Double-blind study of metaclazepam versus diazepam treatment of outpatients with anxiety syndrome

The therapeutic efficacy and tolerance of metaclazepam and diazepam were compared in a double-blind study of outpatients suffering from a generalized anxiety syndrome. The investigators were general practitioners. A total of 168 male and female patients aged between 18 and 60 years were included in the study and received either 15 mg metaclazepam or 15 mg diazepam per day. The analysis of tolerance was made for all 168 included patients, the evaluation of efficacy is based on the results of 131 patients (42 males and 89 females) with valid data over four weeks. During the four-week therapy period four examinations were made on days 0, 7, 14, and 28. A significant improvement of the severity of illness after administering the drugs was found for both drugs in the Clinical Global Impressions (CGI), in the Hamilton Anxiety Scale (HAMA), in the List of Complaints (B-L), and in the Adjective Checklist (EWL-K). Metaclazepam showed a statistically significant superiority over diazepam as far as the CGI items "severity of illness" and "global improvement" were concerned. Metaclazepam was slightly superior to diazepam in the two HAMA subscales "psychic anxiety" and "somatic anxiety". In the items of the selfrating scales (B-L and EWL-K) the therapeutic results of the metaclazepam group were, almost without exception, better than those of the diazepam group. A comparison of tolerance showed that metaclazepam was better tolerated. This can be seen in the greater frequency of side effects like tiredness and drowsiness under diazepam. Especially at the beginning of treatment, tiredness and drowsiness were recorded 2 1/2 times more frequently for the patients on diazepam than for those on metaclazepam.     

Effects of alpidem in anxious elderly outpatients: a double-blind, placebo-controlled trial.

The efficacy and safety of alpidem, a new anxiolytic imidazopyridine, were compared with those of placebo in anxious elderly patients (65-80 years) by means of a randomized, double-blind, parallel group study. Following a 7-day "placebo run-in," 40 anxious patients were randomized to receive either alpidem or placebo. Daily doses ranging from 75 to 150 mg (25-50 mg t.i.d.) were administered for 3 weeks. Hamilton Rating Scale for Anxiety (HRSA), State Trait Anxiety Inventory (STAI-X1), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI) were used on days 0, 3, 7, 14, and 21 for assessing efficacy. Psychomotor and mnesic performances were evaluated at the same time by means of the Digit Symbol Substitution Test (DSST), the Grünberger's test for fine motor coordination, and the Hawie's test for immediate memory. Possible adverse events were also recorded during the five visits. The anxiolytic efficacy of alpidem was significantly (p < 0.01) superior to that of placebo in all the rating scales adopted. The anxiolytic action was clearly evident from day 7. For most of the patients the active dose was 25 mg t.i.d. No relevant adverse effects were observed in both groups. No impairment of psychomotor and mnesic performances could be observed in the alpidem group. Alpidem is a new interesting anxiolytic drug for anxious elderly patients because it appears remarkably safe and, at effective doses, it does not impair psychomotor performances and cognitive functions.     

Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.

BACKGROUND: The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder. METHOD: Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD). RESULTS: The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups. CONCLUSION: Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.     

A double-blind, placebo-controlled study of alpidem, a novel anxiolytic of imidazopyridine structure, in chronically anxious patients

In this double-blind study alpidem, a new imidazopyridine anxiolytic drug, was compared with placebo to assess its efficacy and safety in severely anxious patients at the fixed dose of 150 mg/day (50 mg t.i.d.) for 3 weeks. Fifty-nine patients with a score of at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) entered the trial after a 3- to 7-day placebo run-in period. Symptom improvement was evaluated with the HRSA, the State and Trait Anxiety Inventory (STAI-1 and STAI-2), a Visual Analogue Scale (VAS) and the Clinical Global Impression (CGI). Alpidem was more effective than placebo in improving mean HRSA (total score and factorial scores for somatic and psychic anxiety), STAI-1 and STAI-2 and VAS scores. The efficacy index of the CGI was better for alpidem than for placebo. Side effects were negligible in both groups. Alpidem appears to be a new interesting anxiolytic drug devoid of significant sedative effects on mental functions.     

A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder.

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P 相似文献   

Safety of ipsapirone treatment compared with lorazepam: discontinuation effects.

OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.     

Escitalopram in the treatment of anxiety symptoms associated with depression

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.     

5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo-controlled study with ritanserin

Thirty patients suffering from dysthymic disorder participated in a 6-week double-blind trial comparing ritanserin 10 mg and placebo. After a single-blind placebo wash-out period of one week, the test medication was administered during 5 weeks on a double-blind basis. Twenty-three patients completed the study. At the end of the trial, ritanserin was significantly superior to placebo in its effect as manifested on the 19-item Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety and the State Trait Anxiety Inventory X-1 and X-2. At the end of the study, the therapeutic effect was rated marked or moderate in 75% of the ritanserin-treated patients, but only in 18% of the controls. These data are consistent with the hypothesis of serotonin abnormalities in dysthymic disorder and suggest a therapeutic role of 5-HT2 antagonists. Ritanserin treatment was very well tolerated; no serious adverse experiences were reported.     

Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial

The efficacy and safety of propranolol in the treatment of anxiety was compared with those of chlordiazepoxide and placebo in a 3-week, double-blind study of 212 patients. After a 1-week, single-blind placebo-washout period, patients were randomized to receive either propranolol (80, 160, or 320 mg/day), chlordiazepoxide (30, 45, or 75 mg/day), or placebo. Patients were evaluated by three physician-rated scales--Hamilton Rating Scale for Anxiety (HAM-A), Covi Anxiety Scale (CAS), and Clinical Global Impressions scale--and two patient-rated scales--Symptoms Checklist 90 and Profile of Mood States. Patients in all groups demonstrated significant improvement in their level of anxiety at all time points compared with their baseline level. At Week 1 propranolol and chlordiazepoxide patients were significantly better than placebo patients, as measured by the HAM-A and CAS. At Week 2 only propranolol was superior to placebo, based on HAM-A and CAS scores. Fifteen patients prematurely terminated because of adverse reactions (4 taking propranolol, 4 taking placebo, and 7 taking chlordiazepoxide). The incidence of side effects was similar for the two active drugs; fatigue, drowsiness, and change in libido were significantly more frequent with chlordiazepoxide and drowsiness and indigestion were more frequent with propranolol compared with placebo.     

Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double-blind,randomized, placebo-controlled,phase 2 clinical trial

Aim

To evaluate the efficacy and safety of an oral, once-daily, 14-day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD).

Methods

This multicenter, randomized, double-blind, placebo-controlled study randomized eligible patients (1:1:1) to receive oral zuranolone 20 mg, zuranolone 30 mg, or placebo once daily for 14 days (treatment-period), followed by two 6-week follow-up periods. The primary endpoint was change from baseline in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score on Day 15.

Results

Overall, 250 patients (enrolled: 07/07/2020–05/26/2021) were randomized to receive placebo (n = 83), zuranolone 20 mg (n = 85), or zuranolone 30 mg (n = 82). The demographic and baseline characteristics were balanced between groups. The adjusted mean (standard error) change from baseline in the HAMD-17 total score on Day 15 was −6.22 (0.62), −8.14 (0.62), and − 8.31 (0.63) in the placebo, zuranolone 20-mg, and zuranolone 30-mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for zuranolone 20 mg versus placebo (−1.92; [−3.65, −0.19]; P = 0.0296) and zuranolone 30 mg versus placebo (−2.09; [−3.83, −0.35]; P = 0.0190) groups were observed on Day 15, and also as early as Day 3. A nonsignificant yet distinct drug-placebo separation was observed during follow-up. Somnolence (placebo [3.7%], zuranolone 20 mg [10.6%], and zuranolone 30 mg [20.7%]) and dizziness (3.7%, 9.4%, and 9.8%, respectively) were more common with zuranolone.

Conclusion

Oral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by HAMD-17 total score change from baseline over 14 days in Japanese patients with MDD.     

Duloxetine in treatment of anxiety symptoms associated with depression

Most patients with major depressive disorder (MDD) have symptoms of anxiety associated with their depression. Duloxetine, a potent and balanced dual serotonin and norepinephrine reuptake inhibitor, is effective in the treatmentof depression. We investigated its effects in treating the symptoms of anxiety in depressed patients. This investigation includes all the placebo-controlled studies of duloxetine in MDD but focuses on four trials in which duloxetine was superior to placebo on the primary outcome measure of the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score. Studies 1 and 2 included duloxetine at 60 mg/d (the recommended starting and therapeutic dose) and placebo. Study 3 included duloxetine 120 mg/d (administered as 60 mg b.i.d.), fluoxetine 20 mg/d, and placebo. Study 4 included duloxetine 40 mg/d (administered as 20 mg b.i.d.), duloxetine 80 mg/d (administered as 40 mg b.i.d.), paroxetine 20 mg/d, and placebo. Anxiety was assessed in all studies using the HAMD anxiety/somatization subfactor and the anxiety-psychic item (HAMD Item 10). Studies 3 and 4 also included the Hamilton Anxiety Rating Scale (HAMA). Across the four studies, duloxetine at doses of >/=60 mg was compared with placebo on 10 outcomes and with either paroxetine or fluoxetine on 6 outcomes. In 8 comparisons, mean improvement for duloxetine was significantly greater than placebo at the last study visit and/or across all study visits. In 3 comparisons, the mean improvement for duloxetine was significantly greater than paroxetine or fluoxetine. In these studies, duloxetine provided rapid relief of anxiety symptoms associated with depression. Previous reports have summarized duloxetine's efficacy in treating the core emotional symptoms and painful physical symptoms associated with depression. Duloxetine's efficacy in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical symptoms, may be attributed to dual reuptake inhibition of both serotonin and norepinephrine. Efficacy in these three key symptom domains may in turn explain the high probabilities of remission (43-57%) observed in these studies.     

A multicentre placebo-controlled trial comparing the efficacy of mianserin and chlordiazepoxide in general practice patients with primary anxiety

In a double-blind multicentre trial in general practice, 144 patients with primary anxiety received daily treatment with mianserin or chlordiazepoxide, 30-60 mg, or placebo. There were no statistically significant differences in efficacy between the three treatments in the 106 patients who completed the 6-week trial. However, there was a substantial trend in favour of mianserin (P= 0.1), but not chlordiazepoxide, over placebo as assessed by the difference in overall improvement on the Hamilton Anxiety Scale. This trend may be clinically significant since more patients dropped out from the placebo group because of lack of effect or deterioration than did from the active treatment groups, particularly during the latter part of the trial. Side effects occurred to a similarly low extent with all treatments, except that mianserin caused more weight gain and, initially, more drowsiness than placebo, while placebo produced more nausea and vomiting. Taken together with the evidence from previous trials in patients with anxiety, these results support the notion that mianserin has anxiolytic properties.     

Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study

Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18-65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg escitalopram (n = 167), 10 mg escitalopram (n = 167), 20 mg escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of escitalopram, and 20 mg escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score < or = 2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of escitalopram treatment. It is concluded that doses of 5-20 mg escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD.     

A controlled double-blind study of tetrabamate versus lorazepam and placebo in generalized anxiety

The anxiolytic efficacy of tetrabamate was evaluated in a multicentric double-blind study versus lorazepam and placebo, in 269 patients with a generalized anxiety disorder according to DSM III-R criteria. The anxiolytic activity of tetrabamate (at 900 mg/day) was significantly superior than that of placebo from day 7 of treatment and equivalent to lorazepam efficacy (at 4.5 mg/day). In the tetrabamate group, 55.3% were considered as "good responders" (as defined by a HARS score reduction equal or superior to 50%), versus 51.3 and 32.9% respectively in the lorazepam and the placebo groups (chi-square = 9.63, p = 0.008). Sheehan's scales (parts 1 and 2), Norris visual analogue scales, CHESS 84, CHESS complement 82 for withdrawal evaluation, physician's overall evaluation of efficacy and tolerance, were also used to assess the clinical effects of tetrabamate. The data on these measures confirmed the anxiolytic efficacy of tetrabamate and showed some advantages in the tetrabamate group in comparison with the lorazepam group: a better global tolerance at the study end point (day 35), a greater efficacy on some anxiety somatic items and lesser frequency and severity of withdrawal symptoms during treatment tapering off.     

Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study

OBJECTIVE: Quetiapine monotherapy shows efficacy in bipolar depression. The analyses in this multicenter, double-blind, randomized, fixed-dose, placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression. METHOD: Of 542 outpatients randomly assigned to treatment, 539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600 or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups versus placebo. RESULTS: At week 8, quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo (-10.8 and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved HAM-A total score from week 1. In bipolar I depression, quetiapine showed significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p < .001). In bipolar I depression, quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all p < .001), but not the HAM-D somatic anxiety item. In bipolar II depression, quetiapine reduced the HAM-A total score more than placebo, but the difference was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II depression, quetiapine showed significant improvement versus placebo on the HAM-A anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01). CONCLUSION: Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression; however, the anxiolytic effects in bipolar II disorder require further investigation.     

Paroxetine, clomipramine, and cognitive therapy in the treatment of panic disorder

BACKGROUND: This 12-week, placebo-controlled study was carried out to compare the relative efficacy of paroxetine, clomipramine, and cognitive therapy in the treatment of DSM-III-R-defined panic disorder with or without agoraphobia. METHOD: After a 3-week single-blind, placebo run-in period, 131 patients were randomly assigned to receive double-blind medication or 12 sessions of cognitive therapy based on the model of Clark. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression scale, the Patient Global Evaluation, the Hamilton Rating Scale for Anxiety, the Marks-Sheehan Phobia Scale, the Montgomery-Asberg Depression Rating Scale, and the Sheehan Disability Scale. RESULTS: Comparisons with placebo revealed significant superiority of paroxetine (20-60 mg/day) and clomipramine (50-150 mg/day) on nearly all outcome measures. On most measures, paroxetine also showed higher efficacy than cognitive therapy. With few exceptions, cognitive therapy did not differ significantly from placebo. The number of subjects becoming panic-free (66%) was higher and the onset of action was faster in the paroxetine-treated group. Treatment with cognitive therapy yielded the highest drop-out rate (26%). CONCLUSION: In this short-term study assessing treatment of panic disorder and agoraphobia, paroxetine and clomipramine were consistently superior to pill placebo, whereas cognitive therapy was superior on only a few measures.     

Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial

OBJECTIVE: This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score >/==" BORDER="0">20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.     

Efficacy and tolerability of escitalopram in anxiety disorders: a review

INTRODUCTION: Anxiety disorders are highly prevalent and disabling disorders, for which selective serotonin reuptake inhibitor (SSRI) antidepressants are an effective treatment. Escitalopram is the most selective SSRI available. Beyond its well-established efficacy in depression with or without anxiety, preclinical studies have demonstrated that escitalopram has a broad spectrum of anxiolytic activity. AIM OF THE REVIEW: This review focuses on the therapeutic use and the tolerability issues of escitalopram in the treatment of adult patients with panic disorder, generalized anxiety disorder (GAD), social anxiety disorder, and obsessive-compulsive disorder (OCD), on the basis of numerous recent short-term and long-term controlled studies in these disorders. In a 10-week randomised, double-blind trial in patients with panic disorder, escitalopram (flexible doses 5-10 mg/d) was significantly more effective than placebo in reducing the panic attack frequency, with a faster onset of action than citalopram. Fifty percent of escitalopram recipients and 38% of placebo recipients experienced no panic attacks, with a similar incidence of the most common adverse events for both groups. LITERATURE FINDINGS IN PD: In an open-label study in elderly (>65 years) patients with panic disorder, improvement in panic attack frequency and secondary efficacy variables occurred more rapidly in escitalopram than citalopram recipients. LITERATURE FINDINGS IN GAD: In four double-blind, comparative, eight- to 12-week studies in patients with GAD, escitalopram was more effective than placebo and at least as effective as paroxetine in reducing the mean Hamilton Rating Scale for Anxiety total score. Escitalopram 10-20 mg/d demonstrated continued efficacy in a 24-week extension study of short double-blind trials and in a placebo-controlled, double-blind, 24/76-week relapse-prevention study. In this trial, escitalopram recipients showed a significantly longer time to relapse and reduced risk of relapse than placebo recipients, and the risk of relapse was 4.04 times higher in the placebo group than in the escitalopram group. Escitalopram was well tolerated and only 7% patients withdrew, due to adverse events in the escitalopram group, versus 8% in the placebo group. LITERATURE FINDINGS IN SOCIAL PHOBIA: In two randomised, double-blind, 12- and 24-week studies in patients with social anxiety disorder (social phobia), escitalopram 10-20 mg/d was generally more effective than placebo and at least as effective as paroxetine in reducing the mean Liebowitz Social Anxiety Scale total scores. In a 24-week double-blind, placebo-controlled relapse-prevention study, escitalopram recipients had a longer time to relapse and reduced risk of relapse compared with placebo recipients, and significantly fewer escitalopram than placebo recipients relapsed (22% versus 50%). In these studies, the treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms, and the drug was tolerated well. LITERATURE FINDINGS IN OCD: Finally, in patients with OCD, escitalopram 20mg/d for 12 weeks was more effective than placebo, and at least as effective as paroxetine 40 mg/day, with respect to a mean reduction from baseline in the Yale-Brown Obsessive Scale total score. In a 24-week, randomised, placebo-controlled relapse-prevention study, the proportion of patients who relapsed in the escitalopram group (23%) was 2.74 times lower than in the placebo group (52%). In both groups, the majority of adverse events reported were mild to moderate. CONCLUSION: On the whole, numerous clinical data indicate that escitalopram, 10-20 mg/d, is an effective and well-tolerated first-line treatment option for the management of panic disorder, GAD, social anxiety and OCD. Beyond short-term demonstrations of efficacy in these disorders, several controlled relapse-prevention studies showed the necessity and utility of maintaining the treatment six months or more after the remission has been obtained.     

Acute double-blind,placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome

In a double-blind, placebo-controlled randomized crossover trial, the acute efficacy of a combination treatment of 100 mg regular-release (rr) and 100 mg sustained-release (sr) L-dopa/benserazide in RLS was investigated by means of sleep laboratory methods, with a subsequent open clinical follow-up for 4 weeks. 21 RLS patients classified according to ICSD and IRLSSG criteria were included; 18 completed the study. Objective sleep quality was determined by polysomnography (PSG) in 3 subsequent nights (adaptation/screening, placebo and drug night), subjective sleep and awakening quality was evaluated by rating scales, objective awakening quality by psychometric tests. Clinical follow-up consisted of daily ratings of subjective sleep and awakening quality (SSA) and VAS for RLS symptomatology ratings, completion of the RLS (IRLSSG) Scale weekly and the Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before and after therapy. Acute L-dopa/benserazide significantly (p < 0.001) and markedly (75%) decreased the target variable PLM/h of sleep as well as all other RLS/PLM variables, but failed to improve objective sleep efficiency and subjective sleep quality in comparison to placebo. After 4 weeks of therapy, however, subjective sleep and awakening quality also improved significantly. While RLS/PLM measures showed an immediate significant and marked response to the combination therapy subjective sleep quality only improved after chronic treatment.     

Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.

BACKGROUND: Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline. METHODS: Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group. RESULTS: Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo. CONCLUSIONS: This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy.