ABSTRACT
BACKGROUND: Depression is thought to involve, in part, dysregulation of serotonergic neurotransmission. In depressed individuals, the number of serotonin receptors, including the 5-hydroxytryptamine (serotonin)-1A (5-HT(1A)) autoreceptors, are increased. Clinical improvement with selective serotonin reuptake inhibitors (SSRIs) is not usually observed until several weeks after treatment initiation. This delay may be due to the time it takes for the autoreceptors to downregulate. Roughly one-third of patients with depression do not respond to an initial trial of antidepressant medication treatment, possibly as a result of structural variations in the 5-HT(1A) receptor. AIMS: This study was designed to determine the allelic frequency of seven 5-HT(1A) receptor polymorphisms in a depressed versus a nondepressed population, and in SSRI responders versus nonresponders. All the polymorphisms studied are single nucleotide polymorphisms (SNPs) in the HTR1A gene, which encodes 5-HT(1A). Seven prevalent SNPs were included in the analysis. RESULTS: The study showed no relationship between any of the HTR1A polymorphisms and SSRI responders versus nonresponders. CONCLUSION: While the study has several limitations, the results are consistent with a growing body of literature that suggests that the pharmacogenetics of depression (an inherently complex disorder) may turn out to be multifactorial, and may include the HTR1A gene in concert with other serotonin-related genes.
Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Polymorphism, Single Nucleotide , Receptor, Serotonin, 5-HT1A/genetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Depression/genetics , Drug Resistance , Humans , Middle AgedABSTRACT
OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of aripiprazole for the treatment of schizophrenia. DATA SOURCES: Information was selected from MEDLINE (1995-August 2002). Abstracts, scientific posters, and presentations were also used. STUDY SELECTION/DATA EXTRACTION: All published information regarding the pharmacokinetic, pharmacodynamic, and clinical characteristics of aripiprazole was considered. Studies providing a comprehensive description of aripiprazole were selected. DATA SYNTHESIS: Aripiprazole is a dopamine partial agonist and a serotonin-2A antagonist; it is dosed 10-30 mg/d, with no initial titration necessary. Short-term clinical trials demonstrated efficacy in acute exacerbations, and long-term studies showed that aripiprazole can maintain remission of schizophrenia. Most adverse events were mild. The incidence of extrapyramidal symptoms was low, with akathisia being the most common. CONCLUSIONS: Aripiprazole currently demonstrates comparable efficacy and safety for use in schizophrenia.
