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.

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.

Antidepressant drugs: disturbing and potentially dangerous adverse effects.

Adverse effects associated with antidepressant drug therapy rarely cause significant morbidity or mortality. Nevertheless, the successful management of patients with depression requires recognition of potential adverse effects that have serious consequences, which include the discontinuation of otherwise effective therapy. The aim of this overview is to highlight the more common and potentially deleterious adverse effects of both older and newer classes of antidepressant drugs. Major adverse effects attributed to the tricyclic antidepressant drugs (TCAs) include conduction defects and lethal overdose. Most worrisome with the selective serotonin reuptake inhibitor drugs (SSRIs) is the serotonin syndrome. Although rare, this syndrome can be insidious and lethal. Recent trends toward the use of medication combinations and augmentation therapies significantly enhance the risk of serotonin syndrome. Cognitive impairment also may occur, especially with the TCAs. Apathy is occasionally a problem with SSRI therapy. The syndrome of inappropriate antidiuretic hormone (SIADH) has been reported with most antidepressant drugs but appears to be more common with serotonergic agents and in elderly patients. Although seizures are uncommon in patients receiving antidepressant therapy, the risk must be understood by both the patient and the clinician. Adverse effects related to sexual function are common, especially with TCAs, SSRIs, and venlafaxine. Sexual dysfunction often leads to noncompliance and self-discontinuation of therapy. Sleep disturbances are common in patients with depression, and recent data illustrate how crucial sleep regulation is to mood. Antidepressant drugs vary in their sleep effects. Although antidepressant drugs can cause a variety of adverse effects, these drugs save lives and their benefits far exceed their risks.

Bupropion sustained release: side effect profile.

Bupropion IR (immediate release) has been on the market since 1988 and is an effective and usually well-tolerated antidepressant. In late 1996, a new sustained-release formulation, bupropion SR, was approved and is now available. Compared with the IR formulation, the SR formulation demonstrates similar efficacy and has been found to have similar, but to some degree fewer, side effects. Its efficacy is similar to that of other newer antidepressants. Side effects of bupropion SR are limited and are not dissimilar to those of the serotonergic antidepressants; however, bupropion SR produces neither substantial sexual side effects nor drug interactions. Study data demonstrate that seizure incidence, which is a concern with high-dose IR, is substantially lower with the new SR formulation.

Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression.

Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.

A case of mania associated with fluoxetine.

A depressed woman with no history of bipolar illness developed a manic episode during treatment with fluoxetine. This side effect appears to be a universal property of effective antidepressants, including this new, purely serotonergic agent.

Haloperidol: a quarter century of experience.

Research on haloperidol's pharmacokinetics, side effects, indications, and efficacy is reviewed. Issues related to high-dose therapy, rapid neuroleptization, intravenous administration, use in geriatric patients, and coadministration with lithium in mania are discussed. Overall, 25 years of experience have indicated that haloperidol can be used safely and effectively to manage a variety of psychiatric illnesses, so long as dosage and method of administration are adjusted to individual patients' needs. Research continues on the use of this drug, not only in psychiatry but in several other areas of medical practice.