A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder.

OBJECTIVE: To compare the efficacy of clomipramine hydrochloride (CMI), a serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD). METHOD: Following a 2-week, single-blind placebo washout phase, 17 PD outpatients completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key outcome measures included panic attacks frequency, the NIMH Global Scales for Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger State Anxiety Scale. RESULTS: Both CMI and DMI led to significant improvement from baseline placebo state in panic attacks frequency and behavioral ratings (p<0.001). CMI led to a greater reduction in the frequency of panic attacks (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety, Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No difference was found between the drugs on the NIMH Global Impairment Scale and the Hamilton Somatic and Psychic Scales. CONCLUSION: Both drugs appeared to have significant therapeutic effects in patients with PD, but CMI appeared to be more effective. The effectiveness of the serotonergic drug suggests that the role of the serotonergic system in the pathogenesis of PD should be further explored.     

Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.     

Effect of serotonin uptake inhibitors in anxiety disorders; a double-blind comparison of clomipramine and fluvoxamine

A double-blind comparative study of clomipramine and fluvoxamine was performed in 50 patients suffering from anxiety disorders (DSM-III). Patients were treated for 6 weeks with either 150 mg of clomipramine or 100 mg of fluvoxamine. The results show that both drugs at the dosages used are equipotent in reducing anxiety symptoms as assessed with the Hamilton Anxiety Scale and the Spielberger State-Trait Anxiety Inventory. Clomipramine differed from fluvoxamine in its efficacy with respect to associated depressive symptomatology in that it had a more pronounced effect on the Self Rating Depression Scale. The results support the hypothesis that brain serotonergic pathways are implicated in the pathophysiology of anxiety disorders, particularly in agoraphobia and panic disorders.     

The effect of citalopram treatment on platelet serotonin function in panic disorders

We investigated the effect of the selective serotonin reuptake inhibitor (SSRI) citalopram after 6-8 weeks and 6 months of treatment on clinical and peripheral indexes for central serotonergic function: platelet [14C]serotonin uptake and [3H]paroxetine- and [3H]LSD-binding to platelets membranes in 33 patients with panic disorder. Basal data from patients were compared with data from a control material consisting of 33 healthy volunteers. Bmax for platelet [3H]paroxetine binding was significantly lower in patients than in controls. There were no differences in serotonin uptake or [3H]LSD-binding between patients and controls. The degree of anxiety and depression was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory self-assessment scales, and the Clinical Anxiety Scale and the Montgomery Asberg Depression Rating Scale for clinical evaluation. Complete remission was found in one third of the patients after 6-8 weeks and in two-thirds after 6 months of treatment. The reduction in assessment scores was parallelled with similar reductions in platelet 5-HT2-receptor density, [3H]LSD affinity variable (Kd) and Vmax for platelet [14C]5-HT uptake. Citalopram treatment did not alter Bmax and Kd for platelet [3H]paroxetine-binding. A positive correlation was found between Vmax for the platelet [14C]5-HT uptake and BAI after 6 months citalopram treatment. The present study shows that citalopram has a therapeutic effect in panic disorders. A prerequisite of responding to treatment might be plasticity in the serotonergic system.     

血清脑源性神经营养因子对帕罗西汀治疗惊恐障碍效果的影响

目的:探讨脑源性神经营养因子(BDNF)在帕罗西汀治疗惊恐障碍中的可能作用。方法:接受帕罗西汀治疗12周的惊恐障碍患者45例(治疗组),按治疗前后汉密尔顿焦虑量表(HAMA)减分率分为有效组(≥50%,29例)和无效组(<50%,16例)。采用惊恐相关症状量表(PASS)、17项汉密尔顿抑郁量表(HAMD)、HAMA、临床总体印象量表(CGI)评定疾病严重程度和改善程度;采用酶联免疫吸附法测定其血清BDNF浓度,并与30名正常对照者(对照组)比较;对治疗组的血清BDNF浓度与各相关因素进行Spearman相关分析。结果:有效组BDNF水平高于无效组和正常对照组(P<0.05),无效组的BDNF水平则低于正常对照组(P<0.05);治疗组血清BDNF水平治疗后的PASS分值(r=-0.540,P=0.000)和HAMA分值(r=-0.491,P=0.001)呈负相关,与治疗前后HAMA评分差值(r=0.425,P=0.004)和PASS评分差值(r=0.522,P=0.000)呈正相关。结论:外周循环中BDNF水平减少在惊恐障碍的病理生理机制中起着重要的作用,可能是帕罗西汀疗效的预测因素。     

Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial

The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.     

Effect of citalopram treatment on relationship between platelet serotonin functions and the Karolinska scales of personality in panic patients

Using the Karolinska Scales of Personality (KSP), we investigated the effect of the selective serotonin reuptake inhibitor citalopram on personality traits and the relationship between personality traits and peripheral indexes for central serotonergic function in patients with panic disorder at baseline and after 6 months of treatment. The degree of anxiety and depression was assessed using the Beck Anxiety Inventory, the Beck Depression Inventory, the Clinical Anxiety Scale, and the Montgomery Asberg Depression Rating Scale. A reduction in anxiety and depression scores of 75% was observed after treatment in two thirds of the patients. Mean changes of 12% in the direction of normalization were observed in all KSP anxiety-related items (Somatic Anxiety, Muscular Tension, Psychic Anxiety, and Psychasthenia), the aggression and hostility related items (Inhibition of Aggression, Irritability, and Guilt) and the item of Socialisation. A positive correlation was found between Vmax for the platelet [14C]-serotonin uptake and Inhibition of Aggression before treatment, and a negative correlation was found between the affinity of serotonin uptake and Inhibition of Aggression after treatment. Negative childhood experiences influenced enhanced scores on some KSP items but not the serotonergic function. In panic patients treated with citalopram, effects were seen on personality traits, confirming an association between serotonergic activity and aggression.     

Imipramine and buspirone in patients with panic disorder who are discontinuing long-term benzodiazepine therapy

Pretreatment with imipramine, buspirone, or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use. The average duration of benzodiazepine use was 75 +/- 64 months, and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 +/- 19 mg/d. We hypothesized that pretreatment with either imipramine or buspirone, in contrast to pretreatment with placebo, would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines, thus making the taper process easier to complete. All 3 treatments (imipramine, buspirone, and placebo) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups.     

Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system.

There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the development of IFN-alpha-induced depressive symptoms.     

Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks

Data from animal studies suggest a functional relationship between the cholecystokinin-ergic (CCK) and the serotonergic (5-HT) system. There is increasing evidence that the cholecystokinin-4 (CCK₄) challenge test could be a valid experimental model for panic attacks in man. The aim of the present study is twofold; 1) to validate this model further and 2) to shed more light on the putative CCK\5-HT interaction. To this end, we studied the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on CCK₄-induced panic attacks. Twenty-six panic disorder (PD) patients received, before and after a double blind 8-week treatment period with fluvoxamine (n = 17) or placebo (n = 9), a single blind bolus injection with 50 μg CCK₄. Treatment with fluvoxamine (150 mg daily) significantly decreased the sensitivity of PD patients for CCK₄ while placebo was without effect. Of the patients who responded to treatment, 83% no longer experienced a panic attack when rechallenged with CCK₄, whereas in the non-responders group this was only 28%. In the fluvoxamine group the treatment response evaluated by the Hamilton Anxiety Scale (HAS) showed a statistically significant treatment effect. The results of this study strengthen the validity of the CCK₄ test as an experimental human model for panic attacks and yield evidence supporting the hypothesis that both CCK and serotonin are implicated in the regulation of anxiety. Received: 15 April 1996/Final version: 27 September 1996     

The efficacy of divalproex sodium in the treatment of agitation associated with major depression

BACKGROUND: Agitation is both a feature of major depression and a common side effect of antidepressant treatment. Depressive agitation correlates with overall severity of illness and suicide risk, whereas treatment-emergent agitation may contribute to early discontinuation of pharmacotherapy. Thus, agitation merits investigation as a treatment target in clinical depression. METHODS: In this study, adults with major depression were evaluated for change in agitation and other mood symptoms during adjunctive treatment with divalproex sodium. Twelve patients on antidepressants, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, were given low doses of divalproex sodium and evaluated repeatedly for symptoms of depression, anxiety, and agitation. Agitation severity was evaluated using the Overt Agitation Severity Scale and the Stanford Scale for Agitation Symptoms. Mood symptoms were assessed with the Hamilton Anxiety and the Hamilton Depression Rating Scales. RESULTS: Nine of 12 patients completed 4 weeks of treatment. All agitation scores decreased sharply, whereas depression (Hamilton Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale) symptoms decreased only modestly. Decreased agitation was not merely a function of decreases on the Hamilton Depression or Hamilton Anxiety Rating Scales. Relatively low doses of divalproex sodium appear to be useful in the treatment of agitation associated with major depression. CONCLUSIONS: The observation that decreases in agitation were not simply an artifact of overall change in depressive or anxiety symptoms is in keeping with the previous clinical impression that divalproex sodium has a specific effect on depressive agitation. Controlled clinical trials are needed to fully evaluate the utility and symptom specificity of divalproex sodium in depression.     

Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement.

We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.     

Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study

The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy.Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively.Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores.In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.     

Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks

Fifty-five patients completed a 5-week double-blind study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. There was no concomitant behavioral treatment. Patient and therapist rating scales included Sheehan's Panic and Anxiety Attack Scales, the Marks-Sheehan Phobia Scale, the Hamilton Anxiety Scale, the Hamilton Depression Scale, and the Side Effects Checklist. The results generally support the efficacy of alprazolam, but not propranolol, in the treatment of panic disorder and agoraphobia with panic attacks. The significance of the results are discussed, as well as a number of the unique aspects of our procedures and patient population.     

Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D2 antagonists) and mianserin, a potent 5-HT2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.     

溃疡性结肠炎患者焦虑抑郁状况分析

目的探讨溃疡性结肠炎（UC）患者焦虑、抑郁情况。方法采用汉密顿抑郁量表和汉密顿焦虑量表调查UC患者42例,并与肠易激综合征（IBS）患者20例及正常对照组10例进行比较,观察3组焦虑、抑郁发生情况。结果 3组均有焦虑、抑郁患者。UC组和IBS组汉密顿抑郁评分和汉密顿焦虑评分均高于正常对照组,差异有统计学意义（P〈0.05）,而UC组与IBS比较差异无统计学意义（P〉0.05）。结论 UC患者存在明显的焦虑、抑郁情绪,存在不良的心理状况。     

Clinical efficacy of agomelatine in depression: the evidence

Despite the advances of recent decades, there is still an urgent need for antidepressants with improved efficacy, safety and tolerability. Agomelatine is a new antidepressant with an innovative pharmacological profile. It is the first melatonergic antidepressant, and is a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. The efficacy of 25 mg/day agomelatine in treating major depressive disorder (MDD) has been demonstrated in a number of placebo-controlled studies. Evidence of improvement in depressive symptoms was observed in a dose-ranging study in which 25 mg/day agomelatine was significantly better than placebo, whatever the rating scale used (Hamilton Rating Scale for Depression, Clinical Global Impression, and Montgomery-Asberg Depression Rating Scale). These results have been confirmed in two similarly designed placebo-controlled studies. Agomelatine also produces a significant improvement in anxiety compared to placebo, according to Hamilton Rating Scale for Anxiety scores. The efficacy of agomelatine has been studied in subpopulations with more severe depression, demonstrating its efficacy in these difficult-to-treat patients. In view of the available data on agomelatine, this antidepressant can be regarded as an innovative treatment for MDD patients, offering a new approach in the management of depressed patients.     

A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder

Vilazodone, a selective serotonin (5-HT) reuptake inhibitor and 5-HT(1A) receptor partial agonist, was efficacious in two 8-week placebo-controlled studies in adults with major depressive disorder. This open-label, multicenter study assessed the long-term safety of vilazodone. Adult patients with a 17-item Hamilton Rating Scale for Depression score of 18 or greater received vilazodone according to a fixed-titration schedule to reach a dose of 40 mg/d continued up to 1 year. Safety assessments included adverse events (AEs), physical examinations, clinical chemistry, electrocardiograms, and the Changes in Sexual Functioning Questionnaire. Effectiveness was assessed with the Montgomery-?sberg Depression Rating Scale and Clinical Global Impressions scales. The safety population comprised 599 patients; 254 patients completed 1 year of treatment. The most frequent AEs were diarrhea (35.7%), nausea (31.6%), and headache (20.0%); greater than 90% of these AEs were mild or moderate. Adverse events resulting in discontinuation in more than 1% of patients were nausea (1.3%) and diarrhea (1.2%). There were no clinically important changes in physical examinations, electrocardiograms, or clinical chemistries. Mean weight increased by 1.7 kg (observed cases). Changes in Sexual Functioning Questionnaire mean scores (observed cases) improved throughout treatment for both males and females. Montgomery-?sberg Depression Rating Scale mean scores were 29.9 at baseline, 11.4 at week 8, and 7.1 at week 52 (observed cases). Vilazodone 40 mg/d for 1 year was safe and well tolerated by adults with major depressive disorder.     

Determination of the dose of agomelatine,a melatoninergic agonist and selective 5-HT(2C) antagonist,in the treatment of major depressive disorder: a placebo-controlled dose range study

Agomelatine (S 20098) has a unique and new pharmacological profile. It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder (DSM-IV criteria). The methodology used was a conventional double-blind design comparing three different doses of agomelatine (1, 5 and 25 mg once a day) with placebo over an 8-week treatment period. Paroxetine was used as the study validator. Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were included. On the pivotal analysis, the mean final HAM-D total score (Full Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more effective than placebo. This was confirmed by other analyses and criteria (responders, remission, subpopulation of severely depressed patients, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness). Agomelatine 25 mg alleviated the anxiety associated with depression, as measured on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to validate the study methodology and population. Agomelatine, whatever the dose, showed good acceptability with a side-effects profile close to that of placebo. In conclusion, this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.     

低剂量奥氮平治疗老年慢性失眠症的临床观察

目的:探讨对老年慢性失眠症的有效治疗方法.方法:用随机对照方法,将120例老年慢性失眠症患者按随机数字表法分为奥氮平组和阿普唑仑组,治疗4周.采用匹兹堡睡眠质量指数(pittsburgh sleep quality index,PSQI)及药物不良反应量表评定临床疗效和不良反应.结果:奥氮平组在治疗第四周时PSQI总分、汉密顿焦虑量表(Hamilton anxiety scale,HAMA)、汉密顿抑郁量表(Hamilton depression raling scale,HAMD)、临床显效率分别为(5.2±1.8)分、(11.5±5.4)分、(5.1±2.3)分、91.7％,明显优于阿普唑仑组(6.8±2.5)分、(17.5±7.8)分、(9.9±5.8)分、68.3％,差异具有显著性(P＜0.05).结论:低剂量奥氮平不仅能显著改善慢性失眠症患者的睡眠状况,而且可以明显减少患者日常功能的缺失.