Clinical Psychopharmacology Research Articles

The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder.

Amphetamine (AMP), an indirectly acting psychostimulant approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults, is among the most long-standing therapeutic agents in all of clinical psychopharmacology. This review focuses on AMP absorption, metabolism, and elimination brought to bear on comparative pharmacokinetics in its various formulations. A comprehensive search of the published literature was conducted using MEDLINE (PubMed) and Google Scholar databases through April 2017 to retrieve all pertinent in vitro and human studies for review and synthesis. Additionally, Food and Drug Administration (FDA) databases were accessed for otherwise unavailable data when possible. Initially available as racemic (dl)-AMP, this drug was later supplanted by enantiopure (d)-AMPH or enantioenriched (75:25 dl)-AMP formulations; although racemic AMP returned as an approved drug to treat ADHD in 2014. Presently, there are several immediate-release (IR) formulations available, including d-AMP, dl-AMP, and mixed amphetamine salts, which are neither racemic nor the pure d-enantiomer (i.e., a 3:1 mixture of d-AMP and l-AMP). Furthermore, new modified-release AMP formulations, including an oral suspension and an orally disintegrating tablet, are now available. A lysine-bonded prodrug form of d-AMP also serves as a treatment option. Oral AMP is rapidly absorbed, with high absolute bioavailability, followed by extensive metabolism involving multiple enzymes. Some metabolic pathways exhibit stereoselective biotransformations favoring the l-isomer substrate. Drug exposure exhibits dose-proportional pharmacokinetics. Body weight is a fundamental determinant of differences in observed AMP plasma concentrations. IR formulations typically provide a Tmax from 2 to 3 hours. In replicated studies, children exhibit a shorter plasma T1/2 (∼7 hours) relative to adults (∼10 to 12 hours). There are few documented pharmacokinetic drug interactions of clinical significance beyond influences of drug-induced alteration of urinary pH. The array of AMP formulations addressed in this review offer flexibility in dosing, drug onset, and offset to assist in individualized pharmacotherapy of ADHD.

A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

Likelihood of Being Helped or Harmed as a Measure of Clinical Outcomes in Psychopharmacology.

The likelihood of being helped or harmed (LHH) ratio is an indirect measure of effect size. It tells the reader how much as likely a patient is to benefit from a treatment as to suffer from an adverse outcome with that treatment; larger values for LHH indicate more favorable treatment outcomes. The numerator for LHH is usually a measure of response or remission with a treatment, and the denominator is usually a measure of all-cause discontinuation or discontinuation due to adverse events; so, there can be more than 1 LHH statistic for a study. As an example, an LHH of 5 could indicate that after removal of placebo effects a patient is 5 times as likely to respond to a treatment as to drop out of treatment because of the experience of an adverse event. This article explains the LHH with the help of a worked example, shows how the LHH can be derived from the numbers needed to treat and harm (NNT, NNH) statistics, discusses practical issues related to the concept, and considers its limitations. The LHH is little used in clinical psychopharmacology, and authors who report or review clinical trial data should consider presenting all the LHH information that is clinically relevant in addition to NNT, NNH, and other information. Because LHH statistics present the results of risk-benefit trade-off analyses, they can help clinicians and patients more easily evaluate potential treatments during decision-making processes.

Patterns of Adherence to Oral Atypical Antipsychotics Among Patients Diagnosed with Schizophrenia.

Poor medication adherence contributes to negative treatment response, symptom relapse, and hospitalizations in schizophrenia. Many health plans use claims-based measures like medication possession ratios or proportion of days covered (PDC) to measure patient adherence to antipsychotics. Classifying patients solely on the basis of a single average PDC measure, however, may mask clinically meaningful variations over time in how patients arrive at an average PDC level. To model patterns of medication adherence evolving over time for patients with schizophrenia who initiated treatment with an oral atypical antipsychotic and, based on these patterns, to identify groups of patients with different adherence behaviors. We analyzed health insurance claims for patients aged ≥ 18 years with schizophrenia and newly prescribed oral atypical antipsychotics in 2007-2013 from 3 U.S. insurance claims databases: Truven MarketScan (Medicaid and commercial) and Humana (Medicare). Group-based trajectory modeling (GBTM) was used to stratify patients into groups with distinct trends in adherence and to estimate trends for each group. The response variable was the probability of adherence (defined as PDC ≥ 80%) in each 30-day period after the patient initiated antipsychotic therapy. GBTM proceeds from the premise that there are multiple distinct adherence groups. Patient demographics, health status characteristics, and health care resource use metrics were used to identify differences in patient populations across adherence trajectory groups. Among the 29,607 patients who met the inclusion criteria, 6 distinct adherence trajectory groups emerged from the data: adherent (33%); gradual discontinuation after 3 months (15%), 6 months (7%), and 9 months (5%); stop-start after 6 months (15%); and immediate discontinuation (25%). Compared to patients 18-24 years of age in the adherent group, patients displaying a stop-start pattern after 6 months had greater odds of having a history of drug abuse (OR = 1.46; 95% CI = 1.26-1.66; P < 0.001), alcohol abuse (OR = 1.34; 95% CI = 1.14-1.53; P< 0.001), and a codiagnosis of major depressive disorder (OR = 1.24; 95% CI = 1.05-1.44; P < 0.001) and were less likely to be aged 35-54 years (OR = 0.66; 95% CI = 0.46-0.85; P < 0.001). Longitudinal medication adherence patterns can be expressed as distinct trajectories associated with specific patient characteristics and health care utilization patterns. We found 6 distinct patterns of adherence to antipsychotics over 12 months. Patients in different groups may warrant different types of clinical interventions to prevent hospitalizations, longer hospital stays, and increased clinical complexity. For example, clinicians may consider regular home visits, assertive community treatment, and other related interventions for patients at high risk of immediate discontinuation. Health plans should consider supplementing claims-based adherence measures with new technologies that are able to track patient adherence patterns over time. Otsuka Pharmaceutical Development & Commercialization provided support for this research. MacEwan and Shafrin are employees of Precision Health Economics, which was contracted by Otsuka Pharmaceutical Development & Commercialization to conduct this study. Lakdawalla is the Chief Scientific Officer and a founding partner of Precision Health Economics. Forma is an employee of Otsuka Pharmaceutical Development & Commercialization. Hatch is a former employee of Otsuka Pharmaceutical Development & Commercialization and is a current employee of ODH, Inc. Lindenmayer has received grant/research support from Janssen, Lilly, AstraZeneca, Johnson & Johnson, Pfizer, BMS, Otsuka, Dainippon, and Roche and is a consultant for Janssen, Lilly, Merck, Shire, and Lundbeck. Portions of this study were presented as a poster at the American Society of Clinical Psychopharmacology Annual Meeting in Miami Beach, Florida; June 23, 2015; and at the 28th Annual U.S. Psychiatric and Mental Health Congress; San Diego, California; September 12, 2015. Study concept and design were contributed by Forma, Ladkawalla, MacEwan, and Shafrin, along with Hatch and Lindenmayer. MacEwan, Shafrin, Forma, and Lakdawalla collected the data, along with Hatch and Lindenmayer. Data interpretation was performed by Hatch, Lindenmayer, MacEwan, and Shafrin, assisted by Forma and Lakdawalla. The manuscript was written and revised by MacEwan, Forma, and Shafrin, along with Hatch Lakdawalla, and Lindenmayer.

Assessing Residents' Confidence in the Context of Pharmacotherapy Competence.

We aimed to determine whether residents' confidence initiating medications increased with the number of times they prescribed individual medications and to quantify the relationship between prescription frequency and gains in confidence. From July 2011 to June 2014, PGY-3 residents completed a survey of confidence levels at their psychopharmacology clinic orientation and then again 12months later. The Emory Healthcare electronic medical record was used to identify all medications prescribed by each resident during their 12-month rotation and the frequency of these prescriptions. Confidence in initiating treatment with all medicines/medication classes increased over the 12-month period. For three of the medication classes for which residents indicated they were least confident at orientation, the number of prescriptions written during the year was significantly associated with an increase in confidence. Measuring resident confidence is a relevant and achievable outcome and provides data for educators regarding the amount of experience needed to increase confidence.

Renato Alarcón: Long-Time Advocate for Cultural Awareness in Psychiatry

Renato Alarcón: Long-Time Advocate for Cultural Awareness in Psychiatry

Pharmacotherapy of Tobacco Use Disorder

Pharmacotherapy of Tobacco Use Disorder

Clinical Psychopharmacology Update: What's in a Name? Confusion Prompts Change for Vortioxetine's Brand Name

Similar names between two unrelated drugs have led the FDA to issue warnings about and now approve a name change for vortioxetine, which was branded as Brintellix® until recently. While the trade name had been screened prior to the product's launch, the FDA received numerous reports of prescribing and dispensing errors, specifically with regard to the anti-coagulant drug Brilinta® (ticagrelor). Starting 1 June 2016, vortioxetine will be marketed under the name Trintellix™ in an effort to reduce confusion. Clinicians are advised that while the name and National Drug Code number with this product will change, it will retain the same formulation, indication, and dosage information. To the extent possible, clinicians can and should take actions to identify and reduce potential medication errors in prescriptions, especially when using electronic records and e-prescription systems.

Hyperprolactinemia is a Major Problem in Patients Treated with Antipsychotic Drugs

"Hyperprolactinemia is a Major Problem in Patients Treated with Antipsychotic Drugs." Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, 26(2), pp. 210–211Keywords: hyperprolactinemiaantipsychoticendocrinology

Propolis as a Complex Compound May Contain Many Active Ingredients Like Caffeic Acid Phenethyl Ester (CAPE)

"Propolis as a Complex Compound May Contain Many Active Ingredients Like Caffeic Acid Phenethyl Ester (CAPE)." Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, 26(2), pp. 207–208

Green’s Child and Adolescent Clinical Psychopharmacology, 5th ed

Green’s Child and Adolescent Clinical Psychopharmacology, 5th ed

A European psychopharmacology curriculum: The young psychiatrist's point of view

It goes without saying that psychopharmacologic treatment requires extensive knowledge of topics ranging from pharmacodynamics and efficacy, to pharmacokinetics, side-effects, and toxicity. Knowledge should be supplemented with experience regarding applicability in a clinical setting. It is well accepted that comprehensive psychopharmacologic education is essential to convey necessary knowledge and adequately prepare trainees for independent practice [1]. Currently, a psychopharmacologic curriculum, under the umbrella of the European Psychiatric Association, is in preparation in order to emphasize the importance of psychopharmacologic education in the context of psychiatric training and to foster standardization within the European Union. The aim of this presentation is to discuss psychopharmacologic education and prerequisites for an effective curriculum from the trainee's point of view. We will address challenges facing psychiatric trainees [2] and review existing curricula as well as literature in which they are evaluated. Based on evaluation of the model curriculum by the American Society of Clinical Psychopharmacology, one of the most broadly used psychopharmacologic curricula, it has been emphasized that an effective curriculum should be more than a list of topics. It should also convey pedagogic strategies with a focus on up-to-date technology, and provide a process through which teacher and trainee progress can be assessed [3,4]. Reflection on currently available curricula should aid in the development of an effective and timely EU-wide psychopharmacologic curriculum.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The new neuroscience based nomenclature of neuropsychotropic drugs: A chance for a better understanding and teaching of clinical psychopharmacology

Traditional psychopharmacological terminology is based on historical grounds and under different aspects not systematic and rational. It even tends to confuse patients by prescribing a drug that does not reflect their identified diagnosis, prescribing “antipsychotics” to depression. Four major colleges of neuropsychopharmacology (ECNP, ACNP, Asian CNP, an CINP) proposed a new multi-axial pharmacologically-driven nomenclature. The template has five axes: 1- class (primary pharmacological target and relevant mechanism); 2- family (reflecting the relevant neurotransmitter and mechanism); 3- neurobiological activities; 4- efficacy and major side effects; and 5- approved indications. The results of the surveys suggest that the clinicians found the available indication-based nomenclature system dissatisfactory, non-intuitive, confusing, and doubt-inducing for them and the patients. The proposed five-axis template seeks to upend current usage bay placing pharmacology rather than indication as the primary axes. With the proposed nomenclature relating primarily to Axis 1 – the class, and usage of the other axes would largely depend the extent to which the clinician seeks to deepen the scientific and clinical base of his involvement.Disclosure of interestThe author has not supplied his declaration of competing interest.

Number Needed to Treat Can Be Helpful

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.To the Editor: We read with interest the March 2015 Clinical and Practical Psychopharmacology column by Dr Andrade regarding numbers needed to treat and harm (NNT, NNH). We applaud Dr Andrade for writing an exceptionally clear explanation of what NNT and NNH are and how they may be calculated. In our own experience, NNT and NNH are the simplest ways of explaining effect sizes in a clinically relevant manner to medical practitioners who would otherwise mistakenly believe that all they need to be aware of are P values.

The American Psychiatric Association Practice Guidelines for the Psychiatric Evaluation of Adults.

These Practice Guidelines for the Psychiatric Evaluation of Adults mark a transition in the American Psychiatric Association’s Practice Guidelines. Since the publication of the 2011 Institute of Medicine report Clinical Practice Guidelines We Can Trust, there has been an increasing focus on using clearly defined, transparent processes for rating the quality of evidence and the strength of the overall body of evidence in systematic reviews of the scientific literature. These guidelines were developed using a process intended to be consistent with the recommendations of the Institute of Medicine (2011), the Principles for theDevelopment of Specialty Society Clinical Guidelines of the Council of Medical Specialty Societies (2012), and the requirements of the Agency for Healthcare Research andQuality (AHRQ) for inclusion of a guideline in the National Guideline Clearinghouse. Parameters used for the guidelines’ systematic review are included with the full text of the guidelines; the development process is fully described in a document available on the APA website: http:// www.psychiatry.org/File%20Library/Practice/APA-GuidelineDevelopment-Process–updated-2011-.pdf. To supplement the expertise of members of the guideline work group, we used a “snowball” survey methodology to identify experts on psychiatric evaluation and solicit their input on aspects of the psychiatric evaluation that they saw as likely to improve specific patient outcomes (Yager 2014). Results of this expert survey are included with the full text of the practice guideline.

Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice.

More than half a century after their discovery, benzodiazepines (BDZs) still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons regarding current use of BDZs in clinical practice, and provide an updated overview of their use across specific clinical areas and patient populations. The main results are presented and discussed in this review.

THE AMERICAN SOCIETY OF CLINICAL PSYCHOPHARMACOLOGY SURVEY OF PSYCHOPHARMACOLOGISTS' PRACTICE PATTERNS FOR THE TREATMENT OF MOOD DISORDERS.

Optimal successive treatment decisions are not well established after an initial medication nonresponse in major depressive disorder or bipolar disorder. While practice guidelines offer consensus-based expert treatment recommendations, little is known about "real world" pharmacology decision making by practicing psychopharmacologists. We surveyed via Internet the national membership of the American Society of Clinical Psychopharmacology (ASCP) to study preferred pharmacotherapy strategies and factors that influence medication choices for patients with mood disorders. Surveys were returned by 154/752 ASCP members (21%). After nonresponse to a serotonin reuptake inhibitor in major depressive disorder, participants equally favored switching within or across antidepressant classes. After a partial response, adjunctive bupropion was the preferred intervention, followed by changing antidepressant classes. Atypical antipsychotic augmentation was only a fourth-line consideration, even though moderate or marked efficacy was perceived in most instances with olanzapine, aripiprazole, and quetiapine. Respondents favored avoiding antidepressants in bipolar I patients with mixed/cycling features or prior antidepressant-associated mania/hypomania. In rapid cyclers, they advocated antidepressant cessation and preferred the use of atypical antipsychotics and lamotrigine. Participating psychopharmacologists treating adults with mood disorders report prescribing medications that largely mirror the evidence base with only a few notable exceptions, in consideration of the characteristics of definable clinical subpopulations.

The Role of Mobile Phone Technology in Understanding and Preventing Suicidal Behavior.

In this editorial, we discuss how mobile phone technology has the potential to move the field forward in terms of understanding suicide risk as well as laying foundations for the development of effective treatments/interventions. We have focused on mobile health technology given the rapid growth of mobile health approaches in suicide prevention (De Jaegere & Portzky, 2014; Mishara & Kerkhof, 2013) and psychological research more generally (Myin-Germeys et al., 2009; Nock, Prinstein, & Sterba, 2009; Palmier-Claus et al., 2011) and because mobile phone use is ubiquitous, with 75% of the world having access to a mobile phone (Kay, 2011). (aut. ref.)

Assessing cognitive function in bipolar disorder: challenges and recommendations for clinical trial design.

Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed. The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder, both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (eg, symposium presentation at the 2014 Annual Meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants. A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations. Consensus recommendations, reached by unanimous opinion of the authors, are provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal-level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of prescreening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment. Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges, and a comprehensive effort to formalize best practice guidelines will be a critically important next step.

The Clinical Relevance of Information Sources on Drug-Drug Interaction

issue of this year’s Bulletin of Clinical Psychopharmacology, is deeply appreciated for emphasizing the possible drug-drug interactions (DDIs) and adverse effects (AE) that patients may experience while receiving antipsychotic polytherapy. This subject is of vital importance for patient safety, given that 5-20% of all hospitalizations for AE are reported to be caused by DDIs. Considering the frequency of serious adverse effects, this means that one in 200 hospitalized patients experienced a serious adverse effect as a consequence of DDIs