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Biomedical subjects

B G Pollock

Publications and source records attributed to B G Pollock.

At least 73 records · Page 4Linked to original sources
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.

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PubMed1998

Long-term ECG changes in depressed elderly patients treated with nortriptyline. A double-blind, randomized, placebo-controlled evaluation.

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24-111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Age Factors↗
PubMed1998

Relation of serum anticholinergicity to cognitive status in schizophrenia patients taking clozapine or risperidone.

BACKGROUND: A potential beneficial outcome of treatment with certain of the atypical neuroleptics is the reduced risk of cognitive impairment, stemming from purported low affinity for cholinergic receptors. In vitro experiments have shown that clozapine is highly anticholinergic and risperidone is minimally so. In vivo tests of the anticholinergic burden imposed by these medications and its potential cognitive consequences are needed. This study examines anticholinergic burden in schizophrenia patients taking clozapine and risperidone and tests whether this burden is associated with cognitive deficits. METHOD: Serum anticholinergic levels were determined in a sample of 22 chronic schizophrenia patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen patients received clozapine; 7 received risperidone. Mean +/- SD age of the sample, comprising 12 men and 10 women (68% white), was 44.7 +/- 8.4 years. Mean +/- SD age at onset of schizophrenia illness was 23.5 +/- 7.4 years. Two anticholinergic assays based on blood samples collected 1 week apart were available on each patient. RESULTS: Data indicated that clozapine patients had significantly (p < .001) higher anticholinergic levels at both collection points, and levels for both drugs remained stable over time. The clozapine and risperidone patients had essentially equivalent scores on the cognitive measure. CONCLUSION: These data suggest that anticholinergicity distinguishes clozapine and risperidone in vivo but that this effect is not associated with differences in global cognitive functioning. Results suggest that clozapine, despite producing moderately high in vivo serum anticholinergic levels, still holds clinical advantage over standard neuroleptics in terms of cognitive side effects. Reasons for this lowered risk of cognitive impairment are discussed.

Adult↗
PubMed1998

Psychotropic drugs and the aging patient.

Patients older than age 65 currently compose 13% of the US population, yet they receive 35% of all prescribed medications. In older patients, the complications of psychotropic drugs alone constitute a highly significant health problem. Pharmacokinetic and pharmacodynamic differences secondary to age or illness require careful consideration. Accumulation of drug might result from declining cardiovascular or renal function, alteration of body composition, or genetic or acquired inhibition of drug metabolism. As patients age, there is a general reduction in homeostatic mechanisms such as postural control, orthostatic circulatory responses, and visceral muscle function that may result in adverse drug experiences. specific receptor and neurotransmitter changes associated with senescence include reductions in central cholinergic and dopaminergic activities that lead to greater sensitivity to medications acting on these systems. Clinical vigilance is particularly important when prescribing newly available antidepressants and antipsychotics, since typically these medications are not systematically evaluated in older subjects before their release.

Aging↗
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.

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PubMed1997

Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease.

Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.

Adult↗
PubMed1997

Quantitative determination of paroxetine in plasma by high-performance liquid chromatography and ultraviolet detection.

An accurate, reliable procedure was developed for kinetic and therapeutic monitoring of paroxetine in human plasma. Steady-state plasma levels of paroxetine were measured for 18 geriatric patients (mean age 75) in a double-blinded study. Paroxetine doses ranged from 10 to 40 mg/day. The assay was suitable for patients on concurrent medications, and a small sample volume (1 ml) of patient plasma was used with sufficient sensitivity and specificity. After extraction and separation on a Beckman, Ultrasphere 5-microm C18 column (150x2 mm I.D.), the recovery (mean+/-S.D.) for paroxetine was determined to be 86.5+/-5.2%. The limit of quantitation for paroxetine in this assay was 5 ng/ml. Inter-assay reproducibility (C.V.) for the patient samples and quality controls ranged from 3.7 to 7.6%.

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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.

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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

Plasma levels of citalopram enantiomers and metabolites in elderly patients.

Ten patients with dementia and significant behavioral disturbances (mean age of 77.2 +/- 8.2 years) received citalopram, 10 mg/day for 3 days, followed by 20 mg/day for 2 weeks. Six of the 10 patients completing 17 days of treatment had a clinically impressive response, as assessed by significant improvement in six target items on the Neurobehavioral Rating Scale. Eight patients were also analyzed by measuring the racemic and enantiomeric plasma levels of citalopram (CIT) and desmethylcitalopram (DCIT). A sensitive high-performance liquid chromatography (HPLC) assay for citalopram enantiomers and metabolites was developed using ultraviolet detection. The lower limit of detection was 10 ng/ml for each enantiomer. Steady-state plasma level ranges were 11.2 to 92.2 ng/ml for the biologically active S(+) citalopram and 12.8 to 95.7 ng/ml for the inactive R(-) enantiomer. For the S and R enantiomers of desmethylcitalopram, plasma levels ranged from 11.0 to 22.0 ng/ml and 9.2 to 22.0 ng/ml, respectively. The racemic citalopram plasma level to dose ratio of 3.50 was higher than the ratio (1.96) reported by Overo (1982) for 55 younger patients. The stereoselective metabolism of the enantiomers for citalopram and desmethylcitalopram (S(+) and R(-) enantiomers) in these older subjects differed from that reported in younger patients, suggesting possible age-associated changes in CYP2C19 activities. We hypothesize that quantification of S(+) citalopram will permit a more accurate examination of dose/response relationships. This measure seems to be especially important for older subjects, given the wide ranges and higher concentrations evident from our preliminary results.

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PubMed1997

An open pilot study of citalopram for behavioral disturbances of dementia. Plasma levels and real-time observations.

Citalopram, in European studies, has shown some early promise for treatment of poststroke depression and behavioral complications of dementia. An open pilot study of citalopram was conducted in 16 patients with dementia and behavioral disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a clinically impressive response. A significant overall mean reduction in disruptive vocalizations was observed by means of a novel technique of computer-assisted real-time observation. The mean citalopram plasma level-to-dose ratio was found to be twice that previously reported in younger patients. These pilot findings should encourage future placebo concentration-controlled trials.

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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.

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PubMed1997

Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine.

Elderly depressed patients often require an average of 12 weeks of pharmacotherapy before attaining remission. The delay between treatment initiation and remission may decrease compliance and prolongs suffering; hence, interventions that decrease the time to onset of antidepressant activity are needed. Our objective was to evaluate, in an open trial, the use of one night of total sleep deprivation combined with paroxetine to accelerate antidepressant response in elderly patients. Thirteen elderly patients with major depression were sleep-deprived for one night and started paroxetine on the night of recovery sleep. Patients were followed for twelve weeks, and clinical improvement was rated using the 17-item Hamilton Depression Rating Scale and a version of the Hamilton modified for sleep deprivation studies. 8/13 (62%) patients experienced significant improvement of depressive symptoms by 2 weeks. Within 12 weeks 11/13 (85%) patients responded to the combination of sleep deprivation and paroxetine. Median response time was 2 weeks. Clinical response at 12 weeks was correlated with changes in Sleep Deprivation Depression Rating Scale Scores between baseline and recovery sleep. In an open trial, the combined use of total sleep deprivation and paroxetine appears to be an effective method for speeding the onset of clinical antidepressant activity in geriatric depression and for improving early recognition of non-response.

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PubMed1997

Low-level serum anticholinergicity as a source of baseline cognitive heterogeneity in geriatric depressed patients.

Depressed geriatric patients show substantial intersubject variability in cognitive performance, which complicates attempts to evaluate the cognitive effects of depression and of antidepressant therapy. This variability may reflect the multiple medications older patients take, many of which have anticholinergic effects. This study examined whether serum anticholinergicity (SA) explained some of the variability in depressed geriatric patients' memory performance. Before starting antidepressant treatment, 36 elderly depressed subjects were given a verbal learning test. At the same time, a blood sample was taken and analyzed by radioreceptor binding assay to determine their SA level. Nineteen of the subjects had detectable levels (mean = 0.28 pmole atropine equivalent). Subjects with an SA of zero showed significantly better delayed recall than did those with a positive SA level. Thus, even very low SA may produce subtle decrements in memory performance, an area of cognition known to be highly sensitive to anticholinergic effects.

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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.

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