Alprazolam in clinically anxious patients with depressed mood

A double-blind study compared alprazolam and placebo in 462 clinically anxious patients with accompanying depressed mood. Alprazolam was more effective than placebo as measured by the Hamilton Anxiety Rating Scale, the Self-Rating Symptom Scale, Target Symptoms, Physician's Global Impressions, and Patient's Global Impressions. Alprazolam was not significantly different from placebo in the number of patients reporting drowsiness, the most frequent side effect.     

拉莫三嗪与丙戊酸钠治疗双相抑郁的对照研究

目的评价拉莫三嗪治疗双相障碍抑郁发作的效果和安全性。方法对107例双相障碍抑郁发作患者采用随机、平行分组、对照的方法分别以拉莫三嗪和丙戊酸钠治疗,疗程8周,以汉密尔顿抑郁量表(HAMD)、临床疗效总评量表(CGI)在治疗前和治疗后第1、2、4、6、8周末评价疗效,同时采用治疗时出现的症状量表(TESS)进行安全性评估,在第1、2、4、6、8周末及需要时用Bech-Rafaelsen躁狂量表(BRMS)评定躁狂症状。结果拉莫三嗪组和丙戊酸钠组比较,两组有效率分别为75.5%和51.9%,治疗第6周和第8周末HAMD总分和减分率差异有统计学意义。治疗组不良反应明显较对照组发生率低。结论拉莫三嗪治疗双相障碍抑郁发作疗效优于丙戊酸钠,且前者不良反应较少,安全性高。     

Alprazolam compared to amitriptyline in the treatment of major depression

In a double-blind randomized study the therapeutic effect and safety of alprazolam was compared with amitriptyline in 81 outpatients suffering from major depression. Variable dosages of both drugs were used, the mean final dose of alprazolam being 3.05 and that of amitriptyline 130 mg. Both treatment groups improved steadily, assessed weekly with the use of the Hamilton Rating Scale for Depression, and no significant differences were found between the groups, either on comparison between single items or total scores. On several of the criteria used for assessment of treatment response, however, more patients responded to amitriptyline than to alprazolam. In an analysis of specific subgroups, patients whose depression was accompanied by retardation, those in whom there were no precipitating factors and those with low levels of anxiety, responded better to amitriptyline. Considerably fewer side effects were reported by patients receiving alprazolam. In particular, there was a significantly lower incidence of dry mouth, light-headedness, tremor and tachycardia in patients receiving alprazolam compared with amitriptyline.     

A comparison of the efficacy and safety of alprazolam and desipramine in depressed outpatients

Fifty-two adult depressed outpatients fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine. Twenty-nine patients completed the seven week (one week placebo followed by six weeks of active drug) study. The mean daily dose of alprazolam and desipramine at study termination was 3.34 mg and 192 mg respectively. Based on psychometric ratings of depression (Hamilton Scale) and severity of illness (Clinical Global Impressions) there was no significant difference between alprazolam and desipramine at the end of six weeks of active drug treatment. Both medications were well tolerated with drowsiness being the most common side effect of alprazolam, and insomnia, dry mouth, and constipation, the complaints most associated with desipramine.     

西酞普兰治疗抑郁症的疗效对照研究

目的 探讨选择性五羟色胺再摄取抑制剂西酞普兰治疗抑郁症的疗效及安全性.方法 将60例符合CCMD-3诊断标准的抑郁症病人随机分为两组,分别给予西酞普兰和阿米替林治疗.疗程6周.采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效,并以不良反应量表（TESS）评定不良反应.结果 西酞普兰组显效率为83.33%,阿米替林组为76.67%,差异无显著性.西酞普兰不良反应少而轻微,主要有恶心、口干、头痛.结论 西酞普兰是一见效快、疗效肯定及不良反应少而轻微的抗抑郁药.     

Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline.

The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group.     

Cognitive style, alprazolam plasma levels, and treatment response in panic disorder

This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment.     

A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients

Two hundred twenty-four outpatients with major depression entered a 6-week, five-center, double-blind trial of bupropion 300 mg/day and placebo. A total of 216 patients were included in the efficacy analysis. In the combined center analysis, greater efficacy for bupropion was found on one or more measures (Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions) at treatment Days 21, 28, 35, and 42. Bupropion was well tolerated; only four adverse events were reported at least 5% more often in the bupropion group than in the placebo group. Six bupropion patients versus 5 placebo patients discontinued treatment because of adverse events. This study extends earlier findings of efficacy for higher-dose treatment in an inpatient population to lower-dose treatment in an outpatient population.     

Alprazolam vs amitriptyline in depressions with reduced REM latencies

This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.     

Double-blind study of prochlorperazine, chlordiazepoxide and placebo in psychoneurotic outpatients with dominant symptoms of anxiety.

This was a double-blind study designed to compare 'Compazine', Librium and placebo in a psychoneurotic outpatient population with dominant symptoms of anxiety. The patient participants were accepted for the study when their pre-treatment symptoms of anxiety met a minimum or greater score on the Hamilton Anxiety Rating Scale. The study interval was 4 weeks. Patient psychopathology was rated by the treating physician on the Hamilton Anxiety Rating Scale, the New Physician Rating List and Global Evaluation. Patients completed the Self-Rating Symptom Scale and the Profile of Mood States. All efficacy criteria ranked the study medications in the same order. Prochloroperazine was most effective, chlordiazepoxide was also active and placebo was least effective. There are statistically significant active medication versus placebo comparisons supporting desirable drug action. Chlordiazepoxide versus placebo comparisons approached statistical significance for all efficacy criteria.     

西酞普兰与阿米替林治疗抑郁症的对照研究

目的　探讨选择性五羟色胺再摄取抑制剂西酞普兰治疗抑郁症的疗效及安全性。方法　将 6 0例符合CCMD 3诊断标准的抑郁症患者随机分为两组 ,分别给予西酞普兰和阿米替林治疗 ,共治疗 6周。采用汉密尔顿抑郁量表 (HAMD)、汉密尔顿焦虑量表 (HAMA)、临床总体评定量表 (CGI)评定临床疗效 ,采用副反应量表 (TESS)评定副反应。结果　西酞普兰组显效率 80 % ,阿米替林组显效率 76 .6 7% ,差异无显著性 ,各因子分中西酞普兰组认知障碍减分多于阿米替林组 ,差异有显著性。HAMA减分西酞普兰组少于阿米替林组 ,差异无显著性。西酞普兰常见副反应有恶心、口干、头痛等 ,但比较轻微。结论　西酞普兰见效快 ,疗效肯定 ,副反应发生率少而轻微。     

The comparative antidepressant value of lofepramine and amitriptyline. Results of a controlled trial with comments on the scales used.

A double-blind controlled trial comparing the antidepressant activity of amitriptyline with lofepramine is reported. Forty-six patients entered the 4-week trial. Analysis of the Hamilton Depression Rating Scale scores at the beginning and end of the trial showed no significant difference between the therapeutic efficacy of lofepramine and amitriptyline. However, patients with endogenous depression responded significantly more rapidly to lofepramine as measured by Visual Analogue Scales and showed a significantly greater degree of clinical improvement after 4 weeks' treatment, as measured by Global Assessment. Adverse effects were similar in the two treatment groups. The use of rating scales in trials of depressive illnesses is discussed. The Visual Analogue Scale for depression was found to be a simple, useful and valid measure.     

曲唑酮与文拉法辛治疗抑郁症的对照研究

目的　评价曲唑酮治疗抑郁症的临床疗效和副反应。方法　对 72例抑郁症患者随机分为曲唑酮组 (36例 )与文拉法辛组 (36例 )进行对照性研究 ,疗程 8周 ,采用汉密顿抑郁量表 (HAMD) ,汉密顿焦虑量表(HAMA)、临床总体印象量表 (CGI)及副反应量表 (TESS)评定疗效及副反应。结果　曲唑酮与文拉法辛的临床疗效相似 ,两组的显效率和有效率分别为 6 1%、78%与 6 1%、81% ,差异无显著性 (P >0 0 5 ) ,副反应两组间差异也无显著性 (P >0 0 5 )。结论　曲唑酮与文拉法辛相比 ,在治疗抑郁症方面 ,有相似的疗效和安全性     

Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial

Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.     

Amoxapine versus amitriptyline in endogenous depression. A double-blind study.

A new antidepressant, amoxapine, which is a dibenzoxazepine deprivative, was compared with amitriptyline in a randomised double-blind trial. Forty-eight patients were included and 41 completed a 4-week treatment. Most of the patients were maintained on 150 mg daily. Assessments were made by the Hamilton Psychiatric Rating Scale for Depression (HAM-D), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), Clinical Global Impression (CGI) scale and Patient's Self-Evaluation. The total HAM-D score was considerably reduced in the majority of the patients. Amitriptyline was the most effective with regard to symptoms included in the factor Sleep Disturbances and-secondary maybe-towards some items included in the factor Somatization. For the remaining items,including the items of the factors Anxiety/Depression and Apathy, the last score was lower in the amoxapine group than in those treated with amitriptyline. Among the unipolar cases the amoxapine treated patients were more satisfied with regard to efficacy (P = 6.3%). The frequency of side effects such as tremor and dizziness was considerably lower in the amoxapine group. In total, the side effects lasted longer in the amitriptyline group. We conclude that amoxapine seems to be an effective antidepressant with a low frequency of side effects.     

Duloxetine, 60 mg once daily,for major depressive disorder: a randomized double-blind placebo-controlled trial

BACKGROUND: Despite treatment advances, major depressive disorder (MDD) is still a significant cause of morbidity and mortality. Current therapies frequently fall short of providing full remission. In addition, physical symptoms are commonly seen in MDD patients, increasing overall morbidity and health care utilization. Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms. METHOD: In this multicenter, double-blind, parallel-group study, adult patients with DSM-IV MDD were randomly assigned to receive placebo (N = 122) or duloxetine (60 mg/day, N = 123) for 9 weeks. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Painful physical symptoms were assessed using visual analog scales, and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale, the Patient Global Impressions-Improvement scale, and the Quality of Life in Depression Scale. Safety and tolerability were determined by monitoring discontinuation rates, adverse events, vital signs, and laboratory results. RESULTS: Duloxetine was significantly superior to placebo (p < .001) in reducing HAM-D-17 total scores, starting at week 2. The estimated probability of remission for duloxetine-treated patients (44%) was almost 3 times that of placebo patients (16%). Duloxetine significantly reduced painful physical symptoms in comparison with placebo. Discontinuation due to adverse events for duloxetine-treated patients (13.8%) compared favorably with the rates reported for SSRIs in other studies. Nausea, dry mouth, and somnolence were the most common adverse events; no significant incidence of hypertension was seen. CONCLUSION: Duloxetine, 60 mg/day, is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms. These findings suggest that duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms.     

Alprazolam versus lorazepam in the treatment of anxiety: controlled clinical study

58 patients suffering from anxiety neurosis were divided into two groups, matched for age, sex, marital status and symptomatology. In a double-blind trial of 4 weeks' duration one group (28 patients) received alprazolam 0.75-3 mg/day and the other (30 patients) received lorazepam 3-12 mg/day. Both groups showed a steady and significant reduction in anxiety levels as measured by Hamilton Anxiety Rating Scale and Clinical Global Impression scores at 0, 1, 2 and 4 weeks. However, there was no significant difference in measured anxiety levels between the two groups at any stage. Fewer side effects were reported in the alprazolam treatment group, with the mental confusion symptom occurring significantly less often.     

A comparative trial of fluoxetine versus trazodone in outpatients with major depression

The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients. The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment. However, that difference was no longer apparent during the remainder of the study. The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone.     

Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial.

BACKGROUND: Studies show that selective serotonin reuptake inhibitors are effective for severe premenstrual syndrome and premenstrual dysphoric disorder. This study compares the efficacy of a selective serotonin reuptake inhibitor with that of a tricyclic antidepressant to determine whether efficacy for premenstrual syndrome/premenstrual dysphoric disorder is a general or more serotonergic effect of antidepressants. METHODS: After 3 screening months, 189 subjects were randomized to sertraline hydrochloride, desipramine hydrochloride, or placebo for 3 months of double-blind treatment. The flexible dosage range was 50 to 150 mg/d. The outcome measures included the Penn Daily Symptom Report (DSR), the Hamilton Depression Rating Scale, the Clinical Global Impressions-Severity Scale, the Quality of Life Scale, and Patient Global Ratings of Functioning and Improvement. Analyses included all subjects with treatment data, with the last observation carried forward. RESULTS: Sertraline was significantly more effective than placebo or desipramine; desipramine was not better than placebo (F2,163 = 12.47, P<.001). All DSR factors were more improved with sertraline compared with desipramine and placebo; the factors for mood (P<.001) and pain (P = .05) were significant, and the results of all outcome measures were consistent. A history of depression, postmenstrual symptom levels, and other diagnostic variables added individually as covariates did not alter the treatment results. At end point analysis, DSR symptoms had decreased by more than 50% in 40 subjects (65%) in the sertraline group, 18 subjects (36%) in the desipramine group, and 16 subjects (29%) in the placebo group (P<.001). CONCLUSIONS: The comparison of 2 classes of antidepressants strongly favored the serotonergic drug, which effectively reduced symptoms and improved functioning and was well tolerated by women with severe premenstrual syndrome. A history of depression did not alter the treatment results.     

Risperidone safety and efficacy in the treatment of bipolar and schizoaffective disorders: results from a 6-month, multicenter, open study

BACKGROUND: The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizoaffective disorders. METHOD: 541 patients entered this open, multicenter, 6-month study. Patients were entered provided that they fulfilled DSM-IV criteria for bipolar disorder or schizoaffective disorder, bipolar type, during a manic, hypomanic, mixed, or depressive episode. Risperidone was added to any previous mood-stabilizing medication that the patients were taking. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions scale (CGI). Extrapyramidal symptoms (EPS) were assessed using the UKU Side Effect Rating Scale. RESULTS: 430 patients completed the study. Addition of risperidone produced highly significant improvements (p < .0001) on the YMRS and HAM-D at both 6 weeks and 6 months and on the CGI and the scales of the PANSS at both 4 weeks and 6 months. There was a significant reduction in UKU total and subscale scores at 6 months. The mean dose of risperidone was 3.9 mg/day. There was no single case of new-emergent tardive dyskinesia, and there was a very low incidence of exacerbation of mania within the first 6 weeks (2%). Adverse events were few and mostly mild. the most frequent being EPS and weight gain. CONCLUSION: This large study provides additional evidence that risperidone is effective and well tolerated when combined with mood stabilizers in the treatment of bipolar disorder and schizoaffective disorder, bipolar type. Previous concerns about exacerbation of manic symptoms were not confirmed.