Bupropion effects in attention deficit and conduct disorders.

Children with Attention Deficit and/or Conduct Disorders were treated with bupropion, a new antidepressant, to determine its clinical, cognitive, and EEG effects. Seventeen male patients (age range 7 to 13.4 years; mean 10.4) participated in an open clinical trial consisting of a baseline placebo period (4 weeks), bupropion therapy (8 weeks), and post-drug placebo (2 weeks). Evaluations included clinical assessments, parents, teachers, and self-ratings; cognitive tests and blood level measurements of bupropion. Fifteen patients received a daily maximum of 150 mg, one received 100 mg and one 50 mg. Clinical global improvement with bupropion therapy was marked in 5 patients, moderate in 7, mild in 2, and none in 3. The Children's Psychiatric Rating Scale indicated improvements of hyperactivity, withdrawal, anxiety, hostility/uncooperativeness, sleep disorder, antisocial behaviour, neuroticism, depression and eating disturbance. Parents' Questionnaires indicated significant improvements of conduct disorder, anxiety, hyperactivity, muscle tension and psychosomaticism. While no single cognitive test showed significant improvement, all nine tests changed in the positive direction. Adverse effects were infrequent, transient and mild. There were no clinically significant changes of the laboratory values and vital signs. Two weeks following bupropion discontinuation, clinical global improvement was maintained in 8 patients, 7 showed relapses, while 2 remained unimproved. Analyses of computerized EEG revealed that degree of clinical improvement was indexed by baseline EEG parameters and that there were significant bupropion effects on EEG measures. Double-blind trials of bupropion are recommended in child psychiatry disorders.

Evaluation of the safety and efficacy of bupropion in depression.

A placebo-controlled double-blind study was conducted to test the antidepressant effects of bupropion at dosage levels of 300 or 450 mg/day. Subjects were 30 hospitalized primary major depressives who were treated for 4 weeks. Physical and behavioral measures were obtained at baseline and at the end of each experimental week. The combined results of the two bupropion groups were significantly better than placebo. Preliminary results showed a significant antidepressant effect of the 300 mg/day dose, but not the 450 mg/day dose, compared to placebo. Anxiety symptoms were also somewhat reduced by the 300 mg/day dose. The results are compared with those of a previous study, which utilized higher dosages.

A double-blind comparison of bupropion and amitriptyline in depressed inpatients.

Bupropion and amitriptyline were compared in a double-blind study of depressed inpatients. Treatment ranged from 2 to 4 weeks: early responders (Hamilton Depression Scale scores less than 10) were often removed from treatment after 2 or 3 weeks. Twenty-two patients completed treatment with bupropion and 18 with amitriptyline. Doses ranged from 450 to 750 mg/day for bupropion and 75 to 225 mg/day for amitriptyline. Overall, bupropion and amitriptyline were equally effective, as measured by the Hamilton Depression and Anxiety scales, Clinical Global Impressions, Zung Depression scale, and the SCL-90. Differences in the side effect profile and in weight change are described.

Long-term efficacy and safety of bupropion.

Bupropion is a novel, structurally unique (single ring) compound, radically different from tricyclic antidepressants in its pharmacologic profile. In a random assignment, double-blind, long-term follow-up study of 60 depressed in- and outpatients (DSM-III criteria) in eight centers, the antidepressant actions of bupropion and amitriptyline were compared. Bupropion was as effective as amitriptyline in reducing depressive symptoms over a 6-month period, as measured by Hamilton depression and anxiety scales and Clinical Global Impression scores. Unlike amitriptyline, bupropion did not increase uric acid or cholesterol levels, and was not associated with weight gain. Bupropion was better tolerated than amitriptyline, the most commonly prescribed antidepressant.

Overview of clinically significant adverse reactions to bupropion.

During the clinical development of bupropion (Wellbutrin) 1,153 depressed patients and 157 normal volunteers received bupropion (doses, 15-1200 mg/day); 177 placebo-treated and 196 tricyclic-treated patients (doses, 25-300 mg/day) also participated in these trials to provide a control comparison. Safety measures during the clinical trial program included adverse event symptomatology, vital signs, clinical laboratory examinations, and EEGs. There were no bupropion-related changes in vital signs, clinical laboratory, or EEG results severe enough to warrant treatment discontinuation. The most common cause for discontinuation in the bupropion (9.1%), placebo (6.8%), and tricyclic groups (9.2%) was agitation/excitement. The only adverse experience considered of medical significance in bupropion patients was major motor seizure. The incidence of a seizure was less than 1 per 1,000 at usual outpatient doses and less than 1 per 100 at usual inpatient doses. These incidences appear to be comparable to those seen with equally therapeutic doses of tricyclic antidepressants.

A comparison of the safety and efficacy of bupropion HCL and amitriptyline hcl in depressed outpatients.

1. Thirty adult outpatients diagnosed with depressive illness were treated with either bupropion HCL or amitriptyline HCL. 2. Weekly ratings of efficacy and safety were undertaken using the Hamilton Depression, Hamilton Anxiety, Clinical Global Improvement, and Treatment Emergent Symptom Scales. Periodic physical investigations were also performed. 3. After 4 weeks of active treatment patients in both drug groups showed significant improvement on all rating scales. 4. The side effect profile of each drug was clinically different from one another with a notable absence of anticholinergic side effects characteristic of the bupropion group. 5. No significant laboratory or physical changes were found although slight changes in weight were noted with bupropion patients having a slight weight loss and amitriptyline patients a slight weight gain. There were no withdrawal effects from discontinuing either drug.

Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects.

The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.