Showing papers in "Cns Spectrums in 2000"
TL;DR: Compulsive sexual behavior (CSB) is characterized by inappropriate or excessive sexual behaviors or cognitions that lead to subjective distress or impaired functioning.
Abstract: Compulsive sexual behavior (CSB) is characterized by inappropriate or excessive sexual behaviors or cognitions that lead to subjective distress or impaired functioning. Both abnormal (paraphilic) and conventional (nonparaphilic) forms of sexual behavior are usually included in the definition. CSB is reported to affect 3% to 6% of the general population in the United States, occurring more frequently in men. It typically begins in the late teens or early twenties and is chronic or intermittent. The disorder has been described as a progression through four stages: preoccupation, ritualization, gratification, and despair. Men with CSB typically focus on physical sexual gratification; women focus on romantic or emotional aspects of sexuality. Psychiatric comorbidity is common, particularly substance use, mood, anxiety, and personality disorders. CSB can lead to medical complications. Risk factors are thought to include family history and childhood abuse.
89 citations
TL;DR: This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.
Abstract: Catatonia and neuroleptic malignant syndrome (NMS) are uncommon disorders that can be life-threatening. Many researchers consider them as clinically divergent entities; however, they share similar and overlapping literature on causative agents, phenomenology, and treatment response. This hypothesis considers both disorders as a single entity that result from variable combinations of the following: 1) gamma-aminobutyric acid (GABA) hypoactivity at the GABAA receptor; 2) dopamine hypoactivity at the D2 receptor; 3) serotonin hyperactivity at the 5-HT1A receptor and hypoactivity at the 5-HT2A receptor; and 4) glutamate hypoactivity at the N-methyl-D-aspartate (NDMA) receptor. In this paper, evidence to support this hypothesis is limited to retrospective human studies of catatonia and NMS. The four components of the hypothesis are: 1) GABAA agonists have been shown to alleviate catatonia and NMS; 2) D2 antagonism is proportional to the relative likelihood of NMS and catatonia; 3) 5-HT1A agonism with 5-HT2A antagonism is implicated in catatonia and NMS; 4) NMDA receptor antagonists, such as phencyclidine and ketamine, reduce glutamate transmission. This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.
82 citations
TL;DR: 16 controlled clinical trials conducted across 11 European countries and involves more than 4,500 outpatients with alcohol dependence found alcohol-dependent patients treated with acamprosate had a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treating with placebo.
Abstract: Acamprosate (calcium acetyl-homotaurine) is a synthetic compound that crosses the blood-brain barrier and has a chemical structure similar to that of the naturally occurring amino acid neuromediators, homotaurine and g-aminobutyric acid (GABA). Acamprosate appears to act primarily by restoring normal n-methyl-d-aspartate (NMDA) receptor tone in the glutamate system, and has been shown to have a specific dose-dependent effect on decreasing voluntary alcohol intake in animals with no effects on food and water consumption. The safety and efficacy of acamprosate in alcohol-dependent outpatients is currently under evaluation in the United States. Acamprosate has been available by prescription since 1989 in France and more recently in most European and Latin American coutries as well as Australia, South Africa, and Hong Kong. More than 4 million people have been treated with acamprosate since it became commercially available. The purpose of this article is to review all available double-blind, placebo-controlled clinical trials evaluating the safety and efficacy of acamprosate treatment of alcohol dependence. This work encompasses 16 controlled clinical trials conducted across 11 European countries and involves more than 4,500 outpatients with alcohol dependence. Fourteen of 16 studies found alcohol-dependent patients treated with acamprosate had a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. Additionally, a multinational open-label study of acamprosate in 1,281 patients with alcohol dependence found acamprosate to be equally effective across four major psychosocial concomitant treatment programs in maintaining abstinence and reducing consumption during any periods of relapse. An absence of known strong predictors of response to acamprosate, in conjunction with a modest but consistent effect on prolonging abstinence, and an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol dependence.
76 citations
TL;DR: Patient characteristics and their implications for treatment are summarized and a trajectory of a typical diagnosis and treatment path is provided, as well as important resources for physicians and patients.
Abstract: The management of patients with compulsive sexual behavior requires an understanding of the profile of the sexually compulsive or addicted patient. This article summarizes patient characteristics and their implications for treatment. Data from a study of the recovery of 957 patients who had problematic, sexually excessive behavior are presented. Spanning 5 years, the study shows six distinct stages patients experienced and the clinical activities that were most useful to them. A trajectory of a typical diagnosis and treatment path is provided, as well as important resources for physicians and patients.
61 citations
TL;DR: Lorazepam and related benzodiazepines may reduce recovery time in NMS and compared favorably with prior reports of 5-day to 10-day recovery periods.
Abstract: The authors assessed the ability of lorazepam and other benzodiazepines to affect the course of neuroleptic malignant syndrome (NMS). Records of inpatients who met both stringent research criteria and criteria under the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) (n=11) or DSM-IV criteria alone (n=5) for NMS were identified. All received lorazepam or related benzodiazepines within 24 hours of NMS onset or hospital admission. The records were reviewed for resolution of clinical signs of NMS. Rigidity and fever abated within 24-48 hours, while secondary features of NMS were relieved within 64 hours. These results compared favorably with prior reports of 5-day to 10-day recovery periods. Benzodiazepine administration appeared to be well tolerated. Lorazepam and related benzodiazepines may reduce recovery time in NMS.
56 citations
TL;DR: Brain imaging studies have shown major and specific alterations in a right hemispheric neural network that includes the medial and lateral orbitofrontal and posterior parietal cortex that may be abnormally modulated by altered functional interactions between γ-aminobutyric acid-ergic and glutamatergic transmission.
Abstract: Karl Ludwig Kahlbaum originally described catatonia as a psychomotor disease that encompassed motor, affective, and behavioral symptoms. In the beginning of the 20th century, catatonia was considered to be the motoric manifestation of schizophrenia; therefore, neuropathologic research mostly focused on neuroanatomic substrates (ie, the basal ganglia underlying the generation of movements). Even though some alterations were found in basal ganglia, the findings in these subcortical structures are not consistent. Recently, there has been a reemergence of interest into researching catatonia. Brain imaging studies have shown major and specific alterations in a right hemispheric neural network that includes the medial and lateral orbitofrontal and posterior parietal cortex. This neural network may be abnormally modulated by altered functional interactions between gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This may account for the interrelationship among motor, emotional, and behavioral alterations observed in both clinical phenomenology and the subjective experiences of patients with catatonia. Such functional interrelationships should be explored in further detail in catatonia, which may also serve as a paradigmatic model for the investigation of psychomotor and brain function in general.
47 citations
TL;DR: The potential use of psychostimulants, mood stabilizers, and atypical antipsychotics for paraphilia-related disorders in specific clinical situations is discussed and practical guidelines, augmentation strategies with adjunctive psychopharmacologic agents, and indications regarding pharmacologic combinations are suggested.
Abstract: This article reviews the use of pharmacologic agents to treat nonparaphilic compulsive sexual behaviors (paraphilia-related disorders). Recent data suggest that serotonergic antidepressants, especially serotonin reuptake inhibitors (SRIs), may be effective in treating nonparaphilic sexual behaviors characterized by hypersexuality. The rationale, prescriptive use, and limitations of SRIs are reviewed, as are the proposed mechanisms of action, prescriptive use, and side effects of medications that lower serum testosterone (including triptorelin and the antiandrogens medroxyprogesterone acetate and cyproterone acetate).The potential use of psychostimulants, mood stabilizers, and atypical antipsychotics for paraphilia-related disorders in specific clinical situations is discussed. Practical guidelines, augmentation strategies with adjunctive psychopharmacologic agents, and indications regarding pharmacologic combinations of the above medications are suggested.
46 citations
TL;DR: Differences between catatonic and noncatatonic patients with mixed mania are presented and their relevance to clinical practice is discussed.
Abstract: The historical development of the concept of catatonia in affective disorders and contemporary papers on this topic are reviewed. In addition, data from a current study on the frequency of catatonia in mixed mania are reported. Differences between catatonic and noncatatonic patients with mixed mania are presented and their relevance to clinical practice is discussed.
45 citations
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TL;DR: Modifiable stroke risk factors include hypertension, atrial fibrillation, hypercholesterolemia, cigarette smoking, hyperhomocystinemia, and carotid stenosis.
Abstract: Despite advances in the treatment of acute cerebral infarction, the most effective method of reducing stroke morbidity and mortality is the identification and modification of stroke risk factors Modifiable stroke risk factors include hypertension, atrial fibrillation, hypercholesterolemia, cigarette smoking, hyperhomocystinemia, and carotid stenosis Improved identification of individuals at increased stroke risk due to these factors can reduce individual risk and the cost to society of the consequences of stroke
44 citations
TL;DR: These case studies demonstrate that a neurobiology of hypersexuality may prove of some heuristic value in the clinic, and provide evidence that different brain systems may play a role in this disorder.
Abstract: Relatively few studies of the psychobiology of hypersexuality have been undertaken. Nevertheless, the literature does suggest the possibility of a neurobiology of hypersexuality. Three cases of hypersexual behavior are presented in the context of neuropsychiatric disorders, and the literature on this phenomenon is briefly reviewed. These case studies and the literature provide evidence that different brain systems may play a role in this disorder. Frontal lesions may be accompanied by disinhibition, including impulsive hypersexual response to external cues, while striatal lesions may be accompanied by repetitive triggering of internally generated response patterns. Temporal-limbic lesions may be accompanied by disturbances in sexual appetite itself, including change in the direction of sexual drive. These case studies demonstrate that a neurobiology of hypersexuality may prove of some heuristic value in the clinic. However, further research is required to consolidate the literature in this area.
43 citations
TL;DR: Obsessive-Compulsive Disorder Spectrum: Pathogenesis Diagnosis and Treatment By Jose A. Yaryura-Tobias and Fugen A. Neziroglu.
Abstract: Obsessive-Compulsive Disorder Spectrum: Pathogenesis Diagnosis and Treatment By Jose A. Yaryura-Tobias and Fugen A. Neziroglu. American Psychiatric Press, $69.50 Obsessive-Compulsive and Related Disorders in Adults: A Comprehensive Clinical Guide, By Lorrin M. Koran. Cambridge University Press, $59.95 The Broken Mirror: Understanding and Treating Body Dysmorphic Disorder, By Katharine A. Phillips. Oxford University Press, $15.95
TL;DR: It is suggested that the DSM-IV category of sexual disorders be modified to include explicitly diagnostic criteria for a disorder characterized by hypersexual symptoms involving patterns that fall outside of the current definition of paraphilia.
Abstract: Paraphilias are recurrent and intense sexually arousing fantasies, sexual urges, or behaviors generally involving nonhuman objects. These paraphilias cause the suffering or humiliation of the patient or patient's partner, or children, or other nonconsenting persons. However, in many patients symptoms involve more culturally acceptable patterns (eg, repetitive masturbation, Internet pornography); such hypersexual symptoms have been labeled as compulsive, addictive, or impulsive. Growing evidence supports the existence of a discrete syndrome characterized by recurrent and intense sexually arousing fantasies, sexual urges, or behaviors involving patterns that fall outside the definition of paraphilia. There is, however, high comorbidity with paraphilia. While such symptoms have been labeled as sexual compulsion or addiction, these terms are problematic in this context. Modern nosology has neglected this entity, although the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), category of sexual disorders not otherwise specified includes hypersexual behaviors as an example. We suggest that the DSM-IV category of sexual disorders be modified to include explicitly diagnostic criteria for a disorder characterized by hypersexual symptoms involving patterns that fall outside of the current definition of paraphilia. The disorder might be classified as one of the paraphilias, or as paraphilia-related. In the absence of a comprehensive understanding of the pathogenesis of this disorder, we suggest that it simply be termed hypersexual disorder.
TL;DR: The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.
Abstract: Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.
TL;DR: An implantable VNS device known as the VNS™ NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994 and has reduced seizure frequency by an average of 25% to 30%, with minimal side effects.
Abstract: Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.
TL;DR: It appears that the administration of a neuroleptic intensified the preexisting catatonic state and precipitated a malignant variant of the disorder, which is currently recognized as NMS.
Abstract: This study was conducted to show that catatonia is a predisposing factor for neuroleptic malignant syndrome (NMS) and to review the nosological relationship between catatonia and NMS. Seventeen consecutive cases of NMS were analyzed prospectively with reference to clinical and investigative findings before and after exposure to a neuroleptic. The series comprised eight males and nine females, ranging in age from 18 years to 65 years. Prior to neuroleptic exposure, all patients exhibited features compatible with criteria for catatonia (mutism/excitement) according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R). Following neuroleptic administration (single dose in nine cases), patients deteriorated into a febrile, rigid, and obtunded state accompanied by autonomic dysfunction and raised creatine phosphokinase levels. These features were consistent with a diagnosis of NMS. Neuroleptics were discontinued and supportive medical treatment instituted. Benzodiazepines were beneficial in eight cases in relieving stupor, but bromocriptine and dantrolene were generally ineffective. In all patients diagnosed with NMS in the authors' series, catatonia was an invariable prodromal state. It appears that the administration of a neuroleptic intensified the preexisting catatonic state and precipitated a malignant variant of the disorder, which is currently recognized as NMS. The authors, therefore, challenge the separate nosological status of NMS and catatonia and suggest that these syndromes are part of a unitary pathophysiological disorder.
TL;DR: The growth of the discipline of psychiatric surgery from the earliest lesioning procedures to the neuroaugmentative strategies used today is examined, with special attention to the neural circuitry that underlies psychiatric disorders.
Abstract: In this article, the authors examine the growth of the discipline of psychiatric surgery from the earliest lesioning procedures to the neuroaugmentative strategies used today. Special attention is paid to the neural circuitry that underlies psychiatric disorders and how surgical manipulation of these circuits might result in the amelioration of the disease state. Also examined is the effect that the technology curve has had on psychiatric surgery with regard to functional imaging and neurosurgical equipment. Finally, the authors use the current state of psychiatric surgery to speculate on some of the future directions that psychiatric neurosurgical procedures might take.
TL;DR: It is suggested that psychiatric and medical catatonias are indistinguishable based upon catatonic signs, which appear to share a similar distribution.
Abstract: Patients with psychiatric catatonias vs those with medical catatonias may differ in catatonic phenomenology. To determine if these could be distinguished, the following methods were used: 1) a review of the literature; 2) a chart review; and 3) a prospective series. The literature review of 467 report of medical catatonias yielded 240 cases that met research criteria. A chart review of 47 episodes of catatonia revealed a higher frequency of negativism in patients with medical catatonias. Prospective data obtained from rating scales revealed an increased frequency of echophenomena in patients with medical catatonias; however, no discriminate pattern of catatonic signs for medical catatonias arose. Overall, catatonic signs appear to share a similar distribution. These findings suggest that psychiatric and medical catatonias are indistinguishable based upon catatonic signs.
TL;DR: Surgical intervention remains a reasonable therapeutic option for select patients with a disabling psychiatric disease and may be underutilized, but must be followed by an appropriate psychiatric rehabilitation program.
Abstract: The modern therapeutic approach to most psychiatric diseases involves a combination of well-supervised psychotherapy, pharmacotherapy, and electroconvulsive therapy. Patients who fail to adequately respond to these modern treatment methods and remain severely disabled may be considered for surgical intervention. Cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy are the most common psychosurgical procedures performed today, with response rates in the 35% to 65% range. Modern stereotactic techniques have reduced complication rates, but controversy remains regarding the optimal surgical procedure. The major psychiatric diagnostic categories that might respond to surgery include treatment-refractory major affective disorders, obsessive-compulsive disorder, and chronic anxiety states. Surgery should be considered as one part of an entire treatment plan and must be followed by an appropriate psychiatric rehabilitation program. It should only be carried out by an expert multidisciplinary team consisting of a neurologist a neurosurgeon, and a psychiatrist with experience in these disorders. Surgical intervention remains a reasonable therapeutic option for select patients with a disabling psychiatric disease and may be underutilized.
TL;DR: There is growing evidence to suggest that alcohol-dependent subgroups are differentially responsive to 5-HT pharmacotherapies with respect to drinking-related outcomes.
Abstract: The majority of studies that have examined the usefulness of pharmacotherapies selective for serotonin (5-hydroxytryptamine; 5-HT) as a treatment for alcohol dependence have been standard, double-blind clinical trials that include patients with a variety of clinical presentations. Almost all of the early studies evaluated heavy social drinkers and found only a modest advantage for 5-HT pharmacotherapies in reducing the number of drinks per day. Also, the advantage of these pharmacotherapies was observed primarily when these agents were given at higher daily dosages than suggested prescribing practices for use as an antidepressant. The few studies that evaluated treatment-seeking patients found that 5-HT pharmacotherapies were not instrumental in reducing drinking rates compared with placebo. These results led to a dampening of enthusiasm for use of these agents in treating alcohol dependence. However, more recent investigations have begun to target subgroups with potential abnormalities in 5-HT neurotransmission. The thinking is that these medications should be most useful in alcohol-dependent individuals who have more clearly delineated suggestive signs of 5-HT dysfunction, such as concomitant depression or anxiety. Although few results are available to date, there is growing evidence to suggest that alcohol-dependent subgroups are differentially responsive to 5-HT pharmacotherapies with respect to drinking-related outcomes. This may explain the modest and variable 5-HT pharmacotherapeutic effects that were reported in the earlier studies, which included large heterogeneous patient groups. Further investigations are needed to confirm these initial optimistic results.
TL;DR: The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.
Abstract: This paper discusses the National Bioethics Advisory Commission's (NBAC's) report on research involving persons with mental disorders that may affect decisionmaking capacity. After placing the NBAC recommendations into their historic context, the authors propose a strategy to enroll decisionally incapacitated subjects into neuropsychiatric research. The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.
TL;DR: Depression and apathy are the two most frequent behavioral complications of stroke, as well as their clinical correlates, longitudinal course, and possible mediators, which are reviewed.
Abstract: Depression and apathy are the two most frequent behavioral complications of stroke. This article reviews the prevalence of these conditions in poststroke patients, as well as their clinical correlates, longitudinal course, and possible mediators. A number of controlled clinical trials of the efficacy of various drugs in the treatment of poststroke depression are also reviewed.
TL;DR: The use of QOL scales derived from general medicine and other areas of psychiatry has demonstrated the enormous negative impact of OCD on several domains, including occupational function, social function, and family function.
Abstract: The construct of quality of life (QOL), which has both subjective and objective components, has gained increasing importance in psychiatric research for several important reasons, not the least being the current importance of pharmacoeconomic issues. Obsessive-compulsive disorder (OCD) has been suggested to be the worlds 10th most disabling disorder, and pharmacoeconomic studies have indicated that its cost to the world economy runs into the billions of dollars. The use of QOL scales derived from general medicine and other areas of psychiatry has demonstrated the enormous negative impact of OCD on several domains, including occupational function, social function, and family function. Further work to ascertain the extent of changes in QOL during treatment of OCD is necessary.
TL;DR: Several studies have shown that compared with the CB subtype, the IN subtype has a later age of onset and referral, a relatively larger proportion of affected females, and is much less likely to be associated with symptoms of oppositional defiant disorder or conduct disorder.
Abstract: The predominantly inattentive (IN) subtype of attention-deficit/hyperactivity disorder (ADHD) is a recently defined condition that is often overlooked by professionals and is still not completely understood. Characterized by symptoms of inattentiveness, such as distractibility, failure to complete work, forgetfulness, and disorganization, the IN subtype differs from the more commonly recognized combined (CB) subtype of ADHD in that symptoms of hyperactivity and impulsivity are absent or minimal. Large-scale epidemiologic studies suggest that the IN subtype is at least as prevalent as the CB subtype, and is at least as likely to be associated with academic and/or social impairment. Diagnosis of the IN subtype, however, may be more challenging because in addition to inattentiveness, other symptoms, including learning problems, depression, and anxiety, may also present without externalizing behaviors. Several studies have shown that compared with the CB subtype, the IN subtype has a later age of onset and referral, a relatively larger proportion of affected females, and is much less likely to be associated with symptoms of oppositional defiant disorder or conduct disorder. Research is currently under way to examine the cognitive characteristics of the IN subtype and its genetic and neurobiologic underpinnings, as well as to evaluate the effectiveness of pharmacotherapy and other treatments.
TL;DR: Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection.
Abstract: The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.
TL;DR: Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with psychosis should be adopted.
Abstract: The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (>/=35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.
TL;DR: Patients undergoing two lesioning procedures were much or very much improved 2 years postsurgery and the inherent obstacles to conducting placebo-controlled studies in these severely ill patients mean that further study is required to identify optimal candidates for surgical intervention.
Abstract: Although significant progress has been made over the last decade in the treatment of obsessive-compulsive disorder (OCD), approximately 20% of OCD patients remain refractory to nonsurgical therapies, including pharmacologic and cognitive-behavioral therapy. Because a number of neural circuits involving the basal ganglia, thalamus, limbic system, and frontal lobes have been implicated in the pathophysiology of OCD, the need for an effective intervention in these patients has brought the focus on surgical approaches, including cingulotomy and capsulotomy procedures. Unlike free-hand surgical approaches used in the past, current neurosurgical interventions have been greatly enhanced by advances in technology, which allow lesioning to an accuracy of 1 mm. Today's neurosurgical approaches have shown significant benefit in as many as 60% of refractory patients, while preserving personality and cognitive functioning and limiting morbidity. A study of gamma knife capsulotomy conducted at Brown University School of Medicine showed that 40% of patients undergoing two lesioning procedures were much or very much improved 2 years postsurgery. The inherent obstacles to conducting placebo-controlled studies in these severely ill patients mean that further study is required to identify optimal candidates for surgical intervention.
TL;DR: A sensible approach to the use of multiple-agent cocktails used in combination with thrombolytics is likely to offer the highest chance for benefit.
Abstract: Brain ischemia is a process of delayed neuronal cell death, not an instantaneous event. The concept of neuroprotection is based on this principle. Diminished cerebral blood flow initiates a series of events (the "ischemic cascade") that lead to cell destruction. This ischemic cascade is akin to a spreading epidemic starting from a hypothesized core of ischemia and radiating outward. If intervention occurs early, the process may be halted. Interventions have been directed toward salvaging the ischemic penumbra. Hypothermia decreases the size of the ischemic insult in both anecdotal clinical and laboratory reports. In addition, a wide variety of agents have been shown to reduce infarct volume in animal models. Pharmacologic interventions that involve thrombolysis, calcium channel blockade, and cell membrane receptor antagonism have been studied and have been found to be beneficial in animal cortical stroke models. Human trials of neuroprotective therapies have been disappointing. Other than thrombolytics, no agents have shown an unequivocal benefit. The future of neuroprotection will require a logical extension of what has been learned in the laboratory and previous human trials. A sensible approach to the use of multiple-agent cocktails used in combination with thrombolytics is likely to offer the highest chance for benefit.
TL;DR: The assessment of shame experiences in psychiatric patients could be useful for both pharmacological and psychotherapeutic strategies, and could provide a categorization of a new psychopathology based on abnormal affects.
Abstract: The origins of the word "shame" recall the concept of the infraction of integrity both as scandal and as individualization. The human experience of shame stretches along a continuum from modesty to disabling interpersonal terror. Unlike other basic affects, its emergence is a fundamental moment in the process of self-awareness and self-object differentiation. Neglected by psychiatry because it was regarded as a moral concept, today it is possible to hypothesize that it has a biologic basis that one can attempt to describe in terms of corticothalamic pathways. In this respect, like other affects, it could be considered as a cognitive shortcut to activate specific and evolutionally useful behavioral patterns, such as concealment or a request for affiliation. It is fairly ubiquitous in psychopathology, but is clinically much more structured in its abnormal expressions in anxiety disorders, particularly social phobia, obsessive-compulsive disorder, eating disorders, body dysmorphic disorder, and even in bipolar mood disorder. In schizophrenia it has been described as being one stage in the construction of delusion. Its presence is connected to interpersonal relationship (altruism) though it seems absent in autism. The assessment of shame experiences in psychiatric patients could be useful for both pharmacological and psychotherapeutic strategies, and could provide a categorization of a new psychopathology based on abnormal affects.
TL;DR: Preliminary clinical studies have shown trends toward combination therapy reducing alcohol intake in humans, and findings are encouraging, but they must be explored further in larger, randomized, double-blind trials.
Abstract: Combination pharmacotherapy has proven effective in a number of psychiatric disorders, including depression and schizophrenia. However, compared with other affective disorders, few studies have explored the use of combination therapy in alcoholism, and the majority have been limited to animal models. There is evidence to support a role for combination therapy in alcoholism. For example, several neurochemical systems, including the dopaminergic, serotonergic, and opioidergic, appear to affect alcohol intake. Studies in several different types of alcohol-preferring rats have suggested that coadministration of agents to target more than one of these systems simultaneously may produce beneficial effects on alcohol intake, while avoiding problematic effects, such as alterations in food or water intake. Data from preliminary clinical studies have shown trends toward combination therapy reducing alcohol intake in humans. While such findings are encouraging, they must be explored further in larger, randomized, double-blind trials.
TL;DR: The overall purposes of treating alcohol withdrawal are to relieve patient discomfort, to prevent the development of more serious withdrawal symptoms, and to initiate long-term alcohol rehabilitation.
Abstract: It has been well known for a number of years that abrupt withdrawal from alcohol following chronic use is associated with adverse consequences, ranging from mild tremors to withdrawal seizures. The overall purposes of treating alcohol withdrawal (AW) are to relieve patient discomfort, to prevent the development of more serious withdrawal symptoms, and to initiate long-term alcohol rehabilitation. Several areas of controversy exist in the clinical management of AW, including the optimal treatment setting, the need for pharmacologic management, and the most appropriate agent to prescribe when medication is deemed necessary. This article reviews the clinical features, general management, and treatment of AW.