Fabian, 2004 Paroxetine-induced hyponatremia in older adults: a 12-week prospective study.

[Altostrata]

Potentially dangerous electrolyte imbalances frequently emerge early in treatment with paroxetine.

 

http://archinte.jamanetwork.com/article.aspx?articleid=216611

 

Arch Intern Med. 2004 Feb 9;164(3):327-32.

Paroxetine-induced hyponatremia in older adults: a 12-week prospective study.

Fabian TJ, Amico JA, Kroboth PD, Mulsant BH, Corey SE, Begley AE, Bensasi SG, Weber E, Dew MA, Reynolds CF 3rd, Pollock BG.

 

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/14769630

Free full text at http://archinte.jamanetwork.com/article.aspx?articleid=216611

 

BACKGROUND:

Older depressed patients are at high risk for development of hyponatremia after initiation of the selective serotonin reuptake inhibitor paroxetine, despite clinical monitoring and preventive management. The purposes of this study were to determine the incidence and etiology of paroxetine-induced hyponatremia in older patients and to identify patient characteristics that may account for variability in susceptibility to this adverse event.

 

METHODS:

This prospective, longitudinal study was conducted in a university-based ambulatory psychiatric research clinic from August 1999 through September 2001. Patients included 75 men and women aged 63 through 90 years (mean +/- SD age, 75.3 +/- 6.0 years) who received a diagnosis of a current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive episode and were prescribed paroxetine. We monitored plasma sodium levels before initiating paroxetine therapy and after 1, 2, 4, 6, and 12 weeks of treatment. In a subset of individuals, we measured levels of antidiuretic hormone, glucose, serum urea nitrogen, and creatinine. Hyponatremia was defined as a plasma sodium level of less than 135 mEq/L after initiation of paroxetine therapy.

 

RESULTS:

Hyponatremia developed in 9 (12%) of the 75 patients after initiation of paroxetine treatment. Mean +/- SD time to development of hyponatremia was 9.3 +/- 4.7 days (median, 9 days; range, 1-14 days; n = 8). In the multivariate regression, lower body mass index and lower baseline plasma sodium level (<138 mEq/L) were significant risk factors for the development of hyponatremia in these patients.

 

CONCLUSIONS:

Hyponatremia is an under recognized and potentially serious complication of paroxetine treatment in older patients. Our results provide a foundation for understanding the etiology and risk factors associated with paroxetine-induced hyponatremia.

 

 

From the paper:

 

 

 

MAJOR DEPRESSION IS A common psychiatric disorder in older adults, affecting 10% to 20% of medically hospitalized elderly patients. It is reported that 10% to 34.5% of older persons living in the community also experience clinically significant depressive symptoms.^1,2 Most depression in older patients is managed in the primary care setting. According to a recent report on national trends in outpatient treatment, depressed patients were 4.8 times more likely to receive treatment with an antidepressant in 1997 than in 1987.³ The marked increase in pharmacological treatment of this disorder is due in part to the introduction of a new class of highly effective antidepressant drugs known as the selective serotonin reuptake inhibitors (SSRIs). Owing to the relatively benign adverse effect profile of SSRIs, these agents are often prescribed as the first-line treatment of depression in older adults.^4,5 Although these agents are reportedly safer than the tricyclic antidepressants, they are not without risk or adverse effects.

 

 

 

 

 

Since the introduction of SSRIs more than a decade ago, the medical literature is replete with isolated case reports of clinically significant hyponatremia in aged patients treated with these agents.^6- 8 In a case note review, Strachan and Shepherd⁹ reported hyponatremia in 5 (28%) of 18 elderly patients prescribed fluoxetine hydrochloride and 8 (22%) of 37 prescribed paroxetine, although an earlier retrospective case-control study of 845 patients documented that hyponatremia developed in 1 of 200 patients treated per year with these agents.¹⁰ More recently, Kirby et al¹¹ recently reported a 39% incidence of hyponatremia in a retrospective analysis of 74 elderly inpatients who were receiving treatment with an SSRI or with venlafaxine hydrochloride. Despite the growing number of case and retrospective reports of SSRI-induced hyponatremia, prospective evaluation of the safety of these agents is lacking in individuals older than 65 years, the fastest growing segment of our population.¹² Although severe hyponatremia can be fatal, symptoms associated with mild to moderate hyponatremia are nonspecific (eg, anorexia, nausea, fatigue, lethargy, and confusion) and are common in older patients with depression. Without proper monitoring of sodium levels in elderly patients prescribed SSRIs, these symptoms may be dismissed by health care providers as the inevitable maladies of aging, and the patient may therefore be at risk for serious sequelae. The clinical presentation of hyponatremia associated with SSRIs is often compatible with the syndrome of inappropriate antidiuretic hormone (ADH) secretion,^8,13,14 yet ADH levels are not routinely measured to confirm this impression.

....

 

 

Recent improvements in detection and diagnosis of depressive disorders in the elderly along with use of SSRIs for treatment of anxiety disorders has resulted in an increased number of older patients being prescribed SSRIs. As such, a greater number of individuals are at risk for development of SSRI-induced hyponatremia. Patients with SSRI-induced hyponatremia may be asymptomatic, and therefore routine monitoring of sodium concentrations in elderly patients prescribed an SSRI is essential. Failure to detect and manage mild hyponatremia may result in progression to moderate or severe hyponatremia that can lead to seizures, coma, or death.³³ Thus, early detection, appropriate monitoring, and treatment of hyponatremia in older patients who are prescribed an SSRI will have a significant public health impact by reduction of health care costs associated with preventable adverse medical events.^36- 38

 

 

 

 

 

Hyponatremia is an underrecognized and potentially serious complication of paroxetine treatment in older patients. Hyponatremia associated with SSRIs has been postulated to be due to the syndrome of inappropriate ADH secretion. In this prospective study, we provide evidence in support of a mechanism mediated by the syndrome of inappropriate ADH secretion for paroxetine-induced hyponatremia in these older individuals. Plasma sodium concentrations decreased in nearly all of the older depressed patients prescribed paroxetine in this study. However, the risk for development of hyponatremia was highest in women with a low BMI who had sodium concentrations near the lower end of the physiologic range before initiating treatment. The risk for development of hyponatremia was highest in the first 2 weeks of paroxetine treatment and was not related to paroxetine concentrations. Therefore, we recommend monitoring sodium and SUN levels before initiating treatment with paroxetine or other SSRIs and at 1 and 2 weeks after initiation of treatment. This is especially important for patients who present with additional risk factors such as female sex, low BMI, and a baseline plasma sodium level of 138 mEq/L or less. At minimum, a sodium level should be measured in all elderly patients who exhibit abrupt changes in mental status (eg, lethargy or confusion) any time during treatment with an SSRI. If hyponatremia develops and continuation of SSRI therapy is desired, long-term restriction of daily fluid intake (eg, 800-1000 mL) has been somewhat successful, although patient compliance is often poor.³¹ Failure to respond to fluid restriction warrants discontinuation of the causative medication until sodium levels normalize.

 

 

 

 

....

[btdt]

As I recall this was the problems for Scotty's son he was certainly not old but a teenager for those who don't know.  

 

I was nosing around looking things up and came across a wiki stating what the USA paid for research in 2004 30 billion that is a lot of money.  With that amount of cash one would expect some results or maybe i am naive of course I am naive. 

 

http://en.wikipedia.org/wiki/United_States_Office_of_Research_Integrity

 

"In FY 2004, the PHS provided at least $30 billion for health research and development, primarily in the biomedical and behavioral sciences through its extramural and intramural programs. (Extramural programs provide funding to research institutions that are not part of the Federal government of the United States - medical schools, universities, colleges, hospitals, research institutes. Intramural programs provide funding for research conducted within Federal government facilities.)"

PHS is  Public Health Service could be very body else already knew this but it did surprise me.