Practice Guideline Briefs

Am Fam Physician. 2005 Jan 15;71(2):384-386.

Guidelines for Prescribing Antiepileptic Drugs

The American Academy of Neurology (AAN) has released evidence-based guidelines for prescribing new antiepileptic drugs (AEDs) in patients with new-onset epilepsy and refractory epilepsy. The recommendations, “Efficacy and Tolerability of the New Anti-epileptic Drugs I: Treatment of New Onset Epilepsy” and “II: Treatment of Refractory Epilepsy” are available online at http://www. neurology.org/content/vol62/issue8/.

In the past decade, the U.S. Food and Drug Administration approved felbamate and seven new AEDs: gabapentin, oxcarbazepine, lamotrigine, topiramate, tiagabine, levetirace-tam, and zonisamide. The development of new AEDs was spurred by evidence that the existing AEDs did not provide optimal care for patients with epilepsy. A committee of the AAN evaluated the efficacy, tolerability, and safety of the new AEDs in patients with new-onset epilepsy and refractory epilepsy.

New-Onset Epilepsy. Gabapentin is effective in the treatment of newly diagnosed partial epilepsy. Lamotrigine, topiramate, and oxcarbazepine are effective in a mixed population of patients with newly diagnosed partial and generalized tonic-clonic seizures. However, no recommendations can be made for the individual syndromes.

Oxcarbazepine is as effective as carba-mazepine and phenytoin, but it is superior in dosage-related tolerability. It is equivalent in efficacy and tolerability to valproic acid. Topiramate at dosages of 100 and 200 mg per day was equivalent in efficacy and safety to a 600-mg fixed dose of carbamazepine and 1,250 mg per day of valproic acid. Lamotrigine is as efficacious as carbamazepine and phenytoin and superior in tolerability to carbamazepine. Topiramate at dosages of 100 and 200 mg per day is equivalent in safety and efficacy to 600 mg of fixed-dosage, immediate-release carbamazepine given twice daily in patients with partial seizures, and to 1,250 mg of fixed-dose valproic acid in patients with idiopathic generalized seizures. Gabapentin is as effective as monotherapy at dosages of 900 and 1,800 mg, and it is equivalent in efficacy to a 600-mg fixed dose of carbamazepine. A 900-mg dose of gabapentin is better tolerated than 600 mg of fixed-dose, short-acting carbamazepine given twice daily.

The committee recommends that therapy in patients with newly diagnosed epilepsy be initiated with standard AEDs or lamotrigine, gabapentin, oxcarbazepine, or topiramate. The choice of AED will depend on individual patient characteristics. Lamotrigine can be considered in children with newly diagnosed absence seizures.

Refractory Epilepsy. All of the new AEDs are appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin may be effective for the treatment of mixed-seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate may be effective for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children.

The committee recommends that gabapentin, oxcarbazepine, lamotrigine, topiramate, tiagabine, levetiracetam, and zonisamide be considered as add-on therapy in patients with refractory epilepsy. Oxcarbazepine, lamotrigine, and topiramate can be used as mono-therapy in patients with refractory partial epilepsy. Topiramate can be used for the treatment of refractory generalized tonic-clonic seizures in adults and children. Gabapentin, lamotrigine, oxcarbazepine, and topiramate may be used as adjunctive treatment in children with refractory partial seizures.

Diagnosis of Celiac Disease

The Agency for Healthcare Research and Quality has released an evidence report on celiac disease. “Celiac Disease” is available online at http://www.ahrq.gov/clinic/epc-sums/celiacsum.htm.

Celiac disease represents a spectrum of clinical features. Although “classic” celiac disease (i.e., fully developed, gluten-induced villous atrophy and classic features of intestinal malabsorption) is most commonly described, it appears that most patients have atypical disease (i.e., fully developed gluten-induced villous atrophy in the setting of another disorder such as iron deficiency, osteoporosis, short stature, or infertility). The prevalence of celiac disease is difficult to estimate, but a recent study found rates of approximately 1 percent in the general population and 4.5 percent in high-risk groups, such as first-degree relatives of persons with the disease.

The diagnosis classically is made on the basis of clinical suspicion—recognizing atypical presentations such as isolated iron deficiency, combined iron and folate deficiency, and osteoporosis—compatible with a duodenal biopsy in persons with a gluten-containing diet, followed by clinical and histologic improvement when a gluten-free diet is started. However, several serologic markers are available that have altered the classic diagnostic pathway. IgA antigliadin antibodies (AGA), IgA anti-endomysial antibodies (EMA), and anti-tissue transglutaminase antibodies (tTG) have high sensitivity and specificity in diagnosing celiac disease. However, AGA antibody testing in children and adults has a limited role, and the reported diagnostic parameters for EMA and tTG antibody testing are taken from studies in which the prevalence of celiac disease was much higher than that seen in usual clinical practice. The positive predictive values reported for these tests will not be as high as those reported when these tests are used to screen the general population.

Human leukocyte antigen DQ2/DQ8 testing appears to be useful in the diagnosis of celiac disease. The test has high sensitivity (i.e., 90 to 95 percent). However, approximately 30 percent of the general population and an even higher proportion of high-risk persons also carry these markers, so the specificity of this test is not ideal. Its greatest diagnostic use appears to be its negative predictive value, making it useful when negative at ruling out disease.

Testing for celiac disease in at-risk and symptomatic patients is associated with good outcomes. These patients appear to be more compliant with a gluten-free diet and would be expected to benefit from this intervention. The data are less clear for asymptomatic screen-identified patients. Outcomes in these patients have not been studied extensively, but compliance with a gluten-free diet appears problematic, particularly in patients diagnosed in adulthood.

Guidelines for Pediatric Intermediate Care

Many children admitted to the hospital need a higher level of care than general inpatient pediatric critical care. Therefore, an intermediate care level for children has been developed in some hospitals. “Admission and Discharge Guidelines for the Pediatric Patient Requiring Intermediate Care” is available online at http://pediatrics.aappublications.org/cgi/content/full/113/5/1430.

Admission is guided by physiologic parameters, depending on the type of care needed. Children with respiratory, cardiovascular, endocrine, renal, and gastrointestinal disease who need multidisciplinary intervention and frequent monitoring may be admitted. Patients with non–life-threatening neurologic disease who need multidisciplinary intervention, frequent monitoring, and neurologic assessment every two hours or more also may be admitted, as well as children with potentially unstable hematologic or oncologic disease or non–life-threatening bleeding. Patients who have undergone surgery and require monitoring may be admitted if they do not have hemodynamic or respiratory instability.

Patients will be evaluated and considered for transfer to general or special-care units when the disease process has reversed or the physiologic problem that prompted the admission has resolved. The criteria on which the decision to transfer or discharge the patient will be made include the following: the patient has stable hemodynamic parameters for at least six to 12 hours; respiratory status is stable and the patient has been extubated with evidence of acceptable gas exchange for four or more hours; the patient has minimal oxygen requirements; cardiac arrhythmias have been controlled for at least 24 hours; seizures have been controlled for a reasonable amount of time; and all invasive hemodynamic monitoring devices have been removed.

Other criteria include the following: intravenous inotropic support, vasodilators, and antiarrhythmic drugs are no longer needed; patients who needed mechanical ventilation have returned to baseline clinical status; and the patient is able to receive peritoneal dialysis or hemodialysis on an outpatient basis.

Benefits of Omega-3 Fatty Acids

Consumption of fish oil can help reduce deaths from heart disease, but its effects on other outcomes are inconclusive, according to evidence reports from the Agency for Healthcare Research and Quality (AHRQ). The reports are available online at www.ahrq.gov/clinic/epcindex.htm#dietsup.

An analysis of 10 randomized controlled trials (RCTs) and nine other studies addressed the effects of omega-3 fatty acids on respiratory outcomes. The AHRQ could not conclude whether omega-3 fatty acids are an efficacious adjuvant or monotherapy in improving respiratory outcomes in adults or children.

Six studies were analyzed to determine the role of omega-3 fatty acids in primary prevention of asthma. Dietary fish consumption appears to serve as primary prevention for asthma in pediatric populations. However, asthma prevalence and fish intake were significantly and positively related in studies that included Asian adolescents. Another study found no association between adult asthma onset and dietary fish intake.

In terms of cardiovascular benefits, a number of studies show that fish consumption and fish and α-linolenic acid (ALA) supplementation reduces all-cause mortality and various cardiovascular outcomes, although the evidence is strongest for fish and fish oil. The effects on specific outcomes (especially myocardial infarction [MI] and stroke) are uncertain, and the optimal quantity and type of omega-3 fatty acid, and the optimal ratio of omega-3 to omega-6 fatty acid remain unknown. The most significant benefit may be in reducing sudden cardiac death. Four of six RCTs found a benefit, one found no benefit, and one found harm, although all six were thought to be poorly designed. Adverse events from fish oil and ALA supplementation appear to be minor.

Overall, strong evidence shows that fish oils have a strong, dose-dependent beneficial effect on triglyceride levels. There also is evidence of possible small beneficial effects on blood pressure and coronary artery restenosis after angioplasty, exercise capacity in patients with coronary atherosclerosis, and heart rate variability, particularly in patients with recent MI. Omega-3 fatty acids do not appear to affect total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, or glycosylated hemoglobin levels, and they had no effect on plasma insulin levels and insulin resistance in patients with type 2 diabetes.


Copyright © 2005 by the American Academy of Family Physicians.
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