Combination of inositol and serotonin reuptake inhibitors in the treatment of depression. Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication. CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial.
Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI).
                Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks.
                No significant difference was found between the two treatment groups.
                Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol. It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressants (TCAs) in treatment of melancholic depression. We treated 36 depressed ambulatory patients with doxepin or fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven patients treated with doxepin and 13 patients treated with fluoxetine met diagnostic criteria for melancholic depression. Average daily dose was 169.4 +/- 41.6 mg for doxepin and 36.8 +/- 18 mg for fluoxetine. We observed a 50% response rate in both treatment groups, using as outcome criterion reduction of Hamilton Depression Scale Score to less than 10. Regardless of how strict the definition of response, we found fluoxetine to be as effective as doxepin in our group of melancholic outpatients. The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice. To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression.
                Pragmatic randomised controlled superiority trial.
                6 outpatient clinics in Manchester and Cambridge.
                208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included.
                103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase.
                Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale.
                At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved.
                For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone.
                Current Controlled Trials ISRCNT 83809224. The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical pharmacological properties, and fluoxetine, a selective serotonine reuptake inhibitor (SSRI), were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut effects on sleep measures resulting in higher values for sleep efficiency, total sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the proportion of REM sleep was decreased and REM latency was lengthened, whereas no change in REM sleep parameters was observed in the trimipramine group. The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep, i.e. suppression of REM sleep. To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.
                A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.
                Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).
                The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research. Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n = 52) in comparison to healthy control subjects (n = 73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.
                Copyright 2002 Elsevier Science Ltd. Many claims have been made for superior compliance with selective serotonin reuptake inhibitors (SSRIs) compared with tricyclic antidepressants, but to date meta-analyses have not confirmed reduced dropouts in randomized controlled trials. The authors used a randomized study design to evaluate differential compliance with antidepressant medications in a primary care setting.
                A total of 152 patients treated in 10 primary care practices in the United Kingdom were included in a randomized, open-label, parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks. Compliance was assessed by using pill count, patient questionnaires, and the Medication Event Monitoring System.
                The level of compliance with fluoxetine was numerically higher than the level of compliance with dothiepin on all three primary outcome measures, although the differences were not significant. In a secondary analysis using data from the Medication Event Monitoring System, both a survival analysis for length of time without a gap in medicine taking and a derived compliance index showed a significant advantage to fluoxetine. Patients in the fluoxetine group reported superior response on the health transition scale of the 36-item Short-Form Health Survey Questionnaire and numerically greater improvement on the Hamilton Depression Rating Scale. In both treatment arms patients with a superior compliance index were more likely to have improved in Hamilton depression scale scores by the last study visit.
                This study supports recent meta-analyses of SSRIs versus tricyclic antidepressants in finding no significant differences in crude indices of compliance between fluoxetine and dothiepin, despite marked differences in side effect profile and dose regimen. However, both a survival analysis and a new measure that takes account of prolonged periods of noncompliance distinguished between the treatments and was associated with improvement in both groups. Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce.
                Twenty three non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug.
                After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo.
                The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function. Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment.
                To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI.Design, Setting, and
                Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention.
                Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks.
                Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months.
                Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients).
                The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.
Both TCAs and SSRIs are effective for depression treated in primary care.