Since the risk of antipsychotic-induced adverse events is often related to plasma drug concentrations, factors that influence the metabolic transformation of these agents can substantially influence this risk. The cytochrome P450 (CYP) enzyme system, particularly CYP2D6, is very important for the metabolism of many typical and atypical antipsychotic agents. However, there is substantial ethnic/racial pharmacogenetic variability in the phenotypic (ie, metabolic rate) or genotypic (ie, presence of functional or nonfunctional alleles) expression of these enzyme systems. Caucasians have a bimodal distribution of CYP2D6 enzyme activity, with individuals classified either as extensive or poor metabolizers. In contrast, while there are few poor metabolizers among people of Asian descent, a substantial proportion of this population exhibits an intermediate rate of metabolism. African American populations also have a substantial number of intermediate metabolizers, and about the same number of poor metabolizers as Caucasians. Mexican Americans may have a slightly higher metabolic rate than other ethnic groups. Numerous studies have demonstrated that CYP2D6 metabolic status influences the clearance of conventional and atypical antipsychotics. African Americans and Asians, with CYP2D6 phenotypes or genotypes indicative of poor metabolizers, frequently exhibit significantly higher plasma drug concentrations and longer half-lives compared to extensive metabolizers. Importantly, this increased drug exposure is associated with an increased risk of extrapyramidal symptoms. Data on metabolic polymorphism of antipsychotics are lacking among African Americans. There are also some data suggesting that genetic polymorphism can influence the risk of antipsychotic-induced weight gain. These findings highlight the need to consider race/ethnicity when prescribing, dosing, and monitoring antipsychotic agents.

This discussion focuses on the historical trends of carbamazepine in the treatment of acute mania, acute bipolar depression, and as maintenance treatment for bipolar disorder. Clinical implications of efficacy, safety, tolerability, and drug interactions associated with carbamazepine are discussed as well.

Important progress in bipolar disorders therapeutics began in the 1970s with lithium and the conventional antipsychotics, and continued in the 1980s with carbamazepine, in the 1990s with divalproex, and in the 2000s with lamotrigine and the introduction of the atypical antipsychotics. Electroconvulsive therapy (ECT) has been used throughout these periods and still has a place in bipolar disorder, especially for severe, treatment-resistant, and very acute cases.

Anxiety disorders are currently one of the most common health concerns in the United States. Overall, they are the single largest cost to the healthcare system. They are also underdiagnosed and undertreated. Selective serotonin reuptake inhibitors and benzodiazepines appear to be the most common pharmacologic treatment approaches. Unfortunately, not all patients respond to these treatments. Many augmentation strategies have been tried in the past with varying levels of success or safety. This article describes a safe and highly effective augmentation technique in patients suffering from some of the most serious and debilitating forms of anxiety disorders, namely obsessive-compulsive disorder and panic disorder.

CNS Spectrums is an Index Medicos journal that publishes original scientific literature and reviews on a wide variety of neuroscientific topics of interest to the clinician on a monthly basis. Our mission is to provide physicians with an editorial package that will enhance and increase their understanding of neuropsychiatry; therefore, manuscripts that address crossover issues between neurology and psychiatry will be given immediate priority.

As the United States population continues to grow and diversify, physicians must be equipped to treat patients of different races and ethnicities. Current data suggest that certain ethnic minority groups may be predisposed to a variety of clinical conditions, including obesity, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. Furthermore, as physicians begin to turn more frequently to atypical antipsychotics in psychiatric illness, they face a growing concern regarding the development of metabolic side effects, especially in a US population that is gradually becoming more obese from a demographic standpoint. In addition, certain ethnic groups may be more susceptible to these metabolic effects. The metabolic side effects induced by the atypical antipsychotics vary greatly, with the newer agents generally displaying fewer and less severe side effects, indicating that the particular agent chosen is of critical importance. A risk/benefit assessment, taking into consideration any genetic predisposition, preexisting risk factors, and the side-effect profile of the specific agent, is paramount to the successful management of these patients. The ultimate goal is careful consideration of possible metabolic side effects in patients taking atypical antipsychotics, in order to avoid serious consequences.

Alzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.

Introduction: A wealth of evidence indicates that neurocognitive deficits are evident in patients with schizophrenia at both illness onset and after many years of treatment. Little is known regarding if or how these deficits change during the lifespan. The goal of the study was to evaluate changes in full-scale intelligence quotient and neurocognitive test performance over a 10-year interval in patients with schizophrenia.

Methods: Twelve patients were administered the Wechsler Adult Intelligence Scale-Revised as a measure of intellectual function and a neuropsycshological test battery including measures of attention, verbal and nonverbal memory, language, visuospatial function, problem-solving, and motor function at entry to the study and at a 10-year follow-up.

Results: With the exception of performance on a measure of speeded motor sequencing, there was no significant decline in any of the measures at 10-year follow-up. Results from a measure of sustained auditory attention showed improvement at follow-up.

Discussion: These data support a neurodevelopmental model of schizophrenia for young adult to middle-age patients by suggesting that neurocognitive deficits that emerge either before disease onset or early in the course of the illness remain stable as the patient ages.

Conclusion: Overall, measures of intelligence quotient as well as specific neurocognitive skills, do not decline over a 10-year period in at least a subgroup of patients with schizophrenia.

Objective: Evaluate safety and efficacy of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: 10-week interim analysis of the Quality of life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) trial, an ongoing, 30-week, open-label, multicenter investigation of once-daily MAS XR (10–60 mg/day) in adults (≥18 years of age) with ADHD in community practice settings.

Findings: With up to 10 weeks of open-label MAS XR 10 to 60 mg/day (final visit mean dose: 37.2 mg/day), 725 adults exhibited rapid, sustained improvement in ADHD symptoms. At end point, significant decreases from baseline were seen in ADHD Rating Scale IV total scores (-19.8±11.6; P<.0001), hyperactivity/impulsivity subscak (-8.1±6.1; P<.0001), and inattentive subscale (-11.6±6.7; P<.0001). Most subjects (74.4%) were rated as very much/much improved. Based on the 36- item Short Form Health Survey (version 2), significant improvements in quality of life were seen in the domains of general health, physical and mental health, vitality, and social, emotional and physical role functioning (P<.0001). Few subjects (6.9%) withdrew due to adverse events; the most common MAS XR-related adverse events were decreased appetite and dry mouth (19.2% each), insomnia (17.8%), and headache (16.8%).

Conclusion: In adults with ADHD, MAS XR treatment is generally safe and demonstrates significant improvement in ADHD symptoms and related quality of life.

This discussion reviews data from two 3-week, double-blind, placebo-controlled pivotal trials of carbamazepine extended release capsules (CBZ ERC; SPD417.301 and SPD417.304); pooled results from these trials; data from a 3-week, double-blind, placebo-controlled trial in lithium non-responders or non-tolerators (SPD417.302); and additional supportive data from a 6-month, open-label, extension trial (SPD417.303). In addition, information on a retrospective chart review of 600 adolescent and adult bipolar patients on CBZ ERC is presented.

In the first large double-blind, placebo-controlled study assessing CBZ ERC in acute mania, manic and mixed bipolar patients from multiple centers were hospitalized and all medications were discontinued. After reaching a stable baseline 2–5 days later, the patients were randomized to CBZ ERC (n=101; 59% with mixed states) or placebo (n=103; 47% with mixed states) for 3 weeks. An aggressive initial titration schedule was implemented, beginning with 200 mg BID and increased by 200 mg/day until good clinical response was achieved or the patient could not tolerate the dosage. Many patients were taking 1,200–1,600 mg/day by the end of week 1. Efficacy was assessed using the Young Mania Rating Scale (YMRS). The Clinical Global Impressions (CGI) scale and the Hamilton Rating Scale for Depression (HAM-D) were also followed.

Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical, and epidemiological links. The clinical use of atypical neuroleptics (ie, dual serotonin-dopamine antagonists) to treat both conditions sheds a new light on them. We report the first two cases of obsessive-compulsive symptoms (OCS) induced by quetiapine in schizophrenia patients. A case of successful augmentation by quetiapine in refractory OCD is also presented. A review of the literature on OCS induced by atypical neuroleptics follows. This paradoxically induced OCD symptomology in schizophrenia patients administered atypical neuroleptics is discussed from new pathophysiological and clinical perspectives. The discussion emphasizes the prognostic implications of OCS in schizophrenia and available therapies for this comorbidity.

Panic disorder, frequently complicated by agoraphobia in the clinical setting, is a relatively common disorder that is associated with significant morbid burden and dysfunction in affected individuals. PD treatment is focused on the reduction of panic attacks, avoidance behavior, and anticipatory anxiety, as well as the resolution of comorbid conditions, with the goal of normalizing function and improving overall quality of life. Antidepressants, including the selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, as well as benzodiazepines, are commonly used as primary pharmacotherapies for the treatment of PD, with a variety of other novel interventions potentially useful as well, to optimize treatment outcome.