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.

Patients with schizophrenia have a 20% shorter lifespan than people without the disorder. An increased risk of cardiovascular morbidity and mortality is also associated with schizophrenia. Atypical antipsychotics may contribute to the prevalence of cardiovascular disease by causing weight gain and increased adiposity, risk of insulin resistance, hyperglycemia, diabetes, and hyperlipidemia. Atypical antipsychotics that produce the greatest degree of weight gain also appear to impose the greatest risk of diabetes and hyperlipidemia. Recent evidence suggests that atypical antipsychotics may even affect glucose and lipid metabolism independent of weight gain. Among the currently marketed antipsychotics, clozapine and olanzapine appear to produce the greatest degree of weight gain. Moderate increases in weight are also observed with quetiapine and risperidone. Only ziprasidone and aripiprazole appear to be weight neutral. Atypical antipsychotics that produce the greatest degree of weight gain also appear to carry the greatest risk of diabetes and hyperlipidemia. Because of the potential for atypical antipsychotics to cause weight gain and adversely affect glucose and lipid metabolism, clinical monitoring of these parameters is critical. Dietary modification and exercise may be critical to addressing antipsychotic-induced weight gain and its consequences. In patients with persistent weight gain, evaluation of the risks and benefits of ongoing medications and consideration of switching to an antipsychotic with lower weight-gain liability may improve health outcomes.

Panic disorder (PD) is a complex, multidimensional psychiatric disorder characterized by the presence of panic attacks as well as anticipatory anxiety and panic-related phobias (eg, agoraphobia). Although the etiology of this disabling disorder remains unclear, advances in basic neuroscience and in imaging studies have led to a greater understanding of the neurocircuitry and neurochemistry that are involved in modulating fear and anxiety and that are relevant to understanding PD. A preliminary integrated model can be outlined, but there is a need for additional research that cuts across genetic investigation, provocation studies, neuroimaging techniques, and treatment trials. As research continues and greater insight into the mechanisms underlying PD is achieved, additional treatment strategies may emerge.

A 79-year-old woman is referred by her primary care physician for an evaluation regarding a possible psychiatric diagnosis. Until now, she has had an unremarkable medical and psychiatric history. For the past 4 months, the family has observed increasing confusion. She has been repeating statements that she has just made, evidences increasing forgetfulness, such as misplacing her keys and checkbook, and, on one occasion, went to the grocery store but could not remember which items she needed to purchase. There has also been a history of insomnia, some irritability, and she becomes agitated over trivial issues related to household activities. She has had a reduction in appetite and has lost 5 pounds. Furthermore, she has complained of fatigue and a decrease in energy. Her husband indicated that she rarely drinks alcohol. She has not mentioned suicidal ideation directly but she has become increasingly concerned that her affairs are in order. Two of her friends died in the previous year and one was admitted to a nursing home.

Objective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.

Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.

Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.

Conclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.

Alzheimer's disease is a devastating neurological disorder characterized by cognitive deficits, functional impairment, and often troublesome behavioral symptoms. Unfortunately, Alzheimer's disease can be difficult to diagnose at early and even moderate stages of the disease. This article outlines simple, efficient strategies for identifying patients with potential dementia. The discussion focuses on the key components of a comprehensive assessment plan, which typically involves taking the patient's history, as well as conducting cognitive testing, laboratory testing, neurologic examination, and neuroimaging to evaluate patients for Alzheimer's disease. Finally, opportunities for the improvement of care are discussed, with an emphasis on overcoming barriers to diagnosis such as time limitations and reimbursement issues.

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.