Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study

OBJECTIVE: This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.     

Treatment of cognitive impairment after poststroke depression : a double-blind treatment trial

BACKGROUND AND PURPOSE: Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion. Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy. We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial. METHODS: Patients with major (n=33) or minor (n=14) depression participated in a double-blind treatment study with nortriptyline or placebo. They were examined for change in depressive mood, measured by the Hamilton Rating Scale for Depression (HAM-D), and change in cognitive impairment, assessed by the Mini-Mental State Examination (MMSE), after treatment with nortriptyline or placebo. Cognitive treatment response, as measured by the MMSE, was compared between patients whose depression did and did not respond to treatment. RESULTS: Patients whose poststroke depression remitted (predominantly associated with nortriptyline treatment) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit (predominantly associated with placebo treatment). CONCLUSIONS: Our findings support the contention that poststroke major depression leads to a "dementia of depression." Prior studies failed to show an effect of treatment because the effect size was too small. Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke.     

Treatment of poststroke generalized anxiety disorder comorbid with poststroke depression: merged analysis of nortriptyline trials.

OBJECTIVE: The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression. The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder (GAD) and depression after stroke. METHODS: Data from three studies were merged to provide 27 patients with comorbid GAD and depression, who participated in double-blind treatment studies comparing nortriptyline (N=13) and placebo (N=14). Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety (Ham-A), and severity of depression was measured with the Hamilton Rating Scale for Depression (Ham-D). Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory (JHFI). RESULTS: There were no significant differences between the nortriptyline and placebo groups in demographic characteristics, stroke type, and neurological findings. Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham-A, Ham-D, and JHFI than patients receiving placebo. The anxiety symptoms showed earlier improvement than depressive symptoms in patients treated with nortriptyline. CONCLUSIONS: These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline, and data indicate the need for a trial specifically designed to examine treatment of anxiety disorder.     

Mortality and poststroke depression: a placebo-controlled trial of antidepressants

OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.     

Fluoxetine is not effective in the treatment of post-stroke fatigue: a double-blind, placebo-controlled study

BACKGROUND AND PURPOSE: Although post-stroke fatigue (PoSF) is common, pharmacological interventions to improve PoSF have rarely been carried out. The purpose of the present study was to evaluate the therapeutic effect of fluoxetine on PoSF. METHODS: We studied 83 consecutive outpatients with PoSF at an average of 14 months after the onset of stroke. The presence of post-stroke depression, post-stroke emotional incontinence and post-stroke anger proneness was also evaluated with the use of a standardized questionnaire. The presence of PoSF and pre-stroke fatigue was assessed. The visual analogue scale (VAS) and Fatigue Severity Score (FSS) were used to assess PoSF. The subjects were given either 20 mg/day of fluoxetine (n = 40) or placebo (n = 43) for 3 months. Follow-up evaluations were done 3 and 6 months after the beginning of the treatment. RESULTS: The initial mean fatigue VAS score and the mean overall FSS score were 5.4 +/- 2.0 and 4.4 +/- 1.2, respectively. There were no differences in the number of patients with PoSF between the fluoxetine group and the placebo group at 3 and 6 months after the treatment. The percent changes in VAS scores and FSS at all follow-up assessments were not significantly different either. However, fluoxetine significantly improved post-stroke emotional incontinence (p < 0.05) and post-stroke depression (p = 0.05) in the patients with PoSF. CONCLUSIONS: Fluoxetine does not improve PoSF, although some concomitant emotional disturbances improved significantly. Our results suggest that PoSF may be associated with diverse etiologies but not closely related to serotonergic dysfunction. Further studies are required to elucidate the causative factors and to find an appropriate treatment for PoSF.     

Venlafaxine versus placebo in the preventive treatment of recurrent major depression

BACKGROUND: Major depression is often chronic and recurrent, yet most long-term therapeutic trials are not adequately designed to assess antidepressant efficacy in recurrence prevention. Long-term efficacy and safety of prophylactic venlafaxine treatment were evaluated in outpatients with recurrent major depression. METHOD: Patients with a history of recurrent DSM-III-R major depression received open-label treatment with venlafaxine, 100 to 200 mg/day, for 6 months. Those who responded to treatment (Hamilton Rating Scale for Depression [HAM-D(21)] score < or = 12, day 56) and remained relapse-free (no more than 2 HAM-D(21) scores > 10 and no Clinical Global Impressions-Severity of Illness [CGI-S] score > or = 4, months 2-6) either continued taking venlafaxine, 100 to 200 mg/day, or were switched in a double-blind fashion to placebo for 12 months. The primary efficacy outcome was the number of patients experiencing a recurrence of major depression (CGI-S score > or = 4). The cumulative probability of recurrence was calculated using the Kaplan-Meier method of survival analysis. Data were collected from November 1992 through December 1995. RESULTS: Of the 235 patients who enrolled in the recurrence-prevention period, 225 (N = 109, venlafaxine; N = 116, placebo) provided efficacy data. Survival analysis determined a 22% cumulative probability of recurrence in venlafaxine-treated patients after 12 months compared with 55% for the placebo group (p <.001). More than twice as many placebo-treated patients (48%) as venlafaxine-treated patients (21%) discontinued treatment because of lack of efficacy (p <.001). CONCLUSION: Twelve-month maintenance venlafaxine treatment was significantly more efficacious than placebo in preventing major depression recurrence in patients who had been successfully treated with venlafaxine for 6 months.     

Patterns and predictors of remission,response and recovery in major depression treated with fluoxetine or nortriptyline

OBJECTIVE: The first objective of this paper was to describe the pattern of remission, response and recovery in patients with major depression who were randomised for treatment with fluoxetine ornortriptyline. The second objective was to report on the demographic and diagnostic predictors of the response and recovery in these depressed patients. METHOD: One hundred and ninety-five patients with major depression were recruited for this outpatient study. After a detailed clinical and neurobiological evaluation patients were randomized to receive either fluoxetine or nortiptyline as an initial antidepressant treatment. RESULTS: Of the 195 depressed patients randomised to treatment,154 completed an adequate 6-week trial of either fluoxetine or nortriptyline as their initial antidepressant. Of the 41 patients who did not complete an adequate trial the dropout rate was higher on those randomized to nortriptyline (p = 0.02). There was also an important interaction of drug and gender in determining dropouts in that women did not complete an adequate trial with nortriptyline and men did not complete an adequate trial with fluoxetine (p = 0.002).Of the 154 patients who completed an adequate 6-week antidepressant trial there were no significant differences in 6-week measures of depression severity or of percentage improvement. However, if we use an intention to treat analysis and dichotomise outcomes into response,remission or recovery; then recovery rates were significantly higher with fluoxetine than nortriptyline (p = 0.005).Using an intention to treat analysis fluoxetine was superior tonortriptyline in women, in those less than 25-years old, and in those with atypical depression. Independent of drug, those with chronic depressions had a poorer outcome. CONCLUSION: In this sample of depressed patients randomized tonortriptyline or fluoxetine the change in depressive symptoms over 6 weeks were comparable between fluoxetine and nortriptyline. However,when we look at the more clinically important variable of recovery then fluoxetine was superior to nortriptyline. Predictors of a poorer response to nortriptyline were gender, young age and atypical depression.The results challenge traditional beliefs that selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.     

Early fluoxetine treatment of post-stroke depression

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. Received: 5 February 2002, Received in revised form: 8 October 2002, Accepted: 28 October 2002 Correspondence to Stefan Fruehwald, MD     

Risk factors for and correlates of poststroke depression following discontinuation of antidepressants

The authors randomly assigned nondepressed patients at least 3 months poststroke to receive nortriptyline, fluoxetine, or placebo for 3 months using double-blind methodology. Patients were followed at 3, 6, 9, and 21 months for new onset of depression. In patients treated with antidepressants, lesion volume and degree of social impairment were associated with subsequent late-onset of poststroke depression at 6 and 9 months. In the placebo group, severity of impairment in activities of daily living, at 3 and 9 months, was associated with late onset poststroke depression. Differences in the clinical/pathological correlates may reflect subtle differences in the pathophysiology of poststroke depression following prophylactic antidepressants.     

The effect of remission of poststroke depression on activities of daily living in a double-blind randomized treatment study

Poststroke depression has been associated with impaired recovery of activities of daily living (ADL) during the first 2 years after stroke. This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind randomized treatment study. Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of 23 patients who met criteria for major depression (N = 16) or minor depression (N = 7) were selected and randomly assigned to either active treatment (nortriptyline) or placebo. Functional physical (i.e., ADL) impairment was assessed using the Johns Hopkins Functioning Inventory (JHFI). Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit. There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups, which would explain the significantly greater improvement among the remitted patients. Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication, nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery.     

Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents

OBJECTIVE: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents. METHOD: After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale. RESULTS: Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group. CONCLUSIONS: Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.     

The effect of short-term, low-dose tricyclic and tetracyclic antidepressant treatment on satiation, postnutrient load gastrointestinal symptoms and gastric emptying: a double-blind, randomized, placebo-controlled trial.

Antidepressants are commonly prescribed for patients with functional dyspepsia. However, the effect of tricyclic antidepressants on satiation and gastric emptying remains unclear, and there are no data for tetracyclic compounds. To compare the effects of nortriptyline (maximum dose: 50 mg daily) and mirtazapine (30 mg daily) vs placebo on gastric emptying, gastric satiation and postprandial symptoms after a nutrient load in healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 14 days of nortriptyline (n = 13), mirtazapine (n = 13), or placebo (n = 14) in healthy volunteers. Validated methods were used to study gastric emptying ((13)C-octanoate) and satiation postnutrient drink test. The three arms were comparable with regard to age, gender, body mass index and hospital anxiety/depression scale. There were no statistically significant effects of mirtazapine or nortriptyline on gastric emptying compared to placebo (P = 0.34). Maximum tolerated volume was similar on drug and placebo (P = 0.56). Aggregate symptom score 30 min postmaximum tolerated volume after nutrient drink challenge on placebo was 132 (+/-21), vs 165 (+/-21) on mirtazapine, and 126 (+/-21) on nortriptyline 50 mg respectively (P = 0.28). Tricyclic and tetracyclic antidepressant agents do not appear to have significant effects on gastric motor or satiation postnutrient challenge in healthy individuals at the doses tested.     

Combined pharmacotherapy and psychotherapy as maintenance treatment for late-life depression: effects on social adjustment

OBJECTIVE: This study examined the effects of maintenance treatment for late-life depression on social adjustment. The authors hypothesized that elderly patients recovering from depression would have better social adjustment with medication and interpersonal psychotherapy than with medication or psychotherapy alone. METHOD: Patients aged 60 and older recovering from recurrent major depression were randomly assigned to one of four treatments: nortriptyline and interpersonal psychotherapy, nortriptyline and clinic visits, placebo and psychotherapy, or placebo and clinic visits. The Social Adjustment Scale was administered every 3 months until illness recurrence. Combined treatment was compared to monotherapy on scores over 1 year among patients who remained in recovery (N=49). RESULTS: Patients receiving nortriptyline and interpersonal psychotherapy maintained social adjustment, which declined in those receiving monotherapy. CONCLUSIONS: Treatment of late-life depression with nortriptyline and psychotherapy is more likely to maintain social adjustment than treatment with either alone. Combination therapy improves not only duration but quality of wellness.     

Depression is an independent predictor of poor long-term functional outcome post-stroke

The influence of depression on the long-term outcome of stroke patients was examined among 390 of 486 consecutive patients aged 55-85 years. They completed, at 3 months after ischaemic stroke, a detailed medical, neurological, and radiological stroke evaluation, structured measures of emotion (Beck's Depression Inventory, BDI), handicap (Rankin scale, RS), and assessment of activities of daily living (Barthel Index, BI). Further RS and BI was evaluated at 15-month follow-up from these 390 patients and BDI in 276 patients. A group of 256 patients completed, in addition to the 15-month follow-up, a comprehensive psychiatric evaluation, including the Present State Examination 3 months after stroke. The DSM-III-R criteria were used for diagnosis of the depressive disorders. BDI identified depression (cut-off point > or = 10 for depression) in 171 (43.9%) of 390 and in 123 (44.6%) of 276 patients at 3- and 15-month follow-up. DSM-III-R major depression was diagnosed in 66 (25.8%), and minor depression in 32 (12.5%), of 256 patients 3 months after stroke. Patients with BDI > or = 10, or major, but not minor, depression more often had poor functional outcome (RS > II and BI < 17) at 15 months. Poor functional outcome at 3 months also correlated with depression at 15 months. In logistic regression analysis, depression at 3 months (Beck > or = 10) correlated with poor functional outcome at 15 months (RS > II) (OR 2.5, 95% CI 1.6-3.8). More careful examination and treatment of depression in stroke patients is emphasized.     

Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly

Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.     

A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of "vascular depression"

BACKGROUND: Cerebrovascular disease may cause "vascular depression" (VaD). Calcium channel-blockers are presumed treatments for cerebrovascular disease and might be expected to improve depression and prevent recurrence. OBJECTIVE: To examine the efficacy and tolerability of the use of nimodipine as an augmentation of fluoxetine in the treatment of VaD. DESIGN: A double-blind, randomized clinical trial in which 101 patients with VaD (Alexopoulos criteria) were treated with fluoxetine at standard doses. Patients were randomized to placebo (n=51) or nimodipine (n=50). Treatment outcomes were assessed using the Hamilton Depression Rating Scale (HDRS) regularly up to 8 months after treatment initiation. RESULTS: Depression was reduced in 63% of patients, but those whose treatment was enhanced with nimodipine had greater improvements overall by repeated measures analysis of covariance (ANCOVA) (F(1.80) = 9.76, p=0.001). In addition, a greater proportion of patients treated with fluoxetine-nimodipine (54% vs. 27%) exhibited full remission (chi2(d.f. 1)= 7.3, p = 0.006), with the number needed to treat (NNT) equal to 4 (95% CI 2-12). Of those experiencing full remission in the first 61 days, fewer patients on fluoxetine-nimodipine (3.7%) developed recurrence of major depression as compared to those on fluoxetine alone (35.7%) (chi2(d.f. 1) = 7.56, p = 0.006), NNT 3 (95% CI 2-9). Side-effects were noted in 33.3% of patients in the control group and 48% of the experimental group (chi2(d.f. 1) = 2.25, p = 0.133). CONCLUSIONS: In treating VaD, augmentation of fluoxetine with nimodipine led to better treatment results and lower rates of recurrence. These findings support the argument that augmentation of antidepressant therapy might be helpful in the treatment of cerebrovascular disease, which is involved in the pathogenesis of this type of depression.     

曲唑酮合并氟西汀治疗男性抑郁症的疗效及安全性

目的观察曲唑酮合并氟西汀治疗抑郁症的疗效及安全性。方法将60例符合入组标准的男性抑郁症患者随机分为研究组（30例）和对照组（30例），研究组予以氟西汀合并曲唑酮治疗，对照组单用氟西汀治疗，疗程8周。于入组时及治疗后1、2、4、8周采用HAMD。，项评分、HAMA评分、阿森氏失眠量表（AIS）、亚利桑那性生活问卷（Arizona Sexual Experience Scale，ASEX）、国际勃起功能指数问卷（IIEF-5）进行疗效评定，并进行不良反应评估。结果治疗第八周末两组HAMD总分、体重因子分、认知障碍因子分、迟缓因子分、睡眠障碍因子分的差异具有统计学意义（P〈0．05或P〈0．01），研究组均低于对照组。研究组AIS（P〈0．05）、ASEX（P〈0．01）、IIEF-5（P〈0．01）评分优于对照组。治疗第八周末研究组临床痊愈26例（86．7％），对照组20例（66．7％），两组比较差异无统计学意义（X^2=3．354，P〉0．05）。性功能改善情况：研究组痊愈8例（26．67％），显效16例（53．33％），有效4例（13．33％），无效2例（6．67％）；对照组分别为2例（6．67％），13例（43．33％），6例（20％），9例（30％）。两组疗效差异具有统计学意义（X^2=8．765，P〈0．05）。两组不良反应无显著差异，均为轻度。结论曲唑酮合并氟西汀对男性抑郁症患者抑郁、睡眠及性功能障碍有较好的疗效，安全性高。     

Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up

Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine. Fifteen subjects in each group completed the eight week study. Approximately two-thirds of the patients showed marked or moderate clinical global improvement with both fluoxetine and placebo. Fluoxetine was superior to placebo on all clinical measures except for sleep disorder, but the differences were not statistically significant. Thirty-two of the patients and their parents were interviewed after a mean follow-up interval of 24 months (range: 8-46 months). Mean age at follow-up was 18 years (range: 15-22 years). Both groups had shown further improvement at follow-up but there were no significant group differences. Independent of the study, 19 patients (59%) had received intervening treatment following study termination and nine patients (28%) were still in treatment. Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist, requiring active follow-through.     

Preventing depression after stroke: Results from a randomized placebo-controlled trial

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.     

氟西汀早期干预卒中后抑郁的临床研究

目的观察卒中后抑郁的发生率以及氟西汀早期治疗对卒中后抑郁的干预作用及对神经功能康复的影响。方法选取2005-01～2005-04住院的脑卒中患者66例,随机分为氟西汀治疗组和常规治疗组,常规治疗组仅给神经内科常规治疗,氟西汀治疗组在常规治疗1周后加用氟西汀口服4周。对2组病人均在病程的1周及5周时采用汉密尔顿抑郁量表（HAMD）、日常生活能力量表（ADL）、神经功能缺损评分标准（SSS）进行评定。结果卒中后抑郁发生率为38.24%,治疗后氟西汀治疗组HAMD抑郁评分低于常规治疗组（P〈0.05）,2组患者SSS,ADL分值均有好转,在好转程度上,氟西汀治疗较常规治疗明显（P〈0.05）。结论卒中急性期卒中后抑郁发生率高;早期应用氟西汀治疗可减轻PSD症状、促进神经功能康复。