Treatment resistance, along with its sibling partial response, remains a common phenomenon in schizophrenia, complicating the disability burden inherent in the disease. Antipsychotic medications are the mainstay of treatment, and treatment resistance has mainly been defined in terms of poor response to antipsychotic medication. At the same time, clozapine, the most effective antipsychotic, remains underutilized at the expense of exposing patients to polypharmacy. We review known causes of disability in schizophrenia, how they impact various areas of everyday functioning, and discuss potential treatment options including but not limited to pharmacological approaches aimed at maximizing treatment response and reducing treatment resistance.

The neuropsychiatric examination includes standard neurological and cognitive examination techniques with several additional observations and tasks designed to capture abnormalities common among patients with neuropsychiatric disorders or neurocognitive complaints. Although useful as a screening tool, a single standardized rating scale such as the Mini Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) is insufficient to establish a neuropsychiatric diagnosis. Extra attention is paid to findings commonly seen in the setting of psychiatric disorders, dementias, movement disorders, or dysfunction of cortical or subcortical structures. Dysmorphic features, dermatologic findings, neurodevelopmental signs, signs of embellishment, and expanded neurocognitive testing are included. The neuropsychiatric clinician utilizes the techniques described in this article to adapt the examination to each patient’s situation, choosing the most appropriate techniques to supplement the basic neurological and psychiatric examinations in support of diagnostic hypotheses being considered. The added examination techniques facilitate diagnosis of neurocognitive disorders and enable neuropsychiatric formulation.

NMU of prescription stimulant medications (RxStim) intended for treatment of attention deficit/hyperactivity disorder (ADHD) is a growing public health concern, particularly when used via non-oral routes of administration. However, the role of non-oral routes of administration for RxStim NMU in the larger substance abuse pathway is less well studied. The purpose of this study was to characterize RxStim NMU and investigate substance use trajectories among adults who reported non-oral RxStim NMU recruited from Reddit.

Eligible participants must have been located in the US, English speaking, age 18 y, and have reported RxStim NMU via a non-oral route (any route other than ingestion) within the past 5 y. Participants were recruited from Feb-Sep 2019 using banner ads on Reddit, the 5th most visited website in the US. Participants completed an online survey which captured demographics, lifetime RxStim NMU and illicit substance use; they were compensated for their time. For purposes of this study, NMU included ANY of the following: (1) use for any reason, even once, without their own prescription, (2) use in ways other than prescribed, and (3) use for the feeling or experience the medication caused.

Respondents (n=225) were primarily male (86.2%), 18–24 (48.0%) or 25–34 (43.1%) years of age, and Caucasian (78.2%), Black (7.1%) or Hispanic (5.3%). Lifetime diagnosis of ADHD was reported by 27.6%, with 53.2% diagnosed at age 11–19 and 35.5% at age 20+ years. RxStim NMU via snorting was reported by 99.1%, smoking 3.6% and injecting 6.2% (multiple routes could be reported). Almost all (n=222; 98.7%) also reported lifetime illicit drug use, among whom 182 (82.0%) initiated substance use by using an illicit drug (77.9% marijuana, 1.8% cocaine/crack, 0.9% inhalants, 0.9% hallucinogens, 0.5% methamphetamine/amphetamines) prior to RxStim NMU. Forty (18.0%) respondents initiated with RxStim NMU; 14.4% then initiated marijuana use, 0.9% initiated cocaine/crack use, 0.9% initiated barbiturate use, and 0.5% initiated heroin, inhalant, methamphetamine/amphetamine, and hallucinogen use. Average age of initial RxStim NMU was 18.7 (SD 3.7) years and most often was via swallowing (89.1%) followed by snorting (10.9%). Respondents began using marijuana at age 15.9 (SD 2.5), cocaine or crack at 19.7 (SD 3.3), and heroin at 20.9 (SD 5.5).

Engagement in RxStim NMU via a non-oral route of administration is most often preceded by marijuana use. Among this Reddit-recruited population of non-oral RxStim nonmedical users, only 1 in 4 reported an ADHD diagnosis and <1 in 5 reported RxStim NMU as their first substance use experience; most of these then added marijuana and few moved toward cocaine/crack or methamphetamine. RxStim NMU via non-oral routes is associated with a larger pattern of risky substance use behaviors. Nearly all non-oral RxStim NMU is associated with concomitant drug use, especially marijuana.

Funding. Arbor Pharmaceuticals, LLC

This article reviews the development of forensic psychiatry and mental health services in Australia for the international reader. It covers the legacy of a series of colonial systems that have contributed to a modern health service that interacts with justice systems. The development of relevant legislation, hospitals, prison services, community, and courts services is reviewed. The training and academic development of professionals is covered. Gaps in service delivery and future directions are considered.

The new diagnosis of disruptive mood dysregulation disorder (DMDD) was introduced in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, to address the overdiagnosis of bipolar disorder in children and adolescents. However, there are ongoing debates about its nosology given chronic persistent irritability in children and adolescents has contextual valence. Those meeting the criteria for DMDD may, in fact, have an oppositional defiant disorder, attention deficit hyperactivity disorder, or other behavioral disorders. Similarly, in the last few years, there are many different types of treatment studies that have also yielded mixed results. These counterintuitive findings need a meticulous review for a wider debate given its clinical utility for patients, families, and practicing clinicians.

The relationship between mental illness, violence, and criminal behavior is complex, and involves a multifaceted interaction of biological, psychological, and social processes. In this article, we review the emerging research that examines the neurobiological and psychological factors that distinguish between persons with mental illness who do and who do not engage in crime and violence. Additionally, a novel model for understanding the interaction between mental illness and criminalness is proposed. (As defined by Morgan and colleagues, criminalness is defined as behavior that breaks laws and social conventions and/or violates the rights and wellbeing of others.) Stemming from this model and outlined research, we argue that management and treatment approaches should target the co-occurring domains of mental illness and criminalness to improve criminal and psychiatric outcomes. Specifically, we discuss and propose effective housing (management) and biopsychosocial intervention strategies for improving outcomes.

Beginning in the 1960s, a steady decline in the number of inpatient psychiatric beds has occurred across the United States, primarily as a result of stricter civil commitment criteria and a societal movement toward deinstitutionalization. Concomitant with this decrease in psychiatric beds has been a steady increase in the number of mentally ill individuals who are arrested and processed through the criminal justice system as defendants. One consequence of this has been an explosion in the number of defendants referred for evaluations of their present mental state—adjudicative competence—and subsequently found incompetent and ordered to complete a period of competency restoration. This has resulted in forensic mental health systems that are overwhelmed by the demand for services and that are unable to meet the needs of these defendants in a timely manner. In many states, lawsuits have been brought by defendants who have had their liberties restricted as a result of lengthy confinements in jail awaiting forensic services. The stress on state-wide forensic systems has become so widespread that this has reached the level of a near-national crisis. Many states and national organizations are currently attempting to study these issues and develop creative strategies for relieving this overburdening of forensic mental health systems nationwide. The purpose of this article is to review the current state of the research on competence to stand trial and to highlight those issues that might be relevant to the issue of criminalization of individuals with mental illness in the United States.

The treatment of major depression remains problematic for several reasons. In particular, the therapeutic response to medications usually does not manifest itself until a week after administration has begun, and more than half the patients will not experience a full recovery with the first antidepressant drug administration. There are, however, some pharmacologic strategies that can accelerate antidepressant response. When facing a treatment-resistant depression, combination therapy offers a more time-efficient approach to achieve remission than drug substitution. These interventions have been devised on a better understanding of the basis for the therapeutic response obtained with the first- and second-generation antidepressants, and evidence derived from controlled clinical trials of their superior effectiveness is growing. The rationale for such approaches will be described in this article, as well as their advantages and potential inconveniences. Ongoing research in this field continues to fuel the development of novel, better-tolerated, and more effective pharmacotherapies for depression.

Panic disorder occurs frequently with different forms of cardiovascular disease and hypertension. The 13 panic symptoms described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) often overlap with manifestations of cardiovascular disorders, raising problems in the differential diagnosis. In order to explore in greater detail the phenomenology of panic symptoms in cardiovascular patients, the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS) was administered to 111 patients with hypertension and 29 patients with a recent myocardial infarction.

With regard to the frequency of endorsement of many of the symptoms assessed on the SCI-PAS, more than 40% of the cardiovascular patients who failed to meet the DSM-IV criteria for panic disorder did not significantly differ from the 10% of cardiovascular patients who did fulfill the criteria for panic disorder. A third distinct subgroup comprising 48.6% of the cardiovascular patients reported a significantly smaller number of SCI-PAS symptoms than the other two groups.

These preliminary findings suggest the existence of a relatively large proportion of cardiovascular patients who present with physical and psychological symptoms that are potentially related to panic disorder and that may provoke considerable subjective distress. Further studies are needed to clarify the nature of these symptoms and their potential interference with treatment and symptomatology of cardiovascular disease.

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

Insomnia is a disorder characterized by chronic sleep disturbance associated with daytime disability or distress, such as memory impairment and fatigue, that occurs despite adequate opportunity for sleep. Insomnia may present as difficulty falling/staying asleep or as sleep that is nonrestorative. Studies show a strong correlation between insomnia and impaired quality of life. Pain conditions and depression are commonly associated with insomnia, either as secondary or comorbid conditions. In addition, a greater incidence of anxiety, alcohol and drug dependence, and cardiovascular disease is found in people with insomnia. Data indicate insomnia results from over-engaged arousal systems. Insomnia patients experience increased metabolic rate, body temperature, and heart rate, and elevated levels of norepinephrine and catecholamines. Pharmacologic options for the treatment of insomnia include benzodiazepine hypnotics, a selective melatonin receptor agonist, and sedating antidepressants. However, insomnia may be best treated with cognitive-behavioral therapy and instruction in good sleep hygiene, either alone or in concert with pharmacologic agents. Studies on the effects of insomnia treatment use variable methodologies or do not publish negative results, and there are currently no studies of treatment focusing on morbidity. Further research is necessary to better understand the effects of insomnia therapies on medical and psychiatric disorders.

In this Clinical Information Supplement, Thomas Roth, PhD, describes the nature of insomnia and its pathophysiology. Next, Andrew D. Krystal, MD, MS, reviews morbidities associated with insomnia. Finally, Joseph A. Lieberman III, MD, MPH, provides an overview of therapeutics utilized in patients with insomnia, including behavioral therapies and pharmacologic options.

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1–mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.

Panic disorder (PD) is a complex, multidimensional psychiatric disorder characterized by the presence of panic attacks as well as anticipatory anxiety and panic-related phobias (eg, agoraphobia). Although the etiology of this disabling disorder remains unclear, advances in basic neuroscience and in imaging studies have led to a greater understanding of the neurocircuitry and neurochemistry that are involved in modulating fear and anxiety and that are relevant to understanding PD. A preliminary integrated model can be outlined, but there is a need for additional research that cuts across genetic investigation, provocation studies, neuroimaging techniques, and treatment trials. As research continues and greater insight into the mechanisms underlying PD is achieved, additional treatment strategies may emerge.

Review of extant biological data would suggest that major depressive disorder (MDD) is a term used to subsume a syndrome that may involve a variety of different pathophysiological processes. Current research has implicated a myriad of different factors in the pathogenesis of depressive disorders including: genetic predisposition, “hormonal” abnormalities, disturbances in neurostransmitters, disturbances in neurocircuitry, and immune dysfunction. Our most recent consensus suggests that the depressive disorders reflect the interplay between these biological systems and psychosocial experiences, such as early-life trauma and current life stressors. Thus, MDD truly represents a complex heterogeneous syndrome. This conceptualization suggests that a variety of different types of treatment approaches will be necessary to adequately ameliorate the symptoms of patients suffering from this syndrome. Although this is a daunting task, we are beginning to develop approaches that will enable us to add to our armamentation of biological treatments.

Although treatments for Alzheimer’s disease (AD) currently focus on symptomatic therapies, we are entering into an era of disease-modifying therapies. Central to disease modification is early diagnosis; the disease should be slowed as early as possible, maximizing the preservation of cognitive integrity. Ideally, AD should be diagnosed before the onset of dementia, perhaps with the use of biomarkers.

Some therapies suggest that cholinesterase inhibitors and memantine have disease-modifying properties, though not all studies agree. Doody and colleagues have produced data suggesting that these agents may modify the course of AD, but it is not clear that they affect the underlying mechanisms that lead to cell death. Rather than being disease-modifying agents, cholinesterase inhibitors and memantine have potential as disease-course-modifying agents. Language precision will be extremely important in describing these therapies. One European consensus conference concluded that affecting disease course is not adequate for disease modification, but this has not been largely endorsed.

Symptomatic therapies are those affecting the course of the disease. Their benefits are multidimensional, improving cognition, global assessment, activities of daily living, behavior, and caregiver burden. Symptomatic therapies should defer decline. Clinical trials show that symptomatic therapies produce an initial improvement above baseline. However, some patients experience observable changes and some experience none. These therapies are believed to produce ~1 point improvement on the Mini-Mental State Examination (MMSE) average, and a decline that is otherwise parallel to a placebo group after a period of delayed progression (Slide 1).

Problems with memory are a very common complaint in the elderly and are not synonymous with dementia. Some degree of cognitive decline, manifested as greater difficulty in learning and retrieving new information for instance, develops with normal aging. Thus many older patients do not perform at the same level they did when they were younger but they do perform well when compared to their peers. For many, cognitive change ends at this stage and they proceed to lead normal, healthy, dementia-free lives.

The cohort that has cognitive changes beyond what is expected in normal aging but does not yet meet criteria for dementia concerns clinicians greatly as many of these patients eventually become demented. These patients usually go through a latent stage in which neurodegenerative pathology silently spreads in the brain. Once there is enough pathological burden, cognitive decline beyond what is expected for normal aging can be detected by formal neuropsychological testing. Frequently such patients go through a state called mild cognitive impairment (MCI). In this state patients are still functionally intact and live independently, but show cognitive impairment relative to the age- and education-adjusted norms.

The MCI state in itself is a prominent risk factor for developing dementia. Most patients with amnestic MCI develop Alzheimer’s disease (AD) dementia over time. At six years, as many as 80% progress to AD. Thus, MCI is a very important topic of research and an increasingly important topic of clinical care.