Do antidepressants have an equivalent risk-benefit ratio? Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is an effective antidepressant for treating major depression. The results of some clinical studies have suggested that venlafaxine may have more potent efficacy in sustaining remission in patients with major depression. Comparative clinical studies, however, lack suitable power to discern treatment differences in safety and also lack a quantitative basis for comparing risk and benefit. A global benefit-risk analysis of pooled data from eight randomized, double-blind, clinical trials of the safety and efficacy of venlafaxine and selective serotonin reuptake inhibitors (SSRIs) was performed. By using the ratio measure of risk-benefit, patients treated with venlafaxine (n=851) for 6–8 weeks experienced a relative gain of 1.57 compared with SSRI-treated patients (n=743) and a relative gain of 2.27 compared with placebo-treated patients (n=439). Subgroup analyses showed a relative gain of 1.35 for venlafaxine-treated patients (n=538) compared with fluoxetine-treated patients (n=549) and a relative gain of 2.53 compared with placebo-treated patients (n=357). A dose-response relationship was apparent between low (<75 mg/day), medium (75–150 mg/day), and high (>150 mg/day) dosages of venlafaxine; r values were 0.758, 0.822, and 1.181, respectively (P=.023, high dosage versus placebo; P=.030, medium dosage versus placebo). Important differences in risk and benefit exist between venlafaxine and SSRIs as a group compared with fluoxetine alone. A significant gain in benefit-risk in the treatment of major depression was observed with an increase in venlafaxine dosage from 75–>150 mg/day.

Historically, drugs that increase central cholinergic transmission have primarily been investigated for relieving cognitive symptoms in mild-to-moderate Alzheimer's disease. These efforts have led to the somewhat unexpected findings that cholinergic therapy has a beneficial effect on selected neuropsychiatric symptoms in AD across disease stages. In Parkinson's disease with dementia and dementia with Lewy bodies, cholinergic deficits are more severe than in AD, and there is emerging evidence that cholinesterase inhibitors are efficacious in treating core symptoms of attentional disturbance and psychosis. Recent data also suggest a rational basis for cholinergic therapy in vascular dementia. The cognitive and neuropsychiatric effects of cholinergic therapy observed in AD and other dementias form the crux of an integrative model of cholinergic therapeutic efficacy that encompasses the diverse central nervous system actions of acetylcholine and its complementary interactions with central monoamine transmitters. This heuristic framework highlights the broader therapeutic potential of cholinergic therapy for symptom-based indications in other neuropsychiatric disorders.

A growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.

Diffusion-weighted imaging (DWI) represents a relatively novel magnetic resonance imaging (MRI) technique in which image contrast is related to differences in translational motion of water molecules within the tissue, rather than to differences in total water content. The rate of water motion is characterized by the apparent diffusion coefficient. In addition, full tensor DWI (diffusion tensor imaging, DT-MRI) samples the full diffusion tensor and therefore allows estimation of isotropic and anisotropic diffusion. The degree of anisotropic diffusion is thought to be determined by the local tissue characteristics or tissue architecture and can be quantified by DT-MRI. DWI has proven its clinical effectiveness in the early detection of acute cerebral ischemia. Multiple reports have discussed the value of DWI in a wide variety of other diseases of the central nervous system. DT-MRI appears to be especially promising in the evaluation of diseases that affect the integrity of white matter, in particular of white matter tracts. Herein, the current applications of DWI in clinical neurology are reviewed, with special attention to applications of DT-MRI.

Comorbidity of trichotillomania with different psychiatric disorders is common. However, until recently there have been no reports of trichotillomania in schizophrenia patients. In this article, the case of a female schizophrenia patient with trichotillomania is reported. Her schizophren was being treated with risperidone. Citalopram was later administered as an augmentation to risperidone. This combination therapy presented a partial response of trichotillo mania without exacerbating schizophrenia symptoms.

Until recently, body dysmorphic disorder (BDD) had been vastly ignored in the scientific literature. Despite a recent surge in interest, treatment studies are still surprisingly neglected. Reports from the 1970s–1990s discuss few case descriptions and suggest anecdotal treatment strategies. Since the 1990s, information about the treatment of BDD has increased slightly. The intent of this paper is to review the current state of knowledge regarding cognitive and behavior therapy, which so far has been found to be effective. The current literature suggests that there is no difference between the efficacy of one treatment strategy over another nor the combination of cognitive and behavior therapy over behavior therapy. However, more research is needed in this area before definitive conclusions can be made.

Studies on schizophrenia (SZ) have documented an increased presence of cavum septi pellucidi (CSP) in individuals suffering from the illness. Moreover, the presence of CSP has been cited in support of the early neurodevelopmental hypothesis in SZ. Our objective was to assess the magnetic resonance imaging (MRI) scans of first-episode patients and healthy controls to evaluate the frequency of CSP. The presence and the size of CSP were visually assessed on the MRI scans of 40 first-episode SZ patients, 19 nonpsychotic child and high-risk adolescent offspring of patients with SZ or schizoaffective disorder, and 59 controls. Our analysis revealed an absence of statistically significant differences in the occurrence of CSP between SZ patients, high-risk subjects, and controls. Even when the analysis was restricted to large CSP, no differences were found. Furthermore, no association between CSP and sex or handedness was observed. The absence of CSP abnormalities in first-episode SZ subjects might indicate that SZ is not characterized by developmentally mediated alterations in CSP. Also, family history of SZ might not increase likelihood for CSP.

Taken together, the articles gathered in this supplement underscore the major role in drug development that single-isomer science can play—a role that will undoubtedly take on a greater importance in the future. While the chirality of certain pharmacologically active molecules has been recognized for almost a century, it is only in recent years that drug synthesis and chiral separation techniques have advanced far enough to allow meaningful comparisons among enantiomers. Now that these methods are broadly available, the potential applications of single isomer drug development are considerable.

Numerous examples from a range of therapeutic areas confirm that single enantiomers can enhance clinical efficacy, reduce adverse effects, cause fewer interactions with other drugs, and minimize response variations among patients by offering more predictable pharmacokinetics and greater selectivity. In some cases, these advantages are simply due to the removal of an inactive enantiomer, but in other cases, a given dose of a single isomer offers greater benefits when administered alone than when administered as the racemic mixture, suggesting that the opposite enantiomer (the distomer) actually has detracting effects. As the papers by Drs. Gal and Hurt explain, the different activities of a pair of enantiomers are usually traceable to stereochemical differences in the way they interact with chiral macromolecules such as enzymes, transport systems, and receptors.

As part of an established traumatic stress research and treatment program located in New York City, we experienced the September 11, 2001, terrorist attacks on the World Trade Center first as New Yorkers, but also as professionals with an interest in both treating the survivors and furthering scientific knowledge regarding the neurobiology and treatment of traumatic stress. This paper gives vignettes of calls to our program and the treatment of World Trade Center terrorist attack survivors.

Neuropsychological (NP) test batteries have evolved as an amalgam of intelligence tests, various individual measures of “biological” cognition, and sensory and motor testing. The early emphasis of NP testing was to identify “organicity” and central nervous system lesion localization. More recent approaches have emphasized the profiling of performance across individual neurocognitive domains (eg, attention, memory, and language) to facilitate diagnosis and treatment planning. However, the field is still hampered by the use of many tests that are antiquated, excessively long, or of dubious psychometric quality. Some of these problems may have contributed to the current under-utilization of NP testing in diagnostic workups of neuropsychiatric disorders. This paper reviews some of the recent changes in the field that hold promise for substantially shortening assessments, improving diagnostic reliability, and making NP testing more cost-effective and practical.