Showing papers in "Cns Spectrums in 2006"

The neurobiology of substance and behavioral addictions.

Abstract: Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.

Potential markers for problematic internet use: a telephone survey of 2,513 adults.

Abstract: Objective The Internet has positively altered many aspects of life. However, for a subset of users, the medium may have become a consuming problem that exhibits features of impulse control disorders recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Method This is the first large-scale epidemiological study of problematic Internet use through a random-digit-dial telephone survey of 2,513 adults in the United States. Given the lack of validated criteria, survey questions were extrapolated from established diagnostic criteria for impulse control disorders, obsessive-compulsive disorder, and substance abuse. Four possible diagnostic criteria sets were generated. The least restrictive set required the respondent to report an unsuccessful effort to reduce Internet use or a history of remaining online longer than intended, Internet use interfering with relationships, and a preoccupation with Internet use when offline. Results The response rate was 56.3%. Interviews averaged 11.3 minutes in duration. From 3.7% to 13% of respondents endorsed > or =1 markers consistent with problematic Internet use. The least restrictive proposed diagnostic criteria set yielded a prevalence of problematic Internet use of 0.7%. Conclusion Potential markers of problematic Internet use seem present in a sizeable proportion of adults. Future studies should delineate whether problematic Internet use constitutes a pathological behavior that meets criteria for an independent disorder, or represents a symptom of other psychopathologies.

A virtual reality scenario for all seasons: the virtual classroom.

Abstract: Treatment and rehabilitation of the cognitive, psychological, and motor sequelae of central nervous system dysfunction often relies on assessment instruments to inform diagnosis and to track changes in clinical status. Typically, these assessments employ paper-and-pencil psychometrics, hands-on analog/computer tests, and rating of behavior within the context of real-world functional environments. Virtual reality offers the option to produce and distribute identical "standard" simulation environments in which performance can be measured and rehabilitated. Within such digital scenarios, normative data can be accumulated for performance comparisons needed for assessment/diagnosis and for treatment/rehabilitation purposes. In this manner, reusable archetypic virtual environments constructed for one purpose can also be applied for applications addressing other clinical targets. This article will provide a review of such a retooling approach using a virtual classroom simulation that was originally developed as a controlled stimulus environment in which attention processes could be systematically assessed in children with attention-deficit/hyperactivity disorder. This system is now being applied to other clinical targets including the development of tests that address other cognitive functions, eye movement under distraction conditions, social anxiety disorder, and the creation of an earthquake safety training application for children with developmental and learning disabilities.

The Shorter PROMIS Questionnaire and the Internet Addiction Scale in the assessment of multiple addictions in a high-school population: prevalence and related disability.

Abstract: Objective Taking into account the importance of act prevention on the development of addictions, we assessed the presence of multiple addictions in an adolescent high-school population, also assessing the prevalence of Internet abuse and the impact on disability. Introduction Adolescence seems to be a critical period of addiction vulnerability, based on social but also neurobiological factors.The earlier onset of behavioral/substance dependence seems to predict greater addiction severity, morbidity, and multiple addictive disorders. Methods Data were collected from a sample of 275 students in Florence, Italy, high schools through surveys distributed in classes. The sample had an average age of 16.67±1.85 years (52.4% males, 47.6% females). To assess multiple addiction we used the 16 subscales of the Shorter PROMIS Questionnaire, to assess Internet addiction prevalence we used the Internet Addiction Scale, and to quantify disability symptoms, we used the Sheehan Disability Scale. Results Caffeine abuse, sex, relationship submissive, gambling, food starving, and food bingeing have raised highest scores. 5.4% of the students were found to be Internet addicted similar to other countries. Disability seemed strongly correlated to the subscale of alcohol, gambling, sex, tobacco, food starving and food bingeing, shopping, exercise, and Internet addiction. Gambling, sex, caffeine abuse, compulsive help dominant, work, Internet addiction, relationship dominant, and relationship submissive in this sample were strongly related to substance dependence. Conclusion Level of concerns unexpected compared to the level reported in other countries for the behavioral compulsions, have been highlighted. Behavioral addictions are multiple, a source of disability, and they are related to substance abuse. It has yet to be clarified if they are a temporary phenomenon occurring in adolescents or if they are a stable trait, accounting as marker for the development of substance abuse.

Suicide in bipolar disorder: Risks and management.

Abstract: Bipolar disorders are prevalent, often severe, and disabling illnesses with elevated lethality largely due to suicide. Suicide rates average approximately 1% annually, or perhaps 60 times higher than the international population rate of 0.015% annually. Suicidal acts typically occur early in bipolar disorders and in association with severe depressive or mixed states. The high lethality of suicidal acts in bipolar disorders is suggested by a much lower ratio of attempts:suicide (approximately 3:1) than in the general population (approximately 30:1). Risk factors can help to identify patients at increased suicidal risk, but ongoing clinical assessment is essential to limit risk. Empirical short-term interventions to manage acute suicidal risk include close clinical supervision, rapid hospitalization, and electroconvulsive therapy. Remarkably, however, evidence of the long-term effectiveness of most treatments against suicidal behavior is rare. A notable exception is lithium prophylaxis, which is associated with consistent evidence of major (approximately 80%), sustained relative reductions of risk of suicides and attempts, and lower lethality (increased attempts:suicide ratio). Such benefits are unproved for other treatments commonly used to treat bipolar disorder patients, including anticonvulsants, antipsychotics, antidepressants, and psychosocial interventions. Applying available knowledge systematically, with close and sustained clinical supervision, can enhance management of suicidal risk in bipolar disorders patients.

Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial.

Abstract: Introduction Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood. Method This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults > or =18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S). Results Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P 32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P Conclusion These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours.

Warriors versus worriers: the role of COMT gene variants

Abstract: Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val158) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met158) substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.

Defining and diagnosing involuntary emotional expression disorder.

Abstract: Uncontrollable episodes of emotional expression occur in a variety of neurological conditions. This emotional disinhibition syndrome is characterized by episodes of crying or laughing that are unrelated to or out of proportion to the eliciting stimulus. This syndrome is common among patients with amyotrophic lateral sclerosis, multiple sclerosis, stroke, and traumatic brain injury and a variety of terms and definitions have been used to describe it. The confusing nomenclature has been a barrier to understanding, diagnosis, and treatment of this disorder. The authors propose a unifying term, involuntary emotional expression disorder (IEED), and provide diagnostic criteria for this disorder.

Recent advances in the understanding and treatment of anxiety disorders. Resilience: determinants, measurement, and treatment responsiveness.

Abstract: In human terms, resilience is an ability to cope with stress and varies with context, time, age, gender, and cultural origin. Resilience shifts the focus of psychological investigation onto increasing the positive rather than reducing the negative. Inquiry into resilience has evolved from descriptions of resilient qualities, to discovery of the process to attain resilience, to uncovering the motivation to reintegrate in a resilient manner. Much of the research on resilience has focused on children in settings such as family violence, extreme poverty, war, and natural disasters. A coherent pattern of characteristics associated with successful adaptation has emerged. Salient characteristics include commitment, dynamism, humor in the face of adversity, patience, optimism, faith, and altruism. As such, resilience may represent an important target of treatment in anxiety, depression, and stress reactions. Resilience can be quantified, but available measures need to be validated transculturally. There exist many possible determinants of resilience, including neurobiologic, genetic, temperament, and environmental influences. Resilience is modifiable on individual and cultural levels. Posttraumatic stress disorder is an example of a serious disorder associated with impaired stress coping that can improve with treatment.

Using FMRI to study the neural correlates of virtual reality analgesia.

Abstract: Excessive pain during medical procedures, such as burn wound dressing changes, is a widespread medical problem and is especially challenging for children. This article describes the rationale behind virtual reality (VR) pain distraction, a new non-pharmacologic adjunctive analgesia, and gives a brief summary of empirical studies exploring whether VR reduces clinical procedural pain. Results indicate that patients using VR during painful medical procedures report large reductions in subjective pain. A neuroimaging study measuring the neural correlates of VR analgesia is described in detail. This functional magnetic resonance imaging pain study in healthy volunteers shows that the large drops in subjective pain ratings during VR are accompanied by large drops in pain-related brain activity. Together the clinical and laboratory studies provide converging evidence that VR distraction is a promising new non-pharmacologic pain control technique.

Sleep disturbances in the aftermath of trauma and posttraumatic stress disorder.

Abstract: Sleep disturbances, including nightmares and insomnia, are prominent following trauma and with posttraumatic stress disorder (PTSD) and likely contribute to the pathogenesis of the disorder. Findings from laboratory studies of PTSD have been inconsistent in terms of documenting objective impaired sleep maintenance but have been somewhat more consistent in indicating alterations of rapid eye movement (REM) sleep. Studies of the early aftermath of trauma can reduce the complexity associated with chronicity and comorbidity, and may have implications for early diagnosis and prevention. Multiple studies indicate that dream content is affected by recent threatening experiences. The development of PTSD is associated with a more replicative type of nightmare content. Sleep is reported to be generally disrupted following trauma especially among those developing PTSD. The limited number of studies that provide objective recorded indices during the early aftermath of trauma also provide a mixed picture regarding overall sleep maintenance. Recent data suggest that a more specific disruption of REM sleep may be associated with the development of PTSD and that this disruption is associated with an increased signal of sympathetic nervous system activation during REM sleep. Disrupted REM sleep and increased sympathetic/noradrenergic activity may have implications for understanding recent promising interventions for PTSD sleep disturbance that can be applied to early intervention.

Impulsive-compulsive sexual behavior.

Abstract: Impulsive-compulsive sexual behavior is a little studied clinical phenomenon which affects approximately 5% to 6% of the population. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision, it is classified as an impulse control disorder not otherwise specified or a sexual disorder not otherwise specified. It may be placed in a possible new category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition called substance and behavioral addictions. This clinical entity is reviewed and the merit of classifying it as an addiction is assessed. Information is presented regarding its diagnostic criteria, epidemiology, types of behavior it can involve, relationship to hypersexuality, comorbidities, treatment, and etiology. The data regarding this disorder and its overlap with chemical addiction is limited. If the two disorders are to be grouped together, further data are needed.

Antidepressants and cognitive-behavioral therapy for symptom syndromes.

Abstract: Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for "attention" to noxious stimuli, and the direct effects of the medications on the syndrome. There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness. This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.

Brain network dysfunction in bipolar disorder.

Abstract: Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.

Sexual Dysfunction in Major Depression

Abstract: Little is known about the prevalence, typology, and natural course of non-drug-induced sexual dysfunction in patients with depression. Loss of libido has been reported in various studies to affect from 25% to 75% of patients with unipolar depression, and its prevalence appears to be correlated with the severity of depression. Disorders of arousal also appear to be relatively common in both men and women with major depression, of whom approximately 25% may experience problems with erection or lubrication. The scant available data regarding orgasmic difficulties in patients with depression who have not yet taken antidepressant medication suggest that they are more common than in the general population. The potential causes of sexual dysfunction in patients with depression are complex and little investigated, and future research must distinguish and explore the various biological, psychological, and psychosocial factors that are likely to be involved.

Serotonin dysfunction in pathological gamblers: increased prolactin response to oral m-CPP versus placebo.

Abstract: OBJECTIVE Acute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP), that is used also as a street drug, has been reported to induce a "high" and craving response in various impulsive and substance addiction disorders. INTRODUCTION To clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non-substance addictions, we assessed behavioral ("high" and "craving") and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed. METHOD Twenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and "high" scales. RESULTS Pathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post-administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased "high" sensation after m-CPP administration compared with control. CONCLUSION These results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of "high" might represent the pathway that leads to dyscontrolled behavior in pathological gamblers. Furthermore, the "high" feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behavioral and substance addictions.

An A-B-C model of habit disorders: hair-pulling, skin-picking, and other stereotypic conditions.

Abstract: 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.

Preventing relapse and recurrence of depression: a brief review of therapeutic options.

Abstract: Depression is increasingly recognized as a highly recurrent and potentially chronic illness that imposes a substantial burden on individuals, families, and society. Evidence indicates that the risks of depressive recurrence, treatment resistance, and chronicity increase as the illness becomes more highly recurrent. Up to 1 year of continuation phase therapy is now recommended for virtually all depressed patients who respond to antidepressants, with a longer course of maintenance phase pharmacotherapy recommended for those who have experienced multiple episodes. Antidepressants, when effective during the acute phase of therapy, reduce the risk of depressive relapse (continuation phase) and recurrence (maintenance phase) by at least 50%. Longer-term antidepressant pharmacotherapy is most effective when the full dose of medication effective during acute-phase treatment is continued. As combined treatment with antidepressants and psychotherapy may improve shorter-term outcomes for patients with more severe recurrent depression, ongoing combined therapy may be indicated, especially for patients at particularly high risk. Approximately 5% to 10% of patients maintained on antidepressants relapse yearly, leading some to implicate tachyphylaxis. However, before attributing relapse or recurrence to diminished responsiveness to antidepressant medication at the neurochemical level, clinicians should ensure that the patient has been adherent to therapy as prescribed and consider other explanations.

Psychogenic tremor: long-term outcome.

Abstract: Introduction Psychogenic disorders, also referred to as somatoform, conversion, somatization, hysteria, and medically unexplained symptoms, are among the most challenging disorders to diagnose and treat. Psychogenic movement disorders are increasingly encountered in specialized clinics, and represent approximately 15% of all patients evaluated in the Baylor College of Medicine Movement Disorders Clinic. Objective To characterize psychogenic tremor and provide data on prognosis and long-term outcome in a large group of patients with psychogenic tremor followed in a movement disorders clinic. Methods Patients evaluated at the Baylor College of Medicine Movement Disorders Clinic in Houston, Texas, between 1990 and 2003 with the diagnosis of psychogenic movement disorder (PMD), who consented to be interviewed, were administered a structured questionnaire designed to assess current motor and psychological function. Results psychogenic tremor is the most common PMD, accounting for 4.1% of all patients evaluated in our clinic. We were able to obtain clinical information on a total of 228 of 517 (44.1%) patients with PMD, followed for a mean of 3.4+/-2.8 years. Among the 127 patients diagnosed with psychogenic tremor, 92 (72.4%) were female, the mean age at initial evaluation was 43.7+/-14.1 years, and the mean duration of symptoms was 4.6+/-7.6 years. The following clinical features were considered to be characteristic of psychogenic tremor: abrupt onset (78.7%), distractibility (72.4%), variable amplitude and frequency (62.2%), intermittent occurrence (35.4%), inconsistent movement (29.9%), and variable direction (17.3%). Assessment of long-term outcome showed that 56.6% of patients reported improvement in their tremor. Factors predictable of a favorable outcome were elimination of stressors and patient's perception of effective treatment by the physician. Conclusion This largest longitudinal study of patients with psychogenic tremor provides data on the clinical characteristics and natural history of this most common PMD. The accurate diagnosis of psychogenic tremor is based not only on exclusion of other causes but is also dependent on positive clinical criteria, the presence of which should avoid unnecessary investigation. The prognosis of psychogenic tremor may be improved with appropriate behavioral and pharmacologic management.

The application of mindfulness-based cognitive interventions in the treatment of co-occurring addictive and mood disorders.

Abstract: This article reviews the theory, clinical application, and empirical findings on mindfulness-based cognitive therapy (MBCT) for mental health and addictive disorders. Expanding upon the research demonstrating the efficacy of cognitive-behavioral therapy (CBT) for addiction, this article develops and explores the rationale for combining mindfulness-based interventions with evidence-based CBTs in treating addictive disorders, with an emphasis on substance use disorders with co-occurring mood disorders. This article proposes that deficits in affect--regulation related to the behavioral and emotional effects of neurobiological changes that occur with long-term substance abuse--pose a unique set of challenges in early recovery. Prolonged use of addictive substances impairs the brain pathways that mediate certain affect regulation functions. These functions involve attention and inhibitory control, the saliency of and response to addictive versus natural reward stimuli, and the ability to detach or maintain perspective in response to strong emotional states. In treating this affective dysregulation, which can contribute to the vulnerability to relapse in the early stages of recovery, the affect-regulation-specific focus of MBCT adds a valuable element to augment CBT for addiction. Summarizing magnetic resonance imaging and positron emission tomography findings on the effects of MBCT and the neurobiology of drug addiction, this article outlines directions for further research on potential benefits of MBCT for the recovering individual. Finally, this article describes a structured protocol, developed at the Mount Sinai School of Medicine in New York City, which combines CBT with mindfulness-based intervention, for the treatment of affect-regulation issues specific to co-occurring addictive and mood disorders.

Implications of the CATIE trial on treatment: extrapyramidal symptoms.

Abstract: 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.

Longitudinal studies of PTSD: overview of findings and methods.

Abstract: Posttraumatic stress disorder (PTSD) has a discernible starting point and typical course, hence the particular appropriateness of longitudinal research in this disorder. This review outlines the salient findings of longitudinal studies published between 1988 and 2004. Studies have evaluated risk factors and risk indicators of PTSD, the disorder's trajectory, comorbid disorders and the predictive role of acute stress disorder. More recent studies used advanced data analytic methods to explore the sequence of causation that leads to chronic PTSD. Advantages and limitations of longitudinal methods are discussed.

The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia.

Abstract: Introduction: Efficacy and safety of aripiprazole administered at doses lower than those previously studied systematically were investigated in patients with acute exacerbation of schizophrenia. Methods: In this double-blind, multicenter study, 367 patients requiring inpatient hospitalization for acute relapse of schizophrenia were randomized to one of three fixed doses of aripiprazole (2, 5, or 10 mg/day) or placebo for 6 weeks. Efficacy and safety parameters were assessed weekly. Primary outcome measure was mean change from baseline in Positive and Negative Syndrome Scale (PANSS) Total score at endpoint. Results: Aripiprazole 10 mg/day produced statistically significantly greater improvements from baseline compared with placebo for PANSS Total at endpoint (–11.3 vs –5.3; P=.03) and at weeks 2–5. Aripiprazole 5 mg/day did not produce sigFOCUS POINTS • Aripiprazole 10 mg/day is the minimum effective dose for the treatment of patients with schizophrenia experiencing acute relapse. • Aripiprazole 5 mg/day produced improvements in some outcome measures but not in the primary efficacy measure, suggesting that it may lack efficacy for treating acute psychosis. • Aripiprazole 2 mg/day did not demonstrate significant differences versus placebo on any efficacy measures and, therefore, seems to be below the clinically effective dose. • All doses of aripiprazole were well tolerated; aripiprazole treatment was not associated with significant extrapyramidal symptoms.

Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study.

Abstract: Introduction Many patients with major depressive disorder (MDD) treated with selective serotonin reuptake inhibitors have residual symptoms (eg, persistent fatigue, excessive sleepiness) despite an overall antidepressant response. Placebo-controlled studies indicate that modafinil, a wake-promoting agent, may relieve residual symptoms. Methods This 12-week, open-label, dose titration, extension study followed an 8-week placebo-controlled study of modafinil augmentation in patients with MDD. The dose was 100-400 mg/day. The median stable dose was 300 mg/day. Assessments were the Epworth Sleepiness Scale, Brief Fatigue Inventory, Clinical Global Impression of Improvement scale, 17-item Hamilton Rating Scale for Depression, and Montgomery-Asberg Depression Rating Scale. Results Of the 245 patients treated, 194 completed the study; 70% reported Clinical Global Impression of Improvement scale responses of "much improved" or "very much improved" between open-label baseline and final visit (previous randomized modafinil group: 74%; placebo group: 66%). When data were analyzed for four subsets of patients (former modafinil responders, placebo responders, modafinil nonresponders, and placebo nonresponders), improvements in scores on all outcome measures were at least twice as great among former modafinil and placebo nonresponders compared with responders. Most common adverse events were headache (18%), nausea (9%), and dizziness (7%); all were generally mild to moderate in severity. Conclusion Twelve weeks of modafinil augmentation relieved excessive sleepiness, reduced fatigue, and improved patients' overall clinical condition, including mood.

Psychiatric symptoms associated with brain tumors: a clinical enigma.

Abstract: Patients in psychiatric settings may present with medical conditions, such as brain tumors, which may or may not be associated with neurological symptoms. In some cases, patients may only have psychiatric symptoms, such as mood changes (depression or mania), psychotic symptoms, panic attacks, changes in personality, or memory difficulties. Brain tumors may be detected in patients at their first presentation to mental health services or sometimes in patients with well-established psychiatric diagnoses. This article presents the case of a 29-year-old woman who was treated for >4 years for posttraumatic stress disorder and borderline personality traits, who developed depressive symptoms and memory difficulties. However, she did not develop any major neurological signs or symptoms. Brain imaging showed the presence of a left thalamic tumor, later confirmed as glioblastoma multiforme. She underwent surgical treatment and radiation therapy. With this we show that in some cases, brain tumors can be neurologically silent and only present atypical psychiatric symptoms. We emphasize the need for neuroimaging studies in a patient with atypical changes in mental status, even without neurological signs or symptoms.

Sexual dysfunction and psychotropic medications.

Abstract: Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in >50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.

What is the optimal way to subdivide obsessive-compulsive disorder?

Abstract: The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.

Metabolic findings from the CATIE trial and their relation to tolerability.

Abstract: The overall effectiveness of antipsychotics for the management of schizophrenia is restricted by their side-effect profiles, particularly over an extended treatment period. Intolerable side effects can reduce patient adherence to medication and often lead to treatment discontinuation. Some side effects that result from antipsychotic use are precursors to the metabolic syndrome, which is prevalent among individuals with schizophrenia and represents a significant source of cardiovascular risk. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study assessed the efficacy of the atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone relative to the conventional drug perphenazine. Additional assessments included the metabolic effects of these agents in patients with schizophrenia and the incidence of negative side effects. No significant differences were found between treatment groups for time to discontinuation due to intolerability, but the rates of side effects significantly differed (P=.04). For metabolic parameters, olanzapine was associated with greater and significant adverse effects on weight, lipids, and glucose metabolism versus the other antipsychotics tested. The CATIE results show that important distinctions exist among currently available atypical antipsychotics. Physicians should be aware of the propensity of these drugs to increase the risks of cardiovascular disease and diabetes in treated patients and tailor individual treatment decisions accordingly. This article highlights the metabolic findings from the CATIE schizophrenia study, and explores the differences shown by atypical antipsychotics, with regard to metabolic side effects that increase cardiovascular risk.

The Neurophysiology of Childhood and Adolescent Bipolar Disorder

Abstract: Introduction: Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early-and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course.Methods: Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed.Results: Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder.Conclusion: Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.

The medical traumatic stress toolkit.

Abstract: Children and their parents who are exposed to medical life-threat due to illness or injury are at risk for developing symptoms of posttraumatic stress However, the prevention, detection, and treatment needed are often not available in the acute care settings of the hospital The National Child Traumatic Stress Network and the Substance Abuse and Mental Health Services Administration have created a set of materials for use by hospital health providers and families that is available for download free from the National Child Traumatic Stress Network website, wwwnctsnorg