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The Experimental and Clinical Psychopharmacology journal was examined based on authorship and gender from 2007 to 2020. Data were calculated for total authorship by gender (women and men), authorship as first author by gender, articles with at least one woman as an author, articles with at least one man as an author, and collaborative articles. There were 3,442 listed authors across 794 articles. Women and men accounted for 43.3% and 55.5% authorship, respectively, irrespective of authorship order. Women were listed as first authors 48.3%, and men were listed as first authors 51.5%. Editorial boards were also examined based on gender from 2006 to 2021. The total number (and percentage) of women on editorial boards increased across editorial terms, with the present term showing the highest inclusion of women. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective: The objective of this study was to evaluate the safety and efficacy of medications commonly used in autism spectrum disorder (ASD) and compare this to what current research has shown regarding medical cannabis use in this population. Methods: Searches were performed to collect information surrounding currently used medications and their safety and efficacy profiles, biologic plausibility of cannabis use for symptoms of ASD, and studies detailing cannabis' safety and efficacy profile for use in the ASD population. Results were used to compare medications to cannabis as a proposed treatment. Results: The heterogeneity of ASD produces great difficulties in finding appropriate treatment, leading to many medication changes or treatment trials throughout a patient's life. Commonly prescribed medications display varying levels of efficacy, safety, and tolerability between patients and symptoms targeted. Some of the most common side effects cited are also considered the most troubling symptoms associated with ASD; aggression, anxiety, irritability, and a negative effect on cognition, leading many patients to discontinue use as the side effects outweigh benefits. Recent case reports and retrospective studies have displayed the potential efficacy, safety, and tolerability of cannabidiol (CBD)-rich medical cannabis use for treating both core symptoms of ASD and many comorbid symptoms such as irritability and sleep problems. Studies have also identified circulating endocannabinoids as a possible biomarker for ASD, providing another possible method of diagnosis. Conclusions: Currently, there are no approved medications for the core symptoms of ASD and only two medications Food and Drug Administration approved for associated irritability. Prescribed medications for symptoms associated with ASD display varying levels of efficacy, safety, and tolerability among the heterogeneous ASD population. At the time of this study there are no published placebo-controlled trials of medical cannabis for ASD and the observational studies have limitations. CBD-rich medical cannabis seems to be an effective, tolerable, and relatively safe option for many symptoms associated with ASD, however, the long-term safety is unknown at this time.

This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins's American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author's initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine's neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine's self-reported "reward" and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration's efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Variation in prescription of psychotropic medications to patients with schizophrenia spectrum disorders may underlie health inequities. Using a national U.S. Medicaid sample, the authors examined prescription patterns of psychotropic medications commonly used for managing schizophrenia.Data from the 2011-2012 Medicaid Analytic eXtract were examined for demographic predictors of and variation across states in psychotropic medication prescription among adult patients diagnosed as having schizophrenia spectrum disorders (N=357,914). Percentages of patients in each state who filled prescriptions of at least 15 days of any antipsychotic, clozapine, antidepressant, benzodiazepine, mood stabilizer, or long-acting injectable (LAI) antipsychotic medication were determined after adjustment for demographic and clinical covariates. Multivariate regressions of clinical and demographic factors predicting prescription patterns were conducted.Prescribing patterns for all types of psychotropic medications varied across states. Clozapine and LAI prescriptions showed the most dramatic differences across states and among patients with different demographic characteristics. Across states, adjusted proportions of prescriptions ranged from 4% to 22% for LAIs and from 1% to 11% for clozapine. Non-Hispanic Blacks and people of other race-ethnicities were more likely than non-Hispanic Whites to fill prescriptions for LAIs, and non-Hispanic Whites were more likely than individuals from other racial-ethnic groups to fill prescriptions for clozapine and all other medications.Considerable variation in prescribing patterns of LAIs and clozapine by race-ethnicity and across states suggests uneven quality of care for individuals with schizophrenia spectrum disorders in the United States. A better understanding of what causes this variation could inform policy makers to improve treatment for this vulnerable population.

Psychiatric sequelae of traumatic brain injury (TBI) can cause significant and often chronic impairment in functioning and quality of life; however, their phenomenological and mechanistic complexities continue to present significant treatment challenges. The clinical presentation is often an amalgam of syndromes and co-occurring symptoms that require a highly nuanced and systematic approach to treatment. Although few randomized controlled trials have tested treatments for psychiatric problems after TBI and the synthesis of results continues to be compromised by the heterogeneity of study populations, small samples, and differing inclusion criteria and outcome measures, an increasing body of literature supports evidence-based treatment strategies. We provide a narrative review of pharmacological, psychoeducational/behavioral, and neuromodulation treatments for psychiatric conditions in adults with TBI and discuss known or postulated mechanisms of action for these treatment approaches. Where data are available, we focus on randomized controlled trials and large case series in which a psychiatric condition provides both a selection criterion and a primary or secondary outcome. We conclude by proposing directions for future research, particularly the need for novel neuropharmacological, behavioral, and neurophysiological studies and pragmatic trials of multicomponent and adaptive models that will increase understanding of the mechanisms underlying post-TBI psychiatric disorders and accelerate dissemination and implementation of effective person-centered care.

The best practice for the initiation of symptomatic motor treatment for Parkinson’s disease is an ongoing topic of debate. Fueled by interpretation of the results of the LEAP and MED Parkinson’s disease studies, many practitioners opt for early initiation of levodopa formulations, avoiding dopamine agonists to circumvent potential deleterious side effects, namely impulse control disorder. Compared with levodopa, monoamine oxidase inhibitors may lack necessary potency. Ignored in this academic debate is another therapeutic option for patients with Parkinson’s disease requiring treatment initiation: amantadine. Amantadine was first reported effective in the treatment of Parkinson’s disease in 1969 and several studies were published in the 1970s supporting its efficacy. Currently, amantadine is mainly utilized as an add-on therapy to mitigate levodopa-related dyskinesia and, more recently, new long-acting amantadine formulations have been developed, with new indications to treat motor fluctuations. Amantadine has not been reported to cause dyskinesia and is rarely implicated in impulse control disorder.

Behaviourally-active medication can play an important role in improving the welfare of cats and dogs in both the short and longer term. Drugs can be used to reduce fear, anxiety and panic in the short term, such as to help noise-sensitive dogs cope better with events such as firework displays, or to help fearful dogs and cats cope better with visits to the vets or groomers. Drugs can also play an important role in longer-term reduction of negative emotional states, particularly fear and anxiety, as long as they are used in conjunction with a comprehensive behaviour modification plan. This article outlines some of the behaviourally-active drugs most commonly used to treat dogs and cats in the UK, as well as some of the considerations needed for using medication as part of behaviour modification in cats and dogs.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder identified in 4% to 8% of children, adolescents, and adults. Features of ADHD found in childhood and adolescence persist into adulthood in as many as 70% of pediatric patients with this diagnosis. Various behavioral therapies are helpful for ADHD. This discussion focuses on medications that research has shown to be beneficial for treating the core features of this condition. Drugs that are approved by the US Food and Drug Administration for ADHD are psychostimulants (methylphenidate and amphetamine products), long-acting alpha-2 agonists (clonidine, guanfacine), and a selective norepinephrine reuptake inhibitor (atomoxetine). Clinicians prescribing these drugs should monitor their patients for both beneficial and adverse effects. Although it is often difficult to find a specific medication that is superior to others for all people with ADHD, research does show that methylpheni-date is typically superior to amphetamines. Thus, careful clinician scrutiny is needed to find the optimal formulation for those taking these medications. [ Psychiatr Ann . 2021;51(10):459–466.]

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Method...

Die progressive multifokale Leukenzephalopathie (PML) ist eine meist verheerend verlaufende ZNS-Infektion, die durch das John-Cunningham(JC)-Virus verursacht wird. Die hier dargestellte Fallserie beschreibt die unterschiedlichen Verläufe einer PML und die Möglichkeit, Immuncheckpointinhibitoren in der Behandlung der PML einzusetzen.

Nearly 5% of individuals in the USA had serious thoughts of suicide in 2019 and over 30% of individuals suffering with major depressive disorder reported suicidal ideation with 2 million of those reporting suicidal ideation with some level of intent. However, options to treat depressed individuals considered at imminent risk of suicide remain limited. Until the recent approval of esketamine in the treatment of patients with major depressive disorder with serious suicidal thoughts or actions, no medications had been specifically evaluated for use in this population in the acute setting. This review discusses the history and the current understanding of the role of ketamine and esketamine in depression and suicidal ideation and behavior. It covers some of the pivotal studies in this field and provides a summary of their major findings. The trials of esketamine in patients with major depressive disorder with active suicidal ideation or behavior are the first large-scale trials in patients considered at imminent risk of suicide. As such, the design of these studies is by definition novel, a fact that complicates the interpretation of the data and assessment of the true clinical meaningfulness of the findings. Despite this, the findings in toto draw a consistent picture of benefits that appears to outweigh the potential risks of the treatment. The studies also serve to highlight the complexities and limitations associated with clinical trials aiming to test the ability of novel therapeutics to reduce the burden and risks in patients with suicide ideation and behavior.

Recent decades have been marked by a wave drug treatment research in autism spectrum disorder (ASD). This work has resulted in improved ability to treat commonly occurring behavioral challenges associated with ASD including most prominently irritability marked by aggression, self-injurious behavior, and severe tantrums. While treatment of interfering behavior has progressed in our field, there remain several areas of unmet medical need including most prominently a lack of any approved drug therapies for the core, defining symptoms of autism. We outline the progress to date in the field of autism drug treatment while taking a future look forward into how decades of work can inform better future steps in this field.

OBJECTIVE: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients. METHODS: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N = 1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia–2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB). RESULTS: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage. CONCLUSIONS: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes—including psychotropics used in usual care—should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.

Despite significant progress in the understanding of the frontotemporal dementias (FTDs), there remains no disease-modifying treatment for these conditions, and limited effective symptomatic treatment. Behavioural variant frontotemporal dementia (bvFTD) is the most common FTD syndrome, and is characterized by severe impairments in behaviour, personality and cognition. Neuropsychiatric symptoms are common features of bvFTD but are present in the other FTD syndromes. Current treatment strategies therefore focus on ameliorating the neuropsychiatric features. Here we review the rationale for current treatments related to each of the main neuropsychiatric symptoms forming the diagnostic criteria for bvFTD relevant to all FTD subtypes, and two additional symptoms not currently part of the diagnostic criteria: lack of insight and psychosis. Given the paucity of effective treatments for these symptoms, we highlight how contributing mechanisms delineated in cognitive neuroscience may inform future approaches to clinical trials and more precise symptomatic treatments for FTDs.

Pregnant and postpartum patients with substance use disorders (SUD) often have other co-occurring mental health disorders. Complications of substance use and mental health conditions, such as overdose and suicide, are a significant contributor to maternal morbidity and mortality. For individuals dually diagnosed with SUD and other mental health disorders, the perinatal period can be both a motivating and a vulnerable period for care. Barriers to optimal care include, but are not limited to, lack of screening, lack of referrals for care, a limited number of psychiatric providers available to care for pregnant patients, and stigma around mental health and addiction care in pregnancy. In this review, we discuss approaches to low-barrier perinatal psychiatric care for women with SUD to promote engagement in care. We review (1) appropriate psychiatric assessment and diagnostic work-up; (2) treatment planning incorporating shared-decision making, non-punitive and culturally sensitive patient-centred care, and principles of harm reduction with a focus on psychopharmacology, and (3) the benefits of an integrated and collaborative multidisciplinary care model for this subpopulation of vulnerable patients.

Background Research with the BDSx (Bipolar Disorder Symptom Scale) suggests a 4-factor structure of responses: two depression (cognitive, somatic) and two hypo/mania factors (elation/loss of insight, affrontive symptoms). The two depression and two hypo/mania factors are correlated; and affrontive symptoms of hypo/mania (e.g., furious, disgusted, argumentative) are positively correlated with both depression factors suggesting pathways for mixed symptom presentation. This grouping of affrontive symptoms of hypo/mania organically emerged in exploratory research and has subsequently been supported in confirmatory analyses between samples and over time. The BDSx has been clinically validated with BD outpatients. Results Over 19 days, we recruited an international sample of 784 adults with BD using micro-targeted, social media advertising (M = 44.48 years, range 18–82). All participants indicated that they had BD (subtype, if known) and had been diagnosed with BD (month, year). This sample size was sufficient to confirm the 4-factor model across subtypes and compare the three (BD I, BD II, BD NOS). Responses to 19 of 20 BDSx items were psychometrically consistent across BD subtypes. Only responses to the ‘hopeless’ item were significantly higher for those with BD II. Conclusions When comparing models, it appears that affrontive symptoms are significantly and uniformly associated with hypo/mania and both depression factors across subtypes. In contrast to BD diagnostic criteria, this suggests that affrontive symptoms are central to the clinical presentation of hypo/mania and mixed symptomology across BD subtypes.

Central nervous system stimulants are established treatments for pediatric attention-deficit/hyperactivity disorder with robust efficacy data. Reductions in appetite, weight, and growth velocity are some of the most common concerns regarding the long-term use of central nervous system stimulants in developing children. They are associated with suppression of weight and body mass index in childhood. However, both weight and body mass index often progressively increase over adolescence at rates faster than those seen in non-attention-deficit/hyperactivity disorder youth to the degree that attention-deficit/hyperactivity disorder is associated with elevated body mass index by the end of adolescence regardless of medication use. The capacity of central nervous system stimulants to slow growth was identified 50 years ago. Recent work has established that the growth deficits accumulate during the first 2 years of use and may persist provided medication is used. Early initiation coupled with persistent use through adolescence is most likely to be associated with clinical impactful growth suppression. There has been limited formal investigation of treatments for stimulant-associated reductions in weight and height. The most robust evidence exists for drug holidays improving weight gain. Observational studies suggest that limiting lifetime exposure or discontinuing medication is associated with greater adult height. Additional research is needed to identify the causal mechanisms driving the observed slowing in growth as well as the identification of predictors of clinically impactful growth suppression.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.

Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

Monoamine oxidase inhibitors (MAOIs) were among the first licensed pharmacological treatments for patients with depression but over time have fallen out of mainstream clinical use. This has led to a loss of clinician training opportunities and reduced availability of MAOIs for prescribing. This article provides a concise and practical overview of how to use MAOIs safely and effectively in psychiatric practice. We consider the history of MAOIs, why they are not used more frequently, their mechanisms of action, availability, indications and efficacy, general tolerability, withdrawal symptoms, and safety considerations (including hypertensive reactions and serotonin syndrome). Practical advice is given in terms of dietary restrictions, interactions with other medications (both prescribed and non-prescribed), and how prescribers can stop and switch MAOIs, both within the drug class and outside of it. We also provide advice on choice of MAOI and treatment sequencing. Lastly, we consider emerging directions and potential additional indications.

Purpose: This study aimed to determine the rates of psychiatric medication users in the United States between 1999 to 2018 for different medication categories by age and sex. Methods: The 1999 to 2002, 2006 to 2009, and 2015 to 2018 Medical Expenditure Panel Surveys (MEPS) were used for the analysis. All individuals with a valid age were included. Any antidepressant, benzodiazepine, attention deficit hyperactivity disease (ADHD) medication, antipsychotics, and mood stabilizer report use was defined as a medication user. Separate multivariable logistic regression predicted medication users by age with restricted cubic splines by sex, medication category, and year category (1999 to 2002, 2006 to 2009, and 2015 to 2018). In addition, the rate of prescribing to males and females at different ages was determined for medication categories. Results: Rates of any psychiatric medication users increased during the study period. Females had higher rates of medication users around 20 years of age. Rates of antidepressant users increased over time and were higher for females after earlier adolescence. Rates of benzodiazepine users were higher for females, increased after 1999 to 2002, and had consistent patterns of use over time. Antipsychotic and mood stabilizer user rates were lower than other categories. Adolescent antipsychotic users markedly decreased between 2006 to 2009 and 2015 to 2018. Rates of ADHD medication users increased over time, particularly among younger adults between 25 and 50 years of age. Conclusion: The rates of individuals reporting the use of any psychiatric medications increased over the last few decades. Rates and patterns of medication users have large variations by medication category, age, and sex, but these patterns of use were stable for most medication categories.

Purpose/background Tamoxifen is a selective estrogen receptor modulator widely used for treatment and prevention of estrogenic receptor-positive breast cancer. Tamoxifen is an object of growing interest in psychopharmacology as an antimanic drug, because it inhibits the protein kinase C, a molecular target of bipolar disorder. Consistently, the potential depressive effect of tamoxifen has been repeatedly reported. Methods/procedures This article systematically reviews studies examining tamoxifen impact on mood, exploring either its potential therapeutic use as antimanic agent or its potential depressive effect. Findings Eight studies explored tamoxifen antimanic properties, all, but one, reported a rapid and efficacious antimanic action. As to the depressive effect, 9 cohort studies emerged among which 4 pointed out an increased risk of depression. Seven case reports described the onset or exacerbation of depressive episodes besides 1 case series study reported a high rate of depressive symptoms. In addition, 1 case report study described a tamoxifen-induced manic episode. Implications/conclusions The present review highlights tamoxifen treatment as a possible trigger of mood symptoms onset or exacerbation in vulnerable patients. Accordingly, patients with a history of mood disorders may require a close clinical surveillance during tamoxifen use. At the same time, the use of tamoxifen as an antimanic agent in psychiatric settings requires caution, as available evidence came from small-sample studies with short observation time. More studies are needed to define how long-term tamoxifen use may affect the course of bipolar disorder.

This article casts a critical eye over the development of American psychiatry from 1980 to the present. It notes the rapid decline of psychoanalysis that followed the publication of DSM III; the rising influence of genetics and neuroscience; the re-emphasis on the biology of mental illness; and the collapse of public psychiatry that accompanied deinstitutionalization. It argues that while genetics and neuroscience have made scientific progress, the clinical utility of their findings to date has been very limited. The fifth edition of the DSM was supposed to base itself on this new science but that proved impossible. Diagnosis remains purely phenomenological and controversial. One of the ironies of research on psychiatric genetics is that has failed to find either a Mendelian origin of schizophrenia and depression or to validate the importance of hypothesized candidate genes. Genome-wide association studies have instead uncovered risk factors for major mental illnesses, but these overlap considerably, and the genetic associations are not dispositive. Most of those who carry these genetic variants do not develop mental illness. The status of psychopharmacology since the mid-1950s is scrutinized, as is the influence of the pharmaceutical industry on contemporary psychiatry, and the implications of its recent decision to abandon work in this arena. The paper concludes with an assessment of the crisis that it contends confronts contemporary American psychiatry: its overemphasis on biology; the urgent questions that persist about diagnosis and therapeutics; concerns about the directions of future research; and its inability to reduce the excess mortality that plagues the mentally ill.

Background Despite abundant evidence that emotional distress is frequent in cancer patients and associated with adverse health outcomes, distress screening rates and adequate referrals to psychological support programs among those in need are insufficient in many cancer centers. We therefore aimed to analyze patient- and treatment-related barriers to distress screening and referrals to psychological support as a mandatory component of best-practice cancer care. Method In the present explorative study, latent class analysis was used to identify homogeneous subgroups among 4837 patients diagnosed with cancer between 2011 and 2019. Results Four subgroups were identified. Patients with a mental disorder and psychopharmacology were least probable to be screened for distress. Together with patients aged 65 or older and male patients, they were also less likely to receive psychological support. Patients hospitalized for 28 days or longer were most likely to be both screened and to receive psychological support. Conclusions Clinicians and researchers are recommended not neglect patients with mental disorders and psychopharmacological treatment as well as male and elderly patients when screening for distress and providing access to psychological support.

AACAP's recent policy statement on Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents1 recommends that "clinicians avoid using pharmacogenetic testing to select psychotropic medications in children and adolescents." We agree that there are limitations to the nascent evidence base for using pharmacogenetics, especially in combinatorial form (eg, test results that bin medications based on multiple genes). However, all-or-nothing recommendations fail to recognize the nuance and context of this testing and contrast with the AACAP Facts for Families on pharmacogenetic testing. Moreover, pharmacogenetic testing may inform dosing for antidepressants that are commonly used in child and adolescent psychiatry (eg, sertraline, escitalopram, citalopram, fluvoxamine) as well as the tolerability of some psychotropic medications. With this in mind, we wish to remind the AACAP community of the accumulating evidence and to highlight important principles of pharmacogenetic testing in youths. Specifically: 1) pharmacogenetic testing is not always performed by commercial companies and is not always combinatorial; 2) dosing recommendations or assessment of risk for severe hypersensitivity reactions are based on pharmacogenetics in the Food and Drug Administration (FDA)-approved product inserts for several medications commonly prescribed to children (eg, citalopram, aripiprazole, atomoxetine, carbamazepine, oxcarbazepine at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling); 3) expert consensus guidelines for dosing or identifying hypersensitivity risk for these drugs are available from the National Institutes of Health (NIH)-supported Clinical Pharmacogenetics Implementation Consortium (CPIC, www.cpicpgx.org/), which provides transparent, regularly updated, and evidence-based evaluations of pharmacogenetic data;2 and 4) randomized trials are not required for clinical dose adjustments; for example, dose adjustments because of decreased hepatic function or concomitant interacting medications are based on pharmacokinetic data, similar to many pharmacokinetic gene-based recommendations from CPIC.

The medical model in psychiatry and descriptive psychopathology were established in Germany by Krapelin's textbook and Jaspers' General Psychopathology. In the United Kingdom, Mayer-Gross' textbook synthesized both books, influencing US psychiatry. US psychiatrists from the World War II generation defeated the US academic psychoanalytic establishment by building three pillars: biological psychiatry (brought by Wortis), the psychopharmacology revolution, and the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition (DSM-III). The psychopharmacology revolution included immigrants (e.g., Gershon), Cole's marketing, and textbooks by Klein and Fink. The "neo-Kraepelinians" introduced the medical model in US psychiatry and defined 15 valid psychiatric disorders. Spitzer supervised DSM-III's development. Its 1980 publication started the world dominance of US psychiatry and the multiplication of diagnoses. Major contributions by US psychiatrists include a) McHugh's update of the Jaspersian approach, b) Fink's inclusion of catatonia as a syndrome in DSM-5 (following Abrams and Taylor's studies), and c) DSM-III's departure from the Jaspersian hierarchy of schizophrenia and affective symptoms.

N-glycanase 1 (NGLY1) deficiency is a rare inherited disorder characterized by developmental delay, hypolacrima or alacrima, seizure, intellectual disability, motor deficits, and other neurological symptoms. The underlying mechanisms of the NGLY1 phenotype are poorly understood, and no effective therapy is currently available. Similar to human patients, the rat model of NGLY1 deficiency, Ngly1−/−, shows developmental delay, movement disorder, somatosensory impairment, scoliosis, and learning disability. Here we show that single intracerebroventricular administration of AAV9 expressing human NGLY1 cDNA (AAV9-hNGLY1) to Ngly1−/− rats during the weaning period restored NGLY1 expression in the brain and spinal cord, concomitant with increased enzymatic activity of NGLY1 in the brain. hNGLY1 protein expressed by AAV9 was found predominantly in mature neurons, but not in glial cells, of Ngly1−/− rats. Strikingly, intracerebroventricular administration of AAV9-hNGLY1 normalized the motor phenotypes of Ngly1−/− rats assessed by the rota-rod test and gait analysis. The reversibility of motor deficits in Ngly1−/− rats by central nervous system (CNS)-restricted gene delivery suggests that the CNS is the primary therapeutic target organs for NGLY1 deficiency, and that the Ngly1−/− rat model may be useful for evaluating therapeutic treatments in pre-clinical studies.

Epilepsy is one of the most common and disabling chronic neurological disorders. Antiseizure medications (ASMs), previously referred to as anticonvulsant or antiepileptic drugs, are the mainstay of symptomatic epilepsy treatment. Epilepsy is a multifaceted complex disease and so is its treatment. Currently, about 30 ASMs are available for epilepsy therapy. Furthermore, several ASMs are approved therapies in nonepileptic conditions, including neuropathic pain, migraine, bipolar disorder, and generalized anxiety disorder. Because of this wide spectrum of therapeutic activity, ASMs are among the most often prescribed centrally active agents. Most ASMs act by modulation of voltage-gated ion channels; by enhancement of gamma aminobutyric acid-mediated inhibition; through interactions with elements of the synaptic release machinery; by blockade of ionotropic glutamate receptors; or by combinations of these mechanisms. Because of differences in their mechanisms of action, most ASMs do not suppress all types of seizures, so appropriate treatment choices are important. The goal of epilepsy therapy is the complete elimination of seizures; however, this is not achievable in about one-third of patients. Both in vivo and in vitro models of seizures and epilepsy are used to discover ASMs that are more effective in patients with continued drug-resistant seizures. Furthermore, therapies that are specific to epilepsy etiology are being developed. Currently, ~ 30 new compounds with diverse antiseizure mechanisms are in the preclinical or clinical drug development pipeline. Moreover, therapies with potential antiepileptogenic or disease-modifying effects are in preclinical and clinical development. Overall, the world of epilepsy therapy development is changing and evolving in many exciting and important ways. However, while new epilepsy therapies are developed, knowledge of the pharmacokinetics, antiseizure efficacy and spectrum, and adverse effect profiles of currently used ASMs is an essential component of treating epilepsy successfully and maintaining a high quality of life for every patient, particularly those receiving polypharmacy for drug-resistant seizures.

Traditional therapeutic methods in psychiatry, such as psychopharmacology and psychotherapy help many people suffering from mental disorders, but in the long-term prove to be effective in a relatively small proportion of those affected. Therapeutically, resistant forms of mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder lead to persistent distress and dysfunction in personal, social, and professional aspects. In an effort to address these problems, the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results. For instance, neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity, integration, and segregation of neural networks, focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders. The current review is focused on the translational approach in the management of schizophrenia and mood disorders, as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT, TMS, tDCS and DBS.

Viloxazine has a long history of clinical use in Europe as an antidepressant, and has recently been repurposed into an extended-release form for the treatment of attention-deficit/hyperactivity disorder in the USA. An immediate-release formulation was approved for the treatment of depression in the UK in 1974, and was subsequently marketed there and in several European countries for 30 years with no major safety concerns. In contrast to first-generation antidepressants (e.g., tricyclic antidepressants, monoamine oxidase inhibitors), viloxazine was associated with a relatively low risk for cardiotoxicity. Gastrointestinal symptoms were the most commonly reported side effects. The therapeutic effects of viloxazine are thought to be primarily the result of its action as a norepinephrine reuptake inhibitor, although in vitro and preclinical in vivo animal data suggest that viloxazine may also impact the serotoninergic system. This review summarizes the evolving knowledge of viloxazine based on information from previously published preclinical and clinical investigations, and acquired unpublished historical study reports from both open-label and blinded controlled clinical trials. We review the chemical properties, mechanism of action, safety, and tolerability across these studies, and discuss the contemporary rationale for the development of this agent as an extended-release oral formulation for the treatment of attention-deficit/hyperactivity disorder.

Background Alcohol use disorder (AUD) is a common psychiatric comorbidity in schizophrenia, associated with poor clinical outcomes and medication noncompliance. Most previous studies on the effect of alcohol use in patients with schizophrenia had limitations of small sample size or a cross-sectional design. Therefore, we used a nationwide population database to investigate the impact of AUD on clinical outcomes of schizophrenia. Methods Data from the Health Insurance Review Agency database in South Korea from January 1, 2007 to December 31, 2016 were used. Among 64,442 patients with first-episode schizophrenia, 1598 patients with comorbid AUD were selected based on the diagnostic code F10. We performed between- and within-group analyses to compare the rates of psychiatric admissions and emergency room (ER) visits, and medication possession ratio (MPR) between the patients with comorbid AUD and control patients matched for the onset age, sex, and observation period. Results The rates of psychiatric admissions and ER visits in both groups decreased after the time point of diagnosis of AUD; however, the decrease was significantly greater in the patients with comorbid AUD compared to the control patients. While the comorbid AUD group showed an increase in MPR after the diagnosis of AUD, MPR decreased in the control group. The rates of psychiatric admissions, ER visits, and MPR were worse in the comorbid AUD group both before and after the diagnosis of AUD. Conclusions The results emphasize an importance of psychiatric comorbidities, especially AUD, in first-episode schizophrenia and the necessity of further research for confirmative findings of the association of AUD with clinical outcomes of schizophrenia.

Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease typically presenting with bulbar or limb weakness. There is increasing evidence that amyotrophic lateral sclerosis is a multisystem disease with early and frequent impacts on cognition, behaviour, sleep, pain and fatigue. Dysfunction of normal physiological and metabolic processes also appears common. Evidence from pre-symptomatic studies and large epidemiological cohorts examining risk factors for the future development of amyotrophic lateral sclerosis have reported a high prevalence of changes in behaviour and mental health before the emergence of motor weakness. This suggests that changes beyond the motor system are underway at an early stage with dysfunction across brain networks regulating a variety of cognitive, behavioural and other homeostatic processes. The full impact of non-motor dysfunction continues to be established but there is now sufficient evidence that the presence of non-motor symptoms impacts overall survival in amyotrophic lateral sclerosis, and with up to 80% reporting non-motor symptoms, there is an urgent need to develop more robust therapeutic approaches. This review provides a contemporary overview of the pathobiology of non-motor dysfunction, offering readers a practical approach with regard to assessment and management. We review the current evidence for pharmacological and non-pharmacological treatment of non-motor dysfunction in amyotrophic lateral sclerosis and highlight the need to further integrate non-motor dysfunction as an important outcome measure for future clinical trial design.

Objective Evidence-based treatments for mental health concerns include psychopharmacological and psychosocial approaches. Pediatrics organizations indicate psychopharmacology needs to be a component of training. This study investigated the status of training in psychotropic medication prescribing through a national survey of pediatric chief residents. Method Pediatric chief residents (one per residency program) completed a survey (response rate = 60.2%, 127/211) about their attitudes, knowledge, comfort, practice, and training around prescribing psychotropic medication in primary care. Quantitative data included descriptive statistics and correlational analyses to explore relationships between variables; qualitative data were examined through classical content analysis. Results Almost half of respondents reported prescribing sometimes or often. Frequency of prescribing varied by mental health condition, with highest frequency for attention-deficit/hyperactivity disorder. About two-thirds of respondents reported having at least some/average knowledge. About half of respondents reported being uncomfortable with prescribing; respondents were most uncomfortable with prescribing antianxiety, mood stabilizing, and antipsychotic medications, and with discontinuing medication; about half indicated their competence in progress-monitoring needed improvement. Concurrent psychosocial treatment was perceived as very useful, although often inaccessible to patients. Prescribing frequency was related to knowledge, comfort, progress-monitoring competence, and training quality; training quality was related to knowledge and comfort. Over 60% rated their training as not at all or only somewhat adequate. Conclusions Pediatric chief residents reported having knowledge of psychotropic medication issues, but experience a general discomfort, especially with discontinuing medication, and with medications other than stimulants. Most thought their training needed improvement in terms of comprehensiveness and clinical practice experiences.

We described a case in which a heavily-traumatized patient had been under psychiatric treatment for seven years (five of them in a university mental health clinic) but was never diagnosed with PTSD and, therefore, did not receive the proper treatment for a very long period. After the correct diagnosis was made and personalized treatment instituted, the patient has shown marked improvement in functionality and wellbeing. The key element in this case, was the adequacy of psychiatric training. Our report suggests that psychiatrists are not being adequately trained to identify traumatic events and to diagnose atypical cases of PTSD. With that in mind, we emphasize that theoretical modules on trauma and trauma-related disorders and practical training in specialized PTSD clinics should be incorporated into the psychiatric residency training programs wherever they may be missing, particularly in countries most impacted by violence. Furthermore, continuing medical education on trauma and PTSD should be provided by medical associations and journals to keep physicians updated on recent progress in the field.

Frontotemporal dementia is a heterogeneous spectrum of neurodegenerative disorders. The neuropathological inclusions are tau proteins, TAR DNA binding protein 43 kDa-TDP-43, or fused in sarcoma-ubiquitinated inclusions. Genetically, several autosomal mutations account for the heritability of the disorder. Phenotypically, frontotemporal dementia can present with a behavioral variant or a language variant called primary progressive aphasia. To date, there are no approved symptomatic or disease-modifying treatments for frontotemporal dementia. Currently used therapies are supported by low-level of evidence (mostly uncontrolled) studies. The off-label use of drugs is also limited by their side-effect profile including an increased risk of confusion, parkinsonian symptoms, and risk of mortality. Emerging disease-modifying treatments currently target the progranulin and the expansion on chromosome 9 open reading frame 72 genes as well as tau deposits. Advancing our understanding of the pathophysiology of the disease and improving the design of future clinical trials are much needed to optimize the chances to obtain positive outcomes.

Background and Objective Attention-deficit/hyperactivity disorder (ADHD) treatment rates in adults are low, possibly owing to discontinuation of pediatric care due to various circumstances (including inadequate health insurance coverage, poor disease insight, and patient/family resistance, as well as those who manage their ADHD independent of pharmacologic intervention) during the transition from adolescence to adulthood. To improve the understanding of treatment patterns during this transition, this study characterized pharmacotherapy use in patients with ADHD aged 16–21 years. Methods A retrospective claims analysis of the IBM® MarketScan® Commercial Databases, which represent all census regions of the USA, included patients aged 16–21 years with two or more ADHD diagnoses between 1/1/2008 and 12/31/2017 (one or more diagnoses during the year of age 17) who were continuously enrolled from ages 16–21 years and prescribed ADHD medication for ≥ 6 months at age 17 years. Pharmacotherapy use was assessed longitudinally. Comparisons between ages were conducted using Wilcoxon signed-rank tests and McNemar tests. Treatment discontinuation was estimated using Kaplan–Meier analyses. Results The analysis included 10,292 patients. The overall percentage of patients receiving pharmacotherapy significantly decreased (p < 0.001, regardless of treatment type and presence of co-occurring psychiatric disorders) as patients aged, with a median time to treatment discontinuation of 2.94 years. Among patients using pharmacotherapy at the age of 17 years, more than 30% were no longer using pharmacotherapy at age 21 years. As patients aged, the percentage using long-acting amphetamines or methylphenidates decreased, and the percentage receiving no treatment increased. The percentage of patients with disrupted treatment from age 18 to 21 years ranged from 17.9 to 24.1%. After transitioning to disrupted treatment or no treatment, low percentages of patients returned to pharmacotherapy use (disrupted treatment: 15.7–21.5% per year; no treatment, 2.7–3.8% per year). Across all age groups, statistically significantly greater (p < 0.05) percentages of patients with co-occurring psychiatric disorders used lisdexamfetamine, dextroamphetamine-amphetamine mix short acting, and non-stimulants compared with patients without co-occurring psychiatric disorders. Patients with co-occurring psychiatric disorders remained on ADHD pharmacotherapy longer and switched or augmented their pharmacotherapy more frequently than patients without co-occurring psychiatric comorbidities. Conclusions Patients rarely reinitiated treatment after pharmacotherapy was disrupted or discontinued, emphasizing the need for increased focus on the management of ADHD as patients transition from adolescence to adulthood.

Objectives: To examine the prescribing patterns of antidepressants among a sample of psychiatrists working in Oman and to compare these practices to the current evidence for prescribing specific antidepressant in particular clinical situations. Methods: This retrospective cross sectional study. Massachusetts General Hospital Psychopharmacology Questionnaire, a 10-item questionnaire listing factors that might have influenced the choice of antidepressant medication, was sent to 83 psychiatrists working in governmental health sectors in Oman. The study was done from March to July 2019. Results: A total number of 78 psychiatrists responded to the questionnaire. Of these, 44 of the psychiatrists (56.4%) believed that one type of antidepressant is more efficacious than others, while 74 psychiatrists (94.9%) indicated that selective serotonin reuptake inhibitors (SSRIs) were their first-line treatment preference. Mirtazapine was chosen as the most likely antidepressant to cause weight gain by two-thirds of the participants. For the treatment of anxious depression and depression with melancholic feature, SSRIs were the first choice of treatment for 64.1% and 7% of respondents, respectively. For depression with atypical features, 42.3% indicated that a monoamine oxidase inhibitor would be their first option. Conclusion: There is a discrepancy between the current antidepressant prescribing practices in Oman and empirical antidepressant-prescribing evidence, and this finding is consistent with previous studies.

Insular cortex is a critical brain region that participates in the interoceptive sensations. Here, we combined the iDISCO+ method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. Lateralized activation of the insular cortex is also observed in adult female mice, but not in young or aged male mice. Furthermore, asymmetrical activation of the insular cortex was completely blocked when both sides of the vagal nerve are transected, whereas intravenous injection of lithium chloride has no effect on the insular activation. Combined together, these results indicate that the insular cortex unilaterally responds to aversive visceral stimuli in an age-dependent way and this process depends on the vagal afferent pathways.

In this review, we consider issues relating to the pharmacological treatment of young children with attention deficit hyperactivity disorder (ADHD). ADHD in preschool-age children has a profound impact on psychosocial function and developmental trajectory. Clinical studies on pharmacotherapies for ADHD in young children have expanded rapidly in the past 2 decades, providing some evidence of efficacy for both psychostimulant and non-psychostimulant medications. However, preschool children may be more susceptible to adverse effects of medications, including growth reduction and cardiovascular side effects. Many questions remain regarding the long-term safety and effectiveness of these interventions; thus more research is needed to help clinicians evaluate the risk-benefit ratio for preschoolers with ADHD. As this body of knowledge grows, providers should consider the level of impairment caused by current symptoms in the risk-benefit analysis. Families should be educated not just about potential effects of medication but known complications of untreated ADHD; parents will likely not fully appreciate the long-term psychological effects of chronic behavioral problems and underachievement on a young child. A blanket "wait and see" approach should be avoided, in order to prevent a permanent loss of self-esteem and motivation that may affect some children throughout their lifespan.

Few studies have evaluated the influence of valproate on the deterioration of the lipid profile in psychiatric patients. This observational study aimed to compare the evolution of metabolic parameters in a sample of adult patients starting valproate (n = 39) with a control group (n = 39) of patients starting aripiprazole, a drug associated with a low risk of metabolic deterioration. Data were obtained from a prospective study including psychiatric patients with metabolic parameters monitored during the first year of treatment. During the first month of treatment with valproate (median: 31 days [IQR: 25-36]), mean body mass index increased significantly (from 24.8 kg/m 2 at baseline to 25.2 kg/m 2 after one month; P = .03) and mean HDL-C levels decreased significantly (from 1.39 mmol/L to 1.27 mmol/L; P = .02). In comparison, these metabolic variables remained stable during the first month of treatment with aripiprazole. The proportion of patients with early (ie during the first month of treatment) HDL-C decrease of ≥ 5% was significantly higher under valproate (54%) than aripiprazole (15%) treatment (P < .001). These findings remind the importance of a prospective metabolic monitoring in patients who initiate valproate treatment. Further research should be conducted on larger samples and should focus on finding effective interventions to prevent such metabolic adverse effects.

Background There is urgent need for new medications for psychiatric disorders. Mental illness is expected to become the leading cause of disability worldwide by 2030. Yet, the last two decades have seen the pharmaceutical industry withdraw from psychiatric drug discovery after costly late-stage trial failures in which clinical efficacy predicted pre-clinically has not materialised, leading to a crisis in confidence in preclinical psychopharmacology. Methods Based on a review of the relevant literature, we formulated some principles for improving investment in translational neuroscience aimed at psychiatric drug discovery. Results We propose the following 8 principles that could be used, in various combinations, to enhance CNS drug discovery: (1) consider incorporating the NIMH Research Domain Criteria (RDoC) approach; (2) engage the power of translational and systems neuroscience approaches; (3) use disease-relevant experimental perturbations; (4) identify molecular targets via genomic analysis and patient-derived pluripotent stem cells; (5) embrace holistic neuroscience: a partnership with psychoneuroimmunology; (6) use translational measures of neuronal activation; (7) validate the reproducibility of findings by independent collaboration; and (8) learn and reflect. We provide recent examples of promising animal-to-human translation of drug discovery projects and highlight some that present re-purposing opportunities. Conclusions We hope that this review will re-awaken the pharma industry and mental health advocates to the opportunities for improving psychiatric pharmacotherapy and so restore confidence and justify re-investment in the field.

This article provides a practical review of the diagnosis and management of angle closure induced by psychotropic agents, including tricyclic antidepressants, antipsychotics and anticonvulsants. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and antipsychotics may trigger angle closure by influencing pupil configuration through adrenergic, anticholinergic, serotonergic or dopaminergic mechanisms. Patients with narrow iridocorneal angles are at risk, and these are more common in people with hypermetropia (near-sightedness), older people and individuals with an Asian background. These patients may benefit from a laser peripheral iridotomy, either prophylactically or to relieve an acute angle-closure episode. An idiosyncratic reaction to medications such as topiramate may lead to angle closure through an alternate mechanism, leading to a uveal effusion. Ophthalmological review may be considered prior to commencing medications in high-risk patients.