A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine.

BACKGROUND: Many antidepressants are associated with sexual dysfunction, a side effect that may lead to patients' dissatisfaction and noncompliance with treatment. OBJECTIVE: This study compared the efficacy, tolerability, and effects on sexual functioning of bupropion sustained release (bupropion SR) and the selective serotonin reuptake inhibitor fluoxetine. METHODS: In this multicenter, randomized, double-blind, double-dummy, parallel-group study, patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d, fluoxetine 20 to 60 mg/d, or placebo for up to 8 weeks. Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits; tolerability was assessed primarily by monitoring adverse events. RESULTS: Four hundred fifty-six patients participated in the study, 150 receiving bupropion SR, 154 fluoxetine, and 152 placebo. The majority of patients in each group completed the study (63% each, bupropion SR [n = 94] and fluoxetine [n = 97]; 67%, placebo [n = 102]). Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms. Beginning at week 2 and continuing throughout the study, significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo (P < 0.001); similar results were seen in patients defined as clinical responders (> or =50% decrease from baseline in 21-item Hamilton Rating Scale for Depression [HAM-D] total score) (P < 0.001) and in those experiencing remission of depression (HAM-D total score <8) (P < 0.05). At various time points, worsened sexual functioning, sexual desire disorder, sexual arousal disorder, and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo. Both active treatments were well tolerated. CONCLUSIONS: Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression. Fluoxetine, however, was more frequently associated with sexual dysfunction compared with bupropion SR. Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning.

Bupropion sustained release (SR) for the treatment of hypoactive sexual desire disorder (HSDD) in nondepressed women.

This article describes the results of the first report of bupropion sustained release (SR) in nondepressed females with hypoactive sexual desire disorder (HSDD). Eligible females entered a 4-week, single-blind, placebo baseline phase. Subjects, all of whom did not respond to placebo, continued in a single-blind active treatment phase where they received bupropion SR for up to 8 additional weeks. We assessed HSDD by using investigator ratings of sexual desire and sexual functioning. Of the 51 evaluable subjects who entered the active treatment phase, 29% responded to treatment with bupropion SR. Bupropion SR was generally well tolerated. Pending the results of further study, bupropion SR may offer a treatment option for women with HSDD.

Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline.

Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release (n = 122) or sertraline (n = 126) during a 16-week randomized acute phase treatment study. Both agents had comparable antidepressant activity, and comparable anxiolytic effects using the intent-to-treat sample. Baseline anxiety levels were not related to antidepressant efficacy, and they did not differentiate responders to each agent. Time to clinically significant anxiolysis did not differentiate between treatment groups or between responders to each agent. These results contradict the commonly held, but unsubstantiated, belief that in clinically depressed anxious patients, serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors. Thus, the clinical decision to select between these two agents when treating depressed outpatients cannot rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis.

Does pretreatment anxiety predict response to either bupropion SR or sertraline?

BACKGROUND: A common clinical belief is that more sedating and/or serotonin-selective antidepressants are preferred for depressed patients with symptoms of anxiety compared with more activating and/or catecholamine-selective antidepressants. The purpose of this study was to determine whether higher baseline anxiety is associated with different antidepressant responses to bupropion sustained release (SR) or sertraline. METHODS: A retrospective data analysis was conducted using pooled data from two identical 8-week, randomized, double-blind, placebo-controlled multicenter studies of bupropion SR (n=234), sertraline (n=225), and placebo (n=233) in adult outpatients with recurrent, major depressive disorder. Anxiety symptoms were measured using the 14-item Hamilton Anxiety Rating Scale scores. RESULTS: Baseline anxiety levels were not related to antidepressant response to treatment with either bupropion SR or sertraline, nor did they differentiate between responders to bupropion SR and responders to sertraline. CONCLUSIONS: Baseline anxiety levels do not appear to be a basis for selecting between bupropion SR and sertraline in the treatment of outpatients with major depressive disorder.

Directionality of extruded lithium fluoride thermoluminescent dosemeters in a cobalt-60 beam.

An experimental investigation of the directionality of commercially available extruded lithium fluoride (LiF:Mg,Ti) thermoluminescent dosemeters was carried out in a cobalt-60 beam at a water depth of 5 cm. One-half of a batch of 60 chips (3.1 x 3.1 x 0.9 mm3) was exposed face-on (faces perpendicular to the beam central axis), and the other half was exposed in an edge-on orientation (two edges perpendicular and faces parallel to the beam axis). Measurements show that an edge-on exposure results in a thermoluminescence reading approximately 0.9% lower than a face-on exposure. Although this is of minor importance in every day patient dosimetry, it is relevant in evaluating errors in in-phantom dosimetric measurements where greater accuracy is required.

Bupropion sustained release versus paroxetine for the treatment of depression in the elderly.

BACKGROUND: Depression is a serious and widespread emotional disorder among the elderly. This study compared the efficacy and safety of bupropion sustained release (SR) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly outpatients. METHOD: Elderly (> or = 60 years) outpatients with major depressive disorder (DSM-IV criteria) were evaluated in this 6-week multicenter, randomized, double-blind study comparing bupropion SR, 100-300 mg/day, and paroxetine, 10-40 mg/day. Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Clinical Global Impressions-Severity of Illness and -Improvement scales. Safety was assessed by monitoring adverse events, vital signs, and body weight. RESULTS: A total of 100 patients ranging in age from 60 to 88 years were randomly assigned to treatment with bupropion SR (N = 48) or paroxetine (N = 52). Measurements of efficacy were similar between the 2 treatment groups, with both groups showing improved scores on all depression rating scales. Headache, insomnia, dry mouth, agitation, dizziness, and nausea occurred in > 10% of patients in both groups; somnolence, diarrhea, constipation, and anorexia occurred in > 10% of patients in the paroxetine group. No statistically significant differences between groups in vital signs or weight were found. CONCLUSION: Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly. Because of its favorable side effect profile, bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly.

Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment.

Sexual dysfunction is a frequently reported side effect of many antidepressants, including serotonin reuptake inhibitors. Bupropion, an antidepressant of the aminoketone class, is relatively free of adverse sexual effects. In a randomized, double-blind, multicenter trial, sustained-release bupropion (bupropion SR) and sertraline, a selective serotonin reuptake inhibitor, were found to be similarly efficacious in the treatment of outpatients with moderate to severe depression. This report describes the results of a double-blind comparison of the sexual side effect profiles of bupropion SR and sertraline. Two hundred forty-eight patients who had received a diagnosis of moderate to severe major depression were randomly assigned to receive treatment with bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Eligible patients were required to be in a stable relationship and to have normal sexual functioning. Sexual functioning was assessed by the investigator at each clinic visit using investigator-rated structured interviews. A significantly greater percentage of sertraline-treated patients (63% and 41% of men and women, respectively) developed sexual dysfunction compared with bupropion SR-treated patients (15% and 7%, respectively). Sexual dysfunction was noted as early as day 7 in sertraline-treated patients at a dose of 50 mg/day and persisted until the end of the 16-week treatment phase. Four patients, all of whom were treated with sertraline, discontinued from the study prematurely because of sexual dysfunction. Given the similar efficacy of the two drugs in treating depression, bupropion SR may be a more appropriate antidepressant choice than sertraline in patients for whom sexual dysfunction is a concern.

Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.

This study compared the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (bupropion SR) and sertraline. Three hundred sixty-four patients with normal sexual functioning and recurrent major depression were treated with bupropion SR (150-400 mg/day), sertraline (50-200 mg/day), or placebo for 8 weeks in this randomized, double-blind, multicenter study. Patients' depression, sexual functioning, and overall safety were assessed at regular clinic visits. Significantly (P < 0.05) more patients treated with sertraline experienced orgasm dysfunction compared with patients treated with bupropion SR or placebo. Bupropion SR, but not sertraline, was statistically significantly superior to placebo in improving scores on all depression scales by the end of the study. Headache occurred with similar frequency in all groups. Gastrointestinal disturbances occurred more frequently with sertraline; insomnia and agitation occurred more frequently with bupropion SR. Small decreases in mean weight were seen with both active treatments; the placebo group experienced a minor increase in mean weight. Both bupropion SR and sertraline were generally well tolerated, although sertraline was more often associated with sexual dysfunction. Bupropion SR, but not sertraline, was statistically superior to placebo in relieving depression by the end of the study. Bupropion SR may offer advantages over sertraline in treating depressed patients concerned with sexual functioning.

A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline.

Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients.

Safety profile of sustained-release bupropion in depression: results of three clinical trials.

This series of studies was undertaken to assess the safety profile of sustained-release (SR) bupropion in the treatment of depressed outpatients. Adults with a diagnosis of major depression were evaluated in 1 of 3 multicenter, randomized, double-masked, parallel-group, placebo-controlled trials conducted in private-practice psychiatric outpatient clinics. Following a 1-week, single-masked, placebo lead-in period, patients received bupropion SR for 8 weeks (study 1: 150 or 300 mg/d; study 2: 100, 200, 300, or 400 mg/d; study 3: 50 to 150 or 100 to 300 mg/d). Safety assessments included monitoring adverse events, patient discontinuation rates, changes in weight, vital signs, and clinical laboratory test results. Across studies, the most frequently reported adverse events were headache, dry mouth, and nausea. The incidence of adverse events was similar (< or =5% difference) between the bupropion SR and placebo groups, with the exception of dry mouth (bupropion SR, 16%; placebo, 7%). Dry mouth, nausea, and insomnia occurred significantly more often in bupropion SR-treated patients than in patients who received placebo (P<0.05). Nearly all (94% to 99%) adverse events reported in these studies were mild or moderate. Less than 10% of patients in either group discontinued treatment prematurely because of adverse events, and no deaths or serious drug-related adverse events were reported. Sexual dysfunction was reported as an adverse event by <1% of patients in either group. Bupropion SR was associated with dose-related weight loss in all 3 studies. No consistent patterns of change were observed in vital signs or in the results of clinical laboratory tests. Data from these 3 clinical trials demonstrate the favorable safety profile of bupropion SR in the treatment of depressed outpatients.

A prospective safety surveillance study for bupropion sustained-release in the treatment of depression.

BACKGROUND: This prospective 105-site study was conducted to determine the rate of seizures and other serious adverse experiences associated with the therapeutic use of the sustained-release formulation of bupropion (bupropion SR). METHOD: 3100 patients with a DSM-III-R diagnosis of depression without a current or past diagnosis of an eating disorder and with no personal or family history of seizure disorders were treated for up to 8 weeks with bupropion SR in an open-label study. Dosing was initiated at 50 mg b.i.d. and increased to a maximum of 150 mg b.i.d. unless not tolerated. Patients had the option to continue treatment with bupropion SR (50 mg b.i.d. to 150 mg b.i.d.) in a continuation phase lasting up to 1 year. During the acute and continuation phases, patients were evaluated for the occurrence of seizures and other serious adverse experiences. Clinical response to and tolerability of bupropion SR were also evaluated. RESULTS: Three patients each experienced a seizure associated with the therapeutic use of bupropion SR during the acute and continuation phases combined. The observed seizure rate during the 8-week acute phase was 2 seizures in 3094 evaluable patients, or 0.06%. The observed seizure rate for the acute and continuation phases combined was 3 seizures in 3094 patients, or 0.10%. Survival analysis yielded a cumulative seizure rate of 0.08% for the acute phase and 0.15% for both phases combined. Two patients who intentionally overdosed with bupropion SR also experienced seizures; however, these events were not included in calculations of the overall seizure rate. Therapeutic doses of bupropion SR were well tolerated and clinically efficacious. CONCLUSION: The therapeutic use of bupropion SR at total daily doses up to 300 mg/day in depressed patients without predisposition to seizures is associated with a seizure rate that is well within the range observed with other marketed antidepressants.

A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients.

This multicenter, randomized, double-masked, placebo-controlled, parallel-group study compared the antidepressant efficacy and safety of bupropion sustained-release (SR) tablets (150 mg QD or 150 mg BID) with placebo in outpatients with moderate-to-severe depression. The study consisted of a 1-week placebo phase followed by 8 weeks of active treatment with bupropion SR 150 mg/d (150 mg QD, n = 121) or 300 mg/d (150 mg BID, n = 120) or placebo (n = 121). Efficacy was measured by changes in scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions for Severity of Illness (CGI-S) and Clinical Global Impressions for Improvement of Illness (CGI-I) scales. Safety was monitored by regular assessment of vital signs and adverse events as well as by pretreatment and posttreatment physical and clinical laboratory examinations. By day 56, both bupropion SR treatments were more effective in relieving the symptoms of depression than was placebo. Compared with those receiving placebo, patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced symptoms by treatment day 56, as measured on the 17-item HAM-D, CGI-S, and CGI-I scales (P < 0.05). Bupropion SR was well tolerated, with no serious adverse events reported by bupropion-treated patients; 95% of all reported adverse events were of mild or moderate intensity. No clinically significant changes in vital signs, laboratory test results, or physical findings were observed. A greater mean weight loss was observed at the end of treatment in both the bupropion SR 150-mg (0.5 kg) and bupropion SR 300-mg (1.0 kg) group compared with placebo (0.2 kg). We found that bupropion SR 150 mg administered either once or twice daily was more effective than placebo in treating depression and that once-daily dosing appears to be at least as effective as twice-daily dosing. Should this prove true, depressed patients may be able to benefit from the convenience and improved tolerability associated with once-daily dosing.

The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.

The cardiovascular effects of bupropion hydrochloride and nortriptyline were compared in a double-blind, randomized, 6-week trial in adult outpatients with major depression. After a 1-week placebo phase, 58 patients were randomized to treatment with bupropion (225-450 mg/day) and 57 to nortriptyline (75-150 mg/day). Nortriptyline-treated patients had statistically significant heart rate increases at each assessment as determined by RR intervals on electrocardiogram (14.5-18 bpm). Bupropion-treated patients had small but statistically significant increases in supine diastolic blood pressure of 5.6 mm Hg on day 7 and 7.5 mm Hg on day 28. A few patients in each treatment group had orthostatic changes, but only nortriptyline-treated patients had symptomatic orthostatic hypotension. A slowing of cardiac conduction and possibly of rate-corrected repolarization occurred in patients treated with nortriptyline that did not occur in patients treated with bupropion. Compared to nortriptyline, bupropion appears to have a wider safety margin with regard to cardiovascular effects. This may be particularly true in the elderly, in patients with preexisting cardiovascular disease, or in overdose.

Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion.

BACKGROUND: This study was conducted to determine the effect of bupropion on the sexual functioning of male and female outpatients who developed anorgasmia or delayed orgasm while receiving fluoxetine treatment for depression. METHOD: Thirty-nine patients who satisfied criteria for participation in the study discontinued fluoxetine treatment and entered a 2-week washout phase followed by an open 8-week bupropion treatment phase. Three parameters of sexual functioning were followed throughout the study: orgasm function, libido, and satisfaction with overall sexual functioning. Depression was also evaluated at each visit. RESULTS: All patients reported orgasm delay and/or failure at the time of fluoxetine discontinuation. Orgasm function, libido, and satisfaction with sexual functioning improved during the 2-week fluoxetine washout period and during the bupropion treatment phase. Ninety-four percent of patients (29/31) had complete or partial resolution of their orgasm dysfunction at the end of bupropion treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied with their overall sexual functioning. Most patients entered the study with decreased libido on fluoxetine. Libido was "much" or "very much" increased for 81% of patients (25/31) at the end of the study. In addition, depression scores on the Hamilton Rating Scale for Depression and Clinical Global Impressions-Severity scale significantly improved during the bupropion treatment phase. Finally, bupropion was well tolerated by most patients. CONCLUSION: Bupropion may be an appropriate antidepressant for patients who develop sexual dysfunction during fluoxetine treatment or for whom sexual dysfunction is a concern.

Double-blind comparison of bupropion and fluoxetine in depressed outpatients.

BACKGROUND: This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine. METHOD: Moderately to severely depressed outpatients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression (21 item) participated in this two-center study. Following a 1-week placebo phase, patients were randomly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment. Weekly efficacy assessments included Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. Vital signs and adverse experiences were also assessed weekly. RESULTS: A total of 61 patients were randomly assigned to receive bupropion (225-450 mg/day) and 62 were randomly assigned to receive fluoxetine (20-80 mg/day). The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group. There were no statistically significant differences between treatments on any of the efficacy variables. On the basis of a 50% or greater reduction in the HAM-D scores, 63% (N = 37) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were categorized as responders, and on the basis of CGI scores, 68% (N = 40) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were rated as much or very much improved. HAM-A scores decreased by 59% for both treatment groups. The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments. Twenty-six percent (N = 16) of the bupropion-treated and 29% (N = 18) of the fluoxetine-treated patients prematurely discontinued treatment. CONCLUSION: Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety, and both exhibited a similar, favorable safety profile.

Attention deficit hyperactivity disorder: does it affect adults too?

A review of the literature and our experience suggest that attention deficit hyperactivity disorder does not necessarily disappear in adolescence but may persist into adult life. Detection of the disorder later in life may be made more difficult when it is masked by other diagnostic labels. Once the disorder has been identified in the adult, however, proper intervention with psychotherapy and medical management can make a significant difference in the patient's life.

Phencyclidine-induced psychosis: eight-year follow-up of ten cases.

In 1978, we identified ten patients who were hospitalized for phencyclidine-induced psychosis. Over the next eight years, we used their medical records to document their subsequent hospitalizations and psychosocial functioning. The overall outcome for this group of patients was poor, with chronic unemployment, continuing use of illicit drugs, dependence on relatives for shelter and financial support, and repeated hospitalizations being the rule.

Psychoactive-drug use among adolescents with psychiatric disorders.

Demographic and medical data and data on the use of prescribed and illicit psychoactive drugs were collected retrospectively from medical records of patients admitted for the first time to the adolescent unit of a psychiatric hospital between July 1974 and June 1984. The frequency with which adolescents used prescribed and illicit drugs before admission, during hospitalization, and at discharge from the facility was examined. Data were analyzed for the entire study period and for three time intervals within the 10-year period. Of 204 adolescents between the ages of 11 and 17, 52% were male and 86% were white. The percentage of patients using prescribed psychoactive agents increased during the study period, with the third time interval (1982-84) accounting for the majority of the increase. The use of antidepressants significantly increased over the 10-year period while the use of neuroleptic agents remained fairly constant. Use of at least one illicit drug before admission to the psychiatric facility was reported by 45% of the patient population studied; marijuana was the most frequently used illicit drug. The prescribing patterns reported may be related primarily to individual variation among prescribers. Other factors possibly influencing these prescribing patterns include improved history-taking over the time period studied and less resistance to taking psychoactive medications.