Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders

OBJECTIVE: Few studies exist on pharmacological interventions for adolescents with substance use disorders (SUD). To this end, we evaluated the response of bupropion hydrochloride sustained release (SR) in SUD adolescents with comorbid psychopathology (both attention-deficit/ hyperactivity disorder (ADHD) and a mood disorder). Methods: Fourteen adolescent outpatients were treated naturalistically and followed openly for 6 months. Adolescents were rated using the Drug Use Screening Inventory--Revised (DUSI-R), ADHD Symptom Checklist, and the Hamilton Rating Scale for Depression (HAM-D). Clinical Global Impression (CGI) Scale scores were obtained for Substance Abuse, ADHD, Anxiety, and Depression. The ratings were completed at baseline, at month 3, and at the 6-month endpoint. Bupropion SR was initiated at 100 mg once-daily and titrated naturalistically to a maximum dose of 400 mg/day. RESULTS: Of the 14 subjects followed, 13 subjects completed 6 months of treatment. At the 6- month endpoint compared to baseline, treatment with bupropion was associated with clinical and significant reductions in DUSI scores (-39%; p < 0.05), ADHD symptom checklist (-43%; p < 0.001), HAM-D (-76%; p < or = 0.001); and reductions in the CGIs for ADHD (p < or = 0.001), depression (p < or = 0.001), and substance abuse (p < 0.05). The mean daily dose of bupropion SR was 315 mg (in divided doses). No significant adverse events were noted during the follow-up period. CONCLUSIONS: These naturalistic data suggest that bupropion is well tolerated and may be an effective medication for the treatment of substance abusing adolescents with comorbid mood disorders and ADHD.     

Effect of Bupropion SR on the Quality of Life of Elderly Depressed Patients With Comorbid Medical Disorders

BACKGROUND: There is a need for additional studies of the quality of life (QOL) of elderly depressed subjects with medical comorbidity. METHOD: We conducted an 8-week, open trial of bupropion sustained release (SR) in 18 elderly (60-81 years) subjects with DSM-IV major depressive disorder and one or more serious medical illnesses (e.g., congestive heart failure, type 1 diabetes mellitus, irritable bowel syndrome) with a week-12 follow-up interview. The intent-to-treat method with the last observation carried forward was used to analyze depression and QOL measures. Dosing was initiated at 100 mg once daily and increased at weekly intervals to a maximum of 150 mg twice daily as clinically indicated. RESULTS: Bupropion SR treatment was associated with reductions in Clinical Global Impressions-Severity of Illness scale (p <.0001) score and in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score (p <.0001). QOL as measured by the Medical Outcomes Study Short Form-36 (SF-36) also tended to improve with treatment. The SF-36 "mental health" (p <.01) and "social functioning" (p <.0006) domains improved significantly by week 4. "Vitality" (p <.03) improved significantly by week 12. On the HAM-D, statistically significant improvement was noted on "depressed mood" (p <.0001), "feelings of guilt" (p <.01), "work and activities" (p <.001), "hypochondriasis" (p <.02), and "insomnia" (p <.01) at week 8. The mean dose of bupropion SR at endpoint was 222 mg/day, and the drug was relatively well tolerated. Two subjects dropped out owing to adverse events and 2 owing to other reasons. No drug-drug interactions occurred. CONCLUSION: These data suggest that bupropion SR is well tolerated and may improve depression, insomnia, somatic symptoms, work functioning, and certain quality-of-life measures in elderly depressed subjects with medical disorders. A randomized, placebo-controlled study is warranted to confirm these promising findings.     

Pramipexole in treatment-resistant depression: a 16-week naturalistic study

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study. Bipolar Disord 2002: 4: 307–314. © Blackwell Munksgaard 2002 Objective: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D₂–D₃ dopamine agonist, in patients with drug‐resistant depression. Methods: The study sample consisted of in‐patients with major depressive episode, according to the DSM‐IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a >50% reduction of the Montgomery–Asberg Depressive Rating Scale (MADRS) total score and a score of 1 or 2 on the Clinical Global Impression scale (CGI‐I) at endpoint. Side‐effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). Results: Thirty‐seven patients were enrolled. Of these, 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16‐week follow‐up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9 ± 11.5 at endpoint (p < 0.001) and the CGI‐S decreased from 4.6 ± 0.8 at baseline to 2.8 ± 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI‐I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. Conclusions: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.     

Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression.

BACKGROUND: Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy. METHODS: Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans. For each medication PET data from patients compared with control subjects was analyzed as a function of treatment response (defined as moderate to marked improvement on the Clinical Global Impression Scale). RESULTS: Treatment response rates were similar for buproprion (32%) and venlafaxine (33%). Compared with control subjects, responders but not nonresponders, to both drugs demonstrated frontal and left temporal hypometabolism. Selectively, compared with control subjects bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders (n = 7) showed bilateral temporal and basal ganglia hypometabolism. CONCLUSIONS: These data suggest that pretreatment frontal and left temporal hypometabolism in never-hospitalized depressed outpatients compared with control subjects is linked to positive antidepressant response and that additional alterations in regional metabolism may be linked to differential responsivity to bupropion and venlafaxine monotherapy.     

Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects

BACKGROUND: This study was designed to evaluate the effect of combining bupropion sustained release (SR) with venlafaxine, paroxetine, or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents. METHOD: Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (a serotonin-norepinephrine reuptake inhibitor), eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing. RESULTS: There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (chi2= 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08; women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6.89, df = 4,24; p = .001) accompanied by a decrease in O-desmethylvenlafaxine (F = 14.26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial. CONCLUSION: Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs. Further investigation of combination treatments under randomized, double-blind conditions is recommended.     

A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice.

OBJECTIVE: This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice. METHODS: In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks. RESULTS: More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038). CONCLUSIONS: Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.     

Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression

OBJECTIVE: To determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression. METHOD: Subjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.). Outcomes were global improvement in ADHD and depression (clinician-rated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated). RESULTS: Clinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHD only. Compared with post-placebo ratings, final parents' (p < .0005) and children's (p = .016) ratings of depressive symptomatology improved significantly, as did parents' (p < .0005) but not teachers' (p = .080) ratings of ADHD symptomatology. Final ratings of functional impairment improved significantly from enrollment (p < .0005). No subject discontinued medication because of side effects. CONCLUSIONS: Bupropion SR may be effective and well-tolerated in adolescents with comorbid ADHD and depressive disorders. However, randomized, placebo-controlled studies are needed.     

Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram

BACKGROUND: The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75-150 mg/day with that of citalopram 10-20 mg/day in elderly patients with major depression according to DSM-IV criteria. METHODS: A randomised, double-blind, parallel group 6-month study. Efficacy was assessed by MADRS, CGI Global Improvement, CGI Severity of Illness and GDS-20 scores and safety by physical examinations, vital signs, adverse events and UKU side effect rating. Plasma levels of venlafaxine, its major metabolite O-desmethylvenlafaxine and citalopram were followed. RESULTS: One hundred and fifty-one male and female patients (64-89 years) were enrolled and 118 patients completed the study. Comparable improvements in MADRS, CGI Severity of Illness, CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment. The MADRS remission rate was 19% for venlafaxine and 23% for citalopram. Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment. There were no clinically significant changes in blood pressure or body weight. CONCLUSION: The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects. Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram.     

Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind,randomized, multicenter trial

OBJECTIVE: To date, two randomized, double-blind trials of serotonin reuptake inhibitors (SRIs) have shown that antidepressant drugs are effective in treating adolescent depression. In contrast, tricyclic antidepressants (TCAs) are not superior to placebo. This has led to a serotonin hypothesis in this age group. This study explores this hypothesis and compares paroxetine, a specific SRI, with clomipramine, a TCA with SRI activity. METHOD: One hundred twenty-one adolescents (aged 12-20 years) with major depression were enrolled and randomized (stratified for age) to 20 or 40 mg of paroxetine or 75 mg or 150 mg of clomipramine for 8 weeks. Primary outcome measurements were the Clinical Global Impression (CGI) scale and the Montgomery and Asberg Depression Rating Scale (MADRS). RESULTS: Of the 121 patients, 58 received clomipramine and 63 paroxetine. Based on intent-to-treat analysis, both agents had similar efficacy, with no effect of age; 48.3% and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3% of those receiving paroxetine were rated responders on the MADRS and CGI scales, respectively. Study withdrawals were frequent in both groups (41% and 31%, respectively), but side effects were significantly more frequent with clomipramine (69% versus 49.2%, respectively; p = .027). CONCLUSION: Paroxetine and clomipramine exhibit similar efficacy in adolescent depression. These data support the serotonin hypothesis but do not confirm it in the absence of a placebo arm. Given the adverse event profile of clomipramine, specific SRIs should be preferred. However, more placebo-controlled studies are needed to establish definitively the efficacy of SRIs in this age group.     

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.     

Once-Daily Venlafaxine Extended Release (XR) and Venlafaxine Immediate Release (IR) in Outpatients with Major Depression

This was a randomized, double-blind, placebo-controlled comparison of the efficacy and safety of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR). Outpatients with DSM-III-R major depression were randomly assigned to venlafaxine XR, 75 mg once daily, venlafaxine IR, 37.5 mg twice daily, or placebo for a maximum of 12 weeks. If the response was inadequate after 2 weeks of treatment, the dosage of venlafaxine XR or IR could be increased to 150 mg daily. The primary efficacy variables were the 21-item Hamilton Depression (HAM-D) Rating Scale total score and depressed mood item, the Montgomery–Asberg Rating Scale (MADRS) total scores, and the Clinical Global Impressions (CGI) severity scale. Two hundred seventy-eight patients were evaluated for efficacy. Venlafaxine XR was significantly superior (p < 0.05) to placebo beginning at week 2 for the HAM-D, week 3 for the MADRS, and week 4 for the CGI severity. Similarly, venlafaxine IR was significantly superior (p < 0.05) to placebo beginning at week 2 on the HAM-D total and depressed mood item, week 3 on the MADRS total, and week 6 on the CGI severity scales. Venlafaxine XR exhibited superiority (p < 0.05) over venlafaxine IR at week 12 for all efficacy variables. The most common treatment-emergent adverse event with venlafaxine XR was nausea. The incidence of nausea was highest during the first 2 weeks with a low likelihood of developing nausea thereafter. The results of this study indicate that venlafaxine XR is safe, effective, and well tolerated for the treatment of major depression at once-daily doses ranging from 75 to 150 mg.     

Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials

OBJECTIVES: The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression. METHODS: Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100-400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7-10 weeks. RESULTS: Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery-Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies. CONCLUSIONS: Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression.     

An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder.

BACKGROUND: Despite the increasing recognition of comorbid attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) in adults, there are no prospective trials of pharmacological agents to treat ADHD in these patients. Given the efficacy of bupropion for ADHD in adults, as well as its use in the management of bipolar depression, we studied the tolerability and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD. METHODS: This was an open, prospective, 6-week trial of bupropion SR (up to 200 mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I) (10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic agents (mood stabilizers and antipsychotics) at baseline were included in the study. We used standardized psychiatric instruments for diagnosis and outcome. Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for ADHD and the ADHD symptom checklist. RESULTS: Of 36 patients entered (75% male, mean age 34 years), 30 patients (83%) completed the protocol. At end point (last observation carried forward [LOCF]) compared to baseline, treatment with bupropion SR resulted in significant reductions in the ADHD symptom checklist (-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001). Bupropion was associated with reductions in ratings of mania and depression. CONCLUSIONS: The results from this open study of adults with ADHD plus BPD suggest that sustained-release bupropion may be effective in treating ADHD in the context of a lifetime diagnosis of BPD, without significant activation of mania. Further controlled trials are warranted.     

Steady-state pharmacokinetics of bupropion SR in juvenile patients

OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.     

Acute psychosis following sustained release bupropion overdose

Bupropion is an antidepressant that is structurally related to amphetamines and enhances dopamine neurotransmission through inhibiting neuronal dopamine re-uptake. Bupropion-related psychosis has been recognized in several papers, but these reports of bupropion-related psychosis almost all involve immediate release (IR) formulation. We present a case of acute psychosis following sustained release bupropion (SR) overdose. A 23-year-old male was admitted because of major depression and a suicidal attempt by ingesting 28 tablets of 150 mg bupropion SR and 14 tablets of 7.5 mg midazolam. He developed paranoid delusions 12 h after the bupropion SR overdose. The paranoid symptoms remitted on the third day of his admission. Our case of acute psychosis following bupropion SR overdose indicates the importance of being aware of the rare complication in patients receiving bupropion SR treatment.     

盐酸安非他酮缓释片治疗抑郁症的Ⅱ期临床研究

目的评价盐酸安非他酮缓释片治疗抑郁症的临床疗效和安全性。方法对58例抑郁症患者进行盐酸安非他酮缓释片和氟西汀片的对照研究，其中盐酸安非他酮缓释片组29例（300mg／d），氟西汀组29例（20mg／d），共治疗6周。采用汉密尔顿抑郁量表（HAMD），汉密尔顿焦虑量表（HAMA），临床总体评定量表（CGI）评定临床疗效，不良事件量表评定安全性。结果经6周治疗后，盐酸安非他酮缓释片治疗总有效率为86．2％，氟西汀组为69．0％，两组比较差异无显著性（P〉0．05）。两组不良反应的发生率无显著性差异（P〉0．05），常见的不良反应有恶心、口干、头昏、出汗、食欲减退等。结论盐酸安非他酮缓释片是一种安全有效的抗抑郁药物。     

Bupropion sustained release treatment reduces fatigue in cancer patients.

OBJECTIVE: To demonstrate that bupropion sustained release (SR) can reduce the symptoms of fatigue experienced by cancer patients. METHOD: We studied an open-label case series of outpatients with fatigue referred for psychiatric assessment from a tertiary care cancer centre. Inclusion criteria were the presence of fatigue or depression with marked fatigue. Clinical status was assessed using the Global Clinical Improvement scale. RESULTS: Fifteen subjects with various cancer sites and psychiatric diagnoses were treated with bupropion SR (modal dose 150 mg) for up to 2 years. Most (13 of 15) saw improvement. Thirteen patients had minor, expectable side effects, and 10 patients were able to continue with bupropion for an extended time. All subjects who improved showed improvement within 2 to 4 weeks. CONCLUSIONS: This is the first report that shows bupropion SR can reduce fatigue in cancer patients. Controlled studies with more homogeneous samples would be necessary to establish the efficacy of this intervention. Further studies should address whether this effect of bupropion is separate from its action as an antidepressant.     

Improved Health-Related Quality of Life and Reduced Productivity Loss After Treatment With Bupropion Sustained Release: A Study in Patients With Major Depression

BACKGROUND: This open-label portion of a 2-phase study assessed the effects of the antidepressant bupropion sustained release (SR) on health-related quality of life (QOL) and workplace productivity in patients with major depression. METHOD: Patients (N = 816) with DSM-IV major depression were treated with bupropion SR, 300 mg/day, for 8 weeks. The Clinical Global Impressions scale for Improvement of Illness (CGI-I) was completed at weekly clinic visits. At baseline and week 8, QOL and productivity were assessed. QOL was assessed using the Quality of Life in Depression Scale (QLDS). RESULTS: QOL and productivity were significantly improved from baseline after 8 weeks of treatment with bupropion SR. Mean QLDS scores were 18.98 and 10.36 at baseline and week 8, respectively (mean change = 8.62; p <.001). At week 8 compared with baseline, patients working at a paid job reported missing 1.58 fewer hours of work because of depression during the past 7 days, being 14.6% more effective on the job, working at reduced effectiveness less often, and incurring 6.37 fewer hours of overall lost productivity (p <.001 each variable). Improvements in QOL and productivity were significantly (p <.001) greater in bupropion SR responders (i.e., those with CGI-I scores of "very much improved" or "much improved" during the last 3 weeks of open-label therapy) than in nonresponders. CONCLUSION: Effective treatment of major depression with bupropion SR for 8 weeks is associated with improvements in QOL and reductions in lost workplace productivity. Patients who responded clinically to bupropion SR showed significantly greater improvements in these variables than those who did not respond.     

Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression.

BACKGROUND: This was the first controlled continuation phase study (up to 1-year total treatment) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR. METHODS: Patients with recurrent major depression were treated with bupropion SR 300 mg/day during an 8-week open-label phase. Responders (based on Clinical Global Impressions Scale for Improvement of Illness scores) entered a randomized, double-blind phase where they received bupropion SR 300 mg/day or placebo for up to 44 weeks. After randomization, relapse was defined as the point at which the investigator intervened by withdrawing the patient from the study to treat depression. RESULTS: Four hundred twenty-three patients were randomized. A statistically significant difference in favor of bupropion SR over placebo was seen in the time to treatment intervention for depression when survival curves were compared (log-rank test, p =.003). Statistically significant separation between bupropion SR and placebo began at double-blind week 12 (p <.05). Adverse events in bupropion SR-treated patients accounted for 9% and 4% of discontinuations from the open-label and double-blind phases, respectively. CONCLUSIONS: Bupropion SR was shown to be effective and well tolerated in decreasing the risk for relapse of depression for up to 44 weeks.     

Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers

Introduction: Bipolar patients with breakthrough major depressive episodes despite ongoing adequately‐dosed mood stabilizer medication were randomized in a double‐blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial.

Methods: Subjects included 64 bipolar patients who participated at five sites in a 10‐week double‐blind trial for depression and a 1‐year blinded continuation maintenance phase for responders. Nonresponders were re‐randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health‐Life Chart Methodology (NIMH‐LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI‐BP) and the occurrence of hypomania or mania.

Results: Thirty‐five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI‐BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty‐two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania.

Conclusions: In this randomized double‐blind prospective study of three second‐generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.