The Dobson-Rawlins pact and the National Institute for Health and Care Excellence: impact of political independence on scientific and legal accountability.

This analysis considers whether the independence of the National Institute for Health and Care Excellence (NICE), while safeguarding guidelines from commercial lobbying, may render NICE legally and scientifically unaccountable. The analysis examines the role of judicial reviews and stakeholder consultations in place of peer review in light of current debates concerning the depression guideline.

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.

American Psychological Association practice guidelines for psychopharmacology: Ethical practice considerations for psychologists involving psychotropic use with children and adolescents.

OBJECTIVES: This study discusses the implications of the American Psychological Association's 2011 Practice Guidelines for Pharmacology as they apply to psychologists working with juvenile clients. Special considerations apply due to concerns about the developmental side effects that occur when psychotropic medications are prescribed to children and adolescents. METHODS OR DESIGN: This study provides recommendations for implementing each of the Practice Guidelines. Constructive criticism of the Practice Guidelines is also discussed with the aim of improving service delivery. RESULTS: This study provides specific recommendations for psychologists regarding obtaining adequate knowledge about psychopharmacology to inform clients or consult with physicians. Suggestions are made for continuing education requirements for psychologists who work with juveniles. CONCLUSIONS: Recommendations are made for psychologists working with juveniles to increase their knowledge of psychotropic medications for a more ethical and informed voice regarding the prescribing of such medications.

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 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.

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 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.

The Art of Pharmacotherapy: Reflections on Pharmacophobia.

PURPOSE/BACKGROUND: This commentary deals with the neglected issue of the art of psychopharmacology by recounting the authors' journeys. METHODS/PROCEDURES: First, a model of medical science situated within the history of medicine is described including (1) a limitation of the mathematical model of science, (2) the distinction between mechanistic science and mathematical science, (3) how this distinction is applied to medicine, and (4) how this distinction is applied to explain pharmacology to psychiatrists. Second, the neglected art of psychopharmacology is addressed by explaining (1) where the art of psychopharmacotherapy was hiding in the first author's psychopharmacology research, (2) how the Health Belief Model was applied to the art of medicine, (3) how the second author became interested in the Health Belief Model, and (4) his studies introducing the Health Belief Model in psychopharmacology. The authors' collaboration led to: (1) study of the effect of pharmacophobia on poor adherence and (2) reflection on the limits of the art of psychopharmacology. FINDINGS/RESULTS: Low adherence was found in 45% (116/258) of psychiatric patients with pharmacophobia versus 22% (149/682) in those with no pharmacophobia, providing an odds ratio of 2.9 (95% confidence interval, 2.2-4.0) and an adjusted odds ratio of 2.5 (95% confidence interval, 1.8-3.5) after adjusting for other variables contributing to poor adherence. IMPLICATIONS/CONCLUSIONS: Different cognitive patterns in different patients may contribute to poor adherence. Specific interventions targeting these varying cognitive styles may be needed in different patients to improve drug adherence.

[The problem of small "n" and big "P" in neuropsycho-pharmacology, or how to keep the rate of false discoveries under control]. / A kis "n", nagy "P" probléma a neuropszichofarmakológiában, avagy hogyan kontrolláljuk a hamis felfedezések arányát.

One of the characteristics of many methods used in neuropsychopharmacology is that a large number of parameters (P) are measured in relatively few subjects (n). Functional magnetic resonance imaging, electroencephalography (EEG) and genomic studies are typical examples. For example one microarray chip can contain thousands of probes. Therefore, in studies using microarray chips, P may be several thousand-fold larger than n. Statistical analysis of such studies is a challenging task and they are refereed to in the statistical literature such as the small "n" big "P" problem. The problem has many facets including the controversies associated with multiple hypothesis testing. A typical scenario in this context is, when two or more groups are compared by the individual attributes. If the increased classification error due to the multiple testing is neglected, then several highly significant differences will be discovered. But in reality, some of these significant differences are coincidental, not reproducible findings. Several methods were proposed to solve this problem. In this review we discuss two of the proposed solutions, algorithms to compare sets and statistical hypothesis tests controlling the false discovery rate.

Creativity in psychopharmacotherapy - the bright side of face of psychiatric god Janus.

This paper discusses about challenges to psychopharmacotherapy, evidence-based psychopharmacology, creative psychopharmacology, creativity and dopamine, creative-rational polypharmacy as a paradigm for creativity in psychopharmacotherapy, and about polypharmacy classification as a good, bad and ugly By stimulating the patient to participate in the creative and artistic process we effect on his optimal identification with the role of the sick person. Through creation, imagination and visualization patients can recognize their own reservoir of inner healing and create a healthier new identity. Psychopharmacotherapy can prevent the deterioration of creativity affecting the quality of life and personal recovery. It may also affect the goals and aspirations of patients as well as the way in forming strategies of their realization.

[Therapeutic drug monitoring in psychiatry. A brief summary of the new consensus paper by the task force on TDM of the AGNP]. / Therapeutisches Drug-Monitoring in der Psychiatrie. Kurze Zusammenfassung des neuen Konsensuspapiers der Arbeitsgruppe TDM der AGNP.

In October 2011 the Task Force Therapeutic Drug Monitoring of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update (Pharmacopsychiatry 2011, 44: 195-235) of the first version of the consensus paper on therapeutic drug monitoring (TDM) published in 2004. This article summarizes the essential statements to make them accessible to a wider readership in German speaking countries.

[National and international schizophrenia guidelines. Update 2013 regarding recommendations about antipsychotic pharmacotherapy]. / Nationale und internationale Leitlinien zur Schizophrenie. Update 2013 zum Stand der Empfehlungen zur antipsychotischen Medikation.

Treatment guidelines provide evidence-based recommendations for diagnosis and treatment to assist clinicians, care givers and patients in finding an optimized treatment option in given clinical situations. Specific treatment guidelines for schizophrenia issued by the German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and published under the auspices of the Working Group for Scientific Medical Specialist Societies (AWMF) (i.e. fulfilling the highest quality standards at the S3 level) have been available in Germany since 2006. Currently, a comprehensive revision process is ongoing to update these guidelines with the aim to publish the revision before 2014. However, since publication of the German treatment guidelines many clinical trials and meta-analyses have been published which appear to make a new evaluation of antipsychotic drug treatment necessary. Currently available national and international guidelines, such as the WFSBP, PORT and NICE guidelines, place less emphasis on the general superiority of atypical antipsychotic medication but support the idea to evaluate antipsychotic drugs based on the side effect profiles. The present overview discusses the recent guidelines development processes regarding schizophrenia and compares the available German treatment guidelines with recently published international guidelines. Current developments and issues for discussion are described in detail to provide possible implications for changes in treatment recommendations.

How to increase treatment effectiveness and efficiency in psychiatry: creative psychopharmacotherapy - part 1: definition, fundamental principles and higher effectiveness polypharmacy.

Psychopharmacotherapy is a fascinating field that can be understood in many different ways. It is both a science and an art of communication with a heavily subjective dimension. The advent of a significant number of the effective and well tolerated mental health medicines during and after 1990s decade of the brain has increased our possibilities to treat major mental disorders in more successful ways with much better treatment outcome including full recovery. However, there is a huge gap between our possibilities for achieving high treatment effectiveness and not satisfying results in day-to-day clinical practice. Creative approach to psychopharmacotherapy could advance everyday clinical practice and bridge the gap. Creative psychopharmacotherapy is a concept that incorporates creativity as its fundamental tool. Creativity involves the intention and ability to transcend limiting traditional ideas, rules, patterns and relationships and to create meaningful new ideas, interpretations, contexts and methods in clinical psychopharmacology.

How to increase treatment effectiveness and efficiency in psychiatry: creative psychopharmacotherapy - part 2: creating favorable treatment context and fostering patients' creativity.

Any medical or psychosocial treatment has two components, one associated with the specific effects of the treatment itself, and the other related to the treatment context, individual perception, imagination, subjective meaning and psychobiological response. Psychopharmacotherapy is a context dependent practice because different contexts affect the meaning of biological variables in different ways. Creation of favorable treatment context as well as creative collaboration with patients and their families may significantly improve treatment outcome. Positive therapeutic context is fundamental for treatment success in psychiatry because it may significantly increase placebo and decrease nocebo responses. Creative approach to psychopharmacotherapy reflects a creative synergism between clinical pharmacology and positive psychology of creativity in the frame of transdisciplinary holistic, integrative and person-centered psychiatry.

Creativity, mental disorders and their treatment: recovery-oriented psychopharmacotherapy.

This paper discusses interrelations between creativity, mental disorders and their treatment. The psychology of creativity is very important for successful psychopharmacotherapy, but our knowledge about creativity is still insufficient. Even that which is known is not within the armamentarium of most practicing psychiatrists. In the first part of this article creativity and possible associations between creativity, mental health, and well-being are described. The second part deals with the intriguing relationship between creativity and mental disorders. The third part emphasizes the role of creativity in the treatment of mental disorders. This paper ends by underlining the importance of a creativity-enhancing oriented, and personal recovery-focused psychopharmacotherapy in helping psychiatric patients achieve fulfilled and purposeful lives.

Psychodynamic approach as a creative factor in psychopharmacotherapy.

The treatment of psychiatric disorders often consists of a combined approach that integrates both pharmacotherapy and psychotherapy. Unfortunately, psychiatric texts and the educational process in psychiatry training do not adequately address the combined approach. There is a lack of information concerned with the psychological aspect of prescribing medications. This is striking since many patients require both treatments. There is an inevitable psychological aspect of the administration of medication in psychiatry, and the meaning ascribed to the prescription of drugs has an impact on doctor-patient relationship. Understanding the psychodynamic issues is crucial for the success of psychopharmacology. Psychodynamic psychopharmacotherapy represents an integration of biological psychiatry and psychodynamic insights and techniques. This approach recognizes that many of the core discoveries of psychoanalysis are powerful factors in the complex relationship between the patient, the illness, the doctor, and the medications. Scientific pharmacotherapy is, as it should be, based upon patients' responses to treatments of specific target conditions. Enduring personality traits are being increasingly incorporated as targets for pharmacotherapy. However, in the real world of psychiatric practice we see that transference issues and a patient's character or set of personality traits have a greater impact on the selection, dosage, tolerability, and treatment outcome than is generally recognized or admitted. In contemporary psychiatry, a psychodynamic perspective must be preserved. Without it, meaning will be lost, and both diagnostic understanding and informed treatment planning will suffer.

Psychobiological model of personality and psychopharmacotherapy outcomes in treatment of depression and schizophrenia.

In distinguishing why some patients respond and other do not respond to treatments arraised the clinically very important body of research considering weather patients' personality characteristics might predict outcomes of pharmacotherapeutic treatment. Personality can be a predictor of a psychiatric disorder either owing to their common genetic background or because it enhances exposure of the subject to environmental risk factors. The results of the studies using psychobiological model are reviewed. The studies show that personality temperament dimension Harm Avoidance and character dimension Self-directedness predict outcomes of the pharmacological treatment of depression, but the result for other psychiatric disorders are sparse. The studies are not straightforward in recommendations for treatment choice dependent of personality dimensions.