Exercise and pharmacotherapy in the treatment of major depressive disorder. Placebo-controlled treatment trial of depression in elderly physically ill patients. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. Trimipramine in physical illness with depression. A controlled trial of maprotiline (Ludiomil) in depressed outpatients. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression. Glycemic control improvement through treatment of depression using antidepressant drugs in patients with diabetes mellitus type 1. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychotherapy alone and combined with pharmacotherapy in the treatment of depression. Treatment of minor depression in older adults: a pilot study comparing sertraline and exercise. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Predictive value of pharmacological activity for the relative efficacy of antidepressant drugs. Meta-regression analysis. Effects of exercise training on older patients with major depression. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Maprotiline versus imipramine and placebo in neurotic depression. A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives. A clinical evaluation of depressives found in a rural survey in India. Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression. [A randomized trial of pharmacotherapy with telephone monitoring to improve treatment of depression in primary care in Santiago, Chile]. Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression. Moclobemide versus placebo in the treatment of depression: a multicentre study in Belgium. A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression. A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. Relevance of DMS-III depressive subtype and chronicity of antidepressant efficacy in atypical depression. Differential response to phenelzine, imipramine, and placebo. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder.
To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls.
                Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50-200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D).
                After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23).
                The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. 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. A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.
                One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.
                At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.
                In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety. 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 comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline. We performed a randomized, double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in outpatients with major depression, in particular patients with mixed anxiety/depressive symptomatology. Overall, amitriptyline was more effective than zimelidine and placebo after 4 weeks of treatment. However, when those patients with more severe depression were specifically examined, both antidepressants were equal in efficacy and superior to placebo. We also found no evidence for a greater likelihood of a zimelidine-induced peripheral neuropathy in this study. The present results suggest that zimelidine may be more effective in the treatment of severely depressed patients, rather than those with more mild mixed anxiety/depressive syndromes. Depression is a common disorder among diabetic patients and affects negatively the treatment of their basic disease. The aim of the study was to assess, whether antidepressant medication could positively influence glycemic control of diabetes type 1 in depressive or anxious patients.
                A six-month, double-blinded, randomized, placebo-controlled study was performed to investigate the reaction of type 1diabetic patients (n=21) to treatment of depression and anxiety symptoms using antidepressant drug sertraline. The patients were given sertraline (100 mg/day) or placebo. The evolution of mental change was assessed using Zung Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) along with development of somatic parameters commonly assessed in diabetic patients, especially glycosylated hemoglobin, insulin dose and body weight. The level of active substance in serum of the patients was also measured.
                Mental state improved at the level of statistical significance of p<0.001 in both patients using antidepressant and placebo. From somatic parameters, body weight and systolic blood pressure increased statistically significantly also in both groups of patients.
                The mental state of most patients who successfully completed the study improved regardless of the fact if they were using antidepressant or placebo. No statistically significant connections between the mental and somatic changes were found. This finding points out to the placebo effect of the medication, to the importance of a contact with patients, but also to the need to concentrate on their mental state. General practice depressives were treated for 6 weeks with amitriptyline or placebo in a controlled trial. Overall, drug was found strongly superior to placebo. Interactions were examined between drug effects and a number of variables, principally reflecting demographic characteristics, history of illness, severity of illness, and endogenous depression separately in symptoms and stress. Only in the area of severity were significant interactions found. Amitriptyline was superior to placebo in probable or definite major depression on the Research Diagnostic Criteria, but not in minor depression. It was also superior to placebo in subjects with initial scores on the Hamilton Depression Scale of 13-15, and 16 or more, but not with lower scores. Findings indicate that tricyclic antidepressants are of considerable benefit in relatively mild depressions, except in the mildest range. Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam. To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference.
                Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes.
                31 general practices in Trent region.
                Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms.
                Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria.
                At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse.
                Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment. 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. The relative efficacy of psychotherapy and combined therapy in the treatment of depression is still a matter of debate.
                To investigate whether combined therapy has advantages over psychotherapy alone.
                A 6-month randomised clinical trial compared Short Psychodynamic Supportive Psychotherapy (n=106) with combined therapy (n=85) in ambulatory patients with mild or moderate major depressive disorder diagnosed using DSM-IV criteria. Antidepressants were prescribed according to a protocol providing four successive steps in case of intolerance or inefficacy: venlafaxine, selective serotonin reuptake inhibitor, nortriptyline and nortriptyline plus lithium. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression, the Clinical Global Impression of Severity and of Improvement, and the depression sub-scale of the Symptom Checklist.
                The advantages of combining antidepressants with psychotherapy were equivocal. Neither the treating clinicians nor the independent observers were able to ascertain them, but the patients experienced them clearly.
                The advantages of combining antidepressants with psychotherapy are equivocal. The purpose of this study was to conduct a pilot clinical trial to test the feasibility and efficacy of an exercise program and anti-depressant treatment compared with usual care in improving the emotional and physical functioning of older adults with minor depression. Participants were 37 older adults with minor depression who were randomized to exercise, sertraline, or usual care; 32 participants completed the 16-week study. Outcomes included measures of both emotional (clinician and self-report) and physical (observed and self-report) functioning. There were trends for the superiority of the exercise and sertraline conditions over usual care in improving SF-36 mental health scores and clinician-rated depression scores. Individuals in the exercise condition showed greater improvements in physical functioning than individuals in the usual care condition. Both sertraline and exercise show promise as treatments for late-life minor depression. However, exercise has the added benefit of improving physical functioning as well. To evaluate the efficacy of emotional support and counselling combined with placebo or antidepressants with single or dual mechanism of action in the treatment of depression in primary care.
                Randomised double blind study.
                Several locations in Norway.
                372 patients with depression.
                Improvement (clinical remission) reported both by the patient (Montgomery Asberg depression rating scale) and the physician (clinical global improvement and impression scales).
                Intention to treat analyses showed 47% remission in patients randomised to placebo compared with 61% remission in patients randomised to sertraline (odds ratio 0.56, 95% confidence interval 0.33 to 0.96) and 54% in patients randomised to mianserin (0.75, 0.44 to 1.27). Women responded better than men (1.86, 1.17 to 2.96). Subgroup analyses showed that subjects with recurrent depression (n=273) responded more frequently to sertraline than to placebo (0.43, 0.23 to 0.82) than those having their first episode of depression (1.18, 0.39 to 3.61). Statistically significant interactions between type of drug treatment and history of depression were not shown by logistic regression.
                The combination of active drug and simple psychological treatment (counselling, emotional support, and close follow up over a 24 week period) was more effective than simple psychological treatment alone, in particular for those with recurrent depression. Overall, women may benefit more than men. If confirmed in future studies, the findings should lead to more differentiated treatment guidelines for depression in primary care. Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice. Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects. There is uncertainty about the contribution of specific pharmacological properties to the efficacy of antidepressants.
                To assess whether specific pharmacological characteristics of alternative antidepressants resulted in altered efficacy compared to that of selective serotonin reuptake inhibitors in the treatment of major depression.
                Meta-regression analysis of randomised trials that compare treatment with a selective serotonin reuptake inhibitor and an alternative antidepressant.
                One-hundred-and-five randomised trials were included. None of the factors identified a priori predicted a statistically significant improvement in outcome across the trials.
                This analysis does not provide evidence that antidepressants acting at more than one pharmacological site differ in efficacy from drugs selective for serotonin reuptake in the treatment of major depression. Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated.
                To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial.
                One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions.
                After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms.
                An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD. Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline.
                Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group.
                Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo.
                This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy. In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%). This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline . While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups. Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression.
                Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms.
                Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients.
                Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare. The antidepressant effect of maprotiline, a tetracyclic compound, was compared with that of imipramine in a four-week, double-blind, placebo controlled study with neurotic depressives. On all factors of the Hamilton Depression Rating Scale and on most items of the Zung Self-Rating Scales for Depression and Anxiety, maprotiline appeared slightly more effective than imipramine and showed a faster onset of action. In addition, it appeared to cause fewer anticholinergic side effects. Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comorbid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor antidepressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size. Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned. Eight-seven moderately to severely depressed psychiatric outpatients were randomly assigned to 12 weeks of cognitive therapy (CT) (n = 24), pharmacotherapy (n = 24), CT plus pharmacotherapy (n = 22), or CT plus active placebo (n = 17). Seventy patients completed the treatment protocol. Seventeen dropped out before the end of the treatment period. Patients who completed treatment showed significant improvement in mean scores on two common measures of severity of depression (the Beck Depression Inventory and the Hamilton Rating Scale for Depression) between evaluation and termination. Improvement did not differ as a function of the different treatment modalities. Inclusion of dropout patients' end-point scores did not alter these results. Treatment gains in all groups were maintained at one-month follow-up assessment. A portion of this study replicated an earlier study. While the results were not identical, they indicated that either CT or antidepressant drug treatment can be effective in treating outpatients with primary, nonbipolar depression of moderate or greater severity. Combining treatments did not lead either to additive effects or negative interactions. Depression is a public health problem, due to its high prevalence and its associated disability.
                To compare a pharmacological intervention for depression controlled by phone from a central level (TM) and the usual treatment (TH) in a randomized clinical trial.
                Three hundred and forty five women, aged 22 to 59 years were studied. They were randomly assigned to receive the usual therapy or a pharmacological intervention with periodical telephone contacts with medical collaboration personnel, to reinforce compliance with treatment and educate about the disease. Women were blindly evaluated at 3 and 6 months with the Hamilton depression rating score (HDRS) and the SF-36 to assess depressive symptoms and quality of life, respectively.
                In both evaluations, improvement was significantly greater in the TM group than the TH group. At 3 months, improvement was higher in the TM group in the subscales of physical function, pain, general health, energy, emotional role, mental health and standardized physical and psychic scales of SF-36. At 6 months, this significant difference in favour of TM was maintained for energy, mental health and the standardized psychic scale.
                A telephone reinforcement improves the outcomes of treatments for depression. Two hundred forty-one outpatients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam, diazepam, imipramine hydrochloride, and placebo. Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo. Imipramine-treated patients reported the most and placebo patients the least number of adverse effects. Imipramine and alprazolam, but not diazepam, produced significantly more improvement in depressed symptomatology than did placebo. Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo. These treatment differences were found to be independent of initial severity levels of anxiety and depression. Adinazolam, a triazolobenzodiazepine, was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives. Forty-eight patients entered the study, and 35 completed 6 weeks of evaluation. Patients were well matched in each of the groups. Initially, the adinazolam group showed more improvement than the placebo group, but this trend did not persist beyond day 7. The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups, and final scores were significantly better for amitriptyline. Depressive symptoms in the amitriptyline dropout group appeared improved, whereas in the adinazolam and placebo dropout groups they were unchanged or worse. Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo. Thus, amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo. Moclobemide was compared with placebo for antidepressant activity, tolerance and safety in 2 parallel groups of 23 and 24 depressed patients. At the end of treatment (4 weeks or longer), 9 patients on moclobemide (41%) showed an improvement greater than or equal to 50% on the Hamilton Rating Scale for Depression, compared with only 4 (17%) of those on placebo. The overall assessment of efficacy was significantly better for moclobemide (good or very good results in 50% of patients) than for placebo (80% poor results). Moclobemide was well or very well tolerated by 85% of patients and placebo by 100%. Moclobemide was thus shown to be clearly more effective than placebo and only slightly less well tolerated. To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD).
                This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures.
                Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild.
                Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD. To compare the effectiveness of a multifaceted intervention in patients with depression in primary care with the effectiveness of "usual care" by the primary care physician.
                A randomized controlled trial among primary care patients with major depression or minor depression.
                Over a 12-month period a total of 217 primary care patients who were recognized as depressed by their primary care physicians and were willing to take antidepressant medication were randomized, with 91 patients meeting criteria for major depression and 126 for minor depression.
                Intervention patients received increased intensity and frequency of visits over the first 4 to 6 weeks of treatment (visits 1 and 3 with a primary care physician, visits 2 and 4 with a psychiatrist) and continued surveillance of adherence to medication regimens during the continuation and maintenance phases of treatment. Patient education in these visits was supplemented by videotaped and written materials.
                Primary outcome measures included short-term (30-day) and long-term (90-day) use of antidepressant medication at guideline dosage levels, satisfaction with overall care for depression and antidepressant medication, and reduction in depressive symptoms.
                In patients with major depression, the intervention group had greater adherence than the usual care controls to adequate dosage of antidepressant medication for 90 days or more (75.5% vs 50.0%; P < .01), were more likely to rate the quality of the care they received for depression as good to excellent (93.0% vs 75.0%; P < .03), and were more likely to rate antidepressant medications as helping somewhat to helping a great deal (88.1% vs 63.3%; P < .01). Seventy-four percent of intervention patients with major depression showed 50% or more improvement on the Symptom Checklist-90 Depressive Symptom Scale compared with 43.8% of controls (P < .01), and the intervention patients also demonstrated a significantly greater decrease in depression severity over time compared with controls (P < .004). In patients with minor depression, the intervention group had significantly greater adherence than controls to adequate dosage of antidepressant medication for 90 days or more (79.7% vs 40.3%; P < .001) and more often rated antidepressant medication as helping somewhat to helping a great deal (81.8% vs 61.4%; P < .02). However, no significant differences were found between the intervention and control groups in the percentage of patients who were satisfied with the care they received for depression (94.4% vs 89.3%), in the percentage who experienced a 50% or more decrease in depressive symptoms, or in the decrease of depressive symptoms over time.
                A multifaceted intervention consisting of collaborative management by the primary care physician and a consulting psychiatrist, intensive patient education, and surveillance of continued refills of antidepressant medication improved adherence to antidepressant regimens in patients with major and with minor depression. It improved satisfaction with care and resulted in more favorable depressive outcomes in patients with major, but not minor, depression. The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle. Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.
                Patients (N=1,147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day). Primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).
                Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (-10.1) than placebo (-6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).
                For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196). To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD).
                Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo.
                There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL.
                No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD. To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD).
                Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures.
                Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size.
                No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD. One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response. Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial.
                This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters.
                A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects.
                Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.
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.