SSRIs治疗强迫症对照分析

目的：比较５羟色胺回收抑制剂（ＳＳＲＩｓ）与氯丙咪嗪对强迫症的临床疗效及副反应。方法：对３５例强迫症患者应用ＳＳＲＩｓ（１８例）与氯丙咪嗪（１７例）进行对照分析。采用Ｙａｌｅ－Ｂｒｏｗｎ强迫量表（Ｙ－ＢＯＣＳ）、汉密尔顿抑郁量表（ＨＡＭＤ）、副反应量表（ＴＥＳＳ）和临床疗效评定标准评定疗效及副反应。结果：ＳＳＲＩｓ与氯丙咪嗪疗效相似,两组显效率和有效率无显著差异。ＳＳＲＩｓ组副反应较氯丙咪嗪组少且     

Clinical predictors of response to pharmacotherapy with selective serotonin reuptake inhibitors in obsessive-compulsive disorder

The objective of this study was to investigate the clinical predictors of response to treatment with selective serotonin reuptake inhibitors (SSRI) in a sample of patients with obsessive-compulsive disorder (OCD). A total of 55 patients diagnosed as OCD according to revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders criteria underwent a 12-week standardized SSRI treatment. According to 'treatment response', defined as at least a 35% drop in the Yale-Brown Obsessive-Compulsive Scale total score, OCD patients were divided into two groups. A total of 32 (58.2%) patients who responded to treatment and 23 (41.8%) who did not, were compared in terms of sociodemographic and clinical characteristics. The authors' findings demonstrated that the severity of obsession-compulsions and disability in work, social and family lives at the beginning of treatment were significantly higher in OCD patients who did not respond to treatment in comparison to those who did. Linear regression analysis, however, revealed that Sheehan Disability Scale-work score at baseline was a predictor of response to SSRI treatment. The higher levels of disability at the beginning of treatment in patients with OCD are associated with a poorer response to SSRI.     

Bursts and the efficacy of selective serotonin reuptake inhibitors

We present a new hypothesis for the efficacy of selective serotonin reuptake inhibitors (SSRIs). We propose that SSRIs bring the response to the phasic firing of raphe nucleus cells back to normal, even though the average extracellular 5HT concentration remains low. We discuss burst firing in the raphe nuclei and use mathematical models to argue that tonic firing and phasic firing may be decoupled and may come from different mechanisms. We use a mathematical model for serotonin synthesis, release, and reuptake in terminals to illustrate the responses in terminal regions to bursts in a normal individual and in an individual with low vesicular serotonin. We then show that acute doses of SSRIs do not bring the response to bursts back to normal, but that chronic doses do return the response to normal. These model results need to be confirmed by new electrophysiological and pharmacological experiments.     

Neurological soft signs as predictors of treatment response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.     

Serotonin-norepinephrine reuptake inhibitors in the treatment of obsessive-compulsive disorder: A critical review

OBJECTIVE: To critically review the antiobsessional properties of serotonin-norepinephrine reuptake inhibitors (SNRIs) (venlafaxine and clomipramine) in the treatment of obsessive-compulsive disorder (OCD) as an alternative to selective serotonin reuptake inhibitors (SSRIs), which are currently considered the first-line treatment of OCD. DATA SOURCES: A MEDLINE search was performed to identify clinical trials with the SNRIs venlafaxine and clomipramine published from 1996 to 2004 (keywords: SNRIs, venlafaxine, duloxetine, and clomipramine, each matched individually with the term OCD), focusing on the best-designed studies for inclusion. DATA SYNTHESIS: Much of the literature about SNRIs in OCD supports the efficacy of these compounds in the treatment of OCD. However, double-blind, placebo-controlled studies with venlafaxine are lacking, and the most relevant studies consist of active comparison trials between SNRIs and SSRIs. In these studies, SNRIs seem to be as effective as SSRIs in OCD; SNRIs might be preferred for patients with certain types of treatment-resistant OCD or those with particular comorbid conditions. A large number of placebo-controlled and active comparison trials with clomipramine document efficacy in OCD, and meta-analytic studies suggest a small superiority over SSRIs. Compared with clomipramine, the SNRI venlafaxine showed fewer side effects and better tolerability. CONCLUSION: The SNRIs may represent a valid alternative to the SSRIs, particularly in specific cases. Double-blind, placebo-controlled studies are, however, needed to confirm the positive findings reported by several studies with venlafaxine.     

Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: a practical clinical trial

Clinical effectiveness of group cognitive-behavioral therapy (GCBT) versus fluoxetine in obsessive-compulsive disorder outpatients that could present additional psychiatric comorbidities was assessed. Patients (18-65 years; baseline Yale-Brown Obsessive-Compulsive-Scale [Y-BOCS] scores ≥ 16; potentially presenting additional psychiatric comorbidities) were sequentially allocated for treatment with GCBT (n=70) or fluoxetine (n=88). Mean Y-BOCS scores decreased by 23.13% in the GCBT and 21.54% in the SSRI groups (p=0.875). Patients presented a mean of 2.7 psychiatric comorbidities, and 81.4% showed at least one additional disorder. A reduction of at least 35% in baseline Y-BOCS scores and CGI ratings of 1 (much better) or 2 (better) was achieved by 33.3% of GCBT patients and 27.7% in the SSRI group (p=0.463). The Y-BOCS reduction was significantly lower in patients with one or more psychiatric comorbidities (21.15%, and 18.73%, respectively) than in those with pure OCD (34.62%; p=0.034). Being male, having comorbidity of Major Depression, Social Phobia, or Dysthymia predicted a worse response to both treatments. Response rates to both treatments were similar and lower than reported in the literature, probably due to the broad inclusion criteria and the resulting sample more similar to the real world population.     

Olanzapine addition in obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors: an open-label case series.

BACKGROUND: Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder, a significant number of patients show no or only partial remission of symptoms. Some evidence exists to suggest that risperidone augmentation can be helpful in treating this refractory group. The efficacy of other atypical antipsychotic agents, such as olanzapine, in augmenting SSRIs in refractory obsessive-compulsive patients has yet to be systematically investigated. METHOD: A series of 10 patients with DSM-IV obsessive-compulsive disorder showing significant residual symptoms following an adequate SSRI trial (12 weeks) were given open-label olanzapine augmentation for a minimum of an additional 8 weeks. Treatment response was assessed using the Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impressions scale. RESULTS: Nine of the 10 patients in this series treated with olanzapine and an SSRI completed the 8-week augmentation trial. Of these, 4 demonstrated a complete remission or major improvement in obsessive-compulsive symptoms, 3 had partial remission, and 2 experienced no benefit. Nine patients experienced minimal adverse effects, primarily sedation, which did not interfere with continuing treatment. One patient discontinued olanzapine owing to excessive sedation. CONCLUSION: The results of this preliminary, open-label trial suggest that olanzapine may be effective in augmenting ongoing SSRI treatment for a portion of patients with obsessive-compulsive disorder refractory to SSRI treatment. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of olanzapine augmentation of SSRI treatment in SSRI-refractory obsessive-compulsive disorder.     

Triiodothyronine augmentation of selective serotonin reuptake inhibitors in posttraumatic stress disorder

BACKGROUND: There is considerable comorbidity of major depression and posttraumatic stress disorder (PTSD), and antidepressants have been reported to be effective in treating PTSD. Addition of triiodothyronine (T3) to ongoing antidepressant treatment is considered an effective augmentation strategy in refractory depression. We report the effect of T3 augmentation of antidepressants in patients with PTSD. METHOD: T3 (25 microg/day) was added to treatment with a selective serotonin reuptake inhibitor (SSRI) (paroxetine or fluoxetine, 20 mg/day for at least 4 weeks and 40 mg/day for a further 4 weeks) of 5 patients who fulfilled DSM-IV criteria for PTSD but not for major depressive disorder (although all patients had significant depressive symptoms). The Clinician-Administered PTSD Scale, the 21-item Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Severity of Illness scale were administered every 2 weeks, and self-assessments were performed with a 100 mm visual analog mood scale. RESULTS: In 4 of the 5 patients, partial clinical improvement was observed with SSRI treatment at a daily dose of 20 mg with little further improvement when the dose was raised to 40 mg/day. This improvement was substantially enhanced by the addition of T3. Improvement was most striking on the Hamilton Rating Scale for Depression. CONCLUSION: T3 augmentation of SSRI treatment may be of therapeutic benefit in patients with PTSD, particularly those with depressive symptoms. Larger samples and controlled studies are needed in order to confirm this observation.     

Effects of selective serotonin reuptake inhibitors on thought-action fusion, metacognitions, and thought suppression in obsessive-compulsive disorder

Objective

We aimed to assess whether cognitive processes change over time in patients with obsessive-compulsive disorder (OCD) receiving selective serotonin reuptake inhibitors without cognitive behavioral therapy and to investigate the factors associated with probable cognitive changes.

Methods

During the 16 weeks of the study, 55 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for OCD received open-label treatment with sertraline (100-200 mg/d) or fluoxetine (40-80 mg/d) and were assessed using the Yale-Brown Obsessive-Compulsive Scale, Beck Depression Inventory (BDI), Thought-Action Fusion Scale (TAFS), Metacognitions Questionnaire (MCQ-30), and White Bear Suppression Inventory (WBSI).

Results

The Yale-Brown Obsessive-Compulsive Scale (P < .001), BDI (P < .001), TAFS morality (P < .005), MCQ-30 (P < .01), and WBSI (P < .005) scores at follow-up were significantly lower than baseline scores. When we excluded OCD patients with depressive disorder (n = 12), statistical significance in paired comparisons for MCQ and WBSI disappeared. Similarly, when OCD patients with religious obsessions (n = 16) were excluded, paired comparisons for MCQ and TAF morality were not statistically significant. Changes in BDI, TAFS morality, MCQ-30, and WBSI (P < .005) were significantly correlated with changes in severity of obsessions, but not that of compulsions. After controlling for the change in depression severity, significant correlations between changes in obsessive and cognitive scales did not continue to have statistical significance. The BDI changes (P < .05) significantly explained the changes in symptom severity in a linear regression model.

Conclusions

Our findings suggest that selective serotonin reuptake inhibitors can change appraisals of obsessive intrusions via their effects on negative emotions.     

Quetiapine augmentation in obsessive-compulsive disorder resistant to serotonin reuptake inhibitors: an open-label study

BACKGROUND: The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment. METHOD: In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score. RESULTS: Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events. CONCLUSION: The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.     

Hyponatraemia and selective serotonin reuptake inhibitors

Part 1 describes the case of a 74-year-old woman who experienced a worsening of her psychiatric condition shortly after commencing fluoxetine and was found to have a low serum sodium level. The clinical features of hyponatraemia and its causes are reviewed. Part 2 reviews the reports of hyponatraemia and the selective serotonin reuptake inhibitors (SSRIs) and considers the variation in reports between the different SSRIs. Measurement of a patient's electrolytes is recommended if there is a rapid decline in mental state having started on an SSRI.     

Use of the selective serotonin reuptake inhibitor citalopram in a possible animal analogue of obsessive-compulsive disorder

Canine acral lick dermatitis (ALD) has been suggested as an animal analogue of obsessive-compulsive disorder (OCD). A series of dogs with ALD or similar conditions were treated with citalopram, the most selective of the selective serotonin reuptake inhibitors. Six of nine (66.7%) dogs showed significant improvement. Given the apparent efficacy of citalopram in the treatment of OCD and related disorders, these data provide further evidence that ALD is a useful animal analogue of OCD. Depression and Anxiety 8:39–42, 1998. © 1998 Wiley-Liss, Inc.     

An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder.

OBJECTIVE: Serotonin selective reuptake inhibitors (SSRIs) are now considered the first-line pharmacotherapy for panic disorder. The preferential use and the presumption of greater tolerability of SSRIs relative to older agents, such as tricyclic antidepressants, occurred without direct comparisons between the two classes of medication. In this study the authors used an effect-size analysis to provide an initial comparison. METHOD: The authors conducted an effect-size analysis of 12 placebo-controlled, efficacy trials of SSRIs for panic disorder and compared these results to findings obtained in a recent meta-analysis of non-SSRI treatments for panic disorder. RESULTS: The mean effect size for acute treatment outcome for SSRIs relative to placebo was 0.55, not significantly different from that for antidepressants in general (0.55) and for imipramine in particular (0.48). More recent studies of SSRIs, and studies using larger samples, were associated with lower effect sizes. No significant differences were found in dropout rates between those taking SSRIs and those taking older agents during acute treatment. CONCLUSIONS: An effect-size analysis of controlled studies of treatments for panic disorder revealed no significant differences between SSRIs and older antidepressants in terms of efficacy or tolerability in short-term trials. An inverse relationship was evident between sample size and effect size for SSRIs. Early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder.     

Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder

BACKGROUND: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: 12 patients (mean +/- SD age = 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004. RESULTS: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants. CONCLUSIONS: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.     

Cerebrovascular effects of selective serotonin reuptake inhibitors: a systematic review

OBJECTIVES: An understanding of cerebro-vascular effects of selective serotonin reuptake inhibitors (SSRIs) is essential, since SSRIs are a widely used antidepressant, serotonin is a vasoactive and thrombostatic amine, and there is a bidirectional relationship between depression and cerebrovascular disease. DATA SOURCES: A MEDLINE search was performed to identify published reports over the period of 1966 through 2003, using the terms SSRIs and antidepressants matched with the terms platelets, coagulation, anticoagulation, bleeding, fibrinolysis, thrombosis, embolism, cerebral ischemia, stroke, cerebrovascular accident, acute and chronic cerebrovascular disease, intracranial hemorrhage, cerebrovascular disorder, and cerebral circulation. Adverse event reports collected from the World Health Organization (WHO), manufacturers, and the Physicians' Desk Reference (PDR) were also examined. DATA SYNTHESIS: Two case-control studies failed to show an association between SSRI use and intracranial hemorrhage, and of these, 1 showed no association with ischemic stroke. Sixteen studies of SSRI treatment in poststroke patients found no significant cerebrovascular adverse reactions. The WHO data have shown several hundred cases of SSRI-associated cerebrovascular disease, but definitive causal relationships remain undetermined. Four cases of vasoconstrictive stroke related to drug interactions between SSRIs and other serotonergic drugs have been reported. PDR and manufacturer reference sources categorized cerebrovascular reaction as an infrequent or rare adverse event related to SSRI use. CONCLUSIONS: Available evidence suggests that SSRI treatment has a very low rate of cerebrovascular adverse reaction. Pharmacovigilance is required in the use of SSRIs in high-risk populations for bleeding and vasoconstrictive stroke. More research is warranted to examine the variability of pharmacologic and genetic factors, depressive illness, and stroke on the antiplatelet and vasospastic effects of SSRIs and their significance to cerebrovascular protection or adverse reactions.     

The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review

Background: Selective serotonin reuptake inhibitors (SSRIs) show antidepressant properties in many patients with a diagnosis of depression. An understanding of the underlying mechanisms of the effect of SSRIs in healthy patients may lead to an understanding of the yet unclear pathophysiology of depression. Recent reviews of studies investigating the effect of SSRIs in healthy persons conclude that the results are inconsistent and that—in relation to a wide range of outcomes—the effect of SSRIs is limited; however, reasons for the inconsistencies are poorly studied. Aims and Methods: To investigate whether methodological artefacts can explain the diverging findings, we conducted a systematic review of all randomized multiple-dose, placebo-controlled trials on the effect of treatment by SSRI for at least a week in healthy persons published before January 2009. Results: We identified 33 trials, investigating six SSRIs and 163 outcome tests. The effect of SSRI showed divergence presumably related to methodological issues. Specifically, it is likely that the majority of studies included a mix of healthy persons with and without a family history of affective disorders. Few presented information on factors that may influence outcomes such as age, gender, family history of psychiatric disorder, drug levels and ethnicity. No study fulfilled principles of conducting and reporting randomized controlled trials, according to the CONSORT Statement guidelines. Conclusions: It is unclear whether the effect of SSRIs in healthy persons may lead to an understanding of the pathophysiology of depression, since the present evidence is divergent and may be severely influenced by a number of methodological drawbacks.     

Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine

To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).