Are the orally administered proton pump inhibitors equivalent? A comparison of lansoprazole, omeprazole, pantoprazole, and rabeprazole.
Two reviewers independently selected trials for inclusion and extracted data. Outcomes were: (a) elimination of EDS; (b) mean reduction of EDS; (c) elimination of cataplexy; (d) 50% or greater reduction in cataplexy frequency; (e) mean reduction of cataplexy; (f) mean improvement in quality of life; (g) adverse events; (h) withdrawal from treatment.
Cognitive-behavioral therapy (CBT) and pharmacological treatments are often applied in cases of pediatric obsessive-compulsive disorder (OCD). Especially in combination both methods are particularly efficacious; nonetheless, 40 % of all patients treated remain symptomatic. Exposure with response prevention, based on the principle of habituation, is the intervention with the best evidence. More recent cognitive and metacognitive treatments focus on modifying expectations and may have the potential to improve treatment efficacy. Selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment in severe cases of OCD. With treatment resistance, the SSRI should be changed, or alternatively clomipramine can be employed. Augmentation strategies suggest the combination of two SSRIs, SSRI und clomipramin, or SSRI and (atypical) neuroleptics. Following successful treatment, medication should be reduced very slowly. Novel treatments in children and adolescent have been reported for antiglutamatergic agents as riluzole or D-cycloserine, a partial agonist of N-methyl-D-aspartic acid (NMDA).
Obsessive-compulsive disorder is a chronic psychiatric illness, affecting up to 3% of the general population, to the middle of 60-th it was supposed to be untreatable. Antidepressant pharmacotherapy is one of the treatment alternatives today. We compared efficacy and safety of citalopram versus clomipramine (serotoninergic antidepressants) in 6 weeks in double blind therapy of obsessive-compulsive disorder. The second objective was to compare prolactin response to a fenfluramine challenge test before the treatment of patients and after 6 weeks of the treatment. In a sample of 14 patients we confirmed significant therapeutic response after 3 weeks of pharmacotherapy, better in obsession than in compulsion. We found low level of adverse effects in the first week of therapy--dry mouth, anxiety, nausea, somnolence, tremor, and sexual adverse events. There were no changes in the laboratory, test EEG, and ECG examinations. Fenfluramine challenge test showed statistically significant decrease of prolactin levels 1 hour after administration of fenfluramine. It was not observed after six weeks of the therapy. Statistically significant negative correlation between prolactin plasma levels at the 6th hour after administration of fenfluramine and obsession item of YBOC Scale was showed after the 3rd and 6th week of the therapy. The correlation was not observed for compulsion item YBOC Scale. Side effects observed during and after the challenge test were anxiety and nervousness and gastrointestinal problems, lasted from 1 hour to 10 hours. These preliminary result could support the idea, that obsessions and compulsions have not necessary the same biological background. The challenge paradigm appears to be a possible way to clarify the pathogenesis of OCD. Our study will continue.
Since the introduction of the selective serotonin reuptake inhibitors (SSRIs) a decade ago, they have become first-line agents in the treatment of obsessive-compulsive disorder (OCD). Numerous clinical trials have confirmed their efficacy, and established their superior risk-benefit ratio in comparison with clomipramine, a non-selective serotonin reuptake inhibitor. Relatively higher doses and longer duration of treatment may be necessary to effect a response in OCD, with long-term treatment being required to maintain therapeutic gains. Despite the advances represented by the SSRIs, treatment resistance remains a problem. While no one solution exists, various strategies, including pharmacotherapy augmentation, look promising.
The genetic cytochrome P450 polymorphism is reported in factors affecting the individual response to drugs. The interindividual variation at steady-state levels or also in elimination of drugs, finds an explanation in genetic differences in the metabolism. In particular, activities of the P450-IID6 isoenzyme are related to the sparteine/debrisoquine oxidation polymorphism. Phenotyping such a system has been proposed to analyse variability in the tricyclic antidepressant level. To analyse clinical relevance of a pharmacogenetic approach, we studied the cytochrome P450 CYP2D6 genotypes and the clinical responses to clomipramine in 21 hospitalised patients who met DSM-III-R criteria for major depression. Three patients were predicted as poor metabolizers. We suggested a limitation of clomipramine (CMI) hydroxylation in poor metaboliser (PM) patients which is balanced by a desmethylation. The clinical efficacy pattern does not differ in poor metaboliser and early metaboliser patients. Firstly, there is no significant differences in the evolution of scores on MADRS and specific retardation scale into the two groups. Secondly, outcome of side effects does not occur more frequently in PM patients. Clinical relevance of such an approach needs further study.