Wellbutrin XL NDA 21-515

154 of 100 mg 3 times daily of the immediate-release formulation of bupropion, with regard to both

155 rate and extent of absorption, for parent drug and metabolites.

156 In a longer-term study, outpatients meeting DSM-IV criteria for major depressive disorder,

157 recurrent type, who had responded during an 8-week open trial on bupropion (150 mg twice

158 daily of the sustained-release formulation) were randomized to continuation of their same dose

159 of bupropion or placebo, for up to 44 weeks of observation for relapse. Response during the open

160 phase was defined as CGI Improvement score of 1 (very much improved) or 2 (much improved)

161 for each of the final 3 weeks. Relapse during the double-blind phase was defined as the

162 investigator’s judgment that drug treatment was needed for worsening depressive symptoms.

163 Patients receiving continued bupropion treatment experienced significantly lower relapse rates

164 over the subsequent 44 weeks compared to those receiving placebo.

165 INDICATIONS AND USAGE

166 WELLBUTRIN XL is indicated for the treatment of major depressive disorder.

167 The efficacy of bupropion in the treatment of a major depressive episode was established in

168 two 4-week controlled trials of inpatients and in one 6-week controlled trial of outpatients whose

169 diagnoses corresponded most closely to the Major Depression category f the APA Diagnostic

170 and Statistical Manual (DSM) (See CLINICAL PHARMACOLOGY).

171 A major depressive episode (DMS-IV) implies the presence of 1) depressed mood or 2) loss

172 of interest or pleasure; in addition, at least 5 of the following symptoms have been present during

173 the same 2-week period and represent a change from previous functioning: depressed mood,

174 markedly diminished interest or pleasure in usual activities, significant change in weight and/or

175 appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue

176 feeling of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt,

177 or suicidal ideation.

178 The efficacy of bupropion in maintaining an antidepressant response for up to 44 weeks

179 following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial with the

180 sustained-release formulation of bupropion (see CLINICAL PHARMACOLOGY). Nevertheless,

181 the physician who elects to use WELLBUTRIN XL for extended periods should periodically

182 reevaluate the long-term usefulness of the drug for the individual patient.

183 CONTRAINDICATIONS

184 WELLBUTRIN XL is contraindicated in patients with a seizure disorder.

185 WELLBUTRIN XL is contraindicated in patients treated with ZYBAN® (bupropion

186 hydrochloride Sustained-Release Tablets, WELLBUTRIN (bupropion hydrochloride) the

187 immediate-release formulation, WELLBUTRIN SR (bupropion hydrochloride) the sustained-

188 release formulation, or any other medication that contain bupropion because the incidence of

189 seizure is dose dependent.

190 WELLBUTRIN XL is contraindicated in patients with a current or prior diagnosis of bulimia

191 or anorexia nervosa because of higher incidence of seizures noted in patients treated for

192 bulimia with the immediate-release formulation of bupropion.