatremia involving typical and atypical antipsychotics was 58 and 10 respectively , from 1974 to 2003 .
they also concluded that antipsychotic - induced hyponatremia did not seem to be associated with age or gender and was not dose dependent .
a 63-year - old hindu male , smoker and a known case of prostate enlargement was diagnosed with recurrent depressive disorder , for which he was on escitalopram 5 mg / day for last two years . around two months
back , he complained of unsatisfactory night sleep , feeling low , and experiencing referential ideas with elementary auditory hallucinations .
the current exacerbation was categorized as severe depression with psychotic symptoms as per icd-10 ( dcr ) .
the dose of escitalopram was increased to 10 mg / day and olanzapine 5 mg / day was added .
after two weeks , his sleep pattern was restored , symptoms abated and patient was better for about a month .
he then developed symptoms of mild anorexia , nausea , mild weakness , and occasional muscle cramps .
after 10 days , abrupt exacerbation of excessive weakness , lethargy , muscle cramps , unsteady gait , fleeting disorientation , and urinary retention developed , and the patient was admitted .
his physical examination revealed mild pallor , tachycardia , normal blood pressure , moderate dehydration , and disorientation of time and place .
his respiratory system and abdominal examination was unremarkable and his glasgow coma scale was 11 .
his blood investigations revealed serum sodium was 118 mmol / l , serum potassium was 3.5 mmol / l , and total leucocyte count was 12,100/cmm with 78% neutrophils .
thyroid - stimulating hormone , hemoglobin , albumin , and bicarbonate levels ; liver and renal function ; and lipid profile were normal .
he was treated with oral fluid restriction , stopping olanzapine and starting antibiotics . in view of lack of signs and symptoms of fluid overload ,
it was considered as probable case of normovolemic hyponatremia and 3% nacl was used initially as the correcting fluid .
mmol / l / day . after 4 hours , the patient became alert and regained his sensorium .
later , correction was done using free water restriction , normal saline , and oral salt supplement , and by serially measuring blood na regularly every 6 hours .
his symptoms and general condition improved over the next two days and serum sodium level reached 138 mmol / l .
patient was discharged on third day and he was told to continue escitalopram 10 mg .
olanzapine or any other antipsychotic was not restarted as his mental status examination did not revealing any psychotic psychopathology at that point of time .
the patient and guardians were educated about the risk of hyponatremia , importance of diet and fluid intake habits , and early warning signs , and about quitting smoking . on subsequent three follow ups
, he was maintaining well , and his serum electrolyte estimation was within normal range .
a  possible  causal relation between the drug and adverse event was established by the who - umc scale ( who ) and naranjo algorithm . written informed consent has been obtained from the patient for publication of this case report .
the exact estimate about incidence of hyponatremia induced by antipsychotics is currently not available but many antipsychotics like chlorpromazine , fluphenazine , haloperidol , flupenthixol , trifluoperazine , thioridazine , amisulpride , and risperidone have been implicated .
it has been suggested that the inhibitory effect of dopamine on release of anti - diuretic hormone ( adh ) is blocked by d2 receptor antagonism .
this may be the possible mechanism for the causation of hyponatremia by all d2 receptor antagonists including olanzapine .
the exception is clozapine , which has been found to have a beneficial effect on polydipsic behavior and development of hyponatremia , which may be attributed to its lower binding affinity to d2 receptors .
other contributory factors like old age , diet , salt intake , smoking , original psychopathology like psychogenic polydipsia , diabetes , other comorbid conditions , and side effects of antipsychotics or concurrent medications such as dryness of mouth may also play a role . in this case , the temporal relationship suggests olanzapine as the causative molecule , but it is difficult to pinpoint the offending medication .
all serotonin reuptake inhibitors including escitalopram are also known for causing hyponatremia , and the patient was on escitalopram for two years without any problems . with the worsening of the disease , the dose of escitalopram was increased and at the same time , olanzapine was also initiated .
hence , the causality may be attributed to the combined effect to both of these drugs .
however , escitalopram was restarted with no further episodes of hyponatremia suggesting a stronger possibility of causal relation with olanzapine
. there may be involvement of other possible non - pharmacological factors like water and salt intake pattern and some infection as evidenced by leucocytosis .
olanzapine may be responsible for hyponatremia in vulnerable people , which may be the product of a combination of factors .
emphasis should also be laid on the education of patients and their family members regarding early identification of hyponatremia .
here we report a case of a 63-year - old male diagnosed with recurrent depressive disorder and current episode of severe depression with psychotic symptoms , developed hyponatremia soon after addition of olanzapine and increasing the dose of escitalopram . 
 a possible causality association was established with olanzapine , and the possible etiological reasons of this clinically significant risk were discussed .