Biomedical subjects

K L Lanctôt

Publications and source records attributed to K L Lanctôt.

At least 19 recordsLinked to original sources

PubMed2006

Cholinesterase inhibitors slow decline in executive functions, rather than memory, in Alzheimer's disease: a 1-year observational study in the Sunnybrook dementia cohort.

To determine if there are differential treatment effects of second-generation cholinesterase inhibitors over one year, 130 patients (untreated=65, treated=65) meeting NINCDS-ADRDA criteria for mild or moderate probable AD underwent standardized cognitive testing at baseline and 12 months later at a university memory clinic. Patients were followed either prior to or after the availability of treatment and were matched on education and baseline Mini Mental State Examination (MMSE). A detailed medical history evaluation was conducted. In this well matched longitudinal observational cohort study, there were no differences in the prevalence of comorbid illnesses, concomitant medication use or vascular risk factors except for a greater number of treated patients with a previous history of smoking. Separate repeated measures MANCOVAs on the MMSE, Mattis Dementia Rating Scale (DRS), and its 5 subscores (attention, initiation/perseveration, conceptualization, construction and memory) (Bonferroni corrected), after covarying for the effects of smoking, and SSRI use, showed less decline over one year in the treated group in overall cognition and in all subscores of the DRS except for memory (effect sizes 0.5-0.7). Less decline was also seen in the treated group in function and in instrumental and basic activities of daily living as measured with the Disability Assessment for Dementia Scale (DAD) (effect sizes 0.4-0.8). Executive, language and visuospatial functions, rather than memory, appeared to be more amenable to stabilization over one year by cholinesterase inhibitors in AD.

Aged↗

PubMed2001

Herbal-drug therapy interactions: a focus on dementia.

Older people with dementia are often prescribed numerous medications. Use of herbal therapies in addition to these conventional drug therapies may lead to interactions that result in an adverse drug event. We have conducted a systematic review to identify all studies that examined interactions between herbal and conventional drug therapies (i.e. prescription or over-the-counter). Using a MEDLINE search of English-language studies published between 1980 and 2000, we limited our search to those herbal therapies most likely to be used for the treatment of dementia (memory loss and decreased concentration) and related symptoms. We identified 28 articles that describe interactions between these herbal (i.e. St. John's wort, ginkgo biloba, kava, valerian, and ginseng) and conventional drug therapies. Of these articles, 11 examined St. John's wort, four examined ginkgo biloba, five examined kava, one examined valerian, and seven examined ginseng. We identified a series of potential interactions between herbal and conventional drug therapy that place older people at risk for an adverse drug event. Health care professionals need to be aware of these potential interactions.

Aged↗

PubMed2001

Role of serotonin in the behavioral and psychological symptoms of dementia.

The behavioral and psychological symptoms of dementia (BPSD) can have serious debilitating effects on the patient and increase caregiver burden. Investigations into the underlying neuropathology indicate that the serotonergic system may contribute to BPSD. In addition, serotonergic pathways are known to interact extensively with the cholinergic, noradrenergic, GABAergic, and dopaminergic systems. Hence, serotonergic therapies may be used to manipulate other neurotransmitters systems to alleviate BPSD or in combination with agents specific for the other neurotransmitter receptor sites. Neurotransmitter-modulated behaviors and evidence provided by pharmacological interventions are reviewed, focusing primarily on the serotonergic system.

Aged↗

PubMed2001

Clinical and economic factors in the treatment of behavioural and psychological symptoms of dementia.

The prevalence of behavioural and psychological symptoms of dementia (BPSD) exceeds 50%. They cause distress to patients and caregivers, increase resource utilisation of various kinds, and form a high risk for accelerated psychiatric care through institutionalisation. Although evidence for current pharmacological treatment is not strong and the construct of BPSD is still not very clear, future aspects of treatment of BPSD may be positive. If we look at overall success rates of the antipsychotics, the traditional antipsychotics have the highest combined success rate of 63.1%, whereas the novel antipsychotics have an overall success rate of 56.1%. Haloperidol is the drug with the highest success rate of 65.4%, although this drug is associated with parkinsonian adverse drug reactions. Newer antipsychotics show promise in treating BPSD, but more convincing evidence (e.g. from randomised clinical trials) is required. We provide an overview of the clinical, epidemiological and economic aspects of BPSD and a review of the available literature on their pharmacological treatment. Although only 1 pharmacoeconomic study has been conducted on BPSD, it seems likely that these manifestations drastically increase the burden of dementia.

Aged↗

PubMed2000

Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality.

BACKGROUND: Several rare, potentially fatal types of hematologic dyscrasia, such as agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura (TTP), have been associated with ticlopidine therapy. The extent to which ticlopidine is the causative factor has not been addressed quantitatively. METHODS: We identified 211 published case reports of hematologic dyscrasia associated with ticlopidine therapy from a MEDLINE search. We analyzed the 91 reports that could be evaluated, using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability that ticlopidine caused the hematologic dyscrasia based on epidemiologic and clinical trial data (prior odds) and case information (likelihood ratio). RESULTS: The median posterior probability values (and range) for agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and TTP were 0.95 (0.53-0.98), 0.81 (0.57-0.93), 0.86 (0.75-0.96), 0.78 (0.61-0.89), 0.74 (0-0.92) and 1.0 (0.33-1.00) respectively. The posterior probability was 0.75 or greater in 82 (90%) of the case reports. INTERPRETATION: This systematic analysis provides stronger evidence to implicate ticlopidine as the causative factor in the various types of hematologic dyscrasia in most published case reports.

Bayes Theorem↗

PubMed2000

Donepezil for behavioural disorders associated with Lewy bodies: a case series.

Dementia with Lewy bodies (DLB) has been associated with important behavioural disturbances, such as psychotic symptoms. Unfortunately, neuroleptic sensitivity in these patients limits effective pharmacological management of these symptoms. Seven patients, five male and two female (mean age 75.3+/-4.7 years, range 68-81), diagnosed with DLB were treated with the acetylcholinesterase inhibitor donepezil (5-10 mg once daily) to determine its effect on treating behavioural disorders. Although the intended length of treatment was a minimum of 8 weeks, only three patients completed 8 weeks of therapy, one patient completed 6 weeks, two patients completed 4 weeks and one patient was discontinued after 5 days. The primary outcome (behavioural disturbances) was measured prospectively by the Neuropsychiatric Inventory (NPI), while other outcomes included cognition (Mini-Mental State Examination (MMSE)) and Clinical Global Impression. Three of the seven subjects showed marked improvement in behaviour, with NPI scores dropping significantly over time. Donepezil therapy was discontinued prematurely in three of the cases due to insufficient response and/or adverse events. Overall, five of the seven patients were rated at least minimally improved in behavioural symptoms. Our experience with donepezil in this group of patients shows promise. Given the limited experience with this agent in treating behavioural disorders associated with DLB, further studies are warranted.

Aged↗

PubMed2000

Probing peripheral and central cholinergic system responses.

OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients.

Adolescent↗

PubMed1998

Iatrogenic benzodiazepine withdrawal delirium in hospitalized older patients.

OBJECTIVE: The purpose of this review was to identify cases of benzodiazepine withdrawal delirium in a population of older hospitalized patients and to determine whether the withdrawal was caused by iatrogenic factors. DESIGN: Retrospective chart review of selected cases from a referred sample. A Bayesian Adverse Reactions Diagnosis Instrument (BARDI) was applied to cases of benzodiazepine withdrawal delirium to quantify the probability that drug withdrawal was the causative mechanism. SETTING: A university-affiliated health sciences center. PATIENTS: A review of the psychiatric consultation liaison service database for a consecutive 4-month period yielded 21 cases of delirium in a referred sample of 119 patients more than 65 years of age. Four cases of benzodiazepine withdrawal were identified within the group of patients with delirium, and retrospective chart review identified potential iatrogenic causes for withdrawal in three patients. RESULTS: The posterior possibilities calculated by the BARDI for the three cases of delirium were 0.98, 0.95, and 0.75, indicating a high probability that the delirium was caused by benzodiazepine withdrawal. CONCLUSIONS: Benzodiazepine withdrawal delirium in older hospitalized patients may be associated with iatrogenic factors.

Aged↗

PubMed1998

Efficacy and safety of neuroleptics in behavioral disorders associated with dementia.

BACKGROUND: Neuroleptics are commonly used to treat behavioral disorders associated with dementia. However, their safety and efficacy have not been well established in these patients. METHOD: A meta-analysis of randomized, controlled (either placebo or active drug), double-blind trials published since 1966 (N = 16; 499 treated, 112 active controls, and 123 placebo) was conducted. Data were collected on proportion of patients with clinically significant improvement, significant side effects, and dropout rates. RESULTS: Pooled mean percentages of patients who improved (95% CI): all neuroleptics, 64% (54% to 74%); low potency, 63% (54% to 72%); moderate potency, 70% (56% to 85%); moderate-high potency, 62% (49% to 75%); and high potency, 69% (49% to 90%). Thus, no differences in efficacy existed between different potencies of neuroleptics. Therapeutic effect (neuroleptic minus placebo) was only 26% (14% to 38%). Treatment-emergent side effects were more common for neuroleptics vs. placebo (mean difference = 25%, 13% to 37%), but pooled mean dropout rates were not different (mean difference = 4%, -7% to 14%). Neither weighting by clinical trial quality (3 raters; weighted agreement, 83% to 92%) nor exclusion of poor quality trials changed the results. CONCLUSION: Neuroleptics have small but significant efficacy over placebo in this population, and the efficacy rate is equivalent to the side effect rate. Comparing different neuroleptics shows they have similar efficacy, side effects, and dropout rates. Further study to determine more specific drug-responsive behaviors is needed to maximize benefits of these drugs.

Antipsychotic Agents↗

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

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↗

PubMed1995

Comparison of the Bayesian approach and a simple algorithm for assessment of adverse drug events.

The differential diagnosis of severe adverse drug events can be based on clinical judgment, algorithms, or the Bayesian approach. The Bayesian Adverse Reactions Diagnostic Instrument (BARDI) calculates the posterior probability (PsP) in favor of a specific drug cause based on background (e.g., epidemiologic) and case information (e.g., time of onset). Although BARDI discriminates between drug- and nondrug-induced adverse events, its apparent complexity may limit its use. BARDI results were compared with those from an algorithm for rating the probability that an adverse drug event is drug-induced (Adverse Drug Reaction Probability Scale, or APS) that is still commonly used. APS scores were obtained by two independent raters for 106 challenging cases that had been analyzed from 1 to 5 years ago with BARDI (91 cases of hypersensitivity, 12 cases of hematologic toxicity, and three cases of pulmonary toxicity); 130 ratings were generated because of the use of multiple drugs. APS scores for the two raters were highly correlated (r = 0.79; p < 0.0001). Probabilities of drug causation with use of BARDI versus average APS scores were significantly correlated (rs = 0.45; p < 0.0001). However, BARDI better distinguished cases that were highly probable (n = 83; PsP > or = 0.75) or highly improbable (n = 30; PsP < or = 0.25), whereas the APS rated the majority of these cases in the midrange (n = 128; range of APS, 1 to 8.9). These results suggest that APS and BARDI evaluations are concordant. Thus the APS may be an effective screening tool, although BARDI can better discriminate drug from nondrug-induced cases and may be more appropriate for serious cases of adverse drug reactions.

Algorithms↗

PubMed1995

Effects of citalopram and a brief psycho-social intervention on alcohol intake, dependence and problems.

Citalopram (C) decreased alcohol intake and desire to drink in short-term (2-4 weeks) studies with no other treatment. We tested the long-term effects of C combined with a brief psycho-social intervention. After a 2-week baseline, mildly/moderately dependent alcoholics (35 males, 27 females) were randomized, double-blind to 12 weeks of C 40 mg/day (n = 31) or placebo (P) (n = 31) and a brief psycho-social intervention with follow-ups at 4 and 8 weeks post-treatment. Alcohol intake was monitored daily and alcohol dependence (ADS) and problems (MAST) were assessed at intake and post-treatment. During the first week, the decrease (%) from baseline daily alcoholic drinks (mean +/- SEM) was greater with C (47.9 +/- 5.1 from 6.5 +/- 0.6) than with P (26.1 +/- 4.2 from 5.8 +/- 0.4) (p < 0.01). However, the 12-week decreases with C (35.1%) and P (38.8%) were similar. There were gender differences within the C group. The males had higher MAST scores at intake (mean +/0 SEM = 10.4 +/- 0.8; n = 15) than the females (6.4 +/- 0.9, n = 16) (p < 0.01) and were slightly heavier drinkers during baseline (7.1 +/- 0.9 vs. 5.9 +/- 0.9 drinks/day, NS). The response to C was greater in males (44% decrease) than females (26%) (p < 0.05) and correlated with MAST scores (r = 0.44, p = 0.01), but not with baseline alcohol intake (r = 0.2, NS). Craving and liking for alcohol and alcohol dependence (ADS) and problems (MAST) decreased similarly with C and P (p < 0.01). Thus, the short-term effects of C were replicated but no long-term effect was detected. Tolerance to citalopram, perhaps through some adaptive neurobiological changes, may have developed. The potential therapeutic use of C as a useful pharmacological adjunct in alcoholics remains to be determined.

Adult↗

PubMed1995

Ritanserin, a central 5-HT2 antagonist, in heavy social drinkers: desire to drink, alcohol intake and related effects.

Ritanserin, a 5-HT2 receptor antagonist, decreased alcohol intake in some, but not all, animal studies and in an open clinical study. We tested the short-term effects of ritanserin in 39 (35 male, four female) heavy social drinkers (consuming at least 28 drinks/week), aged 19-63 years, who were not seeking treatment. After an intake assessment, they received placebo for 7 days in a single-blind baseline. They were then randomly assigned to one of three double-blind treatments for 14 days: ritanserin 5 mg/day (n = 12), ritanserin 10 mg/day (n = 13) or placebo (n = 14). Subjects recorded daily outpatient alcohol intake. Feelings of intoxication and interest, desire, craving and liking for alcohol were rated retrospectively at each weekly study visit. Experimental drinking sessions were conducted after baseline (EDS1) and treatment (EDS2); in each session subjects were offered 18 mini-drinks (total = six standard) and rated their desire to drink, intoxication and mood (POMS). Outpatient results: ritanserin 5 mg/day decreased desire and craving for alcohol (vs. baseline, p < 0.05) but not alcohol intake. Liking of alcohol decreased from baseline with ritanserin 10 mg/day (p = 0.01) and placebo (p = 0.05). Changes in alcohol intake from baseline with ritanserin 10 mg/day (increase, p > 0.05) and placebo (decrease, p > 0.05) were different (p < 0.05). EDS results: in EDS2, desire ratings for the first three mini-drinks were lower after ritanserin 5 mg/day than after ritanserin 10 mg/day (p < 0.05), but the decreases were not statistically significant when EDS1 desire ratings were controlled for. Ritanserin 10 mg/day increased alcohol-induced feelings of intoxication and friendliness, compared with placebo (p < 0.05). Both ritanserin 5 mg/day and 10 mg/day enhanced alcohol-induced decreases in fatigue, compared with placebo (p < 0.05). These results indicate that ritanserin may have differential effects on alcohol intake, desire, craving and liking, intoxication and some of alcohol's effects on mood. However, they suggest that ritanserin has limited efficacy in reducing alcohol intake in heavy drinkers.

Adult↗

PubMed1994

Computer-assisted evaluation of adverse events using a Bayesian approach.

The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is complex because for each adverse event there are many possible drug and nondrug causes. Recently efforts have been made to computerize causality assessment methods. A new computerized, user-friendly diagnostic aid for Bayesian assessment of adverse drug events (MacBARDI-Q&A) is described. This computer program performs a differential diagnosis on cutaneous reactions suspected of being drug-induced. The authors' results indicate that development of a valid, simple and user-friendly computerized procedure for evaluating adverse drug events is possible. The ongoing development and application of MacBARDI-Q&A and other similar programs should improve the evaluation of putative adverse drug reactions.

Anticonvulsants↗

PubMed1994

Improving the diagnosis of hypersensitivity reactions associated with sulfonamides.

The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior probability (PsP) of a drug being the etiology of an idiosyncratic ADR. The other, the lymphocyte toxicity assay (LTA), is a biochemical test that determines the percent of cell death because of toxic metabolites of a drug. Cases were assessed independently and blindly by BARDI and then the LTA. Skin reactions consisted of 19 exanthematous eruptions, 2 vasculitis, 1 erythema multiforme, and 5 urticarial rashes. BARDI indicated that the drug was very likely associated with 20 adverse events (PsP = 0.59 to 0.99); and unlikely to have caused 7 (PsP = 0.02 to 0.38). The LTA showed that 19 patients (70%) were test positive, and 8 were test negative. Comparing BARDI to LTA showed that BARDI had 79% sensitivity and 67% accuracy, but only 38% specificity. However, when the results of the LTA were incorporated into the calculation of the PsP based on this comparison, BARDI indicated that the drug was very likely associated with 18 reactions (PsP = 0.61 to 0.99) and unlikely to have caused 9 reactions (PsP = 0.003 to 0.47). The agreement increased from 67% to 96%. These findings indicate that the accuracy of diagnosis of idiosyncratic ADRs improved when the results of BARDI and LTA were combined. These findings also crossvalidate the results obtained by using BARDI.

Adolescent↗

PubMed1994

Enhanced differential diagnosis of anticonvulsant hypersensitivity reactions by an integrated Bayesian and biochemical approach.

OBJECTIVE: The differential diagnosis of hypersensitivity reactions associated with anticonvulsants requires accuracy because of the many implications for patient management. We tested an integrated Bayesian and biochemical diagnostic approach. METHODS: The patients were analyzed clinically by two tests. One test, the Bayesian Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior probability of a drug being the cause based on epidemiologic and case data. The other, the lymphocyte toxicity assay, is an in vitro rechallenge that determines the percentage of cell death attributable to a drug's toxic metabolites. The setting for the study was an adverse drug reaction clinic at Sunnybrook Health Science Centre and the Hospital for Sick Children, Toronto, Ontario, Canada. Fifty-one patients who had hypersensitivity reactions after receiving aromatic anticonvulsants were tested. Four of these patients had more than one reaction reported, with different anticonvulsants generating 56 distinct events. RESULTS: Compared to the lymphocyte toxicity assay, BARDI had 94% sensitivity, 93% accuracy, and 50% specificity. When lymphocyte toxicity assay data were incorporated into BARDI, agreement rose from 93% to 100%. BARDI also identified which drug was a more likely cause for 11 patients receiving multiple anticonvulsants. CONCLUSION: These findings show that BARDI and the lymphocyte toxicity assay have high concordance and, when used in an integrated approach, these tests can improve the diagnostic accuracy and enhance the management of patients with hypersensitivity reactions.

Adolescent↗

PubMed1993

Comparative study on benzodiazepine use in Canada and Chile.

Benzodiazepines are the most prescribed psychotropic drugs in the world. Comparative international data on benzodiazepine use, specifically among developed and developing countries, are unavailable. To determine the different patterns of benzodiazepine use in two representative countries, use of benzodiazepines in Chile (a developing country) and Canada (a developed country) was undertaken. Wholesale data as provided by the Intercontinental Medical statistics and drug import data were used as databases. Data on trends of benzodiazepine use was determined for 5 years using the methodology recommended by the WHO for drug use research, the defined daily dose/1000 inhabitants/day. Total benzodiazepine use was similar in both countries, but Canadian use had increased slowly. Patterns of use, however, differ widely among the two countries. A linear increase of rapidly eliminated benzodiazepines was observed in Canada, whereas the reverse occurs in Chile: the slowly eliminated benzodiazepines are the ones that have increased use. Hypnotic benzodiazepines are used twice as frequently in Canada than in Chile. Striking differences in the use of individual benzodiazepines are observed. Differences in healthcare systems determine wide differences in the way these drugs are prescribed. Demographic characteristics of the two countries also may account for the differences in benzodiazepine use. The authors conclude that, although total benzodiazepine consumption is similar in the two countries, patterns of benzodiazepine use vary widely. The different patterns of use may determine differences in the morbidity rates associated with the use of these drugs.

Anti-Anxiety Agents↗