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Vidyya, from the Sanskrit "vaidya," a practitioner who has come to understand the science of life.

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Back To Vidyya New England Journal Of Medicine Highlights


A Comparison of Nefazodone, the Cognitive Behavioral-Analysis System of Psychotherapy, and Their Combination for the Treatment of Chronic Depression

Background. Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain.

Methods. We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments.

Results. Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness).

Conclusions. Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone. (N Engl J Med 2000;342:1462-70.)

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Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation

Background. Continuous infusions of sedative drugs in the intensive care unit may prolong the duration of mechanical ventilation, prolong the length of stay in the intensive care unit and the hospital, impede efforts to perform daily neurologic examinations, and increase the need for tests to assess alterations in mental status. Whether regular interruption of such infusions might accelerate recovery is not known.

Methods. We conducted a randomized, controlled trial involving 128 adult patients who were receiving mechanical ventilation and continuous infusions of sedative drugs in a medical intensive care unit. In the intervention group, the sedative infusions were interrupted until the patients were awake, on a daily basis; in the control group, the infusions were interrupted only at the discretion of the clinicians in the intensive care unit.

Results. The median duration of mechanical ventilation was 4.9 days in the intervention group, as compared with 7.3 days in the control group (P=0.004), and the median length of stay in the intensive care unit was 6.4 days as compared with 9.9 days, respectively (P=0.02). Six of the patients in the intervention group (9 percent) underwent diagnostic testing to assess changes in mental status, as compared with 16 of the patients in the control group (27 percent, P=0.02). Complications (e.g., removal of the endotracheal tube by the patient) occurred in three of the patients in the intervention group (4 percent) and four of the patients in the control group (7 percent, P=0.88).

Conclusions. In patients who are receiving mechanical ventilation, daily interruption of sedative-drug infusions decreases the duration of mechanical ventilation and the length of stay in the intensive care unit. (N Engl J Med 2000;342:1471-7.)

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A Five-Year Study of the Incidence of Dyskinesia in Patients with Early Parkinson's Disease Who Were Treated with Ropinirole or Levodopa
Background. There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist.

Methods. In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia.

Results. Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group, 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (±SD) daily doses given by the end of the study were 16.5±6.6 mg of ropinirole (plus 427±221 mg of levodopa in patients who received supplementation) and 753±398 mg of levodopa (including supplements).

Conclusions. Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary. (N Engl J Med 2000;342:1484-91.)

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