A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure. A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study. An evaluation of efficacy and safety of reboxetine in elderly patients affected by "retarded" post-stroke depression. A random, placebo-controlled study. A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression. Fluoxetine in early poststroke depression: a double-blind placebo-controlled study. Structured group therapy and fluoxetine to treat depression in HIV-positive persons. Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. The effect of fluoxetine on anxiety and depression symptoms in cancer patients. Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up. Doxepin treatment of depressed patients with chronic obstructive pulmonary disease. Sertraline treatment of major depression in patients with acute MI or unstable angina. Trimipramine in physical illness with depression. The effect of low dose lofepramine in depressed elderly patients in general medical wards. SSRIs in the treatment of depression in Parkinson's disease. Trazodone therapy of the post-stroke depression. Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial. Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients. Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Efficacy and safety of mianserin in the treatment of depression of women with cancer. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. A controlled trial of antidepressants in patients with Parkinson disease and depression. Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial. Antidepressant pharmacotherapy of depression associated with multiple sclerosis. Efficacy of paroxetine in treating major depressive disorder in persons with multiple sclerosis. Placebo-controlled treatment trial of depression in elderly physically ill patients. Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral Research Center Group. Nortriptyline treatment of post-stroke depression: a double-blind study. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Effects of fluoxetine on mood and immune status in depressed patients with HIV illness. The effects of dothiepin on subjects with rheumatoid arthritis and depression. Pharmacological treatment of depression in cancer patients. A placebo-controlled study of mianserin. Fluoxetine in depressed patients on dialysis.
Depression is frequently observed in patients with heart failure and is associated with poor quality of life and adverse prognosis. However, the prevalence of depression in heart failure could be overestimated because symptoms of depression overlap with those of heart failure. Similarly, the importance of depression may be overestimated if depression merely reflects worse heart failure. Because the response to depression treatment has not been evaluated in this patient population, we evaluated the efficacy of controlled-release paroxetine (paroxetine CR), a selective serotonin reuptake inhibitor, on depression and quality of life in chronic heart failure.
                A double-blind, randomized, placebo-controlled design was used to evaluate reductions in depression following 12 weeks of treatment with paroxetine CR (n = 14, age 62.1 +/- 12.3 years) or placebo (n = 14, age = 61.9 +/- 9.0 years). Patients with symptomatic congestive heart failure and a score of at least 10 on the Beck Depression Inventory (BDI) were eligible. Beck Depression Inventory was obtained at baseline and 4, 8, and 12 weeks of follow-up. Quality of life was assessed using the Medical Outcomes Study Short Form and the Minnesota Living with Heart Failure Questionnaire.
                Controlled-release paroxetine resulted in significantly more recovery from depression (BDI <10) than placebo (69% vs 23%, P = .018) and resulted in lower continuous BDI scores throughout the intervention (P = .024). Controlled-release paroxetine was associated with higher general health levels compared with placebo on the Medical Outcomes Study 36-Item Short Form survey (38 +/- 10 vs 30 +/- 6, P = .016) at 12 weeks of follow-up. Reductions in depression were correlated with improvements in psychological aspects of quality of life (P < .05) but not with physical quality of life measures (P > .10).
                Antidepressant therapy with paroxetine CR results in significant reductions in depression among patients with heart failure. The reductions in depression with paroxetine CR are accompanied by improvements in psychological aspects of quality of life. Larger controlled trials are needed to further document the effectiveness of paroxetine CR and other selective serotonin reuptake inhibitors in patients with heart failure and to determine patient subgroups that are most likely to benefit from antidepressive interventions. The prevalence of asthma has increased in recent years and depression is common in this population. Minimal data are available on the treatment of depressed asthma patients.
                Ninety adults with asthma and current major depressive disorder were randomized to receive citalopram or placebo for 12 weeks. At each visit, the Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology - Self-Report, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire were administered, and oral corticosteroid use assessed.
                In the evaluable sample (n = 82), the primary outcome, a random regression analysis of HRSD scores, revealed no significant between-group differences. Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6. Changes in asthma symptoms were similar between groups. The groups had similar rates of oral corticosteroid use at baseline, but the citalopram group had less corticosteroid use during the study. Changes in asthma symptom severity correlated with changes in depressive symptom severity.
                A reduction in depressive symptoms was associated with improvement in asthma. Corticosteroid use, an important measure of severe asthma exacerbations, was lower in the citalopram group. Larger clinical trials in this population are warranted. Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery. Although selective serotonin reuptake inhibitors (SSRI) are often used in post-stroke depression (PSD), it has been observed that only a subset of patients is responsive to this treatment. Other patients respond to tricyclic antidepressants or MAO inhibitors, which, however, may not have a favorable profile of safety and tolerability in post-stroke patients. In this double-blinded, placebo-controlled study, we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor, reboxetine, in a subset of PSD patients classified as affected by "retarded" depression. Reboxetine (4 mg, twice daily, for 16 weeks) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke. We assessed the severity of depressive symptoms by the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). HDRS and BDI scores (mean+/-S.D.) at baseline were, respectively, 24+/-1.31 and 19.87+/-1.46 in the placebo group, 24.06+/-1.52 and 20.56+/-2.16 in the reboxetine group. After 16 weeks, HDRS and BDI mean scores were respectively 22.73+/-2.4 and 18.4+/-3.33 in the placebo group, 9.26+/-2.15 and 8.06+/-3.43 in the reboxetine group [p<0.01 versus the respective baseline (paired t-test); (#)p<0.01 versus retarded depressed patients treated with placebo (one-way analysis of variance (ANOVA) applied to the difference from baseline, associated with Dunnett's t-test to isolate the differences)]. Reboxetine showed a good efficacy, safety and tolerability in PSD patients affected by "retarded" depression. We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with "retarded" depression. This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV.
                In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score.
                Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups.
                The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance. Early poststroke depression (PSD) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients. This trial was designed to study the efficacy and tolerance of fluoxetine (FLX) in the treatment of early PSD.
                This was a multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients (<3 months) suffering from major depressive disorder (determined by International Classification of Diseases, 10th Revision, and Montgomery-Asberg Depression Rating Scale [MADRS] >19) were randomized to receive either 20 mg/d fluoxetine (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS. Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point).
                Of 121 patients screened, 31 were included in the study, 16 in the FLX group and 15 in the placebo group. There were no significant differences in baseline characteristics among the 2 groups. The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point (11.8+/-6. 7 [mean+/-SD] versus 18.7+/-10.0, respectively; P=0.05). FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater mean decrease of MADRS (16.6 versus 8.4, respectively; P=0.02). There were no differences in motor, cognitive, or functional improvement and no significant side effects after FLX treatment, except for a patient with a moderate and transient increase of transaminases.
                FLX is an efficacious and well-tolerated treatment for early PSD. Further research is needed to evaluate the efficacy and safety of long-term treatment in this population. In 1990, 20 asymptomatic persons diagnosed with the human immunodeficiency virus (HIV-positive) and mild-to-moderate depression were divided into 2 comparison groups. One group received structured group therapy plus fluoxetine, while the other received the same therapy plus a placebo. Affective, neurocognitive, and immune variables were measured before and after the intervention. In the patients receiving group therapy and fluoxetine, its administration did not improve treatment outcome compared to the therapy and placebo group. No significant differences between the two groups were noted on immune variables. However, symptoms of depression decreased in both groups, and both groups showed significant incorporation of the skills in active behavioral coping taught in therapy. Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients. The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated.
                A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups.
                Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient.
                This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective. To examine the efficacy of sertraline in the treatment of depression after traumatic brain injury (TBI).
                Double-blind, randomized controlled trial.
                Research center at a major urban medical center.
                Subjects were a referred and volunteer sample of 52 participants with TBI, a diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was male (58%), had less than 14 years of education (73%), had incomes below $20,000 (82%), and were from minority backgrounds (75%). Approximately one third of the sample had mild brain injuries, and two thirds had moderate to severe brain injuries. The mean age was 47+/-11, and the mean time since injury was 17+/-14 years. One participant withdrew from the study because of side effects.
                Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) or placebo for 10 weeks.
                The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL).
                No statistically significant differences were found at baseline between drug and placebo groups on baseline measures of depression (24.8+/-7.3 vs 27.7+/-7.0), anxiety (16.4+/-12.3 vs 24.0+/-14.9), or QOL (2.96+/-1.0 vs 2.9+/-0.9). The income level of those receiving placebo was significantly lower than those participants receiving medication. Analyses of covariance revealed significant changes from preintervention to posttreatment for all 3 outcome measures (P<.001) but no group effects. Random-effects modeling did not find any significant difference in patterns of scores of the outcome measures between the placebo and medication groups.
                Both groups showed improvements in mood, anxiety, and QOL, with 59% of the experimental group and 32% of the placebo group responding to the treatment, defined as a reduction of a person's HAM-D score by 50%. Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short-term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short-term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double-blind, randomized, placebo- controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short-term clinical advantage.
                (c) 2008 Movement Disorder Society. Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients. A double-blind placebo-controlled study was therefore designed to assess the effectiveness of 20 mg fluoxetine. Of 115 cancer patients who fulfilled entry criteria for levels of distress, 45 patients were randomized to a fluoxetine treatment group (FA) and 46 patients to a placebo group (PA) after a 1-week placebo period designed to exclude placebo responders. The Montgomery and Asberg Depression Scale (MADRS), the Hamilton Anxiety Scale (HAS), the Hospital Anxiety and Depression Scale (HADS), the Revised Symptom Checklist (SCL90-R) and the Spitzer Quality of Life Index (SQOLI) were used to assess the efficacy of fluoxetine. The response rate, defined by a HADS score lower than 8 after 5 weeks of treatment, was not significantly higher in the FA group (11%) compared to the PA group (7%). Compared to the PA group, patients in the FA group showed a significantly greater decrease in SCL90-R mean total score after 5 weeks, but not a greater decrease in HADS mean score. No difference between the two groups was found in observer-reported assessments (MADRS, HAS and SQOLI). Significantly more drop-outs were observed in the FA group (n = 15) than in the PA group (n = 7), although the frequencies of side-effects were not significantly different. Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients.
                This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment.
                54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected.
                The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe. During each of two six-week treatment periods, 12 depressed outpatients with chronic obstructive pulmonary disease received increasing doses of doxepin hydrochloride or a placebo as tolerated. The mean maximal doses of doxepin hydrochloride and placebo were 105 and 128 mg, respectively. Three of the 12 patients dropped out because of doxepin's side effects. The depression and anxiety scores at the end of the treatment periods were virtually identical and not significantly different from baseline scores. Changes in the 12-minute walking distance were more closely correlated with changes in the depression and anxiety scores than with changes in the forced expiratory volume in 1 s or forced vital capacity. Thus, doxepin is ineffective in treating depressed patients with chronic obstructive pulmonary disease; improvements in the 12-minute walking distance were closely correlated with improvements in the depression or anxiety scores. Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.
                To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.
                Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.
                A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).
                After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.
                The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.
                Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.
                Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions. To assess whether tricyclic antidepressants are useful in patients with a serious physical disorder who develop symptoms of major depression, 42 medically ill outpatients who met RDC criteria for endogenous major depression and had a Raskin depression score of at least 7 were studied. The patients were randomly assigned to a 6-week trial of trimipramine or placebo under double-blind conditions. In the placebo group, depressive symptoms improved when the physical disorder improved; in the trimipramine group, improvement was seen in the depressive symptoms even when there was no concomitant improvement in physical condition. A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression. nan The incidence of depression following a hemispheric stroke ranges from 25 to 60%. The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known. We studied subjects both with and without evidence of depression, as indicated by any one of three criteria: (i) Clinical diagnosis of depression, (ii) Abnormal Zung-depression score. (iii) Abnormal dexamethasone suppression test (DST). Patients in a stroke rehabilitation program (22) were randomized to receive either placebo or 300 mg/day trazodone-HCl, beginning 30 days after the stroke. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living (ADL) scores, with antidepressant therapy, as compared to patients receiving placebo. An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone, i.e., in post-stroke depression such a treatment seems to be beneficial. The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both, whether severity of immunosuppression is associated with treatment response, and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count.
                A double-blind, randomized, placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic. The fluoxetine-placebo randomization was 2:1. All patients were offered 4 months of additional open treatment. Main outcome measures included the Clinical Global Impression, Hamilton Depression Rating Scale, and CD4 cell count.
                Of 120 patients randomly assigned to fluoxetine or placebo, 87 completed 8 weeks of treatment. In the total group, 51% had AIDS. All but three were men, 35% were nonwhite, and 6% had intravenous drug use as a risk factor. In an intention-to-treat analysis, 57% of fluoxetine patients and 41% of placebo patients were responders. Among patients who completed the study, 74% responded to fluoxetine and 47% to placebo; this difference was statistically significant. Severity of immunosuppression was not related to antidepressant response, attrition, or side effects, and fluoxetine treatment was not associated with change in CD4 cell count.
                Fluoxetine is an effective antidepressant in the context of HIV illness. However, both placebo response and attrition were substantial, suggesting both that nonspecific factors may be more salient and that yet another medication (i.e., an antidepressant) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications. This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection.
                Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12.
                Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%).
                Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group. This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke.
                A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind randomized study comparing nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks. Response to treatment of depression for individual patients was defined as a greater-than-50% reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial, compared with patients treated with placebo, on measures of impairment in activities of daily living and levels of cognitive and social functioning.
                Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression, in improving anxiety symptoms, and in improving recovery of activities of daily living as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients. Fluoxetine in increasing doses of 10-40 mg/day led to an average weight loss of 15. 1 pounds (8% of initial body weight) over 12 weeks of treatment that was not seen with nortriptyline or placebo.
                Given the doses of medication used in this study, nortriptyline was superior to fluoxetine in the treatment of poststroke depression. Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients, alternative measurement scales, or the optimal time of treatment. Depression is a major complication of cancer. The efficacy and safety of mianserin were evaluated in a randomized placebo-controlled trial of 73 depressed women with cancer. According to RDC diagnosis, all patients showed situational major depression. Both groups were well matched for cancer localization, clinical stages, Karnofsky scores, duration of depression, baseline values on the Hamilton Depression Rating Scale (HDRS), Zung Self-Rating Depression Scale (ZSRDS), and Clinical Global Impression of Illness Severity (CGI-S), and for type of depression, whether dominantly depressive or depressive-anxious. Between days 7-21, there were significantly fewer dropouts with mianserin (7) than with placebo (15). When compared with placebo, there were significant improvements for mianserin for HDRS on days 7, 21 and 28, for ZSRDS on days 7 and 28, and for CGI-S on days 7, 14, 21 and 28. According to Clinical Global Impression of Illness Improvement (CGI-I) there were significantly more responders with mianserin (28) than with placebo (18). The efficacy index for mianserin was significantly greater than for placebo on days 21 and 28. At the end of the trial the scores for HDRS sleep disturbance factor and HDRS anxiety-somatization factor were significantly reduced for mianserin than for placebo. There were no significant differences in side-effects between treatment groups. It is concluded that mianserin is superior to placebo in reducing the severity and duration of depression which is present especially in patients with advanced cancer.(ABSTRACT TRUNCATED AT 250 WORDS) While testosterone's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature, no placebo-controlled trial selecting for depressive disorders and including a standard antidepressant has been conducted. Accordingly, this double-blind trial was designed to determine whether testosterone, as well as fluoxetine, is superior to placebo for depression, fatigue, or both.
                One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive disorder entered the 8-week trial and were randomized to testosterone (up to 400 mg IM testosterone cypionate biweekly), fluoxetine (up to 60 mg/d), or double placebo. Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue, the Hamilton Rating Scale for Depression, and the Chalder Fatigue Scale.
                Ninety men completed the trial. In intention-to-treat analyses, mood response rates were 54%, 47%, and 44% for fluoxetine, testosterone, and placebo, respectively. Among completers, mood response rates were 70%, 57%, and 53%, respectively; in neither analysis were differences between treatments statistically significant. In contrast, testosterone was superior to fluoxetine and placebo for completers regarding fatigue. In intention-to-treat analysis, response rates were 39%, 56%, and 42% for fluoxetine, testosterone, and placebo, respectively, and for study completers, 41%, 63%, and 52%, respectively, (P < 0.05),
                While over 50% of patients treated with testosterone reported improved mood, this rate was not statistically superior to placebo. Thus, our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men. However, if validated in additional studies, testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression.
                Copyright 2004 Lippincott Williams and Wilkins Parkinson disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Depression affects up to 50% of these patients and is associated with a variety of poor outcomes for patients and their families. Despite this, there are few evidence-based data to guide clinical care.
                An NIH-funded, randomized, controlled trial of paroxetine CR, nortriptyline, and placebo in 52 patients with PD and depression. The primary outcomes were the change in the Hamilton Depression Rating Scale (HAM-D) and the percentage of depression responders at 8 weeks.
                Nortriptyline was superior to placebo for the change in HAM-D (p < 0.002); paroxetine CR was not. There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks (p < 0.079). Response rates favored nortriptyline (p = 0.024): nortriptyline 53%, paroxetine CR 11%, placebo 24%. In planned contrasts of response rates, nortriptyline was superior to paroxetine CR (p = 0.034). Nortriptyline was also superior to placebo in many of the secondary outcomes, including sleep, anxiety, and social functioning, while paroxetine CR was not. Both active drug treatments were well tolerated.
                Though relatively modest in size, this is the largest placebo-controlled trial done to date in patients with Parkinson disease (PD) and depression. Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not. When compared directly, nortriptyline produced significantly more responders than did paroxetine CR. The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors. Depression is prevalent in patients with diabetes. It is associated with poor glycemic control and is linked to an increased risk for diabetic complications. In this study, we assessed the efficacy of fluoxetine for depression in patients with diabetes.
                Sixty patients with diabetes (type 1, n = 26; type 2, n = 34) and major depressive disorder entered an 8-week randomized placebo-controlled double-blind trial. Patients were given daily doses of fluoxetine (up to 40 mg/day). The Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAMD) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission. GHb levels were obtained to monitor glycemic control.
                Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo (BDI, -14.0 vs. -8.8, P = 0.03; HAMD, -10.7 vs. -5.2, P = 0.01). The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group (66.7 vs. 37.0%, P = 0.03). Additionally, trends toward a greater rate of depression remission (48.1 vs. 25.9%, P = 0.09 per the HAMD) and greater reduction in GHb (-0.40 vs. -0.07%, P = 0.13) were observed in the fluoxetine group.
                Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also produced a trend toward better glycemic control. In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder, 14 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy. Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group. This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores. Side effects limited desipramine dosage in half of the treated patients. The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease. The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS).
                In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life.
                Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls (P=.073).
                Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals. To determine the response of physically ill elderly depressed patients to treatment.
                Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.
                Response rate as defined by the 17-item Hamilton Depression Rating Scale.
                Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).
                The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important. The purpose of this randomized double-blind, placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC classes II, III, and IV.C.2) who had been diagnosed with major depressive disorder (DSM-III-R).
                During a 7-week trial, patients were treated with fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly supportive group psychotherapy. In addition, subjects were rated on the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in the study, 25 were administered fluoxetine and 22 were given placebo.
                Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment. By endpoint, patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13 (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs. 23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17 score > or = 24). Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally mild and transient. The most frequently noted effects reported by subjects treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in decreasing order of frequency.
                This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression. The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients. Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.
                To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.
                The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.
                Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).
                The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017).
                Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11).
                This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.
                isrctn.org Identifier: ISRCTN15858091. To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited.
                In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale.
                Using the "last observation carried forward" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant.
                This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression. Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.
                In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).
                Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in sertraline patients (p < .05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.
                Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy. Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI.
                Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography.
                The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. Conclusions: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event. When present, depression in the context of human immunodeficiency virus (HIV) illness not only detracts from quality of remaining life but may interfere with motivation to obtain good medical care as well, thus directly influencing life's duration. This study was undertaken to assess the efficacy of fluoxetine in treating depression occurring in the context of HIV illness and to assess effects, if any, of fluoxetine on immune status (T-cell subsets).
                Patients had originally participated in a double-blind, placebo-controlled, 6-week study of imipramine. Imipramine nonresponders or relapsers and side effect dropouts were offered open treatment with fluoxetine for 12 weeks. Adjunctive dextroamphetamine was prescribed if the treating psychiatrist considered it clinically indicated. Eligibility criteria for the original study included a DSM-III-R diagnosis of major depression, dysthymia, or both. Concurrent HIV medications were permitted.
                Measures included the clinician-rated Hamilton Rating Scale for Depression and Clinical Global Impressions Scale, and patient-rated Brief Symptom Inventory and Beck Hopelessness Scale. Of the 23 patients receiving only fluoxetine, 83% (N = 19) were classified as responders. Of the 7 (30%) who also received adjunctive dextroamphetamine, all responded. Patients with CD4 cell counts under 200/cu mm did as well as others. CD4 cell count was not influenced by duration of treatment with fluoxetine; the average decline was that expected due to the passage of time alone. Side effects were mild and relatively infrequent.
                In this open treatment study, fluoxetine alone and fluoxetine plus dextroamphetamine were found to be effective treatments for patients with HIV illness and Axis I depression, regardless of the initial level of immune deficiency or number or type of HIV medications used concurrently. No negative effects on immune status were observed. The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis (RA) is not clear.
                Forty-eight female out-patients with RA, with depression and/or anxiety, were entered into a double-blind, placebo-controlled study of dothiepin in doses up to 150 mg daily to assess the effects on mood [Hospital Anxiety and Depression (HAD) scale and Hamilton Rating Scale (HRS) for Depression], pain [visual analogue scale (VAS)] and disability [Health Assessment Questionnaire (HAQ)].
                Repeated measures multivariate analysis of variance revealed that treatment had a significant effect on pain (F(d.f. 1,39) =5.7, P=0.02). There were further interaction effects between treatment and time on pain (F(d. f. 3,117) =3.3, P=0.03), disability (F(d.f. 3,117)=4.2, P=0.008) and duration of early morning stiffness (F(d.f. 3,117) =3.3, P=0.03). Depression (HRS) was considerably reduced in both the dothiepin and placebo groups, and there was no significant difference between groups. Post hoc analyses using analysis of covariance revealed that, in the dothiepin group, pain was significantly reduced by week 4 and remained so at week 12. Disability scores and duration of early morning stiffness were consistently lower in the dothiepin group, although differences failed to reach statistical significance at any follow-up assessment. In the group as a whole, reductions in pain were highly significantly correlated with reductions in HAD depression (r =0.63, P<0.0005), HAD anxiety (r=0.46, P=0.001) and HRS depression (r=0.37, P=0.01).
                Dothiepin is effective in relieving pain, disability and reducing the duration of early morning stiffness in out-patients with RA. Although there is a general association between pain reduction and improved anxiety and depression, the analgesic effect of dothiepin is independent of its antidepressant effect. Individual variation is considerable and further research should try to identify mechanisms of interaction between the antidepressant and analgesic effects of treatment in different patient groups. Depression has a reported mean prevalence of 24% in patients diagnosed with cancer. However, little systematic research on the efficacy of antidepressants in patients with cancer has been performed.
                The efficacy and safety of mianserin were studied in 55 depressed women with breast cancer (stage I or II and without known metastases), in a randomised, double-blind, six-week, placebo-controlled study.
                Statistically significant differences in the decrease in score from baseline on the Hamilton Rating Scale for Depression and the number of responders, favouring mianserin, were present after 28 and 42 days of treatment. Significantly more placebo-treated patients prematurely terminated the study due to lack of efficacy while the safety profile of mianserin was similar to that of placebo.
                Treatment with mianserin resulted in a significant improvement in depressive symptoms in cancer patients, and was well tolerated. To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis.
                Fourteen patients with major depression and end stage renal disease on hemodialysis were randomized into two groups for an eight-week study. Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo. Patients were carefully monitored concerning adverse events, serum fluoxetine and norfluoxetine levels, and psychological measurements of degree of depression.
                No patients discontinued treatment because of adverse events, all of which were minor. All psychological tests showed improvement in depression at the four-week and eight-weeks point, although statistical significance could only be demonstrated at the fourth week of this study. All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks, similar to levels in patients with normal renal function in a previous open label study.
                This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis. It also suggests that fluoxetine may be efficacious in depressed patients on dialysis.
This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population.