Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A double-blind, placebo-controlled trial was undertaken to compare the effects of imipramine and clomipramine in the treatment of panic disorder with or without agoraphobia. The number of dropouts in the placebo-treated group was 7; in the imipramine-treated group, 4; and in the clomipramine treated group, 0. Ten subjects fulfilled the 12 weeks of treatment in the placebo group, 25 in the imipramine group, and 22 in the clomipramine group. To minimize dropouts because of side effects, a flexible dose regimen with a careful escalation of doses was applied. The maximal dose allowed was 250 mg/day. The mean (+/- SEM) daily doses reached were 124 +/- 9 mg (range, 50-250 mg) of imipramine and 109 +/- 8 mg (range, 25-200 mg) of clomipramine. At the end of the trial, the number of panic attacks as well as the anxiety between attacks (measured using the Hamilton Rating Scale for Anxiety) were markedly reduced in patients treated with either of the two antidepressant drugs, but only slightly decreased in patients on placebo. With respect to all major outcome parameters, i.e., full panic attacks, total number of anxiety attacks (full plus mild), and anxiety between attacks, the effect of clomipramine was clearly and significantly superior to that of imipramine (p less than 0.001, p less than 0.002, and p less than 0.002, respectively). Moderate intake of diazepam was allowed; in the clomipramine group (p less than 0.006), but neither in the imipramine group nor in the placebo group, a significant decrement in diazepam intake was observed during the course of the trial. The finding that clomipramine may have a higher potency and/or efficacy than imipramine in the treatment of panic disorder supports the concept that the antipanic effect of antidepressant drugs is due to the influence of these compounds on serotonergic rather than noradrenergic neurotransmission.
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PMID:Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial. 152 28

Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the gamma-aminobutyric acid (GABA)-A/benzodiazepine (BDZ) receptor. In theory, such partial agonists should be anxiolytic but lack the adverse side-effects of sedation, tolerance and withdrawal associated with full GABA-A/BDZ agonists. The objective of the randomized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile. Patients recruited had a diagnosis of Panic Disorder (DSM-IV) with at least one panic attack per week. Following a 2-week screening period, patients entered a 6-week trial consisting of two 2-week treatment periods, each followed by a 1-week washout. Patients were randomly assigned to receive either pagoclone 0.1 mg t.d.s. or placebo on their first treatment period and the converse on their second. The primary measure was daily panic attack dairy. Fourteen patients completed the study, the mean number of panic attacks during screening was 5.8+/-0.8 (SEM), this fell to 3.6+/-0.5 during treatment with pagoclone (p = 0.05) and 4.3+/-0.8 with placebo (p = 0.14). There was no significant difference on direct comparison of pagoclone with placebo or in any of the secondary measures (including Rickels withdrawal scale) or the adverse event profiles. The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects. This is consistent with its theoretical mode of action as a partial agonist at the GABA(A)/BDZ receptor.
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PMID:Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder. 1156 30

This study investigated the chronic use (6.3 +/- 0.5 years; mean +/- SEM) of therapeutic doses of clomipramine (57.0 +/- 8.0 mg/day) by outpatients with panic disorder/agoraphobia who were currently in remission to assess impairment of memory and psychomotor functions. In addition, the association between test performance and serum levels of clomipramine (CMI) and its active metabolite desmethylclomipramine (DCMI) was also assessed. Patients and healthy volunteers matched for sex, age and educational level were submitted to rating scales and to memory and psychomotor tests. There was no significant difference between groups regarding any variable, except for metamemory. Significant associations were found between (i) longer-term clomipramine treatment and poorer performance in the implicit test and (ii) higher serum levels of clomipramine or desmethylclomipramine, or both (CMI + DCMI) and lower performance in central executive tests and metamemory. The results showed that low doses of CMI chronically administered to panic patients are associated with diminished metamemory and impaired priming and working memory. Further investigations are needed to confirm these results and to determine whether the chronic use of higher therapeutic doses of tricyclic antidepressants is associated with more intense deleterious effects on memory and psychomotor functions.
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PMID:Memory performance in panic disorder patients after chronic use of clomipramine. 1223 28