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Biomedical subjects

R A Sweet

Publications and source records attributed to R A Sweet.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Aged↗
PubMed1999

Managing antipsychotic-induced parkinsonism.

Notwithstanding the advent of clozapine and other 'atypical' antipsychotic agents, the conventional ('typical') antipsychotic agents remain in widespread use. Antipsychotic-induced parkinsonism is a highly prevalent adverse effect that may result in increased morbidity and noncompliance. Bedside examination is generally sufficient for the detection of the onset of parkinsonism and should be carried out frequently in the first 3 months of treatment. In addition to decreasing patient discomfort, monitoring for antipsychotic-induced parkinsonism also serves to identify the minimally effective dosage required for the individual patient. Several strategies are utilised in the management of antipsychotic-induced parkinsonism including dosage reduction, switching to other antipsychotic agents and the use of antiparkinsonian drugs such as anticholinergic agents and amantadine. Anticholinergic agents remain the mainstay of the pharmacological management of antipsychotic-induced parkinsonism in younger patients. Amantadine is a better tolerated agent for elderly patients, with similar efficacy to the anticholinergic agents. The routine use of prophylactic anticholinergics is not recommended and is clearly contraindicated in the elderly. An individualised risk-benefit assessment is necessary for the younger patient in whom prophylactic use of anticholinergic drugs is considered.

Aged↗
PubMed1999

Age at onset in geriatric bipolar disorder. Effects on clinical presentation and treatment outcomes in an inpatient sample.

The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission.

Age of Onset↗
PubMed1998

Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer disease.

OBJECTIVE: To examine if selected polymorphisms in the dopamine receptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer disease (AD). DESIGN: A cohort of patients with AD were longitudinally evaluated for behavioral symptoms and classified with regard to the presence of psychotic symptoms and physical aggression. SETTING: Alzheimer's Disease Research Center. PATIENTS: Two hundred seventy-five elderly outpatients diagnosed as having probable AD. RESULTS: Among white patients, psychosis and aggression were both significantly more frequent in DRD1 B2/B2 homozygotes (P < .02), while psychosis was significantly more frequent in DRD3 1/1 or 2/2 homozygotes (P < .05). The joint risk for psychosis due to the DRD1 and DRD3 polymorphisms exceeded the risks due to either locus alone, suggesting an interaction. Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression. CONCLUSIONS: Genetic variation in DRD1 and DRD3 genes may act to modify the course of AD, predisposing to the development of psychotic or aggressive symptoms. Confirmation in other samples of patients with AD is required.

Aged↗
PubMed1998

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain.

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.

Adult↗
PubMed1998

Determinants of spontaneous extrapyramidal symptoms in elderly psychiatric inpatients diagnosed with Alzheimer's disease, major depressive disorder, or psychotic disorders.

Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.

Age Factors↗
PubMed1998

Is delirium different when it occurs in dementia? A study using the delirium rating scale.

The authors studied 61 geropsychiatric patients with delirium from a cohort of 843 consecutive admissions to a geriatric clinical research unit. A central study goal was to assess how the presence of dementia affected the presentation of delirium. Eighteen delirious (D) and 43 delirious-demented (D-D) patients were compared on the Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and EEG. D-D patients had lower MMSE scores, but no differences were found in total DRS or BPRS scores or in EEG grade. DRS items were similar in the two groups except that D-D had more cognitive impairment than D. An exploratory principal components analysis of DRS items identified two core factors. The authors conclude that the presentation of delirium in the setting of concurrent dementia is very similar to delirium without dementia, with subtle differences probably attributable to dementia.

Aged↗
PubMed1998

New atypical antipsychotics. Experience and utility in the elderly.

The atypical antipsychotics are a new class of agents with great promise for use in the elderly because of their reduced propensity to cause acute extrapyramidal adverse effects. Treatment of older patients with these agents, however, needs to take into consideration age-related changes in pharmacokinetics and the risks of drug-drug interactions. Additionally, current evidence of their efficacy in late-life psychoses is derived largely from case series and from the extrapolation of results obtained in studies of younger patients with schizophrenia. Controlled clinical studies of atypical antipsychotics in elderly patients are urgently needed.

Aged↗
PubMed1997

Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report.

Neuroleptic treatment of psychotic symptoms or agitated behavior in elderly patients diagnosed with dementia is associated with reduced efficacy and increased rates of neuroleptic-induced parkinsonism in comparison to younger patients with schizophrenia. We report the first study to examine the relationship between an in vivo measure of dopaminergic function, plasma homovanillic acid (pHVA), and ratings of psychosis, agitation, and parkinsonism before and after neuroleptic treatment in dementia patients. Pretreatment pHVA was significantly correlated with parkinsonian rigidity, with a trend observed with agitation and hostility. Though mean pHVA did not change during perphenazine treatment, intraindividual change in pHVA at day 15 was correlated with improvement in hostility, with a similar trend for improvement in agitation. These preliminary findings are consistent with reports associating dopaminergic function with agitated, but not psychotic, symptoms in patients diagnosed with dementia, and with a reduced responsivity of dopaminergic systems to neuroleptic treatment in these patients.

Aged↗
PubMed1997

Medical comorbidity in elderly psychiatric inpatients.

A multidisciplinary diagnostic evaluation was performed for 868 older psychiatric inpatients during a 46-month interval. A total of 402 (46%) met DSM-III-R criteria for organic mental disorders, 329 (38%) had mood disorders, 90 (10%) had psychotic disorders, and 47 (5%) had other mental disorders or conditions. Concurrent medical problems were systematically assessed and classified according to ICD-9-CM criteria. The patients suffered from a mean of 5.6 +/- 3.1 (SD) active medical problems (range 0-18). This level of medical comorbidity was significantly greater than that of older psychiatric outpatients and comparable to that of elderly inpatients in general medical hospitals. When the effects of age and education were controlled for, there were no significant differences in mean numbers of medical problems among the four groups of psychiatric inpatients. An association of major depression with diseases of the digestive system was observed and may be related to peripheral autonomic dysregulation.

Aged↗
PubMed1997

The effects of perphenazine on the concentration of nortriptyline and its hydroxymetabolites in older patients.

Twenty-five older patients who presented with psychotic depression were treated with a combination of nortriptyline and perphenazine. Plasma levels of nortriptyline, E-, and Z-10-OH nortriptyline (E- and Z-10-OH-NT) were measured before and after addition of perphenazine. The mean (+/-SD) initial nortriptyline dose was 59 +/- 24 mg/day, whereas the mean final nortriptyline and perphenazine doses were 56 +/- 24 and 19 +/- 13 mg/day, respectively. The mean plasma level to dose quotient for perphenazine (0.45 +/- 0.34 nM/mg/day) was comparable to the mean quotient reported previously in older psychotic patients treated with perphenazine alone. After addition of perphenazine, the median quotient of nortriptyline plasma level to nortriptyline dose (L/D) increased significantly (from 6.1 to 8.6). This change was inversely correlated with baseline nortriptyline L/D. The median ratio of E-10-OH-NT to nortriptyline plasma level decreased significantly (from 1.6 to 1.3), whereas the median ratio of Z-10-OH-NT to nortriptyline plasma level did not change significantly. These results are consistent with the known inhibition by perphenazine of the cytochrome P450 2D6 (sparteine/debrisoquine hydroxylase), the major enzyme involved in the oxidative metabolism of nortriptyline, mostly through the formation of E-10-OH-NT. This complex alteration in the metabolism of nortriptyline induced by perphenazine emphasizes the relevance of measuring plasma levels not only of nortriptyline but also of its hydroxymetabolites in older patients who are more likely to be sensitive to their differing cardiovascular, anticholinergic, and cognitive effects.

Aged↗
PubMed1997

Mortality of elderly patients with psychiatric disorders.

OBJECTIVE: The goal of this study was to evaluate the impact of common late-life mental disorders on the life expectancy and causes of death of older psychiatric patients. METHOD: The study population consisted of 809 older psychiatric patients who met DSM-III-R criteria for organic mental disorders, mood disorders, or psychotic disorders and who were discharged after a comprehensive multidisciplinary evaluation and acute inpatient treatment for their behavioral disorders. Dates and causes of death during a 5.75-year follow-up period were provided by the Pennsylvania Department of Health. Univariate and multivariate survival procedures were used to compare the survival rates of the three groups to each other and to a reference population of Pennsylvania residents. Causes of death were also tabulated according to ICD-9-CM and compared across the groups. RESULTS: Age, gender, race, and medical comorbidity made significant independent contributions to survival. When these variables were controlled, the survival of patients with organic mental disorders was less than half of that for patients with mood or psychotic disorders. However, all three groups experienced higher rates of mortality than the reference population, with standardized mortality ratios of 1.5 to 2.5. Deaths occurred from the usual spectrum of natural causes, with the exception that patients with mood disorders were more likely to have died from disorders of the digestive system and suicide. CONCLUSIONS: The mental disorders of late life have a significant negative impact on the survival of older psychiatric patients.

Age Factors↗
PubMed1997

Effect of sertraline on plasma nortriptyline levels in depressed elderly.

BACKGROUND: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. METHOD: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. RESULTS: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). CONCLUSION: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.

1-Naphthylamine↗
PubMed1997

Methodological issues in characterizing treatment response in demented patients with behavioral disturbances.

Despite the proliferation of instruments developed to rate behavioral disturbances associated with dementia, systematic studies of how ratings on these instruments should be analyzed to measure change in disruptive behaviors or distressing symptoms (ie treatment response) are noticeably absent. Using one of these scales, we compared three methods to characterize treatment response in 52 elderly demented inpatients who participated in a standardized neuroleptic trial. While all three analyses identified a statistically significant improvement, they conveyed differently the clinical improvement experienced by the patients. Categorical outcomes communicated the clinical meaning of improvement better than changes in total score; changes in factor scores best revealed the differential impact of treatment on specific behavioral and symptomatic domains. Given the heterogeneity of the problematic behaviors and symptoms exhibited by demented patients included in treatment trials, regardless of the intervention being tested or of the instrument being used to rate behaviors, a focused approach to characterizing treatment response is needed.

Aged↗
PubMed1996

MRI changes in schizophrenia in late life: a preliminary controlled study.

The aim of this pilot study was to compare cerebral changes on magnetic resonance imaging (MRI) scans in elderly schizophrenic subjects with those in psychiatric and normal control subjects. We compared the MRIs of 19 subjects with schizophrenia, 19 age- and gender-matched subjects with recurrent major depression, and 19 age- and gender-matched nonpsychiatric control subjects. Deep white matter hyperintensities (DWMH) in right posterior regions were significantly more prominent in the schizophrenic group than in the two comparison groups. Total ratings of MRI abnormalities were significantly related to age in both the normal control and schizophrenic groups, but not in the depressive group. Age of onset was positively associated with total ratings in the depressive group, but not in the schizophrenic group. Thus, a subset of elderly patients with schizophrenia appear to have cerebral white matter abnormalities; such abnormalities may not be confined to late-onset schizophrenia. Systematic MRI studies of early- and late-onset schizophrenia in late life are needed to resolve this question.

Adolescent↗
PubMed1996

Comorbid anxiety disorders in late-life depression.

We examined the prevalence and correlates of comorbid anxiety disorders in two groups of older depressed patients assessed at the University of Pittsburgh. A total of 336 older outpatients and inpatients with major depression were comprehensively evaluated with several instruments including the Hamilton Depression Rating Scale, and either the SADS-L or the SCID for DSM-III-R. These patients presented with major depression, associated with a wide range of functional, cognitive, and medical impairment. One-third to one-half of them also presented with severe symptomatic anxiety. However, only a small proportion (less than 5%) met diagnostic criteria for lifetime or current panic, obsessive-compulsive, or phobic disorders. At baseline, lifetime comorbid anxiety disorders were associated with a higher rate of alcoholism and higher symptomatic anxiety. Lifetime comorbid anxiety disorders did not affect the rate of response of depression, but they were associated with a higher use of benzodiazepines and a 50% increase in the time outpatients needed to respond. These findings suggest that, even in psychiatric patients with major depression, the lifetime prevalence of anxiety disorders is lower in late life, but that it has important clinical and therapeutic implications.

Aged↗
PubMed1996

Bupropion plasma levels and CYP2D6 phenotype.

All available antidepressants with the exception of fluvoxamine and nefazodone either are metabolized by cytochrome P450 2D6 (CYP2D6) and/or inhibit this isozyme. To date, nothing in this regard has been published concerning bupropion. We report that plasma level/dose ratios for bupropion, and its metabolites erythrohydrobupropion and threohydrobupropion, were not associated with debrisoquine metabolic status in 12 patients, three of whom were poor 2D6 metabolizers. The plasma level/dose ratios for the metabolite hydroxybupropion were, however, significantly higher in poor 2D6 metabolizers. In three patients, who received a second phenotyping test during treatment with bupropion, debrisoquine metabolic ratios were not increased. It is thus inferred that bupropion is neither metabolized by nor inhibits CYP2D6. The potential accumulation of hydroxybupropion after CYP2D6 inhibition may, however, contribute to toxicity and impair bupropion's therapeutic effectiveness.

Aged↗