Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up. Cognitive behavioral psychotherapy for depression following stroke: a randomized controlled trial. Nortriptyline treatment of post-stroke depression: a double-blind study. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. Motivational interviewing early after acute stroke: a randomized, controlled trial. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. Fluoxetine in early poststroke depression: a double-blind placebo-controlled study. Antidepressant therapy after stroke. A double-blind trial. An evaluation of efficacy and safety of reboxetine in elderly patients affected by "retarded" post-stroke depression. A random, placebo-controlled study.
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. There is inconclusive evidence of the effectiveness of psychological interventions for depression after stroke. We report the results from a randomized controlled trial of cognitive behavioral therapy (CBT).
                Stroke patients admitted to hospital were invited to complete mood questionnaires 1, 3 and 6 months after stroke. Patients who were depressed were invited to take part in a trial and randomly allocated to receive CBT (n=39), an attention placebo intervention (n= 43), or standard care (n=41). Outcome assessments were undertaken at 3 and 6 months after recruitment, on the Beck Depression Inventory, Wakefield Depression Inventory, Extended Activities of Daily Living scale, London Handicap Scale, and a rating of satisfaction with care.
                There were no significant differences between the groups in patients' mood, independence in instrumental activities of daily living, handicap, or satisfaction with care.
                CBT in the treatment of depression following stroke was found to be ineffective in this study. However, because of the small sample size, method of recruitment, and selection criteria, further randomized trials are required. 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. 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. The purpose of this study was to determine whether motivational interviewing, a patient-centered counseling technique, can benefit patients' mood 3 months after stroke.
                A single-center, open, randomized, controlled trial was conducted at a single hospital with a stroke unit. Subjects consisted of 411 consecutive patients on the stroke register who were over 18 years of age and who did not have severe cognitive and communication problems that would prevent them from taking part in an interview; were not known to be moving out of the area after discharge; and were not already receiving psychiatric or clinical psychology intervention. All patients received usual stroke care. Patients in the intervention group received 4 individual, weekly sessions of motivational interviewing with a trained therapist in addition to usual stroke care. The primary outcome was the proportion of patients with normal mood at 3 months poststroke measured by the 28-item General Health Questionnaire (normal, <5; low > or=5) using a mailed questionnaire.
                Eighty-one of 207 (39.1%) patients in the control group and 100 of 204 (49.0%) patients in the intervention group had normal mood at follow up. A significant benefit of motivational interviewing over usual stroke care (OR: 1.60, 95% CI: 1.04 to 2.46, P=0.03) was found.
                Our results suggest motivational interviewing leads to an improvement in patients' mood 3 months after stroke. 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. 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. Twenty-seven inpatients participating in a stroke rehabilitation program were randomized to receive either placebo or trazodone hydrochloride (Desyrel) beginning a mean (+/- SEM) of 44 +/- 4 days after stroke. The target dosage was 200 mg/d. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend toward greater improvement in Barthel activities of daily living (ADL) scores with trazodone than with placebo. An abnormal dexamethasone suppression test result was associated with significant improvement in the Barthel ADL scores of patients receiving trazodone (38 +/- 6 vs 20 +/- 6 for placebo). Patients with stroke and evidence of depression are therefore likely to benefit from treatment with trazodone. 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.
A small but significant effect of pharmacotherapy (not psychotherapy) on treating depression and reducing depressive symptoms was found, as was a significant increase in adverse events. More research is required before recommendations can be made about the routine use of such treatments.