Objective: Nearly 50% of patients with schizophrenia hav ecomorbid anxiety disorders. Ziprasidone's unique pharmacological profile, including 5-HT1A agaonism and 5-HT and NE reuptake inhibition, may confer anxiolytic properties. And exploratory analysis was conducted to evaluate improvement in anxiety in stable schizophrenic outpatients, as standard scales assessing psychosis do not adequately address anxity. Stable outpatients were selected to reduce the influence of acute psychosis.

Methods: Patients on conventional antipsychotics (n=93), olanzapine (n=88), and risperidone (n=41) were randomized to one of three dosing schedules and received ziprasidone 40–160 mg/day in three 6-week, open-label trials. Anxiety was measured by the PANSS anxiety item (G2: 1, absent, to 7, extreme). Analysis of patients with moderate or greater anxiety (≥4), as well as analysis of those with at least minimal anxiety (≥2), was conducted. Other symptom items were analyzed to address the speccificity of potential treatment differences.

Results: In patients with moderate or greater baseline anxiety, significant improvement in the PANSS anxiety time was observed (P<0.05). Significant improvement was also seen in the group of patients with at least minimal baseline anxiety (P<0.05). There were no concomitant signigicant changes in depression or somatic concern in the moderate anxiety subsample.

Conclusions: Improvement in the PANSS anxiety item, separate from changes in depression and somatic concern, was observed. In view of the prevalence of anxiety symptoms in schizophrenia, controlled trials utilizing anxiety scales validated in this population are necessary to further evaluate ziprasidone's anxwlytk potential.

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) γ-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.

Autistic disorder and catatonia are neuropsychiatric syndromes defined by impairments in social interaction, communication, and restricted, stereotypical motor routines. Assessments of children with these disorders are typically restricted in scope by the patients' limited ability to comprehend directions. The authors performed systematic assessments of dyskinesias on six prepubertal boys with autistic disorder and mental retardation and on one adolescent male with catatonia to determine if this type of information could be routinely obtained. The boys with autistic disorder had more stereotypies and tics, a greater degree of akathisia and hyperactivity, and more compulsions than the adolescent with catatonia. Catatonia was associated with catalepsy and dystonic postures. The authors conclude that the diagnostic accuracy and specificity of neuropsychiatric syndromes may be enhanced by the systematic assessment of the dyskinesias associated with each condition.

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.

For centuries, emotions and feelings have been considered a domain of poets, writers, novelists, or psychologists who have tried to explore their secretive natures. They have been debating the crucial question of what they are, without providing any exhaustive answer except magnificent descriptions of them or sophisticated psychodynamic interpretations.

The relationship between lesion location and neuropsychiatric sequelae in stroke patients has been extensively studied. Emotional disorders associated with right hemisphere stroke include depression, anxiety, anger, and/or mania. Pharmacotherapy, electroconvulsive therapy, and/or psychotherapy are common treatments for these disorders. This article reviews the clinical presentations of seven right hemisphere stroke patients. The treatment rationale and course of treatment are described for two of these patients. The aims of this paper are to explore the appropriateness of various assessment tools and treatment modalities for stroke patients as well as to demonstrate the techniques of psychotherapy as applied to the two cases featured in this article. Specific factors that may significantly influence treatment outcome, such as lesion location and degree of cognitive impairment, are considered.

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.

The aim of this study was to examine the pattern of comorbidity among obsessive-compulsive personality disorder (OCPD) and other personality disorders (PDs) in a sample of 400 psychiatric inpatients. PDs were assessed using the Semistructured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). Odds ratios (ORs) were calculated to determine significant comorbidity among OCPD and other axis II disorders. The most elevated odds ratios were found for the cooccurrence of OCPD with cluster A PDs (the “odd” PDs, or paranoid and schizoid PDs). These results are consistent with those of previous studies showing a higher cooccurrence of OCPD with cluster A than with cluster C (“anxious”) PDs. In light of these observations, issues associated with the nosologic status of OCPD within the Diagnostic and Statistical Manual of Mental Disorders clustering system remain unsettled.

Obsessive-compulsive disorder (OCD) is now recognized as a frequent and disabling disorder among children and adolescents. The phenomenology is similar to adult OCD, but several reports have indicated that compulsions are more prominent in children and that children are more inclined than adults to include their family surroundings in ritualistic behavior. It is also clear that young children engage in a significant amount of repetitive, ritualistic compulsive activity that appears to be a normal part of their behavioral repertoire.

Although the cause of childhood-onset OCD is unknown, many factors are likely to contribute to the heterogenous clinical phenotypes, including both genetic and environmental factors. The neurobiological circuitry involved in childhood-onset OCD is likely to involve alterations to the same cortico-striatothalamic circuitry implicated in adult OCD, but the develop-mental differences have yet to be fully delineated. The treatment response patterns of adults and children are generally inconsis-tent with each other, and specific OCD subtypes may also respond differentially.

Phenotypic characterization can be undertaken either categorically, as seen with traditional diagnostic categories, or dimensionally. Extended phenotypes can be defined in terms of symptoms and course of the illness, or neuroimaging and neurobiologic study findings, or treatment responses. Phenotypic characterization must also reflect an understanding of the rituals and repetitive behaviors that are associated with normal development. (A proposed categorization of OCD subtypes appears in the “Table library.”)

The materials in the following section are speaker comments from an educational symposium entitled Suicide: Clinical/Risk Management Issues for Psychiatrists sponsored by the American Psychiatric Association, May 16, 1999. The program chairpersons were Drs. Douglas Jacobs and Ross J. Baldessarini. The symposium was supported by an unrestricted educational grant from Solvay Pharmaceuticals.

The symposium focused on critical clinical and risk management issues about suicide as they impact clinical practice. Dr. Douglas G. Jacobs presented a suicide assessment protocol with suggestions on how to include current understanding about suicide in treatment planning. Dr. Kay Redfield Jamison reviewed bipolar disorder with an emphasis on early diagnosis, aggressive treatment, and the phenomenology of suicidal behavior. Dr. Ross J. Baldessarini discussed the lethality of bipolar depression and the effectiveness of lithium maintenance therapy to limit bipolar depression and reduce suicide risk. Dr. Jan A. Fawcett presented four clinical profiles of completed suicide and reviewed suggested treatment approaches appropriate for each that may help psychiatrists reduce the risk of suicide among their patients. Dr. Herbert Hendin explored the role psychiatrists play in performing comprehensive assessments of patients who request assisted suicide. Finally, Dr. Thomas G. Gutheil reviewed the basis for malpractice litigation and provided guidelines for preventing liability following a patient's suicide.

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.

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.

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.

The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).

At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.

Despite advances in therapies, there remain psychiatric patients who are extremely ill and cannot be helped by classic psychiatric treatments, including psychotherapy and drug therapy. Certain of these patients may be helped by use of bilateral brain lesioning. The complication rate of standard stereotactic psychosurgery techniques is very low. The main rationale for the continued experimental use of deep brain stimulation (DBS) in neurosurgery for mental disorders is its reversibility. This reversibility is not an advantage in terms of the benefits obtained, but rather if side effects emerge. In addition, electrical stimulation may provide patients with some autonomy for their treatment. The first, very preliminary results of electrical stimulation for obsessive-compulsive disorder and for a small heterogeneous group of patients with other psychiatric disorders have been published. Electrical stimulation of the brain for psychiatric disorders may become a new treatment option for certain intractable psychiatric disorders. Nevertheless, the mechanism of action of DBS in psychiatric disorders is unknown, and the experience with this modality is extremely limited. The first results look promising, but this treatment option may prove unusable for some time because of a lack of knowledge of appropriate brain stimulation targets and technical problems such as the availability of sufficient current supply.

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.