Introduction: This report demonstrates parameters of quality of care and treatment outcome of acute schizophrenia patients who were involved as subjects in a clinical trial of two marketed widely used antipsychotics compared with their fellow patients who received routine clinical hospital care.

Methods: Patients were newly admitted severely agitated schizophrenia patients who agreed to participate in a double-blind randomized trial of short-term (5 days) rate of improvement in response to two second-generation oral antipsychotics. Treatment outcomes as measured by the Clinical Global Impression and parameters of quality of care were compared with the general population of inpatients in the same county hospital.

Results: Of 145 patients screened, 109 patients did not meet study inclusion and exclusion criteria. It is of note that systematic diagnostic interview did not confirm the clinical diagnosis of schizophrenia in 17 patients (11.7%). Study patients had shorter length of stay (6.75 days vs 15.3 days of total psychiatric patients at the hospital during the study period), no physical restraints (vs 21.9%), no use of antipsychotics as chemical restraints (vs 19.8%), and less recidivism following the trial (28.1%) compared with prior to the trial (64.3%).

Conclusion: Patients who participate in structured clinical research with well-delineated procedures, clinical outcome measures, and clear expectations, faired better than their fellow patients in the same non-research hospital wards. Application of some characteristics of clinical research to the diagnosis and treatment of clinical non-research patients may be considered.

Cardiovascular disease (CVD) remains the number one cause of death in the United States and most developed countries and is expected to remain so for much of this century. Rates of obesity have increased 2–4-fold over the last 2 decades in the US and this condition is linked with early development of hypertension, hyperlipidemia, diabetes, and atherosclerosis. The prevalence of diabetes is also increasing, and the rise of diabetes in young people 18–29 years of age was 40% in the period between 1990 and 2001. The World Heart Federation (WHF) has estimated that CVD will become the number one cause of death in the world by 2020, surpassing infectious disease in developing countries. Metabolic disorders are on the rise in general. However, as highlighted in the discussions presented in this supplement, patients with serious mental illness appear to represent a special population who are particularly vulnerable, with rates that surpass the general population.

Anxiety disorders are common in depressed patients. Several studies of the full range of Diagnostic and Statistical Manual of Mental Disorders-defined anxiety disorders in depressed psychiatric outpatients each found that when diagnoses are based on semi-structured diagnostic interviews >40% of the patients had a comorbid anxiety disorder. The recognition of comorbidity is not simply of academic interest, but it has important clinical significance. Epidemiological studies, such as the National Comorbidity Study, have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from the depression. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients, primary care patients, and epidemiological samples. Recent research has suggested that clinicians underrecognize anxiety disorder comorbidity in depressed patients. The clinical significance of this underrecognition is highlighted by the finding that patients often want treatment to address their anxiety disorder comorbidity. When anxiety disorders are detected they often influence clinicians' selection of antidepressant medication, though some of clinicians' prescribing biases are not supported by empirical data.

In this monograph, Iwona Chelminski, PhD, reviews the significance of anxiety in patients with depression as well as diagnostic instruments for recognizing this comorbidity. Next, Mark Zimmerman, MD, addresses the factors that affect the clinician's choice of antidepressant, focusing on the influence of comorbid anxiety. Finally, Sidney Zisook, MD, discusses the differential efficacy of antidepressants as well as the role of psychotherapy in patients with comorbid anxiety and depression.

Given the frequency with which patients with substance use disorders (SUDs) and those with psychiatric disorders, such as major depressive disorder (MDD) and generalized anxiety disorder (GAD), suffer relapses and recurrences, the issue of long-term treatment for SUDs warrants special attention. Faced with recommending long-term treatment, the clinician must discern the primacy of disorder, which may have been only obliquely addressed at the time of the patient's presentation and then solved by concurrent treatment. Establishing primacy relies on determining whether the psychiatric symptoms were induced by SUD or the psychiatric disorder emerged first and substance use was a means of coping with it. A third possibility exists—that the two disorders developed independently of each other, albeit becoming intermingled over time and serving to exacerbate each other. Clues to the temporal relationship of the disorders can be deduced from a meticulous history obtained from multiple sources, the effects that acute treatment has had on either condition, and the patient's willingness to remain abstinent from the addictive substance. Hasin and colleagues demonstrated the importance that a history of depression has on long-term remission and relapse outcomes in substance dependence (Slide 1).

Acute agitation is a nonspecific term applied to an array of syndromes and behaviors. It is frequently defined as an increase in psychomotor activity, aggression, disinhibition/impulsivity, and irritable or labile mood. Etiologies of acute agitation include medical disorders, delirium, substance intoxication or withdrawal, psychiatric disorders, and medication side effects. Treatment of acute agitation requires both environmental and pharmacologic intervention. Patients should be calmed with sedating agents early in the course of treatment, allowing for diagnostic tests to take place. Failure to correctly diagnose causes of agitation may lead to delayed treatment for serious conditions, and can even exacerbate agitation.The most common cause of agitation in patients with schizophrenia is psychotic relapse due to medication nonadherence. Pharmacologic treatment options for these patients include lorazepam and antipsychotic agents. Lorazepam causes nonspecific sedation and treats some substance withdrawal, but has little effect on psychosis. First-generation antipsychotics treat psychosis and, at high enough doses, cause sedation, but may induce extrapyramidal side effects (EPS). Some second-generation antipsychotics have been approved for the treatment of agitation in schizophrenia. These agents treat psychosis with a favorable EPS profile, but are comparatively expensive and cause risks such as hypotension. However, avoiding EPS may reduce patients' resistance to antipsychotic treatment.

In this expert roundtable supplement, Joseph Battaglia, MD, provides an overview of the definition of acute agitation. Next, Delbert, G. Robinson, MD, outlines evaluation methods for actue agitation. Finally, Leslie Citrome, MD, MPH, reviews interventions for acute and ongoing management of agitation.

Randomized clinical trials remain the most valid method of testing the efficacy and safety of treatments. While efforts to elucidate the genetic and neurodevelopmental bases of autism are underway, clinicians and families are in need of scientifically valid information on how to best treat patients with autism. The effectiveness of many interventions currently used in communities has not been adequately tested. Given the high public health relevance of autism treatment research and the low interest of the pharmaceutical industry in autism, the role of the National Institutes of Health in supporting this research is paramount. Among recently launched initiatives in autism clinical trials, there are the Research Units on Pediatric Psychopharmacology Autism Network and the network of centers for Studies to Advance Autism Research and Treatment. These and other government activities in the area of autism clinical trials are here briefly reviewed.

In awareness of recent developments and upcoming future changes in the conceptualization of obsessive-compulsive disorders (OCDs), a group of 14 experts with specific experience in this area decided that a consensus statement on the present and future of OCD is timely. The group, with their long-term interest and productivity in the area of OCD, met with the specific aim of providing a global perspective. Ten countries from four continents were represented in this 2-day consensus meeting.

The meeting took place in Cape Town on February 27–28, 2006. The participants were asked to prepare and submit a relevant presentation before the meeting in order to enrich the discussion. Six presentations reviewed the following aspects of OCD: diagnosis, epidemiology, neurobiology, treatment, special populations, and pediatric OCD. A draft consensus was prepared, based on the presentations, recent consensus statements, evidence-based guidelines, and the ensuing discussions.

In this article, we discuss the use of venlafaxine, an antidepressant with predominant effects at both noradrenergic and serotonergic reuptake sites, in the treatment of trichotillomania (TTM), a complex psychiatric condition manifested by chronic, severe hair pulling. We review case examples of 10 consecutive patients exhibiting moderately severe TTM symptoms, as judged by self-report, extent of hair loss, and duration of remission, and discuss our observations regarding the effects of venlafaxine therapy (mean dose, 274 mg/day) on these patients over the course of several months (mean, 15.1 weeks). The Massachusetts General Hospital Hair Pulling Scale, Massachusetts General Hospital Trichotillomania Impact Scale (MGH TIS), Psychiatric Institute Trichotillomania Scale (PITS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Clinical Global Improvement (CGI) scale were used to appraise the patients' condition during routine clinical visits. A retrospective chart review of clinical data demonstrated significant improvement in TTM symptoms from baseline to last clinical visit in both behavioral (MGH HPS, P=.02; PITS, P=.02) and psychosocial (MGH TIS, P=.009) terms. Mean improvement on the CGI scale was 2.38±1.51, between “much improved” (2) and “slightly improved” (3). There were no significant differences from baseline to endpoint scores on the BDI or BAI. This retrospective treatment review indicates that short-term treatment with venlafaxine improved TTM symptoms; however, longer controlled trials with extended baseline periods are needed for optimal assessment of pharmacologic treatment of TTM. We look to future studies to confirm and supplement our initial positive findings.

Psychiatric disorders are associated with significant social and economic burdens, many of which are related to issues with current diagnosis and treatments. The coronavirus (COVID-19) pandemic is estimated to have increased the prevalence and burden of major depressive and anxiety disorders, indicating an urgent need to strengthen mental health systems globally. To date, current approaches adopted in drug discovery and development for psychiatric disorders have been relatively unsuccessful. Precision psychiatry aims to tailor healthcare more closely to the needs of individual patients and, when informed by neuroscience, can offer the opportunity to improve the accuracy of disease classification, treatment decisions, and prevention efforts. In this review, we highlight the growing global interest in precision psychiatry and the potential for the National Institute of Health-devised Research Domain Criteria (RDoC) to facilitate the implementation of transdiagnostic and improved treatment approaches. The need for current psychiatric nosology to evolve with recent scientific advancements and increase awareness in emerging investigators/clinicians of the value of this approach is essential. Finally, we examine current challenges and future opportunities of adopting the RDoC-associated translational and transdiagnostic approaches in clinical studies, acknowledging that the strength of RDoC is that they form a dynamic framework of guiding principles that is intended to evolve continuously with scientific developments into the future. A collaborative approach that recruits expertise from multiple disciplines, while also considering the patient perspective, is needed to pave the way for precision psychiatry that can improve the prognosis and quality of life of psychiatric patients.

Pharmacological challenge tests provide a method of assessing the functional responsiveness of serotonin (5-HT) receptor subtypes in the human brain. A number of selective agonist ligands for the 5-HT1B/1D receptor are available for human use; however, these compounds do not distinguish between 5-HT1B and 5-HT1D receptors, which is somewhat of a disadvantage. Acute administration of sumatriptan, rizatriptan, and zolmitriptan all increase plasma growth hormone in healthy subjects, possibly via activation of postsynaptic 5-HT1D receptors. This response is blunted in major depression. Sumatriptan lowers plasma prolactin, perhaps via activation of presynaptic 5-HT1B receptors. This response is not altered during repeated treatment with selective serotonin reuptake inhibitors (SSRIs), suggesting that 5-HT1B receptors retain the ability to restrain 5-HT outflow during short-term SSRI treatment.

Nonepileptic seizures (NES) are clinical events that can resemble almost any seizure phenotype, but are behavioral and emotional manifestations of psychological distress, conflict, or trauma. Intractable NES is a disabling disorder that drastically affects patients' emotional well-being. Differential diagnosis, assessment, and treatment of NES is complex, with differentials scattered across an array of neurological and psychiatric disorders. This paper provides an overview of issues related to the diagnosis and treatment of NES. It highlights characteristics and risk factors of the disorder, issues in differential diagnosis, and treatment considerations.

Whose job is it to discover and manage patients' sexual concerns? If you believe that you have a role to play, just what is that role and how will you perform it? Sexual disorders are common, yet infrequently diagnosed. A willingness to inquire about sexual function is the most critical diagnostic step for clinicians. Once a problem is discovered, a systematic diagnostic process can uncover etiologic organic and psychogenic factors using customary diagnostic tools, including taking a psychosexual and medical history, comprehensive and focused physical examinations, psychological assessment instruments, laboratory tests, and special procedures.