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Biomedical subjects

N Herrmann

Publications and source records attributed to N Herrmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Bipolar disorder in old age.

OBJECTIVE: To review the classification, clinical characteristics, and epidemiology of bipolar disorders in old age with a special focus on neurologic comorbidity, high mortality, and management. QUALITY OF EVIDENCE: Most available data is gleaned from retrospective chart reviews and cohort studies. Treatment recommendations are based on evidence from younger populations and a few anecdotal case reports and series involving elderly people. MAIN MESSAGE: While relatively rare in the community setting, mania in old age frequently leads to hospitalization. It is associated with late-onset neurologic disorders (especially cerebrovascular disease) involving the right hemisphere and orbitofrontal cortex. Prognosis is relatively poor; morbidity and mortality rates are high. Management of bipolarity includes cautious use of mood stabilizers, especially lithium and divalproex. CONCLUSIONS: Mania in old age should trigger a careful assessment of underlying neurologic disease, especially cerebrovascular disease. Close clinical follow up is essential.

AIDS Dementia Complex↗
PubMed1999

The use of non-prescription sleep products in the elderly.

UNLABELLED: While sleep disorders are common in the elderly, the use of non-prescription products for sleep in this population has not been fully evaluated. The objectives of this project were to assess the use, perceived effectiveness and toxicity of non-prescription sleep products in an ambulatory elderly population. METHODS: A self-administered 20-question survey was distributed to seniors, aged 60 years or more, during hospital or pharmacy visits. RESULTS: Of the total respondents (N=176, mean age 74+/-7 years, 59% female), 84 (48%) indicated that they had used one or more therapies for sleep within the past year. These included non-prescription products (50% of therapies), prescription products (17%) and non-drug activities such as walking or drinking milk (34%). For those individuals who had used a non-prescription product in the past year (N=47, 27% of total respondents), the most frequently used products were: dimenhydrinate (21%), acetaminophen (19%), diphenhydramine (15%), alcohol (13%) and herbal products (11%). Most took them at least 1 day per week (79%) and 32% took them daily. These products subjectively improved sleep latency (mean 32 vs 61 minutes, p<0.001), number of nocturnal awakenings (mean 2 vs 3 awakenings, p<0.001) and total hours of sleep (mean 6.6 vs 5.4 hours, p<0.001). Mild side-effects were reported by 35 respondents (75%), the most common being dry mouth (N=22) and daytime drowsiness (N=13). Respondents were taking an average of four (SD+/-3, range 0-10) other medications currently. CONCLUSIONS: Non-prescription products are widely used by this population of ambulatory elderly for sleep disturbances. Most of the products were not marketed for sleep; however, they were perceived to be efficacious with low toxicity. The potential for drug interaction is high. Further research is warranted to evaluate the safety and effectiveness of non-prescription sleep products in the elderly.

Aged↗
PubMed1998

Ultrasonic Spectroscopy Study of Flocculation and Shear-Induced Floc Disruption in Oil-in-Water Emulsions.

Ultrasonic attenuation spectroscopy was used to study flocculation and shear-induced disruption of flocs in oil-in-water emulsions. The ultrasonic attenuation spectra (1 to 150 MHz) of a series of 10 wt% corn oil-in-water emulsions (r32 = 0.2 µm) were measured. Depletion flocculation was induced in the emulsions by adding different concentrations (0 to 0.2 wt%) of a nonadsorbing biopolymer (xanthan) to the aqueous phase. At low frequencies, the attenuation coefficient of the emulsions decreased with increasing flocculation due to overlap of the thermal waves generated by the droplets. These observations were in good agreement with a theory recently developed to account for the influence of droplet flocculation on the ultrasonic properties of emulsions. The ultrasonic technique was also used to monitor the breakdown of flocs under shear flow. The dependence of the ultrasonic properties of emulsions on flocculation means that ultrasonic attenuation spectroscopy can be used to study droplet interactions in concentrated emulsions. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline.

The extent of changes in CYP2D6 and CYP1A2 activities with higher therapeutic dosages (>50 mg/day) of sertraline is not well established in vivo. This study assessed the extent and determinants of changes in CYP2D6 and CYP1A2 isozyme activities after treatment with clinically relevant doses of sertraline. Patients and healthy volunteers aged 19 to 85 years (N = 21) were treated with sertraline for 5 to 55 days. The dosage of sertraline ranged from 25 to 150 mg/day (93.5+/-26.4 mg/day; mean +/- SD). All subjects had an extensive metabolizer phenotype for CYP2D6 and received a single oral dose of dextromethorphan (30 mg) and caffeine (100 mg) before and after sertraline treatment. The log O-demethylation ratio (ODMR) of dextromethorphan and the caffeine metabolic ratio (CMR) in overnight urine were used as in vivo indices of the CYP2D6 and CYP1A2 isozyme activities, respectively. Concurrent medications and lifestyle habits (e.g., smoking and diet) were monitored during the study. Baseline log ODMR (-2.33+/-0.45) but not CMR (5.1+/-1.9) (mean +/- SD) significantly changed after sertraline treatment (-2.19+/-0.62; 4.5+/-1.6, respectively) (p: ODMR = 0.04, CMR = 0.10). There was no significant effect of age, dose, duration of treatment, gender, sertraline and/or desmethylsertraline plasma concentration, subject type (patient or volunteer), and weight on the extent of changes in log ODMR or CMR (p > 0.05). In conclusion, sertraline treatment at a mean daily dosage of 94.0 mg did not significantly change CYP1A2 activity and resulted in a modest inhibition of CYP2D6 activity.

1-Naphthylamine↗
PubMed1998

Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo.

Major depression may require antidepressant treatment for several years. This necessitates consideration of the long-term effects of antidepressants on multiple clinical endpoints. The antidepressants paroxetine and fluvoxamine are potent in vitro inhibitors of CYP2D6 and CYP1A2 isozymes, respectively. CYP2D6 and CYP1A2 are important for the clearance of 30 or more frequently used medications. Moreover, CYP1A2 also contributes to metabolism of 17beta-estradiol and metabolic activation of environmental procarcinogens (e.g., arylamines in cigarette smoke). The aim of this study was to assess the determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition during paroxetine and fluvoxamine treatment. Healthy volunteers and patients received caffeine (100 mg) and dextromethorphan (30 mg) at baseline and at steady state of paroxetine (10-20 mg/day, 5-74 days, N = 13) or fluvoxamine (50-100 mg/day, 5-43 days, N = 8). The caffeine metabolic ratio (CMR) and the log O-demethylation ratio (ODMR) of dextromethorphan in overnight urine were used as in vivo indices of the CYP1A2 and CYP2D6 isozyme activities, respectively. All subjects had an extensive metabolizer phenotype for CYP2D6. After fluvoxamine treatment, baseline CMR 5.1 +/- 1.4 (mean +/- SD) decreased to 2.7 +/- 1.1 (p < 0.01). Paroxetine did not have a significant effect on CMR (p > 0.05). In seven of eight subjects in the fluvoxamine group, posttreatment CMR was comparable with the minimum CMR value (2.0) attainable in nonsmoking healthy volunteers. After paroxetine treatment, log ODMR changed from a baseline value of -2.28 +/- 0.37 to -1.13 +/- 0.44, indicating significant inhibition of CYP2D6 (p < 0.001). Subjects' CYP2D6 phenotype did not change after paroxetine treatment. Fluvoxamine had no significant effect on log ODMR (p > 0.05). The extent of inhibition of CYP2D6 and CYP1A2 by paroxetine and fluvoxamine, respectively, displayed a positive correlation with baseline enzyme activity (p < 0.05). In addition, a negative association was found between the plasma paroxetine concentration and the CYP2D6 activity after paroxetine treatment (r = -0.47, p < 0.05). These data indicate that paroxetine and fluvoxamine treatment with minimum clinically effective doses significantly inhibit CYP2D6 and CYP1A2, respectively. The extent of inhibition of CYP2D6 by paroxetine and of CYP1A2 by fluvoxamine is dependent in part on the baseline enzyme activity. The interindividual variability in CYP2D6 inhibition by paroxetine can also be explained by variability in plasma paroxetine concentration. Most patients treated with fluvoxamine (50-100 mg/day) will reach population minimums for CYP1A2 activity. These results have potential implications for interindividual variability in the risk for drug-drug interactions mediated by CYP2D6 and CYP1A2 as well as for the disposition of 17beta-estradiol and environmental procarcinogens.

Adult↗
PubMed1998

The Sunnybrook Stroke Study: a prospective study of depressive symptoms and functional outcome.

BACKGROUND AND PURPOSE: To assess the prevalence of depressive symptoms, their clinical correlates, and the effects of depressive symptoms on stroke recovery, a relatively unselected, well-diagnosed cohort of consecutive stroke survivors was followed prospectively. METHODS: Consecutive admissions to a regional stroke center who met World Health Organization and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Subarachnoid hemorrhage and brain stem strokes were excluded. Patients underwent CT, single-photon emission CT, and standardized neurological and cognitive examinations at entry. At 3 months and 1 year after stroke, depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and the Zung Self-Rating Depression Scale (SDS). Functional outcome was measured with the Functional Independence Measure, and handicap was assessed by the Oxford Handicap Scale. RESULTS: We assessed 436 patients at entry (mean +/- SD age, 74.9 +/- 11.6 years). There were 150 patients available for assessment at 3 months and 136 at 1 year. Marked depressive symptoms were noted in 22% (SDS) to 27% (MADRS) at 3 months and 21% (SDS) to 22% (MADRS) at 1 year. Patents with marked depressive symptoms had more neurological impairment (P<.008), were more likely to be female (P<.05), and were more likely to have previous histories of depression (P<.03). There was no relationship between depressive symptoms and age, lesion volume, or side of lesion. Depressive symptoms were correlated with functional outcome (r = -.31, P<.0001) and handicap (r = .41, P<.0001) at 3 months and 1 year (r= -.28, P<.001; r = .35, P<.0001). CONCLUSIONS: Depressive symptoms and functional outcome are correlated. In view of the prevalence of depressive symptoms in this population, diagnosis and treatment of depression are important in optimizing recovery.

Activities of Daily Living↗
PubMed1998

Risperidone for the treatment of behavioral disturbances in dementia: a case series.

The authors describe a series of 22 patients with dementia and behavioral disturbances, including agitation, aggression, delusions, and hallucinations, who were treated with risperidone. Risperidone, in low doses, was well tolerated; 50% of patients experienced significant improvement, although 50% experienced some extrapyramidal symptoms.

Aged↗
PubMed1998

Valproic acid treatment of agitation in dementia.

OBJECTIVE: Valproic acid, an anticonvulsant medication that enhances GABAergic neurotransmission, has been shown to be helpful in treating behavioural disturbances associated with dementia in several small case series. In an attempt to further document its effectiveness and safety, valproic acid was used to treat a group of elderly patients with dementia and severe agitation. METHOD: Sixteen patients, aged 68 to 95 years, who were previously unresponsive to other pharmacotherapeutic interventions, were treated prospectively with open-label divalproex sodium. Effectiveness was measured with the Behave AD (B-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression Scale (CGIS). Doses ranged from 750 to 2500 mg, divided, per day, with levels of 184 to 742 mumol/L. RESULTS: Scores on the CMAI declined from 68.8 to 61.0 (P < 0.005), and scores on the B-AD declined from 15.8 to 12.3 (P < 0.004). On the CGIS, 1 patient was rated as very much improved, 3 patients were much improved, 4 patients were minimally improved, and 8 patients were unchanged. The drug was prematurely discontinued in only 1 patient because of side effects. CONCLUSION: Valproic acid was shown to be well tolerated with modest effectiveness.

Aged↗
PubMed1998

The importance of lesion location in poststroke depression: a critical review.

BACKGROUND: Mood disorder may be a specific complication of stroke. An earlier finding of an association between left anterior lesions and poststroke depression stimulated interest in the significance of stroke lesion characteristics. Subsequent research efforts, however, often failed to replicate this finding. OBJECTIVE: This paper represents a critical appraisal of hemispheric lesion localization studies by computed tomography (CT) scanning in poststroke depression. METHOD: Systematic selection of original studies involved a Medline search and a review of the bibliographies of retrieved articles for additional references. Two sets of inclusion criteria were independently applied to the studies by 2 observers blind to authorship, affiliation, and journal name. Studies that satisfied minimum inclusion criteria, as determined by consensus, were included in the review. RESULTS: Twenty-six original articles were retrieved by the search. Thirteen studies satisfied all or nearly all of the minimum criteria for inclusion. Six of those studies found no difference between right- and left-hemisphere lesions leading to depression. Two studies found right-sided lesions more likely to be associated with depression, while 4 studies found depression to be associated more often with left-sided lesions. One study matched subjects with and without depression for lesion location and size to identify nonlesion risk factors. All studies suffered from methodological limitations, and no studies were completely comparable with respect to sample, timing and analysis of CT scan, and psychiatric evaluation. CONCLUSION: Based on a systematic review of the present literature, any definitive statements regarding stroke lesion location and risk for depression are not yet substantiated. The authors suggest methodologies for future localization studies of poststroke depression.

Aged↗
PubMed1998

Clock tests in depression, Alzheimer's disease, and elderly controls.

OBJECTIVE: While clock-drawing tests are commonly used to screen for cognitive impairment in the elderly, little is known about the performance of elderly depressives. METHODS: We compared thirty-three patients with major depression to forty-two Alzheimer's disease and thirty age-matched controls on clock-drawing, copying, and reading. RESULTS: Patients with Alzheimer's disease had significantly lower scores on clock-drawing, copying, and reading than patients with depression or the controls (p < 0.05). Patients with depression did not differ significantly from controls on quantitative scores or qualitative errors. CONCLUSIONS: Clock tests may be useful for identifying depressed patients with underlying dementia.

Aged↗
PubMed1997

Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo.

BACKGROUND: Paroxetine is a frequently used antidepressant and a potent inhibitor of the CYP2D6 isozyme in vitro (inhibition constant [Ki] = 0.15 micromol/L). Most classic antipsychotic agents such as perphenazine are metabolized by the CYP2D6 isozyme and are often coadministered with antidepressant agents. This study assessed the extent of changes in CYP2D6 isozyme activity in vivo after pretreatment with paroxetine and its consequences on perphenazine kinetics and central nervous system effects. METHODS: Eight extensive metabolizers for CYP2D6 were administered a single dose of perphenazine (0.11 mg/kg orally) or placebo following a randomized double-blind design. Perphenazine plasma concentrations and effects were assessed for a period of 8 hours. Subsequently, subjects were treated with a standard therapeutic dose of paroxetine (20 mg/day orally) for 10 days and test sessions with perphenazine and placebo were repeated. RESULTS: Paroxetine treatment resulted in a twofold to 21-fold decrease in CYP2D6 activity (p < 0.001). After pretreatment with paroxetine, perphenazine peak plasma concentrations increased twofold to 13-fold (p < 0.01). This was associated with a significant increase in central nervous system side effects of perphenazine, including oversedation, extrapyramidal symptoms, and impairment of psychomotor performance and memory (p < 0.05). CONCLUSION: Coadministration of perphenazine after pretreatment with a standard therapeutic dose of paroxetine increased the plasma concentration and central nervous system side effects of perphenazine, primarily as a result of inhibition of the CYP2D6 isozyme. In patients who are at steady state with paroxetine, a reduction of perphenazine dose may be required to prevent central nervous system side effects.

Adult↗
PubMed1997

The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis.

BACKGROUND: To determine the efficacy, safety and tolerability of antidepressants in depressed elderly patients. METHODS: Search for randomized controlled double-blind studies evaluating atypical antidepressants (ATYPs), reversible inhibitors of monoamine oxidase-A, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants in moderate/severe depressed patients > or = 60 years for > or = four weeks. The random effects model (single-arm; comparative) was used to aggregate efficacy, safety and dropout. RESULTS: No difference in single-arm aggregation of outcomes for four antidepressant classes. Comparative analyses showed no statistical difference between outcomes, except SSRIs had a higher response rate than ATYPs. CONCLUSION: Elderly show no differences in antidepressant class outcomes. LIMITATIONS: Heterogeneity and lack of power. CLINICAL RELEVANCE: There is little advantage for antidepressant classes over another in the aged.

Age Factors↗
PubMed1997

Pharmacotherapy of late life mood disorders.

The pharmacotherapy of elderly patients with affective illnesses presents clinicians with a number of challenges. Changes associated with normal aging, as well as concomitant medical illnesses and their treatment, can affect the pharmacokinetics and pharmacodynamics of psychotropic drugs. Furthermore, the relative paucity of controlled trials with elderly patients necessitates a reliance on studies done on younger populations, which may be inappropriate. This review attempts to highlight how knowledge of the effects of aging on pharmacokinetics and pharmacodynamics can help clinicians optimize therapy for their older patients with affective disorders.

Aged↗
PubMed1997

From transmitters to treatment: the pharmacotherapy of behavioural disturbances in dementia.

BACKGROUND: Behavioural disturbances in dementia are a common cause of excess morbidity, impairing the quality of life for both patient and caregiver. As part of a comprehensive approach to management, which includes a search for underlying causes and behavioural interventions, pharmacotherapy can be extremely helpful in alleviating symptoms such as agitation, aggression, and psychosis. METHOD: This paper reviews recent studies that examine the neurochemical basis of these behavioural disturbances in order to provide a rationale for the various classes of psychotropics which have been used. RESULTS: While neuroleptics have been the best-studied class of drugs to date, modest efficacy and significant potential side effects often limit their use. Newer atypical neuroleptics may be better tolerated, though controlled data have yet to be published. There is increasing support of the use of carbamazepine and antidepressants such as trazodone and the selective serotonin reuptake inhibitors (SSRIs). CONCLUSION: Further controlled studies of all of these agents are required. In order to determine whether transmitter-specific or behavioural-specific targeted interventions truly provide a rationale for the effective pharmacotherapy of these disorders.

Aged↗