Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.     

Comparison of subperiosteal vs subgaleal elevation techniques used in forehead lifts

OBJECTIVE: To describe the occurrence and management of sexual dysfunction induced by selective serotonin-reuptake inhibitors (SSRIs), to provide an overview of sexual dysfunction, reports of SSRI-induced sexual dysfunction, and management strategies. DATA SOURCES: Information was retrieved from a MEDLINE English-literature search from January 1986 to July 1998 and by review of references. Indexing terms included sexual dysfunction, antidepressants, selective serotonergic reuptake inhibitors, fluoxetine, sertraline, paroxetine, fluvoxamine, clomipramine, buspirone, nefazodone, bupropion, cyproheptadine, amantadine, yohimbine, and central nervous system stimulants. STUDY SELECTION: There are no controlled studies describing SSRI-induced sexual dysfunction or its management. Twenty-one studies are presented, including 2 open-label studies, 12 case series, and 7 case reports. SSRI-induced sexual dysfunction is described with fluoxetine, paroxetine, sertraline, and fluvoxamine for 3-24 weeks of therapy. DATA SYNTHESIS: Data were organized according to the pharmacologic agent used in the management of SSRI dysfunction, target population, SSRI implicated, type of sexual dysfunction, experimental design, and treatment response. Data were extracted from methodology and results sections of reports. Methodologic flaws included failure to account for gender differences, omission of SSRI dose and duration, and use of concomitant drugs. CONCLUSIONS: The frequency of reports suggests that SSRI-induced dysfunction is a common adverse effect; controlled studies are necessary to determine prevalence. Most reports have occurred with fluoxetine, but this phenomenon may be related to its widespread use. Further study is needed to evaluate baseline sexual function, to define target populations, and to compare SSRIs in inducing sexual dysfunction. Serotonin antagonists and dopamine agonists have been used most often to treat SSRI-induced dysfunction and have generally been effective, but controlled studies are also needed.     

Asymptomatic hyponatremia due to inappropriate secretion of antidiuretic hormone as the first sign of a small cell lung cancer in an elderly man

A 72-year-old man was hospitalized with asymptomatic hyponatremia. Despite hyponatremia, urinary sodium excretion with urine osmolality exceeding plasma osmolality persisted. Plasma vasopressin levels were high and independent of plasma osmolality during hypertonic saline infusion. Computed tomography of the chest showed enlarged mediastinal and right hilar lymph nodes. Microscopically, a specimen of lymph nodes obtained by biopsy represented vasopressin-producing small cell lung carcinoma. Chemotherapy plus irradiation improved the hyponatremia. Thus, careful evaluation is necessary to determine the cause of hyponatremia disorders in elderly patients.     

Screening for cognitive deficits in a sample of hospitalized geriatric patients: a re-evaluation of a brief mental status questionnaire

A 30-item screening examination for cognitive deficits was administered to 65 hospitalized elderly patients and to 60 elderly controls. A high proportion (73 per cent) of the hospitalized patients were found to have low cognitive scores indicative of probable organic mental syndrome (OMS). Especially high deficits were found among the patients with orthopedic and cerebrovascular conditions. The test correctly identified the 15 cases of established OMS. The percentage of false positive results in the normal controls was reasonably low. The importance of routine cognitive measurements in medical wards is stressed.     

In situ monitoring with the Tradescantia bioassays on the genotoxicity of gaseous emissions from a closed landfill site and an incinerator

The aging process introduces many changes that affect the whole person, including sleep. Age-related changes in the nervous system, acute and chronic illnesses, medications, primary sleep disorders, and factors associated with hospitalization in the critical care unit are elements identified with sleep disturbance in the elderly patient hospitalized in the critical care unit. One of the most important challenges for critical care nurses is to promote a healing environment for elderly patients where they can obtain the sleep necessary for recovery. Potentially effective nursing interventions for sleep promotion are those caring interventions that focus on the body-mind connection, such as back massage, relaxing music, imagery, and muscle relaxation. Investigations of the effectiveness of nursing interventions for sleep promotion are needed.     

Selective full dopamine D1-like (SKF-82958) and D2-like (N-0923) agonist combination in the MPTP monkey model of hemiparkinsonism

OBJECTIVE: Fluoxetine is widely prescribed for depressed patients. Hyponatremia secondary to inappropriate secretion of antidiuretic hormone has been reported in a few cases associated with routine use of fluoxetine, especially in elderly patients. The mechanism has been postulated to be linked to the inappropriate secretion of antidiuretic hormone. Serum concentrations of antidiuretic hormone and fluoxetine have not been reported in previously published reports. CASE REPORT: We report two new cases of severe and reversible hyponatremia associated with routine use of fluoxetine therapy in two elderly women. Fluoxetine-induced inappropriate secretion of antidiuretic hormone was confirmed by elevated serum concentrations of antidiuretic hormone and fluoxetine.     

Management of hospitalized patients with type 2 diabetes mellitus

Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin-dependent) diabetes mellitus can have adverse consequences, including increased neurologic ischemia, delayed wound healing and an increased infection rate. Poor glycemic control can also affect the outcome of the primary illness. If possible, hospitalized diabetic patients should continue their previous antihyperglycemic treatment regimen. Decreased physical activity and the stress of illness often lead to hyperglycemia in hospitalized patients with type 2 diabetes. When indicated, insulin is given either as a supplement to usual therapy or as a temporary substitute. The overall benefit of the traditional sliding-scale insulin regimen has been questioned. Insulin supplementation given according to an algorithm may be a logical alternative. Any antihyperglycemic regimen should be administered and monitored in a manner coincident with the intake of food or other sources of calories. Factors that can alter glycemic control acutely, including specific medical conditions and medications, should be identified and anticipated.     

Polynucleotide ligase activity of eukaryotic topoisomerase I

1. Extrapyramidal adverse effects have been reported with the selective serotonin re-uptake inhibitor (SSRI) antidepressants, particularly fluoxetine and paroxetine. 2. Recently, the SSRI sertraline has also been associated with treatment-emergent extrapyramidal syndrome (EPS) side effects. A review of the literature identified thirteen published cases of sertraline-induced EPS, several of which were confounded by the presence of concomitant medications, and few reported quantitative data using rating scales. 3. We present another case of EPS associated with sertraline in which daily ratings were obtained using the Abnormal Involuntary Movement Scale. 4. This review and case report add to the small but growing literature suggesting that sertraline, like the other SSRI's may cause significant extrapyramidal side-effects. These movement disorders presumably occur through an interaction between serotonergic and dopaminergic pathways, providing an important clinical correlation of interactions between these neurotransmitter systems.     

Evaluating and treating nutritional problems in older patients

Up to 65% of elderly hospitalized patients are protein-energy undernourished at admission or acquire nutritional deficits while hospitalized. For the elderly patient who requires nutritional support therapy, a strategy of intervention should be carefully formulated based on the results of a clinical assessment. While receiving nutritional support, the patient should be monitored carefully for complications and changing metabolic requirements. Modifications to the original regimen should be made to meet the patient's needs as necessary.     

Clinical audit at the heart of clinical effectiveness

Hyponatremia is often associated with a broad spectrum of neurological symptoms, occasionally leading to death in severe cases. Recent studies have clearly indicated that too rapid correction of severe hyponatremia can cause brain demyelination, which also produces neurological morbidity and mortality in some cases. This has caused a clinical conundrum regarding optimal treatment of hyponatremia, and may leave physicians uncertain about the most appropriate therapy for this important group of patients. Despite ongoing controversy about treatment guidelines and outcomes for specific subgroups of patients, a synthesis of recent clinical and experimental results suggests that the treatment of hyponatremic patients entails balancing the risks of hyponatremia against the risks of correction for each patient on an individualized basis. Although variability for both risks is great and one cannot accurately predict those patients who will develop neurological complications from either hyponatremia or its correction, a general consensus for rational treatment guidelines has nonetheless emerged. Following a discussion of the physiology and pathophysiology of brain adaptation to hyponatremia, this review will focus on the present consensus approach to therapy of hyponatremic patients.     

Long-term results after scleral buckling surgery in uncomplicated juvenile retinal detachment without proliferative vitreoretinopathy

Hyponatremia is a common complication after subarachnoid hemorrhage (SAH). Although the mechanism of hyponatremia is still controversial, cerebral salt-wasting syndrome (CSNS) is currently regarded as being more responsible than the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The aim of our study was to assess the plasma volume status of a patient with hyponatremia following subarachnoid hemorrhage. In doing this it may be possible to indirectly differentiate its pathogenesis. Fifty patients with SAH were studied. Twenty patients demonstrated hyponatremia (serum sodium < 135 mEq/L) during day 7 to 13 after subarachnoid hemorrhage. Patients with hyponatremia were categorized on the basis of their daily body weight, and central venous pressure. Group A consisted of patients with hypovolemia (16 patients), with the onset time of hyponatremia being day 7 to 9. Group B included those with hypervolemia (4 patients); hyponatremia was observed during day 10 to 11 and was corrected in all patients within 72 hours after induction of fluid restriction. Our findings suggest that hyponatremia following subarachnoid hemorrhage usually occurs due to CSWS, although SIADH remains as a minor pathogenesis. We conclude that the combination of daily body weight and CVP measurements is a simple and practical method to distinguish promptly SIADH from CSWS.     

Isolation and expression of murine carbonic anhydrase IV

Many studies have demonstrated the problems patients have with medications. In these studies, the elderly and patients utilizing psychiatric medications are often cited as having the greatest noncompliance. This article reviews the extent of noncompliance in this population and the effect of noncompliance on disease management. Factors related to the health care provider, the patient, and the type of therapy that lead to noncompliance are reviewed. Opportunities and intervention techniques are provided to improve patient outcomes.     

Effects of SSRIs on sexual function: a critical review

Sexual problems are highly prevalent in both men and women and are affected by, among other factors, mood state, interpersonal functioning, and psychotropic medications. The incidence of antidepressant-induced sexual dysfunction is difficult to estimate because of the potentially confounding effects of the illness itself, social and interpersonal comorbidities, medication effects, and design and assessment problems in most studies. Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and arousal difficulties are also frequently reported, although the specific association of these disorders to SSRI use has not been consistently shown. The effects of SSRIs on sexual functioning seem strongly dose-related and may vary among the group according to serotonin and dopamine reuptake mechanisms, induction of prolactin release, anticholinergic effects, inhibition of nitric oxide synthetase, and propensity for accumulation over time. A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another antidepressant drug, and various augmentation strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and alpha2 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists, and phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should not be viewed as entirely negative; some studies have shown improved control of premature ejaculation in men. The impacts of sexual side effects of SSRIs on treatment compliance and on patients' quality of life are important clinical considerations.     

Pathology of MEN-1: morphology, clinicopathologic correlations and tumour development

Augmentation therapy is used for those situations where a patient's depression is either treatment-resistant, or partially and/or insufficiently responsive to treatment. It also may be used to attempt to induce a more rapid treatment response. Using drugs together may increase the risk of adverse effects, through potentiation of existing adverse effects or alterations in plasma concentrations of the drug. It is important that clinicians are aware of potential risks of augmentation therapy. Lithium augmentation of a tricyclic antidepressant is relatively well tolerated and the dangers are no greater than using these medications on their own. There are also no reports of serious adverse events when lithium is added to a monoamine oxidase inhibitor. With lithium augmentation of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) therapy there have been case reports of the development of a central serotonin syndrome, and thus caution must exercised. A serious concern when using a tricyclic antidepressant to augment an SSRI is the effect of the SSRI on the cytochrome P450 system and the resulting significant increase in tricyclic antidepressant blood concentrations. Augmentation with thyroid hormones appears to be well tolerated and effective. Case reports and open studies indicate that augmentation with buspirone and the psychostimulants, carbamazepine and valproic acid (valproate sodium) is effective and results in minimal adverse effects. However, there is no empirical evidence supporting these results. Recent work supports the tolerability and efficacy of pindolol augmentation. Considerable caution should be exercised when combining psychotropic drugs. The practitioner should only do so with a full knowledge of the compounds involved and their pharmacological properties.     

Predictors of aspiration pneumonia: how important is dysphagia?

Aspiration pneumonia is a major cause of morbidity and mortality among the elderly who are hospitalized or in nursing homes. Multiple risk factors for pneumonia have been identified, but no study has effectively compared the relative risk of factors in several different categories, including dysphagia. In this prospective outcomes study, 189 elderly subjects were recruited from the outpatient clinics, inpatient acute care wards, and the nursing home care center at the VA Medical Center in Ann Arbor, Michigan. They were given a variety of assessments to determine oropharyngeal and esophageal swallowing and feeding status, functional status, medical status, and oral/dental status. The subjects were followed for up to 4 years for an outcome of verified aspiration pneumonia. Bivariate analyses identified several factors as significantly associated with pneumonia. Logistic regression analyses then identified the significant predictors of aspiration pneumonia. The best predictors, in one or more groups of subjects, were dependent for feeding, dependent for oral care, number of decayed teeth, tube feeding, more than one medical diagnosis, number of medications, and smoking. The role that each of the significant predictors might play was described in relation to the pathogenesis of aspiration pneumonia. Dysphagia was concluded to be an important risk for aspiration pneumonia, but generally not sufficient to cause pneumonia unless other risk factors are present as well. A dependency upon others for feeding emerged as the dominant risk factor, with an odds ratio of 19.98 in a logistic regression model that excluded tube-fed patients.     

ECG changes after paroxetine. 3 case reports

Selective serotonin reuptake inhibitors (SSRI) are known to exhibit far less cardiac side effects than tricyclic antidepressants. We report three cases in which the SSRI, paroxetine, induced clinically relevant ECG changes in patients with high risk profile. In two cases an increase in QTc time was observed, severe bradycardia was also observed twice.     

Treatment of hypertension in the presence of coexisting medical conditions

Treating hypertension reduces morbidity and mortality. Unfortunately, hypertension often exists in patients with other medical conditions. In these patients, the selection of an antihypertensive agent is often influenced by the presence of the coexisting condition. Conversely, the treatment of the coexisting medical condition may be influenced by the presence of hypertension. Given the vast array of antihypertensive medications available today, appropriate treatment of both hypertension and coexisting conditions can be achieved with careful selection of medications. This review discusses factors to consider when treating elderly patients with hypertension with the following coexisting conditions: dyslipidaemia, glucose intolerance, sexual dysfunction, cardiovascular disease, pulmonary disease, renal disease and neuropsychiatric disorders. Hypothyroidism, hyperthyroidism and various states of high cardiac output may cause hypertension. These conditions should be identified, since they are often treatable with subsequent resolution of the hypertension.     

A review and economic evaluation of bronchodilator delivery methods in hospitalized patients

BACKGROUND: Bronchodilator delivery by metered dose inhaler (MDI) to treat airflow obstruction is considered to be less expensive and as effective as nebulized therapy. OBJECTIVES: To document the utilization of bronchodilator delivery methods in a tertiary care Canadian university teaching hospital and to perform an economic evaluation. METHODS: A prospective 6-week audit of 4 preselected hospital wards (respiratory, thoracic surgery, general surgery, and a general internal medicine clinical teaching unit) and a cost-minimization economic evaluation were performed. Bronchodilator (salbutamol and ipratropium bromide) doses, frequency, and delivery methods, either MDI or wet nebulizer (WN), were recorded for 95 patients treated with aerosolized bronchodilators. Direct costs for medications and hourly wages including benefits and equipment were obtained. Time and motion studies identified time allocated to MDI and WN delivery. We used sensitivity analyses to test assumptions that could significantly affect treatment costs, especially assumptions about medications, labor, and spacer devices. Costs are expressed in Canadian dollars (Can$1 = US$0.75). RESULTS: Sixty-seven patients (70.5%) were treated with WN, 6 (6.3%) with MDI, and 22 (23.2%) with both WN and MDI. Self-administration of salbutamol by MDI was the least expensive: $1.27 for 200-microgram doses and $1.73 for 400-microgram doses compared with $2.62 for a 2.5-mg dose delivered by WN. The difference in cost between equivalent treatments (400-microgram MDI vs 2.5-mg WN) is only $0.89. Sensitivity analyses showed that MDI was the least expensive therapy when self-administration was possible and for all levels of supervision if more than 4 minutes was needed to administer a WN treatment. CONCLUSIONS: Bronchodilator delivery by WN is commonly prescribed for hospitalized patients despite evidence for equivalency of effect using MDI and in the absence of substitution protocols. Previous studies have estimated a far greater cost differential based on unrealistic labor estimates. We found that supervision of patients using MDIs minimized the differential cost between WN and MDI therapy and that cost savings are maximal in patients who can self-administer MDI therapy. Methodologically sound economic evaluations can better identify true cost savings and variables that need further study.     

Underutilization of antithrombotic therapy in elderly rural patients with atrial fibrillation

BACKGROUND: Antithrombotic agents are underutilized in elderly patients with atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural patients were given antithrombotic therapy less often than rural patients for unclear reasons. METHODS AND RESULTS: The charts of 597 hospitalized Medicare patients discharged between October 1, 1993, and December 31, 1994, from urban and rural hospitals in Missouri were reviewed. In addition to antithrombotic therapy prescribed at the time of discharge, patient and physician information, relative contraindications to antithrombotic therapy, and risk factors for stroke were identified. Rural and urban patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 87% of rural patients and in 84% of urban patients. Urban patients were more likely to have a relative contraindication to antithrombotic therapy compared with rural patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58% vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly more often than noncardiologists (69% vs 52%, P =.003). CONCLUSIONS: Elderly rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high-risk profile and fewer relative contraindications. Primary care physicians prescribe antithrombotic therapy less often than cardiologists, which is one of the reasons for this underutilization.