The effect of aging on the positive chronotropic response to amitriptyline.

Amitriptyline (AT) increases sinus heart rate (SHR) due to inhibition of the reuptake of norepinephrine in combination with an antimuscarinic blockade of cardiac vagal inhibition. After 150 mg/day AT for 28 days, the change in SHR was negatively correlated with age in 42 depressed patients who were 18-85 years of age. This finding is consistent with observations that the tachycardic response to antimuscarinics and catecholamines decreases with aging.

Is serum cholesterol a biological marker for major depressive disorder?

An abnormally high serum cholesterol level has been suggested as a biological marker for major depression. However, in 192 depressed and normal subjects, age and sex influenced serum cholesterol level, but the diagnosis of major depression did not.

Private practice evaluation of the safety and efficacy of bupropion in depressed outpatients.

A multicenter uncontrolled 4-week trial of bupropion in depressed outpatients was conducted in the private practices of 25 internists, 9 family practitioners, and 3 psychiatrists. Minimum exclusion criteria were used with respect to concurrent medical ailments, age, and concomitant medications. Of the 380 patients admitted to the study, 325 were included in efficacy analyses, and 359 provided data for safety analyses. The average patient was a 51-year-old married white woman with a high school education and a skilled job. Bupropion administered in doses of 150-450 mg/day was highly effective in reducing depressive symptomatology as evaluated by the Hamilton Depression and Clinical Global Impressions scales, and the Zung Self-Rating Scale. No clinically significant bupropion-related changes in blood pressure, pulse rates, respiration rate, body temperature, or laboratory parameters were recorded; only 41 patients were discontinued due to intolerance to adverse experiences. There was a notable absence of daytime sedation, and of anticholinergic and cardiovascular side effects.

Efficacy of bupropion in tricyclic-resistant or intolerant patients.

Available evidence is reviewed concerning the antidepressant efficacy of bupropion in patients who had failed to respond to or been unable to tolerate tricyclic antidepressants (TCAs) during prior episodes of depression. Inpatients classified as TCA nonresponders were randomly assigned to double-blind treatment with bupropion (N = 19) or placebo (N = 11). Patients receiving bupropion showed an excellent antidepressant response, whereas those receiving placebo showed minimal improvement (p less than .001). Inpatients who were classified as TCA responders responded well to double-blind treatment with bupropion, but also had a substantial, although significantly smaller (p less than .05), response to placebo. Outpatients (N = 33) with a history of nonresponse or nonresponse plus intolerance to TCAs showed marked improvement during open treatment with bupropion. The results from both double-blind and open treatment with bupropion demonstrate that this drug offers a promising alternative therapy for patients with a history of poor response to TCAs.

Effects of bupropion on body weight.

Patients' weights were assessed during placebo-controlled, amitriptyline-controlled, and uncontrolled bupropion trials. Low-moderate (50-450 mg/day) to moderate-high (300-750 mg/day) doses of bupropion were consistently associated with a lack of weight gain (average weight loss of 1-2 pounds); placebo was associated with an average weight gain of 1 lb and 75-225 mg/day of amitriptyline was associated with an increase of 3-9 lb. Bupropion treatment was rarely accompanied by reports of appetite change and had no statistically significant effect on caloric intake when compared to placebo.

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.