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PubMedDate not supplied

[Critical flicker fusion frequency in psychopathology and psychopharmacology. Review of the literature].

As far back as the second century, Ptolemy reported the apparent immobility of wheel radius at a certain speed. The psychophysical laws of this flicker fusion phenomenon related to the frequency of the light stimulus were established in 1834-1835 by the Englishman Talbot and by the Belgian Plateau, whose thesis in Liège is described as a landmark in the field. CFF is more a measurement of cortical arousal than of visual functions. In psychophysiology, CFF underwent periods of success and oblivion, at the mercy of researcher's enthusiasm or disappointment. At the turn of this century, Pierre Janet measured CFF in the laboratory of physiology of the Salpêtrière Hospital and demonstrated its decrease 'in hysteria, in states of depression, of lowered tension'. All reviewers of CFF literature have overlooked these observations, reported by Henri Piéron in the 'Melanges dedicated to Monsieur Pierre Janet'. When CFF falls into disgrace, it is because of the variability of its results, due to differences in apparatus and designs of the trials as well as the great number and the intrication of the variables which modify CFF thresholds, among them the nonsensory variables. When CFF is reappraised, as it has been the case in psychopharmacology in recent years, the reason is that it represents a brief, easy and economical measure of vigilance which, under certain conditions, seems to be also reliable, valid and sensitive. In the present monograph, the first in French on CFF, the authors try to analyze the most important contributions of the literature from the standpoint of the most relevant variables: characteristics of the stimulus (light intensity, wave form, wavelength, light-dark-ratio, diameter of the flickering point), test procedure (light vs. dark adaptation, visual angle, continuous vs. discontinuous presentation, monocular vs. binocular vision), influence of various physiological or psychological conditions (pupillary diameter, age, training, IQ; anxiety, depression, motivation etc.). The authors summarize the prerequisite for CFF to measure vigilance or aging in psychopharmacological research. The present Monograph is dedicated to the authors' 'Maîtres', who recently became Emeritus Professors, namely the ophthalmologist Roger Weekers, the pioneer of the clinical application of CFF in Belgium, and the psychiatrist Jean Bobon, who pioneered clinical psychopharmacology in Belgium.

Adaptation, Ocular↗

PubMed1993

Geriatric psychopharmacology. Management of late-life depression and the noncognitive behavioral disturbances of Alzheimer's disease.

As the proportion of elderly persons in the population continues to grow, the management of the behavioral disorders of later life will become an increasingly important part of clinical practice. Although psychotropic medications are prescribed widely to older persons, the data base derived from well-designed clinical psychopharmacologic trials in elderly patients is surprisingly small. This article reviews the psychopharmacologic management of the two most prevalent categories of behavioral disorders of later life: late-life depression and the noncognitive behavioral disturbances that complicate Alzheimer's disease. Because diagnostic and epidemiologic issues are pertinent to the psychopharmacologic management of both categories of disorders, these issues also are discussed.

Aged↗

PubMed1993

Psychopharmacologic treatment of panic, generalized anxiety disorder, and social phobia.

The anxiety disorders discussed in this article are common, affecting 5% to 10% of the general population. They may cause significant distress and disability and are often complicated by substance abuse and depression. Fortunately, these disorders can be treated successfully in the majority of patients, with alleviation of the most distressing symptoms and significant improvement in occupational and social functioning. Systematic research studies during the past decade have identified both specific medication-responsive anxiety syndromes and a variety of psychopharmacologic agents effective in their management. Psychopharmacologic treatment, often in combination with cognitive-behavioral therapies, can be tailored for the individual patient based on that patient's specific anxiety syndrome, comorbid disorders, and vulnerability to side effects. Careful monitoring of target symptoms can be used to assess the efficacy of treatment. Future research will help to develop new classes of antianxiety agents for currently treatment-resistant patients, and to investigate further the necessary duration of psychopharmacologic treatment.

Anxiety Disorders↗

PubMed2003

Actigraphy in human psychopharmacology: a review.

Over the last 25 years wrist actigraphy has predominantly been used in sleep research and chronobiology where the technique has proved useful in the measurement of sleep and the characterisation of the sleep/wake cycle. Whilst there are a large number of studies published that have used actigraphy, there have only been relatively few studies that have shown that the technique is capable of measuring drug-induced changes in nocturnal and/or diurnal behaviour. Thus the use of actigraphy to measure drug effects in clinical trials has up till now remained on the periphery of psychopharmacology. However this may be because of the disparate nature of the studies published rather than lack of usefulness. This paper reviews the relevant literature and in doing so concludes that there is a convincing body of evidence for the utility of actigraphy as a technique in human psychopharmacology.

Anesthesia↗

PubMed1997

Development and evaluation of a clinical psychopharmacology educational curriculum.

Clinical psychopharmacology training at the University of Toronto (Toronto, Ontario, Canada) was in need of improvement. The authors developed and evaluated a Clinical Psychopharmacology Educational Curriculum to complement the education provided to trainees and staff. The program consisted of journal clubs, case rounds, and didactic research tutorials and lectures. The program was attended by staff, fellows, psychiatry residents, graduate pharmacology students, medical students, and pharmacists. No course credit or continuing medical education credits were offered for participating in the program. The program ran for two academic years (September 1994-June 1996). Anonymous evaluation forms were collected after the sessions. These evaluated content, presentation style, and educational value, each on a scale from 1 (unsatisfactory) to 5 (excellent). Ratings for each component of the curriculum were close to excellent. The case rounds were rated slightly better for presentation style and educational value. Positive ratings suggest that similar efforts, particularly using case-based methods, should be developed in other teaching hospitals contingent on availability of qualified faculty and funding.

Curriculum↗

PubMed2002

Training psychologists in clinical psychopharmacology.

This article first describes three types of psychopharmacology training programs for psychologists: 1. postdoctoral programs that award certificates and/or continuing education credit; 2. postdoctoral programs that award master's degrees in psychopharmacology; 3. a predoctoral program that awards joint psychology and nursing degrees. Next, the postdoctoral masters degree program at Nova Southeastern University is described in some detail. We close with some general comments about the current status of these training efforts.

Curriculum↗

PubMed1992

Mathematical models of complex dose-response relationships: implications for experimental design in psychopharmacologic research.

We develop a mathematical model to account for the complex relationship between drug dose and clinical response in psychopharmacologic research. The model specifies relationships among drug dose, drug bioavailability, pharmacokinetic factors, course moderators, clinical response and the heterogeneity of the disorder, and allows for the derivation of results that have implications for experimental design in psychopharmacologic research. These results form the basis for computer simulations which indicate that random assignment to two fixed doses is more powerful and less sensitive to heterogeneity than assignment to clinically determined doses. Fixed dose designs, however, tend to overestimate the magnitude of drug bioavailability-clinical response relationships. Clinically determined dose designs are useful in some experimental situations; their effectiveness is enhanced by systematically reducing the clinically determined dose. Larger dose reductions improve the ability to detect bioavailability-clinical response relationships.

Antipsychotic Agents↗

PubMed1981

On the use of repeated measures designs in psychopharmacology.

A popular paradigm in psychopharmacology is the repeated measures design. Unfortunately the test of equal means across the repeated trials requires an assumption that is often untenable and which can lead to erroneous interpretations. In order to minimize this bias three approaches have been suggested. The authors discuss the three approaches in the context of a psychopharmacologic example.

Analysis of Variance↗

PubMed1991

Use of recombinant inbred strains to identify quantitative trait loci in psychopharmacology.

Unlike simple Mendelian characteristics, individual differences in complex quantitative phenotypes studied in psychopharmacology are generally distributed continuously and are likely to be influenced by many genes. Recombinant inbred (RI) strains are valuable not only for their traditional use of detecting major gene segregation and linkage but also for identifying associations between quantitative traits and quantitative trait loci (QTL) that account for relatively small amounts of variation in phenotypes as well as loci that account for greater amounts of variation. When applied to published data on genetic markers and on amphetamine, alcohol, and morphine responses in BXD RI strains (RI strains developed from the cross between C57BL/6J and DBA/2J progenitor inbred strains), the RI QTL approach identified several significant associations beyond known major gene effects. Together, significant associations explain more than half of the genetic variance for these measures. The RI QTL approach is especially valuable for investigating the QTL underpinnings of genetic correlations among measures. It is recommended that psychopharmacogenetic research focus on the BXD RI strains. The cumulative and integrative nature of such a program of research is the major benefit of the RI QTL association approach for molecular genetic analysis of psychopharmacological processes, their physiological infrastructure, and their interface with other behavioral and biological systems.

Animals↗

PubMed1999

Theory and method in the quantitative analysis of "impulsive choice" behaviour: implications for psychopharmacology.

Impulsive choice refers to the selection of small immediate gains in preference to larger delayed gains, or the selection of large delayed penalties in preference to smaller immediate penalties. Current theoretical interpretations of impulsive choice are reviewed, and a synthesis of these ideas, the "multiplicative hyperbolic model of choice", is presented. The model assumes that the value of a positive reinforcer increases as a hyperbolic function of its size, and decreases as a hyperbolic function of its delay and the odds against its occurrence. Each hyperbolic function contains a single discounting parameter which quantifies the organism's sensitivity to the variable in question. The hyperbolic discounting functions combine multiplicatively to determine the overall value of the reinforcer. Equivalent functions are postulated to govern the (negative) value of aversive events, the net value of an outcome reflecting the algebraic sum of the positive and negative values. The model gives rise to a quantitative methodology for studying impulsive choice, based on a family of linear indifference (null) equations, which describe performance under conditions of indifference, when the values of the reinforcers are assumed to be equal. This methodology may be used to identify individual differences in sensitivity to the magnitude, delay and probability of reinforcement. The methodology is also suitable for the quantitative evaluation of the effects of some pharmacological interventions on discounting parameters. Recent psychopharmacological studies of impulsive choice are reviewed, and the utility of indifference equations for extending this work, and developing a quantitative psychopharmacology of impulsive choice is discussed.

Animals↗

PubMed2003

Ethical considerations in psychopharmacological research involving decisionally impaired subjects.

RATIONALE: Research subjects who are unable to provide informed consent must be protected from exploitation. The federal regulations governing human subjects research mandate additional protections for "mentally disabled" subjects but include neither a definition of this "vulnerable" population nor any guidance on what safeguards should be employed or how they should be implemented. OBJECTIVES: This article begins with a definition of vulnerability due to a mental disorder in the context of the clinical research setting. It is organized along the following sequential phases of psychopharmacological research: study design and methodology; protocol review; subject recruitment and enrollment; conduct and monitoring of the study; and manuscript preparation and publication. Practical recommendations are then offered to clinical researchers and Institutional Review Boards (IRBs) for implementing additional protections for decisionally impaired subjects at each phase of the psychopharmacological research process. METHODS: A computer-assisted literature review was performed to identify descriptions of safeguards for decisionally impaired subjects. Recommendations for additional protections were also drawn from the authors' experiences with the IRB review process and the conduct and monitoring of clinical research with decisionally impaired subjects. RESULTS: The use of informed consent monitoring and the independent assessment of decision-making capacity are two feasible safeguards that IRBs can mandate for research with decisionally impaired subjects. There has been little systematic implementation of other safeguards such as research advance directives or prospective authorization for research participation. CONCLUSIONS: Clinical investigators and IRBs are under considerable scrutiny with respect to the protection of decisionally impaired research subjects. There is a pressing need for data-driven strategies for the optimal protection of decisionally impaired research subjects.

Biomedical Research↗

PubMed2003

Psychopharmacological research ethics: special issues affecting US ethnic minorities.

RATIONALE: This article is intended to explore how minority status and cultural factors affect the participation of subjects in clinical psychopharmacology research. OBJECTIVES AND METHODS: A literature review was performed using key words "clinical psychopharmacology trials", "psychiatric ethics" and "minority groups". Major goals of this review were to examine current knowledge base and identify existing gaps in this fairly new area of psychiatric research. RESULTS: We found extremely few papers addressing the issue directly. Most references to minority groups were made peripherally, and many of these were extrapolated to psychiatric patients from work done on medical populations. We found no empirical studies done in psychiatric populations. CONCLUSIONS: Systematic, well-designed research studies are needed to elucidate how culture, race and ethnicity impact on such issues as accrual, retention, informed consent and safeguards against the potential exploitation of minority research subjects. On the basis of the literature review and our personal experience doing clinical research with minority patients, we provide several recommendations and specific suggestions to clinical researchers who include minority patients in their clinical trials.

Biomedical Research↗

PubMed2006

Research in child and adolescent psychopharmacology: recent accomplishments and new challenges.

RATIONALE: Research in pediatric psychopharmacology has expanded considerably in the last 10 years. Still, controversy remains about the effectiveness and safety of commonly used psychotropics and their role in child treatment, thus pointing to the need for more in-depth and targeted investigations. OBJECTIVES: To review recent accomplishments and current limitations of pediatric psychopharmacology, and discuss approaches to further research. METHODS: Selective review of the relevant literature and research in progress. RESULTS: Controlled clinical trials have been conducted in many common psychiatric disorders in children and adolescents, thus providing a basis on which evidence-based treatment guidelines can be constructed. Little innovation has, however, occurred in treatment development and testing. Safety concerns are prominent and have a major influence on clinical practice and drug utilization. CONCLUSIONS: While a research infrastructure has been successfully built for conducting pediatric clinical trials, important aspects such as long-term treatment effects, optimal sequencing and individualization of interventions, and integration of neuroscience findings into innovative, theory-driven treatment development remain to be addressed.

Adolescent↗

PubMed2004

Electrocardiographic safety profile and monitoring guidelines in pediatric psychopharmacology.

A number of medications commonly used in pediatric psychopharmacology can prolong the QTc interval of the electrocardiogram. QTc prolongation can in turn predispose to torsades de pointes, a sometimes deadly arrhythmia. These considerations are clinically relevant given documented, if still controversial, reports of sudden deaths associated with the use of the tricyclic antidepressant (TCA) desipramine in children. While most reports of QTc prolongation have involved adult patients, this adverse effect can occur in children. After discussing the QTc parameter's derivation, accuracy, and limitations, this article reviews current knowledge about the propensity of the antipsychotics (both atypical and traditional), TCAs, and alpha agonists to prolong the QTc interval in young patients. Based on the literature reviewed, guidelines are provided for clinical and electrocardiographic monitoring in pediatric psychopharmacology.

Electrocardiography↗

PubMed1980

The use of human observers in psychopharmacological research.

During 1974-1978, over 40% of the nonhuman drug studies that appeared in Psychopharmacology, Pharmacology Biochemistry and Behavior, and Journal of Pharmacology and Experimental Therapeutics involved human observers; far fewer studies published in Journal of the Experimental Analysis of Behavior did so. In all of these journals, measures of interobserver agreement seldom were provided. The great majority of studies also failed to utilize one or more "blind" observers, unaware of experimental conditions. These findings are of interest in light of reports that observational data are affected by a wide range of factors and often provide an inaccurate index of behavior. The believability of observational data seemingly is enhanced by careful descriptions of recording procedures coupled with the use of two or more blind observers whose concordance in rating behavior has been determined. These procedures characteristically are followed in some behavioral sciences, such as applied behavior analysis, but not to the same degree in psychopharmacology.

Animals↗

PubMed1993

Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology: a review.

1. Transcultural psychopharmacology is a discipline that seeks to determine the relative importance of society, culture, environment, genetics, and biophysiology on the prescribing and metabolism of, and response to psychotherapeutic medications. 2. Studies and surveys comparing psychotropic medication use in Asian and non-Asian populations suggest that differences may exist in drug dosage requirements, plasma drug concentrations corresponding to therapeutic and toxic effects, and the incidence and severity of adverse drug reactions. 3. This paper reviews and critiques the published controlled studies on Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology, provides guidelines for the use of psychotropic medications in Asian populations, and offers suggestions for future transcultural studies. 4. Anecdotal reports suggest that differences exist between Asian and non-Asian populations in the pharmacokinetics of tricyclic antidepressants. Controlled studies have not consistently supported this view. 5. Studies with larger sample sizes and more rigorous controls are needed to determine if such differences do, in fact, exist.

Antidepressive Agents, Tricyclic↗

PubMed1979

Psychopharmacological studies in genetically determined subgroups of psychiatric patients.

1. As a prerequisite for psychopharmacological studies in subgroups of psychiatric patients two approaches will be described: a. A multiaxial classification system for affective disorders (MULTI-CLAD). b. Studies of ABO- and HLA-systems in patients with affective disorders. HLA: In 107 manic-melancholic patients selected according to the very strict MULTI-CLAD criteria confirmatory evidence was obtained that there is a positive association between affective disorders and HLA-Bw 16; the results were also strongly suggestive of a positive association between HLA-7 and such disorders. ABO: In sixty-six manic-melancholic patients selected along the same criteria, the differences between all patients combined versus controls were not significant, but a significantly higher percentage of bipolar patients (70%) than of unipolar patients (22%) had blood group O, while a significantly higher percentage of unipolar patients (65%) than of bipolar patients (23%) had blood group A. 2. The findings are in the process of further study involving some 300 patients from the Psychochemistry out-patient-clinic. The purpose is to see whether less selected groups of patients with affective disorders show less marked profiles for ABO and HLA, as this will have importance for the selection of subgroups of patients for psychopharmacological studies.

ABO Blood-Group System↗

PubMedDate not supplied

Commentary: psychopharmacological assessment in neurobehavioral teratology.

Pharmacological agents can be teratogenic but they can also be valuable tools in behavioral teratology. In this paper we describe some considerations we believe to be important in the use of psychopharmacology to assess the neurological underpinnings of behavioral deficits resulting from teratogenic exposure. Pharmacological challenges of animals exposed in utero to teratogenic agents can increase the sensitivity of behavioral tests and the specificity of the assessment of neural dysfunction. We discuss also some general guidelines for the conduct and interpretation of psychopharmacological experiments with teratogen-exposed animals.

Animals↗