Wellbutrin Pharmacology 3

Wellbutrin Pharmacology

Click here to buy cheap wellbutrin sr.

Pharmacology Page 3

Indications And Clinical Uses: For the symptomatic relief of depressive illness. The effectiveness of bupropion in long-term use (more than 8 weeks) has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use bupropion for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Contra-Indications: Patients receiving Zyban or any other medications that contain bupropion HCl because the incidence of seizure is dose dependent.

Seizures: Bupropion is contraindicated in patients with a seizure disorder.
Bulimia/Anorexia Nervosa: Bupropion is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures (see Warnings) noted in patients treated for bulimia with the immediate release formulation of bupropion.

Experience in Clinical Trials: The effectiveness of bupropion in the treatment of moderate depression has been systematically evaluated at doses ranging from 50 to 400 mg/day in 3 multicentre, randomized, placebo-controlled, double-blind, parallel-group studies involving a total of 1 420 patients of whom 1 021 received active doses of the bupropion and 399 received placebo. Each study included a 1-week placebo lead-in phase to identify and exclude placebo responders, followed by an 8-week treatment phase.
The response to treatment was evaluated at regular intervals using the Hamilton Rating Scale for Depression (HAMD), Clinical Global Impressions Scales of Severity (CGI-S) and Improvement (CGI-I) Scale. Both the observed and the last observation carried forward (LOCF) values were analyzed.
In 1 study comparing fixed daily doses of either 150 mg once daily (n=121) or 300 mg as 150 mg twice daily (n=120) bupropion to placebo (n=121), the HAMD, CGI-S (change from baseline) and CGI-I scores for both bupropion groups at endpoint were statistically significantly superior to placebo. Both active treatment groups showed a similar magnitude of improvement during the trial.
In a second study patients received fixed daily doses of either 100 mg, 200 mg, 300 mg or 400 mg/day (given on a twice daily schedule) bupropion or placebo. The magnitude of the mean change scores were consistently greater for all active groups than placebo by day 21. At endpoint, scores in the 100 mg group were statistically significantly superior to placebo on all rating scales, while the higher dose groups followed a similar pattern but did not achieve statistical significance.

A third study compared 2 flexible doses; 50 to 150 mg/day (given once daily), and 100 to 300 mg/day (twice daily schedule) to placebo (n=approximately 150 patients per group). Patients began at the lowest dose in the range and were titrated to the highest tolerated dose in the range over a period of 7 days. Investigators had the option to titrate down when a higher dose was not well tolerated. The mean daily dose calculated from day 8 onwards was 144 mg in the 50 to 150 mg arm and 276 mg in the 100 to 300 mg arm, indicating that the vast majority of patients remained on the highest allowable dose in their respective groups for the duration of the study. Efficacy measures at endpoint for the 50 to 150 mg/day group were statistically significantly superior to placebo. The higher dose group followed a similar pattern but did not achieve statistical significance at endpoint. A combined endpoint analysis of all patients treated with bupropion in the trial, demonstrated statistically significant superiority on all efficacy measures compared to placebo.
In summary, patients receiving bupropion at doses of 100 to 150 mg/day in single or divided doses experienced improvement relative to placebo on the major indices of depression. Clinical response did not improve with increasing dose, indicating a flat dose-response relationship in the range of doses studied.