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Biomedical subjects

B Vitiello

Publications and source records attributed to B Vitiello.

At least 55 records · Page 3Linked to original sources

Medication treatment strategies in the MTA Study: relevance to clinicians and researchers.

OBJECTIVE: Clinicians have difficulty applying drug research findings to clinical practice, because research protocols use methods different from those used in daily office practice settings. METHOD: To design a medication protocol for a multisite clinical trial involving 576 children with attention-deficit hyperactivity disorder (ADHD) while maintaining relevance to clinical practice, investigators from the NIMH Collaborative Multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA study) developed novel medication strategies. These were designed to work either in a monomodal or multimodal format and to ensure standard approaches are used across diverse sites. Each child randomized to medication (projected N = 288) is individually titrated to his or her "best" methylphenidate dose and has individual ADHD symptoms monitored. Decision rules were developed to guide "best dose" selection, dose changes, medication changes, the management of side effects, and integration with psychosocial treatments. CONCLUSIONS: The MTA study uses a controlled method to standardize the identification of each child's "best" methylphenidate dose in a national, multisite cooperative treatment program. Although the titration protocol is complex, the study's individual dosing approach and algorithms for openly managing ADHD children's medication over time will be of interest to clinicians in office practice.

Adolescent↗

Psychopharmacology in HIV-positive patients: research perspectives.

Psychotropic medications play an important role in the treatment of human immunodeficiency virus (HIV)-positive subjects suffering from neuropsychiatric disorders or other acquired immunodeficiency syndrome (AIDS)-related symptomatology. The quality of life of these patients can be significantly improved by the appropriate use of these agents. Various aspects of psychopharmacology that are relevant to HIV-positive patients include assessment of efficacy, tolerability, drug-drug interactions, and effects on cognition. These topics need further investigation and require focused research efforts. This report highlights current research needs and presents specific recommendations that emerged at a recent meeting on psychopharmacology for HIV-positive patients organized by the National Institute of Mental Health (NIMH).

AIDS Dementia Complex↗

Developmental perspectives in pediatric psychopharmacology.

Compared with adults, children and adolescents respond to psychotropic medications in some distinctive ways that have implications for both efficacy and safety. Age-related differences in pharmacokinetics and pharmacodynamics account for some of these differences. But while the disposition of several psychotropics in children has been studied, the pharmacodynamic effects of the interaction between the drug and the developing brain are still largely unknown. There is now evidence that the major neurotransmitter systems undergo developmental changes that can extend into the second decade of life. Data from various animal models also show that the administration of psychotropics in the pre-and perinatal period can interfere with the development and produce permanent changes in the neurotransmitter system in question. The extrapolation of these data to humans is difficult. Given the increase use of psychotropics in the pediatric age, the need emerges for systematic investigation on long-term effects of these drugs on the developing brain.

Aging↗

Scopolamine effects on the pressor response to thyrotropin-releasing hormone in humans.

Thyrotropin-releasing hormone (TRH) produces a marked pressor effect, which may be mediated by central cholinergic neurons, which in turn enhance sympathetic nervous system activity. In this study, 22 subjects (10 patients with Alzheimer's disease and 12 elderly controls) were administered IV scopolamine or placebo prior to administration of IV high-dose TRH (0.5 mg/kg). Systolic blood pressure was less on the day scopolamine was administered prior to TRH administration, as compared with placebo (F[1,20] = 6.12, p < 0.02). Results indicate that the pressor effect of TRH is attenuated by scopolamine, indicating a role of the cholinergic system in this response in humans.

Aged↗

Autonomic dysfunction in patients with dementia of the Alzheimer type.

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.

Aged↗

Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone.

BACKGROUND: Attention deficit-hyperactivity disorder is a well-recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of a familial predisposition. Symptoms suggestive of this disorder have been reported in subjects with generalized resistance to thyroid hormone, a disease caused by mutations in the thyroid receptor-beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone. We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18 families with a history of generalized resistance to thyroid hormone. METHODS: We studied 49 affected and 55 unaffected family members; 52 were adults, and 52 were children. All subjects were evaluated with structured psychiatric questionnaires by interviewers who were unaware of the medical diagnosis. The number of symptoms of attention deficit-hyperactivity disorder was calculated for each subject. RESULTS: Among the adults, 11 of 22 subjects with generalized resistance to thyroid hormone (50 percent) and 2 of 30 unaffected subjects (7 percent) had met the criteria for attention deficit-hyperactivity disorder as children (P < 0.001). Among the children, 19 of 27 subjects resistant to thyroid hormone (70 percent) and 5 of 25 unaffected subjects (20 percent) met the criteria for the disorder (P < 0.001). The odds of having attention deficit-hyperactivity disorder were 3.2 times higher for affected male subjects than for affected female subjects and were 2.7 times higher for unaffected male subjects than for unaffected female subjects. The mean symptom score was 2.5 times higher in the affected group than in the unaffected group (7.0 vs. 2.8, P < 0.001). The frequency of other psychiatric diagnoses was similar in the two groups. CONCLUSIONS: In our study sample, attention deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone.

Adult↗

Psychotherapeutic Medications Development Program (PMDP).

The Psychotherapeutic Medications Development Program (PMDP) of the National Institute of Mental Health was established in 1990. The purpose of the PMDP is to improve, enhance, and speed the development of new medications and improve the therapeutic usefulness of existing medications for the treatment of mental illness. The PMDP will fulfill this mission by implementing four initiatives. In the drug discovery and development initiative, the PMDP will aid in the development of promising new drugs. This initiative will also include improving the therapeutic usefulness of existing medications. In the technology transfer initiative, PMDP will improve the technology transfer from academic and government researchers to the pharmaceutical industry; improve the dissemination of information concerning technology transfer opportunities as it pertains to psychotherapeutic medications; and enhance technology transfer by acting as a broker to bring interested parties together. For the third initiative, the PMDP will develop and maintain a capability to clinically evaluate psychotherapeutic medications. The PMDP will also act to facilitate the development and testing of new concepts and models of mental illness. There is a detailed description of the steps that are involved in developing a new chemical entity (NCE) from the conceptual stage to a medication that is approved for the treatment of a particular illness. The pharmaceutical industry estimates that this medication development process costs $238 million.

Humans↗

Alzheimer's disease and feeling-of-knowing for knowledge and episodic memory.

The metamemory (knowledge of the veracity of memories) of moderately impaired Alzheimer's patients was compared to that of aged controls. Despite their profoundly impaired recall of information from both long-term (knowledge) and recent (episodic) memory, Alzheimer's patients were as accurate as controls in assigning confidence ratings related to the probability that their recalls were correct. They were impaired, however, at predicting the likelihood that they would subsequently recognize correct answers (feeling-of-knowing) to knowledge memory questions which they had been unable to recall correctly. Nevertheless, their performance on this task did exceed chance. Thus, the moderately impaired Alzheimer's patient demonstrates intact awareness of the veracity of recall from knowledge and episodic memory but shows impaired feeling-of-knowing for knowledge memory.

Aged↗

Mental retardation and psychiatric illness.

Although traditional diagnostic criteria are accepted for use with mentally retarded persons, diagnosis of psychiatric disorders in this population is often complicated by clinicians' ignoring or underestimating such disorders and by patients' communication problems. The revision of DSM-III and changes in policies of third-party payers have sensitized clinicians to the presence of psychopathology among mentally retarded persons. The authors discuss the relationship between mental illness and mental retardation and review recent research on the diagnosis of specific psychiatric disorders in these patients. Some problems, such as behavioral disruptiveness, psychoses, and phobias, are more prevalent among mentally retarded persons than among other populations, whereas other problems, such as alcoholism and suicide, may be less common.

Comorbidity↗

Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.

Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.

Aged↗

Lack of seasonal variation in the births of patients with dementia of the Alzheimer type.

Seasonal variation in the birth rates of patients suffering from dementia of the Alzheimer type (DAT) was investigated in 150 patients, aged 42-88 years, and in 132 normal control subjects of comparable age and gender. No seasonal variation or cyclic trend could be demonstrated in the DAT patients compared with control subjects. The exclusion from the analysis of the patients with a positive family history did not change the results of the study, which further suggests that a seasonality in DAT birth rates is unlikely.

Adult↗

Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients.

Platelet imipramine binding was measured in 16 drug-free nondepressed patients (aged 20-61 years, mean +/- SD 35 +/- 8) suffering from obsessive-compulsive disorder (OCD) and in 16 sex-, race- and age-matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5-HT) uptake capacity, Vmax, was also measured in 15 of these patients and their matched controls. Vmax was significantly higher in the patients (309 +/- 149 pmol/10(9) cells/min) than in the controls (181 +/- 110). An increase in platelet 5-HT uptake supports the involvement of 5-HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder.

Adult↗

P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study.

BACKGROUND: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. METHOD: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM-III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. RESULTS: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. CONCLUSION: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity.

Administration, Oral↗