Volume status is critical in determining the sodium balance and etiology of low serum sodium levels. In states of volume depletion, there is loss of both sodium and water but the primary sodium loss exceeds the total body water loss. In states of volume excess such as edematous states, the total body water is increased in relation to the total body sodium. Though there is an excess of extracellular fluid, the effective plasma volume is reduced. And this causes secretion of antidiuretic hormone (ADH) and further lowering of the sodium level. In some conditions, as with central nervous system disorders, ADH is secreted inappropriately, causing water retention and a secondary reduction in serum sodium levels.

Medications cause release of ADH resulting in a state similar to syndrome of inappropriate ADH (SIADH) . Some of the effect on sodium is also postulated to be a change in renal collecting tubule response to ADH.

Primary polydipsia, a condition where there is excess water consumption, is common in patients with mental illness. Hyponatremia occurs as the water consumption exceeds the capacity of the kidney to excrete free water, which is either because the water consumption is excessively high or there is a defect in the excretory capacity of the kidney.

Many medications, including some psychotropic agents, cause an SIADH like state.

Pseudohyponatremia is a condition where the serum sodium and serum osmolality are both normal but serum sodium is artificially low due to presence of other solutes in blood such as glucose or lipids.

See table in appendix for common etiologies of hyponatremia with corresponding volume status with each condition.

Carbamazepine and oxcarbazepine are two agents associated with the highest prevalence of hyponatremia (15% and 30%, respectively). Though prevalence is high, very low sodium levels <130 meq/L occur only at a prevalence of 1.29% in oxcarbazepine and 0.1% with carbamazepine. Hyponatremia also occurs with other psychotropic agents [1]. The prevalence of hyponatremia with SSRIs and SNRIs is low (0.06% and 0.08%, respectively). Antipsychotics are rarely associated with hyponatremia, though some studies report a high prevalence [2]. Risk of hyponatremia increases if combined with other agents that reduce sodium level such as diuretics.

Hyponatremia from medications usually occurs early in treatment but can be seen later. There is no clear evidence that medication dose or serum levels have any correlation with the risk or degree of hyponatremia. Usually once the hyponatremia develops, it persists as long as the medication is continued. One clearly established risk factor is advanced age.

Symptoms depend on both the severity and rapidity of decline in sodium levels. The symptoms are mainly neurological and related to the hyposmolality that accompanies hyponatremia causing increased movement of water into cells. Brain edema causes the neurologic symptoms.

The earliest signs of hyponatremia are nausea and malaise and may be seen in serum sodium levels less than 130 meq/L, but more likely below 125 meq/L. Headache, lethargy, obtundation, and eventually coma can occur when the serum sodium falls below 120 meq/L. These symptoms occur only when the hyponatremia develops over 24 h or so. When the serum sodium falls more slowly, the brain cells compensate by creating a gradient for the extracellular fluid out of the brain into the cerebrospinal fluid. In chronic hyponatremia, symptoms are generally nonspecific such as nausea, malaise, dizziness, forgetfulness.