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PubMed1978

Tardive dyskinesia and psychotropic drug history.

The adult population of a large mental hospital was screened for tardive dyskinesia (TD). Approximately 11% of the hospital population showed signs of TD; females and the elderly were over-represented in the TD group. A representative sample of those with TD was selected and a control (non-TD) patient was chosen to match each of the TD subjects in age, sex, length of hospitalization, diagnosis, and race. The charts of these subjects were searched for any indices of brain damage and the complete psychotropic medication history was recorded. There was no difference between the TD and controls in the amount of psychotropics ingested, in the duration of administration, in the kinds of drugs, or in the organicity history. Women as a group, however, tended to have more polypharmacy than men. The role of neuroleptics in TD is discussed as well as other possible etiological factors.

Adult↗

PubMed1989

Agranulocytosis and significant leucopenia with neuroleptic drugs: results from the AMUP program.

In the Federal Republic of Germany adverse drug reactions (ADR) have been continuously assessed at the departments of Psychiatry of Berlin and Munich since May 1979. About 13,000 neuroleptic-treated inpatients were monitored until August 1988. Approximately 1100 patients were exposed to clozapine, 6800 to haloperidol and 6000 to perazine, the two most frequently used neuroleptic drugs. In this 9-year period seven cases of agranulocytosis were observed, all in women. One case occurred with clozapine in monotherapy, the other six with perazine, three times in monotherapy, once in combination with trimethoprim/sulfamethoxazole and in one case each in combination with tricyclic antidepressants. Significant leucopenia (less than or equal to 3000/mm3) was observed in an additional eight cases. On four occasions each butyrophenones (twice in combination with TCA) and tricyclic neuroleptics (once in combination with TMS) were involved. The number of exposed patients per drug is too small for calculation of statistically valid incidence rates, especially in view of the frequent polypharmacy. The course of agranulocytosis was benign in all seven cases and required no other treatment than drug withdrawal in three cases. The early detection by regular WBCs is supposed to be mainly responsible for this and is therefore recommended at weekly intervals. This measure of safety appears most important for all medium potency tricyclic neuroleptics. As to treatment of agranulocytosis, additional measures (antibiotics, intensive medical care) depend upon the severity of the clinical picture.

Adult↗

PubMed1987

Psychomotor impairment and anticonvulsant therapy in adult epileptic patients.

Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p less than 0.05; p less than 0.001), card sorting (p less than 0.01; p less than 0.001), Simple Simon (p less than 0.05; p less than 0.001) and finger tapping (p less than 0.05; p less than 0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially "toxic" plasma anticonvulsant concentrations did no worse than those within or below the "therapeutic" range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on "quality of life" should not be neglected in the pursuit of perfect seizure control.

Adolescent↗

PubMed1989

Thyroid hormone concentrations in epileptic patients.

Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volunteers were included as controls. Total thyroxine (T4) concentrations were reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin) compared with both controls and patients taking sodium valproate. Similar differences were shown with each individual drug. All nine patients whose circulating T4 was below the lower limit of the reference range were taking enzyme inducers. Free thyroxine concentrations were also reduced in individuals treated with carbamazepine and phenytoin with five values falling beneath the reference range. Tri-iodothyronine and thyrotropin appeared unaffected by anticonvulsant administration. Thyrotropin releasing hormone stimulation revealed no true hypothyroidism. The lowering effect of anticonvulsant drugs on circulating total and free T4 was not exhibited by the non-inducing sodium valproate. These data support the influence of enzyme induction as a likely mechanism for reduced thyroxine concentrations in treated epileptic patients.

Anticonvulsants↗

PubMed1986

Consistency of assessment of adverse drug reactions in psychiatric hospitals: a comparison of an algorithmic and an empirical approach.

Within an ongoing drug surveillance project (AMUP) in psychiatric hospitals, a comparative study was carried out to evaluate two methods commonly used in the field of adverse drug reaction assessment. Two raters, who have cooperated with the project since its inception, evaluated 80 randomly selected ADRs twice; first, by an empirical (implicit) approach, and second, 4 weeks later, by using an algorithm as proposed by Kramer et al. 1979. Agreement on medication and related probability ratings was obtained in 81% of all 80 cases for the empirical method (weighted Kappa = 0.41), and in 69% for the algorithmic method (weighted Kappa = 0.62), indicating that agreement exceeded chance for both methods. By comparison with assessments made in previous case conferences of the project, empirical ratings were found to be reliable over time due to homogeneous use of criteria by project raters. In contrast to the reports on the subject, agreement between raters appeared to be superior in the empirical method as compared to the algorithmic assessment. Analysis of disagreements suggested that probability ratings based on the empirical method were nonspecific, due to conventional criteria applied in the project. Inter-rater agreement was reduced by polypharmacy, especially in the case of algorithmic assessments. The consistency of assessment was also lowered by the fact that the 2 methods assigned different weights to particular assessment criteria.

Drug-Related Side Effects and Adverse Reactions↗

PubMed1996

Psychotropic drug prescription in rehabilitation. A survey in Hong Kong.

Rational pharmacotherapy helping chronic psychiatric patients in the difficult process of reintegration into the community is an important prerequisite of successful rehabilitation. Results of a survey conducted at the opening of a rehabilitation facility in Hong Kong revealed a number of illogicalities in prescription patterns. Frequently encountered faulty treatment decisions incompatible with the recommendations of modern literature included polypharmacy, higher than necessary doses of anticholinergic antiparkinsonian agents and giving psychotropic drugs in inconveniently divided doses. With the newly emerging subspecialty of rehabilitation-community psychiatry in Hong Kong, it is expected that large numbers of chronically hospitalized patients will enter rehabilitation programmes. The present survey indicated that it is imperative to pay continued attention to their medication status.

Adult↗

PubMed1978

Drug utilization in a general intensive care unit.

Drug utilization in 200 general ICU patients was retrospectively studied. One hundred and two different drugs were prescribed with a mean of 7.0 +/- 4.6 drugs/patient. The potential for polypharmacy and drug interactions is discussed, as is the cost of such therapy.

Adolescent↗

PubMed2004

P-glycoprotein-based drug-drug interactions: preclinical methods and relevance to clinical observations.

Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

[Detection and evaluation of adverse drug reactions].

Adverse drug reactions (ADRs) occur in about 5% of drug-treated patients. Hospital admissions are caused by ADRs in 5% of patients and roughly 2% of hospitalized patients will experience an ADR. The economic burden of ADRs can only be estimated. Type A reactions can be explained by the pharmacological action of the drugs, and are preventable in many cases. However, Type B reactions involving the immune system and/or idiosyncratic reactions occur rarely and most of them are not fully understood. Genotyping represents an elegant method to explain the presence of abnormal enzyme activities and allows prediction of adverse drug effects in individual cases. Typical time frames have been identified for the occurrence of hypersensitivity reactions, although definite causality assessment is often impeded due to the absence or unavailability of specific laboratory tests and the impossibility of rechallenge. Diagnosis of an ADR is often difficult due to comorbidity and polypharmacy, thus causality assessment is often divergent even between specialists. In Germany, ADRs are reported preferably to the manufacturer of the suspicious drug and then collected and evaluated at the Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM. However, total number and quality of reported ADRs could be improved.

Adverse Drug Reaction Reporting Systems↗

PubMed1991

Accidents in the institutionalized elderly: a risk analysis.

Among a total of 4,862 admittances to a Swedish geriatric hospital and its associated nursing homes, 827 accidents occurred in 588 patients during one year. The purpose of the present study was to establish the direct causes of these accidents and to identify possible risk factors. Information was collected from medical records, interviews with patients and staff, examination of the mental and physical state of the patients, and through reconstruction of the accidents. The investigation embraced 270 patients with 308 major accidents (fractures, sprains, open wounds, concussions and injuries to ligaments), and 318 patients with 519 minor accidents (bruises, contusions, abrasions and minor burns). Injury-free patients with nearest lower bed number in relation to patients with major accidents formed a control group. Patients with previous injuries, balance disturbances, and polypharmacy were at high risk, and intrinsic factors such as dizziness and impaired balance proved to be more significant as direct causes for the occurrence of accidents than environmental factors. The estimated risk for a patient with all these risk factors to have an accident during one year was 94%.

Accidents↗

PubMed2005

[Interactions of cardiac and antiretroviral medication].

New therapeutic options such as the highly active antiretroviral therapy (HAART) have significantly improved morbidity and mortality of HIV-infected patients. Consequently, age-related diseases become more manifest. In addition, HIV infection itself causes certain cardiovascular morbidity. Therefore, treatment of cardiovascular symptoms of HIV-positive patients becomes more and more important. Pharmacotherapy in these patients is complex and requires polypharmacy with drugs carrying a high risk of drug-drug interactions.

Anti-Retroviral Agents↗

PubMed2006

[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy].

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.

Administration, Oral↗

PubMed2003

[Drug interactions and the anesthesiologist].

Modern anesthesiology employs the combined administration of several drugs belonging to different pharmacological classes. Additionally, anesthesiologists are facing the challenge of polypharmacy regimens utilized by patients considered for surgical treatment When drugs are combined, the pharmacological effect may considerably differ from the individually expected properties. This may be beneficial or potentially lead to adverse drug reactions harming the patient. The incidence of drug interaction increases exponentially with the number of drugs administered. Depending on the mechanism involved, drug interactions can be classified as pharmaceutical, pharmacodynamic, or pharmacokinetic. Although there are enormous possibilities for adverse drug reactions nd the complexity is hard to identify, prediction of drug interaction is possible. Besides recognizing the general risk factors, fundamental knowledge of basic and clinical pharmacology is important to prevent serious or fatal drug interactions before they occur.

Anesthetics↗

PubMed2002

The role of oral antidiabetic agents: why and when to use an early-phase insulin secretion agent in Type II diabetes mellitus.

Evidence obtained in the 1990's strongly supports the notion that glycaemic control is important not only in Type I (insulin-dependent), but also in Type II (non-insulin-dependent) diabetes mellitus. Although measurement of HbA(1c) is the standard for assessing the effect of glucose control in the occurrence and prevention of diabetic sequelae, more recent evidence indicates that other glucose parameters are also important. Postchallenge and postprandial hyperglycaemic peaks seem to be prospective determinants of vascular damage in early Type II diabetes. Currently, there is no overall accepted standard approach for the pharmacological management of Type II diabetes. The United Kingdom Prospective Diabetes Study has shown that reaching a near-normal glycaemic target is critically important and the pharmacotherapy of this progressive disease is difficult. Loss of endogenous insulin secretion has been substantiated to cause the progression of Type II diabetes in the United Kingdom Prospective Diabetes Study. Early insulinization, however, was not advantageous over other forms of therapy. The advent of polypharmacy in recent years has greatly strengthened the treatment of this disease. This synergy has been extended of late with the development of early-phase insulin secretion agents. Two such agents, nateglinide and repaglinide, can be used to reduce mealtime glucose excursions and HbA(1c) as monotherapy, and in combination with metformin; their antidiabetic potential is similar to the combination treatment with glibenclamide and metformin. Additional substantiation of their long-term effect on improving life expectancy and reducing diabetic complications in Type II diabetic patients is now required.

Blood Glucose↗

PubMed2004

Establishing the compliance in elderly women for use of a low level mechanical stress device in a clinical osteoporosis study.

Non-pharmacologic approaches to prevent bone loss are well suited for elderly patients to avoid polypharmacy and medication side effects. One potential treatment is a vibrating platform that delivers low-level mechanical loading stimulating bone remodeling. However, compliance is a major concern with any daily treatment, and is unknown for an elderly group using this device. Thus we assessed compliance with standing 10 min/day on a vibrating platform device in elderly women, the target population for osteoporosis therapy. We also assessed satisfaction with daily use of the device. We conducted a randomized, placebo-controlled, double-blinded 6-month study for daily use of a 10-min vibrating platform treatment in elderly women who were residents of a Continuing Care Retirement community. Compliance for each subject was calculated as the number of days attended divided by the 182 days in the 6-month trial. The 24 elderly women (mean age 86, range 79-92 years) had 83% compliance (95% CI: 70.5, 94.5) for daily treatment over 6 months. Excluding three study drop-outs, the 21 women had 93% compliance (95% CI: 89.8, 95.6), with no difference in compliance between active and placebo treatment. Main reasons for missing treatment days over the 6 months were vacation (54% of missed days) and illness (29%). Three adverse events occurred; one (syncope) was possibly related to device use, whereas the other two were not related to device use. Among participants, 95% reported overall satisfaction with daily use of the vibrating platform, and 57% preferred the platform versus daily oral medications for prevention of bone loss. Elderly women showed high compliance, high satisfaction and few adverse experiences with a daily non-pharmacological treatment designed to inhibit bone loss. Larger randomized controlled trials should evaluate the long-term efficacy of vibrating platform devices for treatment of low bone mass and osteoporosis in elderly individuals.

Aged↗

PubMed2005

Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia.

RATIONALE: Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. OBJECTIVE: To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. METHODS: Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. RESULTS: Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. CONCLUSIONS: The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia.

Adult↗

PubMed2005

Reliability of a modified medication appropriateness index in primary care.

OBJECTIVE: To evaluate the inter-group and intra-group reliability of a modified Medication Appropriateness Index (MAI) for use in primary care. METHODS: Elderly (>65 years) polypharmacy (> or =5 drugs) patients in Copenhagen County participated in the study. Information concerning their medical history and information regarding each drug taken by them was provided by their own general practitioners. A MAI was scored by two groups of evaluators for every drug. To evaluate inter-group agreement, 211 drugs taken by 30 patients were rated according to the ten criteria making up the MAI. Both evaluator groups provided summaries of comments on the medication of each patient. Intra-group agreement was determined from MAI ratings performed twice at two different times on 86 drugs taken by ten patients. Agreement and chance-adjusted agreement were determined, the latter through kappa statistics. The proportion of positive (ppos) and negative (pneg) agreement was also determined. RESULTS: The overall chance-adjusted inter-group agreement (kappa) was moderate. The agreement was good on the criteria practical directions and drug-disease interaction, moderate on the criteria dosage and duration, fair on the criteria indication, effectiveness, duplication and expense, and poor on the criterion drug-drug interaction. The overall chance-adjusted intra-group agreement was good for all criteria and very good for the criteria indication and practical directions. CONCLUSION: The MAI is used to quantify appropriate and inappropriate prescribing and changes in prescribing quality in intervention studies. However, caution should be used when comparing results across different settings and evaluators. Our study suggests that the index should only be used in intervention studies if the same group rates the appropriateness pre- and post-intervention.

Aged↗

PubMed2000

Tuberculosis in the elderly.

Tuberculosis (TB) today remains one of the world's most lethal infectious diseases. An estimated one-third of the world's population is infected with the tubercle bacillus-Mycobacterium tuberculosis (Mtb), and 7 to 8 million people develop TB disease each year (27). For purpose of clarity, TB infection (latent TB) is defined as harboring Mtb without evidence of active infection, and TB disease is active infection without Mtb based on clinical and laboratory findings. Recognizing that TB has been one of the most neglected international health problems and that the TB epidemic is rampant in many parts of the world, the World Health Organization (WHO) declared TB to be a global health emergency in 1993 (23). Despite the steady decline in TB cases since this time resulting from the overall implementation of more effective infection control practices, directly observed therapy (DOT), and efforts to control the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic, preventive and control strategies among other high-risk populations such as the elderly evidently remain a clinical and epidemiological challenge. The geriatric population among all ethnic groups and both genders, represent the largest reservoir of TB infection, particularly in developed nations (9). Clinical features of TB in older adults may be atypical, non-specific, and confused with concomitant age-related diseases (28). Underlying acute or chronic diseases, malnutrition, and the biological changes with aging, can disrupt integumental barriers, impair microbial clearance mechanisms, and contribute to the expected age-associated decline in cellular immune responses to infecting agents such as Mtb. Diagnosis of TB can be difficult and consequently overlooked; this treatable infection may unfortunately be recognized only at autopsy. Furthermore, therapy of TB in the elderly is challenging because of the increased incidence of adverse drug reactions. Optimal treatment of associated chronic diseases, minimization of invasive procedures, limitation of polypharmacy, and adequate nutritional support are essential for this vulnerable population. The institutionalized elderly in addition are especially at high risk for reactivation of latent TB as well as susceptible to new TB infection. This article will discuss the global epidemiology, pathogenesis and immunologic aspects, unique clinical consideration, treatment and prevention of TB, briefly inclusive of the recent published guidelines for targeted tuberculin testing and treatment of latent TB infection as it pertains to the elderly.

Aged↗