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Biomedical subjects

P N Tariot

Publications and source records attributed to P N Tariot.

At least 19 recordsLinked to original sources
PubMed2001

Impact of molecular medicine on neuropsychiatry: the clinician's perspective.

Clinical neuropsychiatry has traditionally relied on individual practitioner experience or the apprentice-training model for formulating cases and choosing treatment. Scientifically-based diagnostic criteria and treatment algorithms have been lacking in the overlap area between psychiatry and neurology, owing largely to the complexity of this population population. However, the novel application of new molecular technologies is promising to change the care of neuropsychiatric patients. This review will highlight recent advances in molecular medicine pertaining to neuropsychiatry.Introduction

Genetic Heterogeneity↗
PubMed2001

Pharmacologic therapy for behavioral symptoms of Alzheimer's disease.

Behavioral signs and symptoms in dementia are common, morbid, classifiable, and treatable. The current state-of-the-art approach is to evaluate carefully for social or environmental causes, intercurrent medical conditions, or other triggers of the behavior and attempt to deal with those directly. When these conservative steps fail, there may be a role for medication. A rational approach typically hinges on matching the most dominant behavioral target symptoms to the most relevant medication class, the key information of which is summarized.

Aged↗
PubMed2001

Maintaining cognitive function in Alzheimer disease: how effective are current treatments?

Cognitive impairment, a core feature of Alzheimer disease (AD), is highly correlated with functional decline and caregiver time. Over 12 months, patients with mild-to-moderate AD deteriorate by 5-6 points from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Stabilizing cognitive decline is, therefore, an important treatment outcome in AD. Cognitive deficits are thought to result in part from central cholinergic impairment, which provides the rationale for the enhancement of cholinergic neurotransmission as a treatment approach for AD. Acetylcholinesterase (AChE) inhibition has, to date, produced the most promising outcomes in clinical trials. Galantamine appears to be novel among marketed agents in that it inhibits AChE and modulates cholinergic nicotinic receptors, perhaps increasing neurotransmission via both mechanisms. Long-term effects of AChE inhibitors and galantamine on ADAS-cog scores of patients with mild-to-moderate AD have been studied in placebo controlled trials as well as open-extension studies that followed randomized, double-blind studies for up to 6 months. Conventional AChE inhibitors (rivastigmine and donepezil) have maintained ADAS-cog baseline scores for up to 40 weeks in open extension studies, and Mini-Mental State Examination (MMSE) scores for up to 52 weeks in a placebo-controlled study. The mean ADAS-cog score of galantamine-treated patients did not change from baseline at 12 months (6 months double-blind study followed by 6 months open-label extension), suggesting that cognitive function had been maintained. These results suggest that cholinergic treatments, including galantamine, may stabilize cognitive decline of AD patients. This outcome is likely to make an important difference to patients and caregivers.

Aged↗
PubMed2001

Placebo-controlled study of divalproex sodium for agitation in dementia.

The authors assessed the efficacy, tolerability, and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week, randomized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium. Participants were blinded to treatment except for a physician-monitor and a pharmacist. When several covariates were taken into account, the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant (P=0.05). Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale, vs. 52% on placebo (P=0.06 in the adjusted analysis). Side effects occurred in 68% of the divalproex group vs. 33% of the placebo group (P=0.03) and were generally rated as mild. This placebo-controlled study, despite some limitations, suggests possible short-term efficacy, tolerability, and safety of divalproex for agitation in dementia and supports further placebo-controlled studies.

Aged↗
PubMed2001

National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer disease trial methodology.

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Aged↗
PubMed2001

A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting.

OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities. DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed. CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes.

Aged↗
PubMed2000

A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.

OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. METHODS: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. RESULTS: After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild. CONCLUSIONS: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Activities of Daily Living↗
PubMed2000

Long-Term use of quetiapine in elderly patients with psychotic disorders.

BACKGROUND: Quetiapine is an atypical antipsychotic agent that does not appear to increase patient risk for treatment-emergent extrapyramidal symptoms (EPS) or anticholinergic symptoms. Previous studies of quetiapine use in elderly patients with schizophrenia and other psychoses examined short-term administration (< or = 12 weeks). Given the growing elderly population, the commensurate increase in elderly patients with psychoses, and the expected increase in disease treatment-years, the effect of long-term quetiapine administration in older patients is of considerable interest. OBJECTIVE: This study assesses the long-term tolerability, safety, and clinical benefit of quetiapine in elderly patients with psychosis. METHODS: Elderly patients (> or = 65 years of age) with psychotic disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, participated in this 52-week, open-label, multicenter trial. Investigators increased (and later adjusted) daily doses of quetiapine on the basis of clinical response and tolerability, and assessed safety and efficacy. Efficacy assessments were made using the 18-item Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI), Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale (AIMS). For patients who withdrew before week 52, analyses were performed using observed data and the last observation carried forward. RESULTS: One hundred eighty-four patients with psychotic disorders (98 women and 86 men) with a mean age of 76.1 years entered the trial. Seventy-two percent had psychotic disorders due to general medical conditions such as Alzheimer's disease, and 28% had other psychotic disorders, most commonly schizophrenia. Overall, 89 (48%) patients completed treatment through 52 weeks. Median total daily dose was 137.5 mg. Reasons, for withdrawal included lack of efficacy (19%), adverse events or intercurrent illness (15%), failure to return for follow-up (13%), protocol noncompliance (3%), and diminished need for treatment (2%). Somnolence (31%), dizziness (17%), and postural hypotension (15%) were common adverse events, but they rarely resulted in withdrawal from therapy. EPS-related adverse events occurred in 13% of patients. At end point (week 52), mean total score on the Simpson-Angus Scale had decreased from baseline by 1.8 points, whereas changes in AIMS scores were negligible. No clinically important effects were reported relative to mean changes in hematologic, thyroid function, or hepatic function variables. Quetiapine treatment appeared to have no associated cardiovascular adverse outcomes despite cardiovascular comorbidities and unrestricted use of concomitant cardiovascular medications. Significant decreases in BPRS total score (n = 170, P < 0.001) and CGI Severity of Illness item score (n = 177, P < 0.002) were seen at end point (observed data and last observation carried forward). Decreases of > or = 20% in mean BPRS total score were observed in 83 (49%) patients. CONCLUSIONS: These results provide preliminary information to clinicians regarding tolerability, safety, and clinical improvement with quetiapine in elderly patients with psychotic symptoms, and support controlled studies of quetiapine in this patient population.

Aged↗
PubMed2000

A 12-week, open trial of donepezil hydrochloride in patients with multiple sclerosis and associated cognitive impairments.

Cognitive dysfunction occurs in up to 65% of patients with multiple sclerosis (MS), but there is no effective treatment for the symptoms. The authors conducted a 12-week, open-pilot study to assess the efficacy and tolerability of donepezil HCl administered in patients with MS and cognitive impairment. Seventeen patients at a long-term care facility with Mini-Mental State Examination scores of < or = 25 received 5 mg of donepezil HCl for a 4-week period, followed by 8 weeks of 10 mg of donepezil HCl. Cognitive, neurologic, functional, and behavioral assessments were conducted at baseline and at 4 and 12 weeks. Statistically significant improvement was observed in several cognitive domains including attention, memory, and executive functioning, as well as different aspects of behavior. These data suggest that donepezil HCl merits further study as a potentially viable treatment option for patients with cognitive impairment associated with MS.

Adult↗
PubMed1999

Physiologic and neuroendocrine responses to intravenous naloxone in subjects with Alzheimer's disease and age-matched controls.

BACKGROUND: Prior work showed that administration of naloxone HCl had different behavioral effects in patients with Alzheimer's disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous naloxone of patients with probable Alzheimer's disease to aged-matched controls. METHODS: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin were obtained at regular intervals. RESULTS: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p < .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. CONCLUSIONS: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.

Adult↗
PubMed1999

Diabetes and dementia in long-term care.

OBJECTIVES: To examine the presence or absence of dementia, and the prevalence rates for different dementias, in patients with and without adult onset diabetes (AODM). DESIGN: Chart survey. SETTING: A public long-term care facility in Rochester, New York, chosen to provide an enriched sample with respect to the diseases and demographic variables of interest. PARTICIPANTS: All long-term care residents in the facility aged 50 years or older (n = 476), mean age 74.8 years. Thirty-six (7.6%) had probable Alzheimer's disease (AD), 49 (10.3%) had possible AD, 38 (8.0%) had clinically diagnosed vascular dementia, 84 (17.6%) had unspecified dementias, and 269 (56.5%) were not demented. MEASUREMENTS: Demographic data, dementia and diabetes determined on the basis of extraction of chart data, and hypertension, myocardial infarction, congestive heart failure, and hypercholesterolemia determined on the basis of chart diagnoses. RESULTS: There were 99 residents with AODM in the sample, a prevalence rate of about 21%. The rates of both dementia and AODM were as expected for this age group and setting. Patients with probable or possible AD had the lowest rates of AODM (0 and 6.1%, respectively), and patients with vascular dementia had the highest rates of AODM (47.4%). Age, sex, and race influenced both the risk of having a dementia and the type of dementia. When these variables were adjusted for in multiple logistic regression, however, AODM remained a robust predictive factor because of its significant negative association with AD. Patients with unspecified dementias and no dementia showed rates of AODM (about 20%) that were roughly comparable and intermediate between vascular dementia and AD. CONCLUSIONS: In our study, AD diagnosed clinically and AODM did not co-occur, whereas AODM was associated with vascular dementia diagnosed clinically. Conversely, in non-Alzheimer, nonvascular dementias diagnosed clinically, the rates of AODM were equivalent to those in nondemented patients. These findings are in agreement with some, but not all, previous studies.

Age Distribution↗
PubMed1999

Behavior Rating Scale for Dementia: development of test scales and presentation of data for 555 individuals with Alzheimer's disease.

We studied 555 Alzheimer's disease patients on the Behavior Rating Scale for Dementia (BRSD), which uses informant interviews to measure behavioral pathology in demented patients. For the 45 items, ratings of present ranged from 5% to 66% of the subjects, with 39 rated present in at least 10%. Twenty-nine items were significantly correlated with dementia severity. The mean number of items present per subject was 13.5; only two subjects had none rated present. Factor analysis identified six factors common to mildly and moderately demented subjects. Six subscales were developed: Depressive Symptoms, Inertia, Vegetative Symptoms, Irritability/Aggression, Behavioral Dysregulation, and Psychotic Symptoms. Interitem consistency was high for three subscales (alpha's from .75 to .80) and moderate for three (alpha's from .48 to .56). Four subscale scores and total scores were significantly but weakly correlated with dementia severity. Detailed results and test instructions are presented in the BRSD manual, available from The Consortium to Establish a Registry for Alzheimer's Disease.

Aged↗
PubMed1999

Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia.

BACKGROUND: The aim of this study was to assess the effects of withdrawal from placebo and carbamazepine administered for agitation associated with dementia and to assess safety, tolerability, and efficacy of subsequent ongoing carbamazepine therapy. METHOD: We previously reported the results of a 6-week, randomized, parallel-group study of placebo versus carbamazepine in 51 nursing home patients with dementia who were agitated; 47 subjects completed that study. This report first presents the results of withdrawal from that experimental treatment assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary outcome measures addressed other aspects of behavior, cognition, function, safety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), with the same assessments performed. RESULTS: Patients who had previously shown behavioral improvement with carbamazepine therapy reverted to their baseline state after washout, whereas there was no change in the patients previously treated with placebo. There were no other significant effects of washout. During subsequent therapy with carbamazepine at a modal dose of 300 mg/day, there were 2 deaths and 4 other adverse events resulting in dropout. Neither of the deaths, and only 1 serious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavior ratings showed ongoing improvement in agitation and aggression, as well as in other aspects of psychopathology. CONCLUSION: The washout data provided independent confirmation of efficacy found in the prior placebo-controlled phase of this trial. Ongoing treatment was not associated with unexpected toxicity and was associated with improvement in measures of agitation and aggression that appeared to continue for up to 12 weeks. These findings confirm and extend results from earlier placebo-controlled studies.

Aggression↗
PubMed1999

Treatment of agitation in dementia.

Behavioral and psychological signs and symptoms associated with dementia are common and often confusing because they do not meet criteria for typical discrete psychiatric disorders. Although the symptoms tend to occur in clusters, the clusters often vary with time and between patients. Recognizing the behavioral pathology associated with dementia is important because it can be distressing to the patient, lead to dangerous interactions with others or the environment, and result in the use of inappropriate psychotropic medications. A practical, general approach to the evaluation and management of agitation in dementia for psychiatric consultants confronted with such problems is proposed.

Caregivers↗
PubMed1999

The older patient: the ongoing challenge of efficacy and tolerability.

The clinical management of older schizophrenic patients presents particular clinical challenges. Antipsychotics are among the most widely prescribed class of medications for elderly patients. However, the increased frequency of chronic illnesses and thus the potential need for polypharmacy means that the most appropriate treatment strategy for the older schizophrenic patient is not easily extrapolated from the wealth of clinical trials conducted in younger patients. The development of atypical antipsychotics, with their lower propensity to cause adverse effects and cognitive impairment, offers considerable potential benefits to the older schizophrenic patient. The particular problems and key issues that should be addressed when selecting an appropriate antipsychotic for schizophrenic patients in this sensitive population, as well as the place of the new atypical antipsychotic agents in treating this population, are discussed.

Age Factors↗
PubMed1998

Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline).

Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.

Biogenic Amines↗