Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled trial. Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Multicenter study comparing thioridazine with diazepam and placebo in elderly, nonpsychotic patients with emotional and behavioral disorders. Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder. Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study. Double blind, controlled study of the efficacy and safety of alpidem in the treatment of anxiety in schizophrenic in-patients.
The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates. Thirty-six outpatients with generalized anxiety disorder (DSM III-R), after a 2-week wash-out, were randomized to one of the following three treatments for 4 weeks (n = 12 per group): valepotriates (mean daily dose: 81.3 mg), diazepam (mean daily dose: 6.5 mg), or placebo. A parallel, double-blind, flexible-dose, placebo-controlled design was employed. No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale (HAM-A) or in the trait part of the state-trait anxiety inventory (STAI-trait). Moreover, the three groups presented a significant reduction in the total HAM-A scores. On the other hand, only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait. Although the principal analysis (HAM-A between group comparison) found negative results (probably due to the small sample size in each group), the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety. However, since the number of subjects per group was very small, the present results must be viewed as preliminary. Thus, further studies addressing this issue are warranted.
                Copyright 2002 John Wiley & Sons, Ltd. The current study examines whether antidepressants, contrary to current thinking, are safe and effective treatments for generalized anxiety disorder (GAD) not complicated by depression or panic disorder.
                Randomized, double-blind, placebo-controlled, flexible-dose, 8-week treatment study comparing imipramine hydrochloride (mean maximum daily dose, 143 mg), trazodone hydrochloride (255 mg), and diazepam (26 mg).
                Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded, and who had a Hamilton Anxiety Scale total score of at least 18.
                Seventy-five percent of patients were treated in family practice settings in the community, with the remainder treated in psychiatric practices, either academic or private.
                Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. From week 3 through week 8 trazodone achieved comparable, and imipramine somewhat better, anxiolytic efficacy when compared with diazepam, with psychic symptoms of tension, apprehension, and worry being more responsive to the antidepressants. Among completers, moderate to marked improvement was reported by 73% of patients treated with imipramine, 69% of patients treated with trazodone, 66% of patients treated with diazepam, but only 47% of patients treated with placebo. Overall, patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients, but attention rates were the same across all treatments.
                The results of the study need replication, but suggest a potentially important role for antidepressants, particularly imipramine, in patients suffering from GAD. This randomized, double-blind clinical trial involving 198 generalized anxiety disorder (GAD) patients was conducted to more clearly define gepirone's role for the treatment of anxiety in daily dosages of 10 to 45 mg compared with diazepam and placebo. A secondary goal was to test for possible discontinuation symptoms after abrupt discontinuation of therapy. After a 1-week washout period, patients were treated for 8 weeks and then abruptly shifted under single-blind conditions for 2 weeks on placebo. The highest attrition rate occurred with patients on gepirone (58%) and the lowest on diazepam (34%). Medication intake for week 4 was 19.5 +/- 12.5 mg/day diazepam and 19.0 +/- 11.5 mg/day gepirone and was similar at week 8. The major adverse events were light-headedness, nausea, and insomnia for gepirone and drowsiness and fatigue for diazepam. Clinical improvement data showed gepirone's anxiolytic response to be delayed, being significant from placebo beginning at week 6, whereas diazepam caused significantly more relief than placebo from week 1 onward. Taper results showed that only diazepam, but not gepirone, caused a temporary worsening of anxiety symptoms or rebound. Two hundred forty-one outpatients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam, diazepam, imipramine hydrochloride, and placebo. Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo. Imipramine-treated patients reported the most and placebo patients the least number of adverse effects. Imipramine and alprazolam, but not diazepam, produced significantly more improvement in depressed symptomatology than did placebo. Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo. These treatment differences were found to be independent of initial severity levels of anxiety and depression. The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents.
                The study subjects were 22 children and adolescents age 5-17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16. The patients underwent a 2-3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale.
                The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment.
                The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents. Thioridazine was compared with placebo or diazepam or both in 610 elderly, nonpsychotic inpatients in geriatric wards of state hospitals or nursing homes. All patients manifested disruptive and difficult-to-manage behavior that interfered with adjustment to their environment and with proper care and treatment of their medical and emotional problems. Target symptoms such as agitation, anxiety, tension, apprehension, depressed mood, and sleep disturbances showed consistently marked improvement throughout the four-week study, as measured by the modified Hamilton Anxiety Scale, the modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and global ratings. Significantly greater improvement on all measures was achieved with thioridazine than with placebo. In addition, greater improvement in the majority of symptoms assessed by the Hamilton Anxiety Scale and NOSIE were seen in patients who received thioridazine than in those given diazepam. To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).
                Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.
                Outpatient clinic.
                One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.
                After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.
                An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.
                The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested. The prevalence of generalized anxiety disorder (GAD) represents an important public health issue. Hydroxyzine, an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients.
                This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score >/= 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo.
                In the intent-to-treat analysis, the mean +/- SD change in HAM-A scores from baseline to endpoint was -12.16 +/- 7.74 for hydroxyzine and -9.64 +/- 7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups.
                Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription. In this double-blind study, alpidem, a new imidazo-pyridine anxiolytic drug, was compared with placebo in order to test its efficacy and safety in chronic schizophrenic in-patients suffering from anxiety not directly related to the schizophrenic process. Sixty-six patients aged from 18 to 65 entered the trial. They also scored at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) after a seven-day placebo run-in. Improvement in symptoms was evaluated by means of the HRSA, the Brief Psychiatric Rating Scale (BPRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression score (CGI). Thirty-three patients were randomly allocated to alpidem and 33 to placebo. Alpidem was significantly more effective (P less than 0.0001) than placebo in improving HRSA scores (total score and factorial scores for somatic and psychic anxiety), BPRS, and VAS. Considering the results of CGI at 21 day, more patients were moderately to markedly improved on alpidem (30/33) than on placebo (2/33) (P less than 0.0001). The efficacy index, according to CGI, was significantly better (P less than 0.001 at least) for alpidem than for placebo. Side-effects were negligible in both groups.
Since only one small study is currently available, there is insufficient evidence to draw any conclusions about the efficacy or safety of valerian compared with placebo or diazepam for anxiety disorders. RCTs involving larger samples and comparing valerian with placebo or other interventions used to treat of anxiety disorders, such as antidepressants, are needed.