[Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness]. Fluoxetine in early poststroke depression: a double-blind placebo-controlled study. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. Preventing depression after stroke: Results from a randomized placebo-controlled trial. [Influence of Jieyu Huoxue Decoction on rehabilitation of patients with depression after cerebral infarction]. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. [Observation on effect of Wuling Capsule in treating poststroke depression]. Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up. Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients. Fluoxetine as a treatment for post-stroke emotionalism. A double-blind, placebo-controlled study of sertraline in the prevention of depression in stroke patients. [Effects of Linggui Bafa on the therapeutic effect and quality of life in patients of post-stroke depression]. The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) and fluoxetine on post-stroke depression. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. Sertraline in stroke-associated lability of mood. Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study.
Only few studies investigated the effectiveness of psychotherapy in post-stroke depression (PSD). The aim of this feasibility study was to compare interpersonal psychotherapy, pharmacotherapy, and their combination regarding depression and rehabilitation outcome.
                Post-stroke depression was found in 35% of 485 stroke patients examined. Seventy-four PSD patients were randomised to one of three treatment conditions. Severity of depression was measured by the Hamilton Depression Rating Scale and the Hospital Anxiety and Depression Scale. The Barthel Index and a questionnaire for health-related quality of life were used as measurements of rehabilitation outcome.
                There were no significant differences between the three groups in patient mood or rehabilitation outcome. Concerning the severity of depression, quality of life, and social support, all patients showed benefits from antidepressive treatment. In addition a correlation was found between rehabilitation outcome and depression.
                In this feasibility study all antidepressive treatments were successfully implemented in the rehabilitation of post-stroke depressed patients. Combination therapy (interpersonal psychotherapy plus medication) was as effective as one of those elements alone. Because of the small sample size however, further randomized trials are required. 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. 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. We designed this study to determine whether the daily treatment of nondepressed acute stroke patients with sertraline reduced the incidence of depression at follow-up.
                111 patients with recent stroke (< 2 weeks; International Classification of Diseases, Tenth Revision criteria) were randomly assigned to treatment with placebo (N = 56) and sertraline (N = 55, 50 mg once daily) in this double-blind, placebo-controlled 24-week clinical trial. Subjects were recruited from the 2 largest teaching hospitals of Western Australia between June 2002 and June 2004. The primary endpoint of interest was development of clinically significant depressive symptoms as assessed by a Hospital Anxiety and Depression Scale-depression subscale score of 8 or above, or as diagnosed by the treating physician during 24 weeks.
                There was no significant difference in the incidence of depressive symptoms during 24 weeks of treatment (16.7% [8/48] sertraline vs. 21.6% [11/51] placebo, rate ratio = 0.8, 95% CI = 0.3 to 2.1, p = .590). The trial medication was discontinued by 51.8% (29/56) of patients assigned placebo and 47.3% (26/55) assigned sertraline (p = .634), most often because of perceived side effects or because the treating physician introduced an antidepressant medication.
                Twenty-four-week treatment with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute stroke is not a significantly more effective strategy to prevent 6-month depression than usual care plus placebo among nondepressed stroke patients. New pharmacologic and nonpharmacologic strategies need to be developed to reduce the health and financial burden associated with depression after stroke. To study the influence of Jieyu Huoxue Decoction on rehabilitation of patients with depression after cerebral infarction.
                Fifty four patients suffered from the depression after acute cerebral infarction were randomly divided into three groups: depression control group, fluoxetine treated group and Jieyu Huoxue Decoction treated group. Eighteen patients of cerebral infarction without depression were enrolled in the no depression control group randomly. The Zung self-rating depression scale (SDS), the modified Edinburgh-Scandinavia stroke scale (MESSS) and the activities of daily living (ADL) were evaluated before treatment, 30 and 60 days after treatment.
                After 30 and 60 days of treatment, SDS evaluation of the Jieyu Huoxue Decoction treated group showed significant difference as compared with the condition before treatment and that of the depression control group (P < 0.05 or P < 0.01), MESSS evaluation and ADL evaluation also showed significant difference as compared with the condition before treatment and that of the depression control group (P < 0.05 or P < 0.01); there was no obvious difference between the fluoxetine treated group and the Jieyu Huoxue Decoction treated group, but the Jieyu Huoxue Decoction treated group showed fewer symptoms and less side effect.
                Jieyu Huoxue Decoction can not only relieve depression after cerebral infarction, but also improve neurological functions. 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. To evaluate the efficacy of Wuling Capsule (WLC) in treating patients with poststroke depression.
                One hundred and eight patients with poststroke depression were randomly assigned to three groups, 36 in each. All were treated with routine medicine, but to the WLC group and the FLX group, additional WLC and fluoxetine was given respectively, while to the combined group, both of the two were given. Patients' neurological and cognitive function were estimated by HAMI) scale, MMSE scale, SSS scale and Barthel index (BI) before treatment and at 4 weeks and 12 weeks after treatment.
                HAMD score and SSS score significantly decreased (P < 0.01) while MMSE score and BI score significantly increased (P <0.05) in all the three groups, but the improvement in decrease of HAMD score and in increase of BI score in the combined group was more significant than those in the other two groups respectively (P<0.05).
                WLC is effective in treating patients with poststroke depression and shows synergism with fluoxetine. 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. In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy.
                Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale.
                The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms.
                Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone. In order to determine the influence of a single dose of fluoxetine on the cerebral motor activation of lacunar stroke patients in the early phase of recovery, we conducted a prospective, double-blind, crossover, placebo-controlled study on 8 patients with pure motor hemiparesia. Each patient underwent two functional magnetic resonance imaging (fMRI) examinations: one under fluoxetine and one under placebo. The first was performed 2 weeks after stroke onset and the second a week later. During the two fMRI examinations, patients performed an active controlled motor task with the affected hand and a passive one conducted by the examiner with the same hand. Motor performance was evaluated by motor tests under placebo and under fluoxetine immediately before the examinations to investigate the effect of fluoxetine on motor function. Under fluoxetine, during the active motor task, hyperactivation in the ipsilesional primary motor cortex was found. Moreover, fluoxetine significantly improved motor skills of the affected side. We found that a single dose of fluoxetine was enough to modulate cerebral sensory-motor activation in patients. This redistribution of activation toward the motor cortex output activation was associated with an enhancement of motor performance. Motor excitability is increased in both hemispheres in stroke patients during motor recovery. Pharmacologically controlled changes of cortical excitability might be beneficial for synaptic plasticity and therefore facilitate functional recovery after a brain lesion. In particular, it has been suggested that antidepressant drugs can modulate motor excitability. Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). The aim of this study was to investigate motor area excitability in patients with stroke after oral administration of citalopram. We conducted a prospective randomised placebo controlled study. Twenty patients with unilateral stroke were included in the study: ten patients treated by antidepressive drug and ten patients with placebo. A selective serotonergic drug (citalopram) or a placebo was administered using a mean dosage of 10 mg/day in combination with physiotherapy. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation. TMS recording was tested before (T1) and 1 month after (T2) beginning drug treatment. Patients treated by the serotonergic drug, compared to patients that received a placebo, showed a significant improvement in neurological status as measured by NIHSS and a decrease of motor excitability over the unaffected hemisphere, while no differences were observed over the affected hemisphere. Our findings suggest that treatment with serotonergic drugs can bring about a significant decrease of the motor cortex excitability in stroke patients with effects on both the affected and unaffected hemispheres associated with a better motor recovery. The effectiveness of fluoxetine compared to placebo in the treatment of post-stroke emotionalism was investigated in 20 patients using a double-blind protocol. A total of 19 patients completed the study, as one subject in the treatment group had to be withdrawn. The subjects receiving fluoxetine showed a statistically and clinically significant improvement in their emotionalism compared to the placebo group, which was apparent in the majority of subjects from the third day of treatment. The authors tested the effect of sertraline in the prevention of poststroke depression. After experiencing an acute ischemic stroke, nondepressed patients (N=137) were randomly assigned to 12 months of double-blind treatment with either sertraline (N=70) or placebo (N=67). Kaplan-Meier analysis showed sertraline to have significantly superior prophylactic efficacy compared with placebo. Two definitions of clinical depression were used: total score >18 on the HAM-D(17) and score >or=9 on the HAM-D(6). Approximately 10% of the sertraline-treated group developed depression according to either definition, whereas 30% developed depression in the placebo group. On the HAM-D(6) the superiority of sertraline to placebo was demonstrated already after 6 weeks of therapy. Treatment was well tolerated; patients treated with sertraline experienced significantly fewer adverse events. To probe into effects of Linggui Bafa (method for picking eight points linked with extraordinary meridians according to time) on the therapeutic effect and quality of life in patients of post stroke depression.
                One hundred and twenty cases were randomly divided into 3 groups, an observation group 1, an observation group 2 and a control group, 40 cases in each group. All patients were given routine clinical treatments and second level medical prevention. Patients in the observation group 1 received Linggui Bafa acupuncture treatment 2 weeks after stroke; at the same time the observation group 2 was treated with oral administration of Sertraline. The control group did not receive any form of either acupuncture or oral medication, but early rehabilitative intervention and psychological treatment were initiated. Curative effects were evaluated with Hamilton Depression Scale (HAMD), Function Independent Measure (FIM), National Institutes of Health Stroke Scale (NIHSS) and SF-36 after the treatment and 6 months later, respectively.
                The scores of HAMD, FIM (cognition function) and general health, role-physical, role-emotional, social function, vitality, mental health in SF-36 in the observation group 1 were significantly higher than those in the control group after treatment and 6 months later (P<0.01, P<0.05). The scores of physical function in SF-36 after treatment and NIHSS 6 months later in the observation group 1 were significantly improved than those in the control group (P<0.01, P<0.05). The scores of FIM (cognition function) and role-physical, social function, mental health in SF-36 after treatment and HAMD and general health, social function, mental health in SF-36 6 months later in the observation group 2 were significantly better than those in the control group (P<0.01, P<0.05). The scores of HAMD, FIM (cognition function) and general health, role-emotional, social function, vitality, mental health in SF-36 in the observation group 1 were significantly improved than those in the observation group 2 after treatment and 6 months later (P<0.01, P<0.05). The scores of NIHSS and role-physical in SF-36 in the observation group 1 were significantly higher than those in the observation group 2 6 months later (P<0.05).
                Acupuncture can improve depression symptoms and quality of life of patients with post stroke depression and the effects were better than Sertraline. Depression occurs frequently in post-stroke patients and appears to be associated with impairment of their rehabilitation and functional recovery. In this study, we evaluated the efficacy and tolerability of the herbal drug, Free and Easy Wanderer Plus (FEWP), in patients affected by post-stroke depression (PSD).
                One hundred fifty (150) moderately to severely depressed patients as determined by a score >20 on the Hamilton Depression Scale (HDS) after a single ischemic or hemorrhagic stroke were randomly divided into the FEWP group (n = 60), the fluoxetine group (n = 60), and the placebo group (n = 30). The FEWP, fluoxetine, and placebo were administered to the patients over a period of 8 weeks. Depression was evaluated by HDS and the Barthel Index (BI) before, during, and after the treatment.
                Significantly higher clinical response rates were observed in both the FEWP and fluoxetine groups compared to the placebo group (60% and 65.5% versus 21.4%, chi(2) = 15.9, p < 0.01) and there was no difference in the response rates between the FEWP group and the fluoxetine group at the end of this study (60% versus 65.5%, chi(2) = 0.38, p > 0.05). Compared to fluoxetine, FEWP produced significantly greater improvement in depression at week 2 (15% versus 3.3%, chi(2) = 4.9, p < 0.05). Furthermore, FEWP produced significantly greater improvement in the activities of daily living (ADL) than fluoxetine at the end of this trial (BI: 43.8 +/- 5.6 versus 40.7 +/- 3.7, p < 0.01).
                FEWP showed good efficacy, safety, and tolerability in PSD patients. We conclude that FEWP is well tolerated and may be a useful therapeutic option in patients with PSD. Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits.
                In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163.
                118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [<1%] vs 0).
                In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit.
                Public French National Programme for Clinical Research.
                Copyright Â© 2011 Elsevier Ltd. All rights reserved. Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal.
                To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.
                A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59).
                The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria).
                Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.
                In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.
                clinicaltrials.gov Identifier: NCT00071643. To assess whether a selective serotonin reuptake inhibitor is effective in the treatment of stroke-associated lability of mood.
                Twenty-eight non-depressed patients suffering from post-stroke lability of mood took part in an 8-week double-blind randomized placebo-controlled trial of a selective serotonin reuptake inhibitor (50 mg sertraline per day).
                There were statistically significant improvements in a global rating of emotionalism and a specific benefit on tearfulness. The results are discussed in the light of proposed serontonergic mechanisms for emotional lability following stroke.
                50 mg of sertraline per day may be an effective and well-tolerated treatment for stroke-associated lability of mood in the absence of depression. This is supportive evidence for the serontonergic hypothesis of lability of mood following stroke. 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.
SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke.