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.     

The Post-Stroke depression rating scale: A test specifically devised to investigate affective disorders of stroke patients

Abstract

Owing to the lack of instruments specifically constructed to study emotional and affective disorders of stroke patients, the nature of post-stroke depression (PSD) remains controversial. With this in mind, the authors constructed a new scale, the Post-Stroke Depression Rating Scale (PSDS) which takes into account a series of symptoms and problems commonly observed in depressed stroke patients. The PSDS and the Hamilton Depression Rating Scale (HDS) were administered to a group of 124 stroke patients, who had been classified, on the basis of DSM III-R diagnostic criteria, in the following categories: No depression (n =32); Minor PSD (n =47); Major PSD (n =45). Scores obtained by these stroke patients on the PSDS and on the HDS were compared to those obtained on the same scales by 17 psychiatric patients also classified as major depression on the basis of DSM III-R diagnostic criteria. An analysis of the symptomatological profiles clearly showed that: (1) a continuum exists between the so-called “major” and “minor” forms of PSD; (2) in both groups of depressed stroke patients the depressive symptomatology seems due to the psychological reaction to the devastating consequences of stroke, since the motivated aspects of depression prevailed in depressed stroke patients, whereas the (biologically determined) unmotivated aspects prevailed in patients with a functional form of major depression; and (3) in stroke patients a DSM Ill-based diagnosis of major PSD could be in part inflated by symptoms (such as apathy and vegetative disorders) that are typical of major depression in a patient free from brain damage, but that could be due to the brain lesion per se in a stroke patient.     

Is left stroke a risk-factor for selective serotonin reuptake inhibitor antidepressant treatment resistance?

The objective of the study was to detect changes of depression and cognitive level associated with right and left brain damage during SSRI treatment in subjects with post-stroke Major Depressive Disorder (MDD). After the baseline evaluation, the 45 patients included received a single oral dose of 20–40 mg of fluoxetine or 50–100 mg of sertraline. At day 0, 7, 14, 28, 42, and 56 a psychometric test battery comprising the Hamilton Depression Rating Scale (HDRS) and the Mini Mental State Examination (MMSE) was administered. In the whole group repeated measures ANOVAs revealed a highly significant (p < 0.0001) time effect for HDRS and MMSE scores. However, depression improved much more in right stroke subjects in comparison with left stroke subjects (p < 0.001 for the HDRS by laterality interaction). Moreover, there is a suggestion of a possible selective serotonin reuptake inhibitor (SSRI) efficacy in cognitive impairment associated to post-stroke MDD but in treatment-responders only. At the endpoint, chi-square analysis showed that there was a different prevalence rate of MDD between left (n = 10; 50 %) and right (n = 4; 16 %) stroke patients, whereas the prevalence rate of Minor Depression was identical (25 %). The SSRIs fluoxetine and sertraline could be efficacious treatments for post-stroke MDD but these findings suggest that left stroke could be a predictor of treatment resistance. Received: 6 August 2002, Received in revised form: 4 November 2002, Accepted: 11 November 2002 Correspondence to Gianfranco Spalletta, MD     

The efficacy of long-term psychodynamic psychotherapy,fluoxetine and their combination in the outpatient treatment of depression

Abstract

Objective: There are few randomized controlled trials examining the efficacy of long-term psychodynamic psychotherapy (LTPP) in depression treatment. LTPP was compared with fluoxetine treatment and their combination; Methods: 272 depressed patients (aged 26–34, 72% with a first episode of depression) were randomized to receive LTPP (one session/week), fluoxetine treatment (20–60 mg/day) or their combination for 24 months. Beck Depression Inventory (BDI) was the outcome measure. The psychotherapy was not manualized and the treatment took place under real-life conditions in an outpatient psychiatric clinic. Results: Intention-to-treat analyses indicated that all the treatments were associated with significant reductions in the BDI scores (mean reduction of 18.88 BDI points). Furthermore, LTPP and combination therapy were more effective in reducing BDI scores than fluoxetine alone (22.08 and 22.04 vs. 12.53 BDI points). Conclusions: LTPP, pharmacological treatment with fluoxetine and their combination are effective in reducing symptoms of patients with moderate depression. LTPP and combined treatment were more effective compared to fluoxetine alone. These findings have implications for patients with depression who may benefit from long-term psychotherapy or combined treatment, or for depressed patients who do not wish to take medications such as fluoxetine.     

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.     

General self-efficacy as a driving factor of post-stroke depression: A longitudinal study

ABSTRACT

Post-stroke depression (PSD) is the most common psychiatric condition after stroke, affecting one third of survivors. Despite identification of meaningful predictors, knowledge about the interplay between these factors remains fragmentary. General self-efficacy (GSE) is closely linked to PSD, yet direction and magnitude of this relationship remains unclear. The authors assessed the relationship between GSE and depression during the first two years post-stroke while controlling for stable inter-individual differences using continuous time (CT) structural equation modelling (SEM). Patients of two German rehabilitation centres (N?=?294, mean age?=?63.78 years, SD?=?10.83) were assessed six weeks after ischemic stroke and at four follow-ups covering two years. GSE Scale and Geriatric Depression Scale (GDS) were used to assess GSE and depression. CT-analysis revealed significantly higher within-person cross-effects of GSE on GDS (a₂₁?=??.29) than vice versa (a_12?=??.17). Maximal cross-lagged effects emerged six months post-stroke. Our results show that decreasing GSE led to increasing depressiveness, and only to a smaller extent vice versa. This suggests that fostering GSE by strengthening perceived control after stroke can counter PSD emersion and exacerbation. Six months post-stroke, when patients face social re-integration, programmes focusing on GSE could potentially help to prevent later PSD.     

A Double-Blind Study of Paroxetine, Fluoxetine, and Placebo an Outpatients with Major Depression

We report results from a multicenter, placebo-controlled, randomized, double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 ± 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles.     

Double-blind randomized parallel-group clinical trial of efficacy of the combination fluoxetine plus modafinil versus fluoxetine plus placebo in the treatment of major depression

Background: There is growing interest in the identification of novel therapeutic agents for the treatment of affective disorders, with modafinil being one promising substance. The purpose of the present investigation was to compare the efficacy of a combination of fluoxetine plus modafinil with that of fluoxetine plus placebo in the treatment of major depression in a 6‐week double blind and placebo‐controlled trial. Methods: Forty‐six adult outpatients who met the DSM‐IV‐TR criteria for major depression participated in the trial. Patients had a baseline Hamilton Rating Scale for depression score of at least 18. Patients were allocated in a random fashion, 23 to fluoxetine 40 mg/day plus modafinil 400 mg/day (200 mg bid) (morning and evening) and 23 to fluoxetine 40 mg/day plus placebo. Patients were assessed at baseline and after 1, 2, 4, and 6 weeks after start of medication. Results: Forty‐four patients completed the trial. Fluoxetine+modafinil and fluoxetine+placebo significantly decreased the Hamilton Rating Scale score for Depression over the trial period. However, the combination of fluoxetine and modafinil was significantly superior over fluoxetine alone in the treatment of symptoms of major depression. The difference between the two treatments was significant as indicated by the effect of group, the between‐subjects factor ( df = 1, F = 4.42, P = 0.046). There were no significant differences in the two groups in terms of observed side‐effects. Conclusion: These findings suggest modafinil as a well‐tolerated and potentially effective agent in combination with fluoxetine in the management of patients with major depression. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects

OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.     

心理干预对脑卒中后抑郁治疗效果的观察

目的观察心理干预对脑卒中后抑郁的治疗效果。方法从2013年4月到2014年1月,选取我院的96例脑卒中后抑郁患者进行回顾性分析。将其分为两组:对照组44例患者,采用早期康复和脑卒中常规药物治疗;观察组52例患者,在对照组基础上采用心理干预治疗。结果治疗前两组HAMD评分差异无统计学意义(P0.05)。治疗8周后,两组的HAMD评分较治疗前均有降低,差异均有统计学意义(P0.05)。但观察组降低更明显,治疗后HAMD评分两组间比较,差异有统计学意义(P0.05)。观察组痊愈占比61.54%(32/52),有效率为98.08(51/52),均显著高于对照组的38.64%(17/44)和79.55%(35/44),差异均有统计学意义(P0.05)。两组患者完全依从和总依从在治疗前差异无统计学意义(P0.05),治疗8周后,两组患者完全依从和总依均较治疗前提高,差异有统计学意义(P0.05),观察组较对照组提高更显著,差异有统计学意义(P0.05)。结论对脑卒中后抑郁患者,在早期康复和常规药物治疗的同时采用心理干预治疗,不但可以改善抑郁症状,而且可以提高患者康复依从性,促进脑卒中后神经功能的恢复,值得临床进一步推广。     

脑卒中合并抑郁治疗前后对比分析

目的　观察、分析脑卒中后抑郁症状的干预对患者康复的影响。方法　脑卒中合并抑郁患者 33例 ,常规脑血管病治疗同时予抗抑郁药物治疗或心理疏导 ,于治疗第 1、2、4、6周末分别进行HAMD抑郁量表评分和神经功能缺损、生活能力状态评定。结果　于 6周末HAMD评分明显降低 (P <0 0 1) ,神经功能缺损和生活能力状态评定明显减低 (P <0 0 1) ,神经功能缺损评定与HAMD评分减低有相关性 (r=0 4 4 5 ,P <0 0 1)。结论　对脑卒中后抑郁症状的干预治疗 ,不但能有效改善抑郁症状 ,而且有利于患者神经功能缺损的康复和生活能力的提高。     

Foreløbige erfaringer med lobotomia frontalis

Objective: To study the correlation of personality traits measured by the Temperament and Character Inventory (TCI) with the prognosis of major depressive disorder in patients treated with either fluoxetine or short-term psychodynamic psychotherapy in a randomized comparative study. Method: 35 patients with DSM IV-defined major depressive disorder of mild or moderate severity were randomized to receive either short-term psychodynamic psychotherapy or fluoxetine treatment for 16 weeks. Prior to beginning of the therapy, patients were assessed with TCI. The Hamilton Depression Rating Scale (HDRS) was used as the outcome measure completed at the baseline and follow-up at 4 months. Results: In the combined group (n=35), Harm Avoidance was associated with the severity of the depression measured by the HDRS at the baseline (P=0.01) and baseline Self-Directedness with the HDRS at 4 months follow-up (P=0.03). In the fluoxetine treatment group, Reward Dependence (P=0.03), Self-Directedness (P=0.01) and Cooperativeness (P=0.02) at the baseline associated with HDRS at 4 months follow-up. No statistically significant associations between personality traits and depression scores at the follow-up were found in the patients treated with psychotherapy. Conclusion: In this whole cohort of depressive patients, baseline high Self-Directedness predicted higher depression scores after 4 months of treatment. In the fluoxetine treatment group, subjects with high baseline Reward Dependence, Self-Directedness or Cooperativeness were likely more severely depressed at the 4 months follow-up. We suggest that associations between personality traits and remaining depressive symptoms after 4 months treatment with fluoxetine could be caused by the potential differences in the placebo effect.     

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。     

Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial

Background: The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses. Cyclooxygenase‐2 inhibitors such as celecoxib reduce the production of pro‐inflammatory cytokines. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six‐week double blind and placebo controlled trial. Methods: Forty adult outpatients who met the DSM‐IV‐TR criteria for major depression participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. Patients were allocated in a random fashion: 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 20 to fluoxetine 40 mg/day plus placebo. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4, and 6 weeks after the medication started. Results: Although both protocols significantly decreased the score of Hamilton Rating Scale for Depression over the trial period, the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression. There were no significant differences in the two groups in terms of observed side effects. Conclusion: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti‐inflammatory therapies should be further investigated. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release (XR) and fluoxetine in outpatients with major depression and concomitant anxiety. METHOD: Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were randomly assigned to once-daily venlafaxine XR, fluoxetine, or placebo for 12 weeks. Efficacy was assessed with the Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scale. RESULTS: Among 359 outpatients, venlafaxine XR and fluoxetine were significantly superior (p < .05) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study. Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item. At week 12, the HAM-D response rate was 43% on placebo, 67% on venlafaxine XR, and 62% on fluoxetine (p < .05). The HAM-D remission rate was significantly higher (p < .05) at weeks 3, 4, 6, 8, 12, and final evaluation with venlafaxine XR and at weeks 8, 12, and final evaluation with fluoxetine than with placebo. The HAM-A response rate was significantly higher (p < .05) with venlafaxine XR than with fluoxetine at week 12. The incidence of discontinuation for adverse events was 5% with placebo, 10% with venlafaxine XR, and 7% with fluoxetine. CONCLUSION: Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine.     

Preventing poststroke depression: a 12-week double-blind randomized treatment trial and 21-month follow-up

This study examined the effect of antidepressants in preventing depression after stroke. Nondepressed poststroke patients (N = 48) were randomly assigned to receive nortriptyline, fluoxetine, or placebo for 3 months by using double-blind methodology and were followed-up for 21 months by using a naturalistic design. During the treatment period, one minor depression developed in the nortriptyline group (n = 13 at 3 months), one minor depression developed in the fluoxetine group (n = 13), and five minor depressions developed in the placebo group (n = 15; p <.05). When treatment was discontinued, nortriptyline-treated patients were more likely to develop depression and had significantly more severe depressive symptoms during the next 6 months compared with patients in the other two groups. Both nortriptyline and fluoxetine appeared to be efficacious in preventing depression after stroke. However, nortriptyline produced an increased vulnerability to depression for more than 6 months after it was discontinued. This finding suggests the need to extend prophylactic treatment and monitor patients carefully after the discontinuation of nortriptyline.     

Placebo-controlled treatment trial of depression in elderly physically ill patients

Objectives. To determine the response of physically ill elderly depressed patients to treatment. Design. Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. Main outcome measure. Response rate as defined by the 17-item Hamilton Depression Rating Scale. Results. Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p=0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N=37) showed a significant improvement in mood if treated with fluoxetine (p=0.02). Conclusions. The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important. © 1997 John Wiley & Sons, Ltd.     

Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression

BACKGROUND: Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination. METHOD: In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records. RESULTS: Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.     

养血清脑颗粒联合盐酸氟西汀治疗卒中后抑郁的临床研究

目的：观察养血清脑颗粒联合盐酸氟西汀治疗卒中后抑郁的疗效。方法：68例卒中后抑郁患者随机分组后分别接受养血清脑颗粒＋盐酸氟西汀联合治疗（治疗组）和单纯盐酸氟西汀治疗（对照组），疗程为8周；采用汉密尔顿抑郁量表（HAMD）进行评定。结果：在治疗8周后，治疗组的显效率（48．7％对47．1％）和总有效率（79．4％对76．5％）与对照组相比均无显著差异，HAMD总评分和各项目评分也无显著差异。两组之间的睡眠障碍项目评分在第2周时有显著差异（P〈0．05），焦虑-抑郁情绪和躯体症状2个项目评分在第2周和第4周均有显著差异（P〈0．05）。结论：养血清脑颗粒联合盐酸氟西汀治疗可改善卒中后抑郁的某些症状，优于单用盐酸氟西汀。     

Post-stroke Fatigue is an Independent Predictor of Post-stroke Disability and Burden of Care: A Path analysis Study

Post-stroke fatigue (PSF) is a common and one of the most distressing symptoms in stroke survivors. However, little is known about the relationship between severity of fatigue and the overall impact it has on post-stroke disability and burden of care. We aimed to examine the role of PSF in post-stroke disability and burden of care among stroke survivors after their first-ever stroke.

Methods: We prospectively recruited 163 subjects (35 females) from patients examined consecutively in a tertiary stroke care center in India, after their first-ever ischemic or hemorrhagic stroke (>3 months after event). In addition to demographic and clinical characteristics, the following assessments were done – SF-36 vitality domain (fatigue), Modified Rankin Scale (functional recovery), Hospital anxiety and depression scale (depression), Functional independence measure (disability and burden of care). We used path analysis to identify a model that will capture the interactions of fatigue, depression, and degree of functional recovery in stroke survivors.

Results: The severity of PSF positively correlated with the severity of disability and PSF had significant contribution to disability over and above functional recovery and depression, with all three factors accounting for 43% of the variance. Among the four models that were proposed to explore these relationships, the best fitting model showed that the effect of PSF is mediated through both the direct effect of fatigue on disability and through its interaction with depression, which remained a separate contributor to post-stroke disability and burden of care.

Conclusions: PSF, therefore, is an important determinant of post-stroke disability and should be evaluated for successful post-stroke rehabilitation.