Essential psychopharmacology最新文献

While stimulant medications are the primary pharmacological treatment for ADHD across the lifespan, a subset of patients with ADHD do not experience significant symptom relief from stimulants or can not tolerate effective stimulant doses. Psychosocial therapies, particularly behavioral modification techniques, should be considered for children with ADHD and oppositional behaviors, while Cognitive Behavioral Therapy (CBT) may be a helpful adjunct for adolescents and adults with ADHD. Among the nonstimulant medications, atomoxetine (Strattera) is the only the FDA approved option. It has been found to be efficacious for the entire spectrum of ADHD symptoms in both children and adults. However, daily compliance is essential, and it may take several weeks to achieve full therapeutic effect. Other nonstimulants that have been used to treat ADHD include bupropion (Wellbutrin), the alpha-2 agonists guanfacine (Tenex) and clonidine (Catapres) as well as the tricylic antidepressants. Modafinil (Provigil) is actively being studied for the treatment of pediatric ADHD, and there has been some preliminary studies assessing the efficacy of cholinergic agents for ADHD. Recently, there has been increasing interest in combining nonstimulant therapies with stimulants to further enhance treatment effects. However, more controlled data on the safety and efficacy of combining pharmacological therapies are needed.

This article provides a clear and succinct description of the components of inheritance, such as trait transmission, genetic variability, and gene interaction. Genetic sequences constitute the prime focus of pharmacogenetic studies. Variations in drug-metabolizing enzyme systems tend to be monogenic, whereas the pharmacologic effects of medications appear to be polygenic, i.e., complex phenotypes shaped by the interaction of genes and environment. Translated into clinical terms, a history of a good response to a drug in a close relative of a patient is presumed to predict a good response to the same medication by the patient. This seems to hold for antidepressants, antipsychotics, and lithium, but the evidential studies generally have meaningful limitations. Bit by bit, information about the relationship between particular genetic formations and the effectiveness of these medications as well as their side effects, is appearing. The authors cite a number of examples, one such being an association between impaired antidepressant activity and the short allele of SLC6A4. This research promises to strengthen the accuracy, effectiveness, safety, and cost of our psychopharmacological practices.

Among the atypical antipsychotics, clozapine and olanzapine are known to cause significant weight gain. Along with quetiapine, they may impair glucose metabolism and increase the risk for type 2 diabetes. They are also associated with a rise in triglyceride levels and an increased risk for coronary artery disease. Clinicians should take these risks seriously in prescribing these antipsychotics and employ intelligent safeguards if and when they use them.

This article is a review of what is currently known about optimal treatments for patients with attention-deficit hyperactivity disorder (ADHD). It begins with a description of assessment techniques and the differential diagnosis, which includes learning disorders, anxiety disorders, and bipolar disorder. The high rate of comorbidity in patients with ADHD and the impact of comorbidity on treatment decisions are also discussed. Detailed descriptions of various pharmacologic treatments are provided, including a description of the role of combination pharmacotherapy and the integration of nonpharmacologic therapy. A decision-making model for selecting the most appropriate pharmacologic therapy versus combining pharmacotherapy with psychosocial interventions is described. The advantages and disadvantages of various pharmacologic agents--including long-acting stimulants and atomoxetine--are examined. Particular attention is paid to the recent Multimodal Treatment Study of Attention-Deficit Hyperactivity Disorder, sponsored by the National Institute of Mental Health, which includes a comparison of long-term pharmacotherapy, behavioral therapy, or a combination thereof, as well as an evaluation of the role of community-based therapy (i.e., treatment as usual). This article focuses on children and adolescents, because most of the research on ADHD has been conducted in this age group. However, a brief section on adults is also provided.

This article addresses the question of what defines a "mood stabilizer." Dr. Bauer expands upon his comprehensive 2004 review by (a) summarizing the conceptual and methodological approach to evaluating the evidence for pharmacotherapeutic options for bipolar disorder; (b) updating the evidence base from recently published controlled monotherapy trials; and (c) review the evidence base for combination therapy options. Finally, he identifies the shortcomings and sources of potential bias in our evidence base, which is critical for an accurate reading of the literature now and in the future.

General principles of the "outcome-focused" model of psychopharmacologic management of patients with BPD are illustrated using the case of Ms. A, a patient with borderline personality disorder (BPD) experiencing impulsivity such as suicidal behavior, chronic insomnia and concurrent substance abuse. The model includes (1) measurement of specific behavioral outcomes related to functioning; (2) assessment of the role of substance use/abuse in patients with BPD; (3) consideration of interventions to clarify and strengthen the boundaries of the therapeutic relationship-including short lengths of time between prescription refills, medication contracts outlining consequences if substances are obtained outside of the relationship, and urine testing to ascertain compliance; (4) an understanding of the psychodynamic meanings attributed to medication while positive and negative medication effects are monitored with treatment response or transference issues, and; (5) use of the N-of-1 approach to test the new medication vs previous medications using patient specific outcomes that are anticipated to change with the pharmacologic management.

Sleep deprivation has multiple effects on endocrine and metabolic function. In particular, sleep restriction is accompanied by increased cortisol levels in the afternoon and early evening and a shorter quiescent period compared with extended sleep periods. Those alterations could facilitate central and peripheral disturbances that are associated with glucocorticoid excess, such as memory deficits, and are similar to those observed in aging. Thus, chronic sleep loss could contribute to acceleration of the aging process. Sleep restriction is also associated with an impairment of carbohydrate tolerance, similar to that observed in individuals with clinically significant impaired glucose tolerance. Thus, chronic sleep deprivation may increase the risk for diabetes. Finally, sleep plays an important role in energy balance. Partial sleep deprivation was found to be associated with a decrease in plasma levels of leptin and a concomitant increase in plasma levels of ghrelin; subjective ratings of hunger and appetite also increased (the appetite for protein-rich foods was not significantly affected). Moreover, a remarkable correlation was found between the increase in hunger and the increase in the ghrelin:leptin ratio. Thus, the neuroendocrine regulation of appetite and food intake appears to be influenced by sleep duration, and sleep restriction may favor the development of obesity.

Neurosteroids, such as dehydroepiandrosterone (DHEA) and DHEA-sulfate (the most abundant steroid in the body), regulate neuronal functions by influencing neuronal excitability. Prominent effects are exerted on the gamma-aminobutyric (GABA) receptors. DHEA has demonstrated efficacy in improvement of mood in humans, especially in middle-aged and elderly individuals. In the author's study, administering DHEA to patients with schizophrenia who had moderate to severe negative symptoms and who were maintained on antipsychotic medications induced significant improvement, more so in women and corresponding to increased plasma levels of DHEA and DHEA-S. Possible mechanisms of action include enhanced dopamine release, enhanced responsiveness at the N-methyl D-aspartate (NMDA) receptor, facilitation of sigma receptor activity, selective potentiation of dopaminergic neurotransmission, and a general anxiolytic action. Side effects are reviewed, and the currently experimental status of DHEA augmentation is emphasized.

Clinical trials of antidepressants are difficult to design and conduct. In fact, more than half of all recent clinical trials of commonly used antidepressants failed to show statistical superiority for the drug over placebo. This is not necessarily because of the ineffectiveness of the antidepressant, but rather because of an increased response to placebo. Factors that may contribute to these findings remain elusive. Using data from U.S. Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports and from studies conducted by our group, we reviewed methodological factors used in clinical trials of antidepressants. The 2 most notable factors affecting positive trials are (1) the inclusion of patients with more severe depression, and (2) the use of a flexible-dose design; these may yield results identifying true antidepressant-placebo differences. Severely ill patients with depression respond well to antidepressants but poorly to placebo. Flexible dosing paradoxically reduces the response to placebo without augmenting the response to the antidepressant. All of these findings suggest that the use of placebo is mandatory when assessing new antidepressants.