Incident psychopharmacological treatment and psychiatric hospital contact in individuals with newly developed type 2 diabetes - a register-based cohort study.

To investigate the association between newly developed type 2 diabetes (T2D) and incident psychopharmacological treatment and psychiatric hospital contact. Via Danish registers, we identified all 56 640 individuals from the Central and Northern Denmark Regions with newly developed T2D (defined by the first HbA1c measurement ≥6.5%) in 2000-2016 as well as 315 694 age- and sex-matched controls (without T2D). Those having received psychopharmacological treatment or having had a psychiatric hospital contact in the 5 years prior to the onset of T2D were not included. For this cohort, we first assessed the 2-year incidence of psychopharmacological treatment and psychiatric hospital contact. Secondly, via Cox regression, we compared the incidence of psychopharmacological treatment/psychiatric hospital contact among individuals with T2D to propensity score-matched controls - taking a wide range of potential confounders into account. Finally, via Cox proportional hazards regression, we assessed which baseline (T2D onset) characteristics were associated with subsequent psychopharmacological treatment and psychiatric hospital contact. A total of 8.3% of the individuals with T2D initiated psychopharmacological treatment compared to 4.6% of the age- and sex-matched controls. Individuals with T2D were at increased risk of initiating psychopharmacological treatment compared to the propensity score-matched controls (HR = 1.51, 95% CI = 1.43-1.59), whereas their risk of psychiatric hospital contact was not increased to the same extent (HR = 1.14, 95% CI = 0.98-1.32). Older age, somatic comorbidity, and being divorced/widowed were associated with both psychopharmacological treatment and psychiatric hospital contact following T2D. Individuals with T2D are at elevated risk of requiring psychopharmacological treatment.

How a Psychopharmacology Clinical Trial Site in the Seattle Area Managed Clinical Trials and Patient Care During the COVID-19 Pandemic.

OBJECTIVES: As the COVID-19 pandemic developed in March 2020 in greater Seattle, our clinical trial site faced several ethical and clinical dilemmas. We remained open to research patients including high-risk elderly patients and adapted to changing health recommendations. METHODS: Beginning March 14, 2020 we developed an in-person evaluation for potential risk of COVID-19. Included are the first 3 weeks of screening by our physicians for potential exposure to COVID-19, common symptoms, temperature, blood oxygen saturation, and heart rate. Individuals with higher risk (n = 23) were identified and managed. RESULTS: The 825 evaluations included 37 staff, 167 patients, and 152 visitors. No one needed isolation or transfer to acute care facility, staff attendance was 95%, all 33 geriatric patients continued in phase II trials, and others decreased by 5%. CONCLUSION: We share how we incorporated COVID-19 Center for Disease Control health recommendations to a clinical trial center and addition of pulse oximetry.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Executive (dys)function after stroke: special considerations for behavioral pharmacology.

Stroke is a worldwide leading cause of death and long-term disability with concurrent secondary consequences that are largely comprised of mood dysfunction, as well as sensory, motor, and cognitive deficits. This review focuses on the cognitive deficits associated with stroke specific to executive dysfunction (including decision making, working memory, and cognitive flexibility) in humans, nonhuman primates, and additional animal models. Further, we review some of the cellular and molecular underpinnings of the individual components of executive dysfunction and their neuroanatomical substrates after stroke, with an emphasis on the changes that occur during biogenic monoamine neurotransmission. We concentrate primarily on changes in the catecholaminergic (dopaminergic and noradrenergic) and serotonergic systems at the levels of neurotransmitter synthesis, distribution, reuptake, and degradation. We also discuss potential secondary stroke-related behavioral deficits (specifically, poststroke depression as well as drug-abuse potential and addiction) and their relationship with stroke-induced deficits in executive function, an especially important consideration given that the average age of the human stroke population is decreasing. In the final sections, we address pharmacological considerations for the treatment of ischemia and the subsequent functional impairment, as well as current limitations in the field of stroke and executive function research.

Executive (dys)function after traumatic brain injury: special considerations for behavioral pharmacology.

Executive function is an umbrella term that includes cognitive processes such as decision-making, impulse control, attention, behavioral flexibility, and working memory. Each of these processes depends largely upon monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission in the frontal cortex, striatum, and hippocampus, among other brain areas. Traumatic brain injury (TBI) induces disruptions in monoaminergic signaling along several steps in the neurotransmission process - synthesis, distribution, and breakdown - and in turn, produces long-lasting deficits in several executive function domains. Understanding how TBI alters monoamingeric neurotransmission and executive function will advance basic knowledge of the underlying principles that govern executive function and potentially further treatment of cognitive deficits following such injury. In this review, we examine the influence of TBI on the following measures of executive function - impulsivity, behavioral flexibility, and working memory. We also describe monoaminergic-systems changes following TBI. Given that TBI patients experience alterations in monoaminergic signaling following injury, they may represent a unique population with regard to pharmacotherapy. We conclude this review by discussing some considerations for pharmacotherapy in the field of TBI.

Advances in Drug Discovery and Development in Geriatric Psychiatry.

PURPOSE OF REVIEW: This article reviews recent advances in drug discovery and development for geriatric psychiatry. Drug discovery for disorders of the central nervous system is a long and challenging process, with a high attrition rate from the preclinical stages through to marketing a compound. Developing drugs for geriatric neuropsychiatric conditions presents additional challenges, due to the complexity of the symptoms, comorbid diagnoses, and the variability of the population. Despite there being limited success over the past two decades, a number of new approaches have identified potential targets for preclinical development and ultimately clinical testing. RECENT FINDINGS: Recent approaches have tried to address specific mechanisms that relate to the disease progression. These approaches include combining a number of ligands into to multi-target compounds, or targeting specific types of cells such as protein kinases or myeloid cells. In addition, the increased use of induced pluripotent stem cell cultures has enabled new compounds to be tested on disease-specific tissues, increasing the success rate of the lead compounds going through the preclinical stages. New pharmacological agents designed with advanced screening techniques and the shift towards systems pharmacology is changing the landscape of drug discovery in geriatric psychiatry. There is potential for these new agents to produce targeted effects in the framework of disorders that have long been untreatable.

The practice of experimental studies in psychopharmacology: Top 10 tips from one centre's experience.

OBJECTIVE: Recent efforts to optimise translation of basic research findings to successful clinical trials have led to a sharper focus on experimental medicine translational studies. This is coupled with a movement towards greater methodological integrity and openness. Although this can be achieved through preregistration and detailed reporting of study methodology, the reality of study application can often be lost. METHODS: In practice, challenges in study application can often lead to diminished scientific robustness, even in well-designed studies. A detailed description of experiences is essential for learning and subsequent improvement. To this end, the authors undertook a description of the experience of a specialised psychopharmacology experimental study centre. RESULTS: This centre's experiences reveal that even supposedly routine study elements, such as screening parameters, peri-drug administration, and peri-discharge procedures, can pose significant practical obstacles to the achievement of minimal protocol deviation. Ultimately, these factors impact on academic standards such as enhanced data reliability; but they have additional implications for participant clinical safety and well-being, for instance in relation to adverse event and incidental finding recording. CONCLUSIONS: The facilitation of a scientific culture that is more transparent even at the operational level will hopefully augment translational process and probability of success.

Treat the Patient, Not the Rule Book : The Art of Psychopharmacology!

Experienced clinicians are aware that the results from clinical drug trials do not always translate to office practice. This essay suggests that clinicians use their own diagnostic and interviewing skills when treating with medications rather than simply relying on published data or suggested treatment algorithms.

Prescribing of medication for attention deficit hyperactivity disorder among young people in the Clinical Practice Research Datalink 2005-2013: analysis of time to cessation.

The aim of this study was to examine the time to cessation of ADHD medication amongst young people with ADHD aged 16 in the period 2005-2013. Previous studies of prescribing in primary care reported high rates of medication cessation amongst 16 and 17 year olds with ADHD. The examination of trends since the introduction of new NICE guidance in 2008 will support service planning and improvement of outcomes over the vulnerable transition period from child to adult services. We used primary care records from the Clinical Practice Research Datalink and identified cases prescribed ADHD medication at the time of their 16th birthday during the study period. The outcome was time to medication cessation from the age of 16. Cessation of medication was defined as occurring at the beginning of a gap of over 6 months in prescriptions. 1620 cases were included. The median time to cessation was 1.51 years (95% CI 1.42-1.67).The estimated probability of remaining on medication was 0.63 (95% CI 0.61-0.65) at age 17 (i.e., at 1 year) and 0.41 (95% CI 0.39-0.43) at age 18. Young people with ADHD remain at high risk of cessation of medication during the transition from child to adult services. Despite the restriction that only primary care prescribing data were available, the results suggest continuing disparity between expected levels of symptom persistence and continuation of medication.

Psychopharmacology for Borderline Personality Disorder.

Treating individuals with borderline personality disorder (BPD) is a complex and challenging process fraught with clinician stigma and bias. Clinically, polypharmacy is the most common approach, even though it is more likely to produce greater drug-drug adverse effects and interactions than effective improvement in symptoms. Currently, there are no approved medications specific for the treatment of BPD. The current article reviews the extant literature on psychopharmacology and provides treatment recommendations. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 8-11.].

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 3: The Clinical Guidelines.

Background: The current paper introduces the actual International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder. Concept and structure of the guidelines: The current clinical guidelines are based on evidence-based data, but they also intend to be clinically useful, while a rigid algorithm was developed on the basis of firm evidence alone. Monotherapy was prioritized over combination therapy. There are separate recommendations for each of the major phases of bipolar disorder expressed as a 5-step algorithm. Discussion: The current International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder are the most up-to-date guidance and are as evidence based as possible. They also include recommendations concerning the use of psychotherapeutic interventions, again on the basis of available evidence. This adherence of the workgroup to the evidence in a clinically oriented way helped to clarify the role of specific antidepressants and traditional agents like lithium, valproate, or carbamazepine. The additional focus on specific clinical characteristics, including predominant polarity, mixed features, and rapid cycling, is also a novel approach. Many issues need further studies, data are sparse and insufficient, and many questions remain unanswered. The most important and still unmet need is to merge all the guidelines that concern different phases of the illness into a single one and in this way consider BD as a single unified disorder, which is the real world fact. However, to date the research data do not permit such a unified approach.

Strategies for Utilizing Neuroimaging Biomarkers in CNS Drug Discovery and Development: CINP/JSNP Working Group Report.

Despite large unmet medical needs in the field for several decades, CNS drug discovery and development has been largely unsuccessful. Biomarkers, particularly those utilizing neuroimaging, have played important roles in aiding CNS drug development, including dosing determination of investigational new drugs (INDs). A recent working group was organized jointly by CINP and Japanese Society of Neuropsychopharmacology (JSNP) to discuss the utility of biomarkers as tools to overcome issues of CNS drug development.The consensus statement from the working group aimed at creating more nuanced criteria for employing biomarkers as tools to overcome issues surrounding CNS drug development. To accomplish this, a reverse engineering approach was adopted, in which criteria for the utilization of biomarkers were created in response to current challenges in the processes of drug discovery and development for CNS disorders. Based on this analysis, we propose a new paradigm containing 5 distinct tiers to further clarify the use of biomarkers and establish new strategies for decision-making in the context of CNS drug development. Specifically, we discuss more rational ways to incorporate biomarker data to determine optimal dosing for INDs with novel mechanisms and targets, and propose additional categorization criteria to further the use of biomarkers in patient stratification and clinical efficacy prediction. Finally, we propose validation and development of new neuroimaging biomarkers through public-private partnerships to further facilitate drug discovery and development for CNS disorders.

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm.

Background: The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety. Material and Methods: The PRISMA method was used in the literature search with the combination of the words 'bipolar,' 'manic,' 'mania,' 'manic depression,' and 'manic depressive' with 'randomized,' and 'algorithms' with 'mania,' 'manic,' 'bipolar,' 'manic-depressive,' or 'manic depression.' Relevant web pages and review articles were also reviewed. Results: The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice. Conclusions: A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 4: Unmet Needs in the Treatment of Bipolar Disorder and Recommendations for Future Research.

Background: The current fourth paper on the International College of Neuropsychopharmacology guidelines for the treatment of bipolar disorder reports on the unmet needs that became apparent after an extensive review of the literature and also serves as a conclusion to the project of the International College of Neuropsychopharmacology workgroup. Materials and Methods: The systematic review of the literature that was performed to develop the International College of Neuropsychopharmacology guidelines for bipolar disorder identified and classified a number of potential shortcomings. Results: Problems identified concerned the reliability and validity of the diagnosis of bipolar disorder and especially of bipolar depression. This, in turn, has profound consequences for early detection and correct treatment of the disorder. Another area that needs improvement is the unsatisfactory efficacy and effectiveness of therapeutic options, especially in special populations such as those with mixed features and rapid cycling course. Gender issues and adherence problems constitute an additional challenge. The literature suggests that while treatment providers are concerned more with treatment-related issues, patients and their caregivers worry more about issues pertaining to the availability of services and care, quality of life, and various types of burden. The workgroup identified additional unmet needs related to the current standard of research in bipolar disorder. These include the fragmentation of bipolar disorder into phases that are handled as being almost absolutely independent from each other, and thus the development of an overall therapeutic strategy on the basis of the existing evidence is very difficult. Trials are not always designed in a way that outcomes cover the most important aspects of bipolar disorder, and often the reporting of the results is biased and unsatisfactory. The data on combination treatments and high dosages are sparse, whereas they are common in real world practice. Conclusions: The workgroup endorses the full release of raw study data to the scientific community, and the development of uniform clinical trial standards (also including more realistic outcomes) and the reporting of results. The 2 large appendices summarize the results of this systematic review with regard to the areas of lack of knowledge where further focused research is necessary.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines.

Background: This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity. Methods: The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines. Results: The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option. Conclusion: The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper.

Implementing Psychopharmacology Rounds in a Nursing Facility to Improve Antipsychotic Usage.

OBJECTIVES: Evaluate whether implementing of pharmacy-led psychopharmacology rounds in a nursing facility will improve the rate of antipsychotic use. DESIGN: Single-center, prospective; medication use evaluation (MUE). SETTING: Rutland Nursing Home, Brooklyn, New York. PARTICIPANTS: Nursing facility residents, excluding the pediatric unit. INTERVENTIONS: Weekly interdisciplinary psychopharmacology rounds that include: clinical pharmacists, nurse managers, medical director, social workers, and administration. Antipsychotics were analyzed for all residents for appropriateness of use, proper documentation, and adequate monitoring. MAIN OUTCOME MEASURE: Assess the overall rate of reduction of antipsychotic use after implementation of psychopharmacology rounds. Secondary outcomes assessed improvements in monitoring and documentation for residents on antipsychotics. RESULTS: A total of 81 residents were evaluated over the six-month MUE. Of those residents, 20 had their antipsychotics discontinued, and 11 had their antipsychotics tapered. The overall use of antipsychotics decreased from 14.6% (62/422) to 12.2% (50/411) (P = 0.285). Compliance with indications generally approved by the Centers for Medicare & Medicaid Services improved from 65% (37/57) to 85% (46/54) (P = 0.008). Matching indications on the psychiatry consult and the medication order improved from 58% (33/57) to 80% (43/54) (P = 0.015). Metabolic laboratory monitoring improved from 58% (33/57) to 83% (45/54) (P = 0.003). Improvements in timeliness of psychiatry and ophthalmology consults were not statistically significant. CONCLUSION: Implementing interdisciplinary psycho-pharmacology rounds in a nursing facility resulted in a reduction of inappropriate antipsychotic use and improved monitoring and documentation.

Pharmacotherapy in Psychiatric Disorders of Children: Current Evidence and Trends.

Pharmacotherapeutic interventions are available for most psychiatric disorders in children. Evidence for these interventions varies, depending on the targeted disorders. For attention-deficit/hyperactivity disorder, a sound database on efficacy and safety of medication exists. For other common disorders or psychopathological phenomena like disruptive behavior, anxiety disorders, depressive disorders, or autism, data on efficacy and safety are much scarcer. This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry. The literature indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases. Most guidelines recommend psychopharmacotherapy in children to be embedded in a psychosocial or therapeutic intervention plan. Decision for medication depends on the severity of symptoms, chronicity, and, most important, impairment of the child in academic performance, family relationships, and everyday life. The high rates of off-label use in the age group of children are often due to a lack of market authorization studies less indicative of low efficacy. As adverse events need to be monitored closely, pharmacotherapy should mainly be restricted to experienced mental health care providers.

Challenges in psychopharmacology: a drug information centre perspective.

WHAT IS KNOWN AND OBJECTIVE: Questions about psychotropic drugs are frequently submitted to drug information centres (DICs). Twenty years' experience from Norwegian DICs was used to identify particular challenges in responding to those questions. COMMENT: Questions about psychopharmacological therapy are usually patient-related and are often difficult to answer. Frequent questions about psychotropic drugs come from experienced senior physicians in disciplines like psychiatry, geriatrics, general practice and neurology. The physicians often ask about specific drug use in pregnancy or breastfeeding, drug combinations and interactions, drug switching and formulations, and drug-withdrawal reactions. WHAT IS NEW AND CONCLUSION: There is a lack of relevant information in drug monographs and guidelines to inform answers to the questions posed for the care of individual patients. There is a clear need for these topics to be highlighted in the pre- and postgraduate teaching of physicians. The issues highlighted are likely to be of international relevance based on our experience of the use of international sources of drug information.

Practical clinical trials in psychopharmacology: a systematic review.

Practical clinical trials (PCTs) are randomized experiments under typical practice conditions with the aim of testing the "real-life" benefits and risks of therapeutic interventions. Influential PCTs have been conducted in cardiology, oncology, and internal medicine. Psychotropic medications are widely and increasingly used in medical practice. This review examines recent progress in conducting PCTs in psychopharmacology. The January 2000 to October 2014 MEDLINE, Scopus, and ClinicalTrials.gov databases were searched for peer-reviewed publications of PCTs with at least 100 subjects per treatment arm. Most PCTs in psychiatry evaluated mental health services or psychosocial interventions rather than specific pharmacotherapies. Of 157 PCTs in psychiatry, 30 (19%) were in psychopharmacology, with a median of 2 publications per year and no increase during the period of observation. Sample size ranged from 200 to 18,154; only 11 studies randomized 500 patients or more. Psychopharmacology PCTs were equally likely to be funded by industry as by public agencies. There were 10 PCTs of antidepressants, for a total of 4206 patients (in comparison with at least 46 PCTs of antihypertensive medications, for a total of 208,014 patients). Some psychopharmacology PCTs used suicidal behavior, treatment discontinuation, or mortality as primary outcome and produced effectiveness and safety data that have influenced both practice guidelines and regulatory decisions. Practical clinical trials can constitute an important source of information for clinicians, patients, regulators, and policy makers but have been relatively underused in psychopharmacology. Electronic medical records and integrated practice research networks offer promising platforms for a more efficient conduct of PCTs.