From the perspective of efficacy, the main advantages of the group of new antipsychotic drugs, including ziprasidone, clozapine, quetiapine, olanzapine, and risperidone, are their ability to improve cognitive function. Other advantages are more selective, eg, clozapine in treatment-resistant schizophrenia, while the advantages for positive and negative symptoms in neuroleptic responsive patients are modest and sometimes difficult to demonstrate. The advantage for cognitive function is important because of abundant evidence that cognitive function is a key predictor of work and social function acquisition. The drug-induced cognitive improvement can synergize with typical rehabilitation programs and more experimental cognitive retraining programs to optimize these areas of improvement. Improved cognition also has implications for better compliance and decreased caretaker burden. It is also important to consider the efficacy of antipsychotics to improve mood and negative symptoms and to provide a biological framework for their ability to achieve these advantages over typical neuroleptic drugs. This article will provide new data on efficacy of this class of drugs relative to each other and to typical neuroleptics. Current theories linking efficacy in cognition to unique effects on cortical dopaminergic and cholinergic function and improved patterns of connectivity in the brain during cognitive task performance will be discussed. Finally, pharmacologic strategies to augment affect and cognitive improvements due to the new antipsychotic drug therapies will be discussed.

Depression is one of the world's great public health problems. As there are no perfect or uniformly effective treatments for depression, it is not surprising that treatment-resistant depression (TRD) is likewise an important public health problem. Although the potential benefits of antidepressants are now well documented, no widely used antidepressant can be expected to be effective in more than half the patients who begin to take it. Even under optimal circumstances (ie, a patient who is fully adherent to 12 weeks of treatment), there is only a 60% to 70% chance that the first choice of medication will be effective. The need for effective alternate strategies for TRD, as well as the need for innovations in service delivery systems to ensure those strategies are implemented in a timely manner, are foremost to fully realizing the potential benefits of antidepressant therapies.

Over the years, hierarchies of treatment strategies for TRD have been based on the widespread use of particular treatments, their ease of use, and their safety or complexity. One of the strategies consistently used since its introduction 20 years ago has been augmentation of the ineffective antidepressant by a second medication. The second agent may or may not have antidepressant effects of its own, but when used in combination with a primary antidepressant the agent reliably increases a patient's likelihood of response and symptom remission.

Complementary and alternative medicine (CAM) is very popular in the United States, Canada and other Western societies, and the number of patients seeking treatment by CAM practitioners is increasing. This trend also affects treatment-seeking patients with affective disorders. Many patients and mental health providers update their information and formulate opinions and decisions based on second-hand digested summaries and scientific reviews of the literature. This results in the proliferation of review articles and journals that are exclusively dedicated to reviews. Since most medical schools do not teach CAM and most continuing medical education programs still ignore these subjects, it is of interest to examine the reliability of reviews that claim to be “systematic” and not to take their procedures and conclusions for granted.

Atypical antipsychotics—clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole—differ from conventional antipsychotics primarily by virtue of their actions at multiple central receptor sites. Each agent has its own unique receptor profile. The discovery of dopaminergic receptor-blocking capabilities of conventionblockingal antipsychotic drugs led to the dopamine hypothesis of schizophrenia. More recently, the role of serotonergic and other receptors in the pathophysiology and symptomology of schizophrenia and schizoaffective disorder has been identified, and the receptor actions of atypical antipsychotics have been linked to both antipsychotic efficacy and the propensity for extrapyramidal symptoms and other adverse effects. Receptor occupancy is directly related to antipsychotic dose, and the nature of the relationship between clinical utility and receptor occupancy is beginning to emerge. As our understanding of this relationship becomes more clear, the mechanism underlying clinical distinctions between agents will be understood.

The advent of the newer “atypical” antipsychotics has revolutionized pharmacologic treatment of schizophrenia (SZ) and other psychotic disorders. In contrast to the first-generation conventional neuroleptics, these second-generation antipsychotic agents possess a broader spectrum of efficacy and cause fewer motor side effects such as extrapyramidal symptoms and tardive dyskinesia. Despite their substantial advantages, however, these second-generation agents also have significant limitations in terms of both efficacy and adverse effects. Several strategies to address these shortcomings are currently under study and some of these are likely to become part of our therapeutic armamentarium in the future. Current shortcomings in the pharmacologic treatment of SZ and strategies under investigation to address each of these deficiencies are reviewed. New formulations of existing medications and new antipsychotics under development are discussed. Developing adjunctive treatment strategies to address each of the major psychopathologic domains in SZ are summarized. The potential application of genetic information to treatment-matching in SZ is reviewed and likely refinements in the practice of evidence-based medicine in the pharmacotherapy of SZ are considered.

Psychopathy is a severe form of personality disturbance, resulting in a detrimental impact on individuals, healthcare systems, and society as a whole. Until relatively recently, most research in psychopathy has focused on male samples, not least because of its link with criminal behavior and the large proportion of violent crime committed by men. However, psychopathy in women also leads to considerable problems at an individual and societal level, including substance misuse, poor treatment outcomes, and contribution to ever-increasing numbers of female prisoners. Despite this, due to relative neglect, most research into adult female psychopathy is underpowered and outdated. We argue that the field needs revitalizing, with a focus on the developmental nature of the condition and neurocognitive research. Recent work international consortia into conduct disorder in female youth—a precursor of psychopathy in female adults—gives cause for optimism. Here, we outline key strategies for enriching research in this important field with contemporary approaches to other psychiatric conditions.

In this article, we review attempts to account for the thought disorder present in some schizophrenic patients in terms of cognitive deficits in the domains of working memory, attention, language, and semantic memory. Although each psychological construct can account for some of the data described here, establishment of a primary cognitive impairment responsible for thought disorder is not forthcoming, perhaps due to its underlying multidimensional pathology. While the relationship of working memory, attention, and language processing to thought disorder is ambiguous, semantic memory is emerging as a promising construct, that may yield insight into cognitive mechanisms that underlie thought disorder and neuroleptic responsiveness.

There are currently >5 million people in the United States who have been diagnosed with Alzheimer's disease. That prevalence rate is expected to triple as the population ages. The health and economic burden due to Alzheimer's disease is a worldwide problem, with some of the greatest burden coming from the developing world as people live longer in those societies. Throughout the world, the projected growth of Alzheimer's disease is dramatic. This is a worldwide public health problem of the highest order, and there is a compelling need to develop new treatments and methods of earlier diagnosis need to slow the progression of the disease and lessen its impact.

The lifetime incidence of mood disorders is twice as great in women compared with men, with the highest risk occurring during the childbearing years. The management of mental illness during pregnancy and lactation is a particularly complex clinical situation. The cornerstone of such a clinical decision is a completion of an assessment of the risks of the illness vs the risks of treatment. The following article reviews the factors influencing infant outcome and outlines the essential elements of the process of determining risk for the use of psychotropics in women during pregnancy and lactation. As the available data rapidly change, the facets of the risk benefit assessment are consistent and often the issue of specific medication is decided by prior history and exposure.

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1–associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatrie functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatrie functioning, potential treatment implications will also be discussed.

Patients with psychiatric disorders have an increased rate of cardiovascular morbidity and mortality compared with the general population. Metabolic issues such as weight gain, dyslipidemia, diabetes mellitus, diabetic ketoacidosis, and pancreatitis have been reported with the use of antipsychotic agents. Although atypical antipsychotics have not been linked directly to the development of metabolic syndrome, these medications have been shown to increase risk factors that can lead to metabolic and endocrine disturbances. Therefore, clinicians should provide ongoing monitoring for patients who are being treated for psychiatric disorders with these agents. According to the 2004 Consensus Report on Antipsychotics, screening measures should include baseline and follow-up monitoring of personal/family histories, weight (body mass index), waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile.

Most antidepressants and other psychotropics in clinical use are available as generic formulations (Table). The availability of lower-priced, generic drugs can benefit patients and third-party payers, but it should not be assumed that all generic drugs are equally beneficial. There are numerous reports in the literature of unexpected and untoward consequences that occur when a generic drug is substituted for the original brand-name drug. A previously stable clinical response may suddenly deteriorate, or the patient may experience new or more severe adverse events (AEs). The United States Food and Drug Administration requires that manufacturers of generic drugs demonstrate that their formulation has pharmacokinetic properties similar (or bioequivalent) to the brand-name drug. Bioequivalency studies are conducted in healthy volunteers, not in patients who would be treated with that drug. Moreover, bioequivalency studies are conducted on a current lot of the branded drug and do not account for variability between lots of the generic formulation. The manufacturer is only required to submit bioequivalency data that support the Abbreviated New Drug Application (ANDA); the FDA does not require disclosure of failed bioequivalence studies. Unlike brand-name drugs, lengthy and costly clinical studies are not required to show that the generic drug is effective and safe.

Although the FDA has taken the position that bioequivalence and therapeutic equivalence are equal, many questions related to the use of generic drugs remain unanswered. The following question-and-answer session is an excerpt of an interview with Pierre Blier, MD, PhD, conducted by Diane Sloan, PharmD, which addresses the issue of generic substitution of psychotropic drugs.