Journal of clinical psychopharmacology
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J Clin Psychopharmacol · Aug 1997
Letter Case ReportsSerum and urine risperidone concentrations in an acute overdose.
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J Clin Psychopharmacol · Jun 1997
ReviewSelective serotonin reuptake inhibitor-induced serotonin syndrome: review.
The selective pharmacology of the selective serotonin reuptake inhibitors (SSRIs) results in a lower potential for pharmacodynamic drug interactions relative to other antidepressants such as the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). However, the SSRIs have been implicated in the development of the serotonin syndrome--a potentially life-threatening complication of treatment with psychotropic drugs. The syndrome is produced most often by the concurrent use of two or more drugs that enhance central nervous system serotonin activity and often goes unrecognized because of the varied and nonspecific nature of its clinical features. ⋯ The exceptionally long washout period required after fluoxetine discontinuation may cause additional problems and/or inconvenience. Patients with serotonin syndrome usually respond to discontinuation of drug therapy and supportive care alone, but they may also require treatment with antiserotonergic agent such as cyproheptadine, methysergide, and/or propranolol. To reduce the occurrence, morbidity, and mortality of the serotonin syndrome, it must be both prevented by prudent pharmacotherapy and given prompt recognition when it is present.
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J Clin Psychopharmacol · Aug 1996
Comparative StudySteady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4'-hydroxylation status in Japanese depressive patients.
The steady-state plasma concentrations of imipramine and desipramine were measured after a more than 2-week treatment with 0.39 to 1.39 mg/kg/day of imipramine hydrochloride in 28 Japanese patients with major depression who had been phenotyped simultaneously with mephenytoin (for CYP2C19-related status) and with metoprolol (for CYP2D6-related status) before initiating the antidepressant therapy. Patients consisted of five poor metabolizers (PMs) of CYP2C19 with an extensive metabolizer (EM) phenotype of CYP2D6, whereas the remainder were EMs for both of the phenotypes. The mean respective concentrations (corrected by mg/kg) of imipramine and the sum of imipramine plus desipramine were 2.4 and 1.8 times greater in the CYP2C19-related PM than in the EM group, and these two variables correlated with the log10 urinary excretion of 4'-hydroxymephenytoin (rs = -0.73 and -0.64, both p < 0.01, respectively), but not with the metabolic ratio (MR) of metoprolol/alpha-hydroxymetoprolol. ⋯ This index correlated with the 4'-hydroxylation of S-mephenytoin (rs = -0.51, p < 0.01), but not with the alpha-hydroxylation of metoprolol, implying that imipramine N-demethylation is under a coregulatory pharmacogenetic control of CYP2C19, but not of CYP2D6. In conclusion, by taking into account that the incidence of the PMs of CYP2C19 is much greater (18-23%) than that of CYP2D6 (< 1%) in Japanese population, the individually predetermined assessment of the CYP2C19-mediated metabolic capacity of imipramine would be more valuable than that of the CYP2D6-mediated capacity for forecasting the steady-state concentrations of imipramine and desipramine in Japanese depressive patients, thereby attaining an individualized optimization of imipramine therapy. Obviously, a pharmacodynamic assessment study conducted simultaneously with predetermined CYP2C19 status is required for supporting this contention.
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Depression is often related to disturbances of norepinephrine and serotonin neurochemical systems within the brain that affect functional neurobehavioral systems. Classes of antidepressant agents have been developed that directly affect proposed brain neurochemical alterations. ⋯ Because of the recurrent and potentially chronic nature of depression, safety and tolerability of available treatments are especially important. An overview of antidepressant options is presented, with a particular focus on venlafaxine.