Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.     

Effect of kainate on the membrane conductance of hilar glial precursor cells recorded in the perforated-patch configuration

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.     

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.     

Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study

BACKGROUND: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. METHOD: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety. RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated. CONCLUSION: The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.     

A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder

The objective of this study was to evaluate the safety and efficacy, over a 1 year treatment period, of three dose levels of sertraline and placebo in the treatment of non-depressed adult out-patients with obsessive-compulsive disorder (OCD). Following 1 week of single-blind placebo washout, patients (n = 325) from 11 sites following identical protocols were randomly assigned to 12 weeks of double-blind treatment with one of three fixed doses of sertraline (50, 100 or 200 mg) or placebo. At the end of 12 weeks, treatment responders (including placebo patients) were offered an additional 40 weeks of double-blind treatment at their assigned doses. Efficacy measures were the Yale-Brown Obsessive Compulsive Scale, the NIMH Global Obsessive Compulsive Scale, Clinical Global Impressions of Severity of Illness and Global Improvement and the Maudsley Obsessive Compulsive Inventory. Patients in the pooled sertraline group showed greater improvement than placebo-treated patients on all efficacy measures, based on the endpoint analyses. Moreover, pairwise comparisons at endpoint revealed a significant effect on all three investigator-rated scales in patients receiving 50 or 200 mg of sertraline; in the 100 mg group, there was a significant effect on the NIMH Global Obsessive Compulsive Scale only. Patients completing 3 months of sertraline treatment exhibited excellent toleration and sustained improvement during an additional 40 weeks of therapy. Results support the safety, efficacy and tolerability of daily doses of 50-200 mg of sertraline in the long-term treatment of patients with OCD.     

Tropisetron or ondansetron compared with placebo for prevention of postoperative nausea and vomiting

In a prospective, randomized, double-blind, placebo-controlled, multicentre study, the efficacy of prophylactic tropisetron (2 mg) or ondansetron (4 mg) for the prevention of post-operative nausea and vomiting after abdominal or non-abdominal surgery with general balanced anaesthesia was studied in 842 ASA I-III patients. In patients undergoing abdominal surgery, ondansetron and tropisetron reduced the frequency of emetic episodes compared with the placebo (29%, 30% vs. 42% respectively). In men, neither tropisetron nor ondansetron had an effect different from the placebo, whereas in women both drugs led to lower rates of emetic episodes and nausea. In comparison with abdominal surgery, fewer patients in the non-abdominal surgery subgroup had emetic episodes (42% vs. 23% in the placebo group). However, neither tropisetron nor ondansetron was significantly different from the placebo in this patient subgroup. In conclusion, for patients at increased risk of post-operative nausea and vomiting, a prophylactic therapy at the lowest effective dose with tropisetron or ondansetron may be useful.     

Short-lasting behavioural effects of thyrotropin-releasing hormone in depressed women: results of placebo-controlled study

The rapid and short-lasting behavioral effects of thyrotropin-releasing hormone (TRH) were investigated in female patients with DSM-III-R major depression syndrome (MDS). Twenty-six depressed patients free of any medication received 0.2 mg of Protirelin (synthetic TRH) intravenously and 16 received placebo. All patients completed the Zung Self-Rating Depression Scale and the Spielberger State and Trait Anxiety Inventory (SSAI and STAI) twice: before and 2 hr after protirelin or placebo administration. The significant improvement in patients' emotional state after TRH injection was observed on STAI (p < .001) and SSAI (p < .01). Protireline was superior to placebo on STAI (p < .005). There was no significant correlation between behavioral effects of Protirelin and changes in thyroid hormones and TSH secretion. The improvement in patients' emotional state was more evident in depressed patients without associated panic attacks than in MDS with panic. These findings suggest that TRH has rapid positive effects on depression and that they depend more on patients' emotional state than on the function of the hypothalamus-pituitary-thyroid axis.     

Serotonin Type 3 Receptors Modulate the Aggression-Stimulating Effects of Adolescent Cocaine Exposure in Syrian Hamsters (Mesocricetus auratus).

Repeated cocaine (0.5 mg/kg) exposure throughout adolescence stimulates offensive aggression in hamsters. These studies examined whether the cocaine-induced aggressive response was regulated by serotonin Type 3 (5-HT?) receptor activity and correlated with altered 5-HT? receptor expression. Cocaine-treated Syrian hamsters (Mesocricetus auratus) were tested for aggression after the administration of either the 5-HT? antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron; 0.01-1.20 mg/kg) or the 5-HT? agonist l-(m-chlorophenyl)-biguanide hydrochloride (mCPBG; 5.0-15.0 mg/kg), alone or in combination. Tropisetron alone dose dependently reduced cocaine-induced aggression, with a significant reduction at 0.3 mg/kg, whereas mCPBG was ineffective. mCPBG administered prior to tropisetron required a higher dose (1.2 mg/kg) of antagonist to block aggression, indicating a selective 5-HT? effect. Cocaine-treated hamsters showed altered 5-HT? immunoreactivity in several brain areas implicated in aggression control. These data support a role for 5-HT? receptors in adolescent cocaine-induced aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of mesoglycan in patients with cerebrovascular disease: a psychometric evaluation

Mesoglycan is a preparation of natural glycosaminoglycans, containing mainly heparan sulphate and dermatan sulphate. A clinical trial was conducted to evaluate the efficacy and the tolerability of once-daily mesoglycan in 30 patients with clinical evidence of cerebrovascular insufficiency. Clinical effectiveness was assessed using psychometric and neurological scales: Sandoz Clinical Assessment for Geriatric Patients (SCAG); Parkside Behaviour Rating Scale Modified; Geriatric Depression Scale; and Anxiety Evaluation. Mesoglycan was given as a single oral once-daily dose of 100 mg for a period of 6 months. This treatment was shown to have positive effects on the cognitive and behavioural parameters evaluated. The effects on SCAG were already evident after 3 months' treatment and a significant improvement was observed after 6 months in those patients with a moderate to severe disease. During the treatment period only one patient suffered an adverse reaction attributed to the drug investigated.     

Prevention of emesis by tropisetron in children receiving combined chemotherapy with cisplatin

We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its use in 15 children with malignant disease who received cisplatin (CDDP) either alone (1/15) or in combination (14/15) with other cytostatic drugs. Tropisetron was given to 15 children (8 boys and 7 girls, ranging from 6 months to 17 years of age) with miscellaneous neoplasms. Generally, tropisetron (5 mg/m2/day, maximum 5 mg/day) was administered intravenously the first day of CDDP-based chemotherapy and orally for 4 subsequent days of chemotherapy. The dose of tropisetron was reduced to 0.2 mg/kg/day in children less than 1 year of age and/or those weighing less than 10 kg. Vomiting and nausea were controlled completely in 8 of 15 (53.3%) children on day 1 with a single intravenous infusion of tropisetron. Partial control was observed in 40% of patients on day 1. Complete control of delayed nausea and vomiting ranged between 40% and 80% in patients over days 2 to 5. The results obtained during administration of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of malignant disease in pediatric patients.     

Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.     

A clinical trial of escalating doses of flumazenil for reversal of suspected benzodiazepine overdose in the emergency department

STUDY OBJECTIVE: To determine if flumazenil, when used in doses higher than those currently recommended, could reverse the effects of a benzodiazepine (BDZ) overdose in patients who might not otherwise respond and whether the higher dose was associated with increased adverse effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, balanced, with parallel groups. Open-label flumazenil administration was available if a patient failed to respond or became resedated. SETTING: Sixteen emergency departments in the United States. POPULATION: Patients presenting to the ED with clinically significant signs and symptoms of a known or suspected BDZ overdose. INTERVENTIONS: Patients were randomized to receive 10 mL/min of placebo or flumazenil (1 mg/10 mL) each minute for ten minutes. If there was no response, up to 3 mg of open-label flumazenil could be administered. MEASUREMENTS AND MAIN RESULTS: Of 170 patients enrolled, 87 received flumazenil and 83 received placebo. The demographic characteristics of both groups were comparable. Ten minutes after the beginning of study drug infusion, patients were evaluated using the Clinical Global Impression Scale (CGIS), Glasgow Coma Scale (GSC), and Neurobehavioral Assessment Scale (NAS). The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil. The mean +/- SD dose of flumazenil administered during the double-blind phase was 71.3 +/- 34.2 mL (7.13 mg) compared with 95.06 +/- 16.03 mL of placebo. Of the 39 patients who had BDZ-positive drug screens and received flumazenil, 29 (74%) responded to 3 mg or less. Six additional patients responded to 4 or 5 mg, and one patient responded to 8 mg. The most common adverse effects in patients who received flumazenil were injection site pain (10.3%), agitation (8%), vomiting (3.4%), dizziness (3.4%), headache (3.4%), tachycardia (3.4%), and crying (3.4%). Three patients developed seizures. Two were associated with significant tricyclic antidepressant overdoses and one with propoxyphene ingestion. Two patients had positive drug screens for BDZ. CONCLUSION: Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose. Most patients will respond to 3 mg or less, but a small number may require a higher dose for reversal of clinical symptoms. Patients with concomitant tricyclic antidepressant overdose may be at risk for developing seizures.     

Prophylactic antiemetic therapy with patient-controlled analgesia: a double-blind, placebo-controlled comparison of droperidol, metoclopramide, and tropisetron

This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (i.v.) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT3) antagonist was given as a single i.v. dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of lorazepam on film-induced differentiated emotions in healthy volunteers

We studied the effects of lorazepam, a benzodiazepine, on differentiated emotions in healthy volunteers. In order to induce differentiated emotions, film excerpts were selected on the basis of the type of emotion they induced (fear, anger and for affective tone neutral film). For 6 days (D1 to D6), ten healthy volunteers received lorazepam (1 mg bid) or placebo in a randomized cross-over double-blind trial. During each treatment period, emotional induction occurred on D4, D5 and D6. One film excerpt (fear, anger or neutral) was presented each morning after relaxation. Evaluation was performed before and after each emotional induction and included questionnaires (Differential Emotions Scale and physical activation visual analog scales), and neurophysiological parameters (systolic and diastolic blood pressure, heart rate and norepinephrine levels). Globally, the film excerpts induced the predicted emotions. An analysis of variance was undertaken and revealed a significant effect of lorazepam versus placebo. On the Differential Emotions Scale and during fear induction, lorazepam induced a significantly higher increase in fear, anxiety and disgust emotions than placebo, whereas no effect was observed after anger induction. Lorazepam also induced a significantly higher increase in diastolic and systolic blood pressure with no change in heart rate, and physical activation items ("tears" and "faster breathing") without no significant change in norepinephrine. In conclusion, our results are consistent with an overall increase in emotional reactivity with lorazepam (1 mg bid) as compared to placebo. The pertinence of film-induced differentiated emotions has to be confirmed for clinical pharmacological use.     

5-HT3 receptor blocking properties of the antiparkinsonian agent, talipexole

1. Talipexole showed moderate displacement activity of 3H-GR 65630 binding to 5-HT3 receptors in both rat cortical and intestinal membrane fractions with Ki values of 0.35 microM and 0.22 microM, respectively. 2. Bromocriptine failed to displace the binding activity in either experimental system even at a concentration of 10 microM. 3. Both talipexole and tropisetron were found to significantly inhibit 5-HT3 receptor-mediated effects of 5-HT in isolated guinea-pig ileum or atrium; however, the effect of talipexole was weaker than that of tropisetron. 4. Bromocriptine, in contrast, had no antagonistic effects on 5-HT3 receptor-mediated activity in guinea-pig ileum or atrium. 5. It was concluded that talipexole might act as an antagonist on 5-HT3 receptors in both brain and intestinal tissues.     

A comparison of cue-controlled relaxation and study skills counseling in the treatment of mathematics anxiety.

36 undergraduates were assigned to 1 of 4 experimental conditions: (a) mathematics study skills training, (b) cue-controlled relaxation, (c) a combined study skills and cue-controlled relaxation treatment, or (d) no treatment. Data from both the self-report and performance domains were collected at pre- and posttreatment and at a 3-wk follow-up (Mathematics Anxiety Scale, Anxiety Differential, Test Anxiety Scale, State-Trait Anxiety Inventory, Digit Symbol Test and Differential Aptitude Test). Results indicate that the study skills condition produced significant improvements on self-reported mathematics anxiety and mathematics performance, and the cue-controlled relaxation and combined conditions led to significant declines in generalized test anxiety. By follow-up, however, cue-controlled relaxation was found to be superior to the other treatments on level of mathematics anxiety and performance. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid relief of anxiety in cancer patients with both alprazolam and placebo

This study evaluated 36 cancer patients who were enrolled in a randomized, double-blind, placebo-controlled trial conducted over a 4-week period to evaluate the efficacy of alprazolam in the treatment of anxiety associated with cancer. Hamilton Anxiety Scale scores declined significantly between baseline and the end of the first week of the study in both treatment groups. There was no significant difference in response between the patients receiving alprazolam and placebo. Similar results were obtained from other instruments. These results suggest that nondrug factors or spontaneous improvement may play a more important role than pharmacotherapy in the treatment of anxiety associated with cancer.