The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was an effectiveness/”pragmatic” clinical trial designed to compare the efficacy, tolerability, and cost-effectiveness of four atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a conventional antipsychotic (perphenazine) for an 18-month period in patients with schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria than in most trials in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Olanzapine demonstrated significant superiority in time to discontinuation for all cause and for lack of efficacy, as well as likelihood of hospitalization for relapse; however, it was associated with a significantly higher rate of metabolic side effects. Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and ziprasidone, and appeared to be as well tolerated as the atypicals. However, it had the highest rate of drop out due to extrapyramidal symptoms and was restricted to patients who did not have tardive dyskinesia (TD). This article examines the phase 1 CATIE results to guide the clinician in understanding how to interpret the findings, which were intended to be a guide for clinical practice. The nature of the patient population, the doses of drugs relative to one another, inclusion of patients who were treatment resistant, and exclusion of patients with TD from randomization to perphenazine were potential sources of bias in the study. In particular, the use of a higher-than-usual peak dose of olanzapine may have led to the superior results achieved with it. Practical suggestions are given for choice of antipsychotic medication in patients with chronic schizophrenia.

There is an ongoing debate about how best to conceptualize the unconscious. Early psychodynamic views employed theories influenced by physics to explain clinical material, while subsequent cognitivist views relied on computational models of the mind to explain laboratory data. More recently, advances in cognitive-affective neuroscience have provided new insights into the workings of unconscious cognition and affect. We briefly review some of this recent work and its clinical implications.

Body dysmorphic disorder (BDD) is characterized by preoccupation with a defect in appearance. Concepts of beauty play a particularly crucial role in humans' mental and social life, and may have specific psychobiologic and evolutionary underpinnings. In particular, there is a growing literature on the neurocircuitry underpinning the body schema, body image and facial expression processing, and aesthetic and symmetry judgments. Speculatively, disruptions in cognitive-affective processes relevant to judgments about physical beauty lead to BDD.

Most people with epilepsy maintain normal reproductive and sexual lives. However, a significant minority of women with epilepsy (20% to 30%) have some degree of sexual dysfunction, including problems with libido, arousal, and orgasm. Men with epilepsy are at risk for decreased sexual functioning, including sexual interest and sexual performance, at least in part because of increased sex hormone-binding globulin levels and lower bioactive testosterone levels, particularly in association with the use of enzyme-inducing antiepileptic drugs, such as phenytoin and carbamazepine. A decrease in bioactive testosterone levels probably has a significant effect on the sexuality of women with epilepsy as well. Antiepileptic drugs may also affect sexual function in women through alterations of serotonergic neurotransmission. Epilepsy itself appears to have the potential to affect sexual function. The amygdala is emerging as a brain structure with significant involvement in sexuality in patients with epilepsy, as shown by alterations in sexual functioning after temporal lobectomy. Preliminary evidence suggests that people with temporal lobe epilepsy have reduced genital blood flow in response to erotic stimulation; the etiology of this phenomenon is not well understood, but disruption of the limbic and frontal cortex by epileptic activity may be implicated. Psychosocial factors, including sexual anxiety and stigma associated with epilepsy, can also affect the sexual life of patients with epilepsy.

The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Severe hair-pulling is characteristic of trichotillomania, an impulse control disorder not otherwise classified. Other pathological habits, including severe nail-biting and skin-picking, are also prevalent and are potentially diagnosable as stereotypic movement disorder. There is increasing awareness of the morbidity associated with these kind of habit disorders but, to date, relatively few randomized controlled trials of pharmacotherapy or psychotherapy have been undertaken. Advances in the understanding of the underlying cognitive-affective mechanisms driving stereotypies in animals and humans may ultimately lead to new approaches. An affect regulation, behavioral addiction, and cognitive control (A-B-C) approach is outlined to conceptualizing and managing these conditions.

In the United States, more individuals suffer disability from stroke than from any other disease, and as many as 11 of the 43 presidents have been affected. In this article, the authors review the cases of the United States presidents who have had strokes, some of which have occurred while the president was in office, having a direct effect on the country.

One cannot get through a day (certainly not in the United States) without hearing about the devastation that substance abuse, addiction, and, in many cases, co-occurring disorders (ie, substance abuse or addiction in conjunction with a major psychiatric clinical syndrome and/or personality disorder) cast upon countless numbers of lives. For years, there has been a controversy as to whether addiction was simply a moral failing or a brain disease. Obviously, the latter is true.

As with any disease, addiction and co-occurring disorders are frequently considered to be primary, progressive, chronic, and, if untreated, fatal. With the advent of more sophisticated neurobiological and multivariate research, we can get beyond trivializing this serious disease entity by labeling it as a weakness or character defect, and get on with the significant work of focusing on those neurological pathways and their etiology that are responsible for addictive patterns of behavior.

Response and remission rates are commonly used to evaluate the efficacy of treatments for anxiety disorders and other psychiatric illnesses. Response is generally regarded as a clinically meaningful improvement in symptoms, while remission, the goal of treatment, is generally thought of as the absence or near absence of symptoms following illness, accompanied by a return to premorbid levels of functioning. Response and remission are often defined using psychiatric rating scales, based on score cutoffs or the magnitude of score changes from baseline. While no universally accepted criteria exist, a commonly used threshold for response is a >50% improvement in the total score, while for remission, various cutoff points have been used. Comparison of cutoffs or change scores for disease-specific scales with Clinical Global Impressions ratings is a useful way of evaluating response and remission criteria across disorders. To illustrate the use of disease-specific and global measures, this article summarizes data from randomized, placebo-controlled studies of adult patients with generalized anxiety disorder, social anxiety disorder, or panic disorder treated with the serotonin norepinephrine reuptake inhibitor venlafaxine extended release, for which acute-phase data are available (a total of 13 trials).

Posttraumatic stress disorder (PTSD) is a well-defined clinical syndrome that develops in individuals who have witnessed or been exposed to an event that involves a direct threat to life or physical and/or psychological integrity.

While numerous studies indicate that PTSD will develop in 15% to 25% of trauma victims, time-limited responses develop in a larger portion of victims during the first 48–72 hours (acute stress reaction) and to a lesser extent over the first 4 weeks (acute stress disorder). Many of those who suffer from acute posttraumatic symptoms eventually recover and overcome the consequences of the traumatic event. However, ∼30% to 50% of those with acute stress disorder will eventually develop PTSD. It is obvious that some individuals are vulnerable to the adverse effects of trauma while others have neurobiological and psychological resources that make them resilient to the long-term impact of traumatic exposure. The identification of risk factors and early predictors for PTSD is thus of major importance for identifying those at risk and for initiating therapeutic interventions aimed to reduce long-term morbidity and suffering.

Optimal management of depression remains a long-term challenge. Long-term maintenance treatment with antidepressants has been shown to be effective for preventing or delaying recurrence for many patients with a history of previous multiple episodes. However, aside from a history of multiple recurrences, it remains difficult to identify patients who are most likely to experience recurrence and when. Thus we do not really know who might particularly benefit from maintenance therapy and what type may be efficacious. In patients with depression, research has shown there are structural and functional alterations in the brain, particularly in patients with recurrent or chronic depression. These changes have been generally viewed to be consequences of the disease, which are seen to worsen with a longer duration of untreated illness and with a greater number of depressive episodes. However, these neurobiological characteristics may also represent risk factors or vulnerabilities that predispose some patients to chronic or recurrent depression. Additional research has demonstrated that antidepressant treatment may reduce or modulate these functional and structural changes, suggesting that long-term treatment may, in fact, benefit patients not only by controlling symptoms but also by managing these underlying vulnerabilities. A new treatment paradigm, which focuses on identifying patients with risk factors and managing the disease process rather than suppression of symptoms, is needed for recurrent depression.

A case of pure mutism without pseudobulbar palsy and other neurological findings resulting from simultaneous bilateral lenticulostriate artery territory infarction is presented. A 45-year-old woman suffered a transient ischemic attack with nonfluent aphasia and right hemiparesis. Six months later, she developed pure mutism without oral apraxia, pseudobulbar signs, and motor deficits. Magnetic resonance imaging revealed bilateral infarction in the lentiform nucleus regions. In the available data, there is only one report of simultaneous bilateral lenticulostriate infarction.To date, in all reported cases of mutism of subcortical vascular origin there are also various degrees of pseudobulbar signs and motor deficits and the responsible lesions are mostly consecutive.The case presented here is the first to show pure vascular mutism without other neurological findings.

Development of extrapyramidal symptoms (EPS), particularly tardive dyskinesia (TD), has long been a troubling side effect for patients taking antipsychotics. Atypical antipsychotics have been hailed as an improvement over conventional antipsychotics, offering similar efficacy with more favorable EPS profiles. In the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which compared the conventional antipsychotic perphenazine with atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone in patients with schizophrenia, no significant differences in time to treatment discontinuation due to intolerability were observed between treatment groups. However, perphenazine was associated with a higher rate of patients experiencing EPS as well as a significantly higher rate of discontinuation due to EPS, despite the fact that patients with TD at baseline were excluded from the perphenazine group. Unfortunately, due to short treatment duration, the CATIE study did not have the assay sensitivity to detect differences in TD risk among any of the drugs. Thus, the atypical antipsychotics remain the first line of treatment for most patients, with specific drug selection based on benefit-risk profiles that best fit the individual patient's needs. Frequent monitoring, while noting a patient's subjective experience, remains the best strategy for choosing therapy to maximize symptom relief and minimize the impact of EPS and other side effects over the long-term. This article explores the reported results of the CATIE trial regarding EPS and emphasizes the differentiation of the atypicals from perphenazine on EPS and how these results should be incorporated into daily practice for the clinician.