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Biomedical subjects
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BACKGROUND: The tricyclic antidepressant trimipramine exhibits several features (e. g., dopaminergic effect, molecular structure similar to a neuroleptic, receptor-binding profile similar to clozapine) that suggest its potential as an antipsychotic medication. The aim of the study was to investigate the antipsychotic potential of trimipramine in a controlled clinical trial comparing its antipsychotic efficacy with that of a neuroleptic. METHOD: In a German multi-center, randomized, double-blind trial, the antipsychotic efficacy of trimipramine was compared with that of the phenothiazine neuroleptic perazine, using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions (CGI). Antidepressant efficacy of both agents was measured by use of the Bech-Rafaelsen Melancholia Scale (BRMES). Ninety-five patients with acute schizophrenia (DSM-III-R) and a BPRS total score > 40 at baseline were treated with either 300-400 mg trimipramine or 450-600 mg perazine for 5 weeks. RESULTS: Therapeutic equivalence of both treatments (in the dosages used) could not be demonstrated (change in BPRS total score, per-protocol [PP] analysis, one-sided equivalence testing). However, intention-to-treat (ITT) as well as PP analysis showed a statistically significant decrease in the BPRS total scores in both treatment groups (PP: trimipramine, 56.5 +/- 9.8 to 44.1 +/- 17.9; perazine, 56.4 +/- 10.8 to 37.9 +/- 12.9). Significant decreases in all BPRS and PANSS subscores as well as CGI results and response rate support the antipsychotic efficacy of trimipramine. The BRMES total scores significantly decreased in both treatment groups without showing a significant difference between the two agents. Trimipramine was better tolerated than perazine and did not elicit extrapyramidal symptoms. CONCLUSION: Trimipramine failed to exhibit therapeutic equivalence to perazine in the dosages used. However, there was evidence of a substantial antipsychotic effect of trimipramine. It may be a useful medication if depressive symptoms in psychotic patients require antidepressant treatment or if other antipsychotics cannot be administered.
Primary sclerosing cholangitis (PSC) in eight children, five males and three females between the ages of 4 and 13 years, presented with minimal clinical symptoms and few signs of liver disease. Diagnosis was made by a highly characteristic histology in all and additional endoscopic retrograde cholangiography (ERC) in four patients. Six children suffered from concomitant inflammatory bowel disease (IBD). Laboratory abnormalities consisted of mild elevation of transaminases and alkaline phosphatase, with marked elevation of immunoglobulin G in seven and detection of anti-nuclear antibodies in four of the eight children. In all cases, needle liver biopsy specimens revealed portal tracts considerably expanded by edema and chronic inflammation diagnostic of nonsuppurative cholangitis and nonsuppurative fibrosing pericholangitis. ERC showed decreased arborization in the whole biliary tree. In two patients, changes were confined to the intrahepatic portion of the biliary tract. No specific drug therapy was given to our patients. Those with concomitant IBD were treated with salazosulfapyridine (SASP). The clinical course has been mild in all patients up to now. It is concluded that PSC may be much more frequent in childhood than was considered before, especially in children with IBD.