Table 8.5.3 Differences in Effect of Bupropion Sustained-Release vs. Placebo on Vital Signs (S=Systolic BP, D=Diatolic BP, P=Pulse, W=Weight) (↑=Increase in Parameter, ↓=Decrease in Parameter) (*= p ,=0.05, + = p <=0.01)
Week	Protocol 203 Dosage		Protocol 205 Dosage
	150 mg/d	300 mg/d	100 mg/d	200 mg/d	300 mg/d	400 mg/d
1	↑D+, ↓W+	↑W+	↑P+	↑P+, ↓W*	↑P*, ↓W+	↑P*, ↓W+
2		↑W+		↑S*, ↓W+	↓W+	↓W+
3	↓W+	↓W+		↓W+	↓W+	↓W+
4	↑P+	↓W+		↑D+, ↓W+	↑P*, ↓W*	↓W+
5	↓W+	↓W+			↓W*	↓W+
6	↓W+	↓W+		↑D*	↑P*, ↓W*	↓W+
7		↓W+			↓W*	↓W+
8		↑S*, ↓W+			↑D*	↑P*, ↓W+

 

8.5.4                       Electrocardiograms

 

Electrocardiograms were not systematically obtained in the phase 2-3 trials presented.  Electrocardiograms were obtained on 164 subjects at screening whose history of physical examination suggested to investigators the potential value an of EKG.  Sixteen subjects had EKG’s during the treatment phase of the protocol and 156 subjects had EKG’s at discontinuation from the protocols.  In the opinion of the individual investigators, there were no clinically important drug-related alterations in electrocardiograms. Nevertheless, one 63-year-old white female (Patient 5058, protocol 205) who dropped out the study due to an anxiety attack while being treated with bupropion sustained-release 400 mg/d was noted at a discontinuation EKG to have atrial enlargement and negative precordial T-waves that were though to be changes consistent with increased anxiety.

 

8.5.5                       Special Studies

 

Protocol 208 was conducted specifically to assess the cumulative incidence of seizures and other adverse events occurring during and an eight week period of intake of 100-300 mg/day bupropion sustained-release.  This study was an open trial of bupropion sustained-release conducted in 109 centers nationwide that enrolled 367 patients.  Of these, 48 did not receive study medication, and it is unknown whether another 19 ingested study medication.  These 67 patients were excluded from all further summaries.  Six patients were excluded from seizure incidence summaries because they were found to have had a prior history of treatment with bupropion.  A “100-300 mg cohort” was defined as patients who during their participation in the treatment phase received at lest one daily dose of 100 mg and a minimum of 90% of the total cumulative dose required for a 100 mg/day regimen.  This cohort was made up of 2958 patients, more than two-thirds of whom were at the 300 mg/day dosing level.  The number of patients at each dosing level at each week of the protocol is listed in Table 8.5.5. below: The treatment setting and population was intended to represent a general treatment population.  To be included in the study patients were required to be at least age 18, have a diagnosis of depression, and be considered appropriate for treatment with bupropion sustained-release.  Exclusion criteria were as follows:

 

 

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