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Monotherapy treatment of bipolar disorder with levetiracetam.

Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and mixed episodes are difficult to treat and frequently require rational polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant with antikindling, inhibitory, and neuroprotective properties that is effective in an animal model of mania. This case report describes a patient with treatment-resistant rapid cycling bipolar disorder who failed 15 psychotropics, individually or in various combinations (maximum of 6), but ultimately responded to levetiracetam monotherapy and remained without bipolar features during 1 year of maintenance treatment, excluding 1 week during which the patient was medicine noncompliant. Further, methylphenidate used to treat comorbid attention deficit disorder did not precipitate manic features. Levetiracetam should be further studied for its potential use in the treatment of bipolar disorders.

Adult↗

Assessment of a 1-year teaching programme in Zanzibar, Tanzania.

We assessed whether a 1-year teaching programme in northern Zanzibar would improve prescribing practice. Data on polypharmacy and appropriateness of the treatment of upper-respiratory infection, anaemia, and scabies from the 17 primary health-care units in northern Zanzibar were analysed before and after the teaching programme. There was a significant and sustained reduction in polypharmacy and an improvement in the treatment of upper-respiratory infection, scabies, and anaemia. This teaching programme has been successful in improving prescribing practices in a less-developed country.

Anemia↗

The use of drug monotherapy in psychiatric inpatient treatment.

OBJECTIVE: Monotherapy has always been the goal in psychiatric drug treatment, but it does not seem to be very common in everyday practice. METHOD: The available literature on the frequency of monotherapy or polytherapy with psychotropic agents in psychiatric inpatient treatment is reviewed. FINDINGS: Taken all together (28 studies on 42 treatment facilities), the mean number of psychotropics prescribed was 2.47, the rate of monotherapy was 36.2% and 37.9% of inpatients received > or = 3 different drugs. Comparing the last three decades, a significant decline of the rate of monotherapy was found, topping at 47.8% in the 70s and falling to 19.6% in the 90s. The mean number of psychotropic drugs prescribed rose from 2.2 to 2.9 and the number of patients receiving > or = 3 psychotropics rose from 27.5 to 49.7%. CONCLUSION: Though it is still mandatory to avoid unsound polypharmacy, we must assume that the occasions for polypharmacy are increasing. New psychotropic drugs, increasing comorbidity and augmentation strategies may be incentives for polydrug use. Since in most countries the number of psychiatric beds declines, inpatient treatment has to deal with the most severe, often treatment-resistant patients requiring special therapies.

Drug Therapy, Combination↗

Overtreatment in epilepsy: adverse consequences and mechanisms.

The most important determinant of quality of life in patients with epilepsy is complete seizure control, and therefore this should be the ultimate goal of pharmacological therapy. Seizure freedom, or a reduction in seizure frequency, however, should not be sought at all costs, and the situation should never arise where a person with epilepsy is made to suffer more from the side effects of treatment than from the consequences of the underlying disease. Overtreatment is not uncommon in patients taking antiepileptic drugs, and it may occur in many forms and with a variety of mechanisms. Long-term use (or continuation) of anticonvulsant therapy in situations where it is not indicated (e.g. in children with simple febrile seizures, or in non-epileptic seizure-free patients who underwent brain surgery) constitutes a blatant case of overtreatment. Other forms of overtreatment include the use of unnecessarily fast dose escalation rates, which may expose the patient to potentially serious or severe side effects, or the prescription of unnecessarily high maintenance dosages. The latter occurrence may result from inadequate understanding of dose-response relationships, from misinterpretation of serum drug concentrations (e.g. targeting concentrations within the 'range' in patients who are well controlled at lower concentrations) or, at times, from failure to recognize a paradoxical increase in seizure frequency as a manifestation of drug toxicity. The most common form of overtreatment, however, involves the unnecessary use of combination therapy (polypharmacy) in patients who could be treated optimally with a single drug. Adverse effects associated with polypharmacy often result from undesirable drug-drug interactions. While pharmacokinetic interactions are somewhat predictable and can be minimized or controlled by monitoring serum drug concentrations and/or dose adjustment, pharmacodynamic interactions leading to enhanced neurotoxicity (as seen, for example, in some patients given a combination of lamotrigine and carbamazepine) can only be identified by careful clinical observation. There is evidence that not all antiepileptic drug combinations are equally adverse, and that the combined use of specific drugs (e.g. lamotrigine and valproic acid) may even exhibit an improved therapeutic index compared with either agent given alone, provided appropriate dose adjustments are made. Although the suggestion has been made that adverse effects are more likely to result from combining anticonvulsants having a similar mode of action, our knowledge of the pharmacology of individual agents is insufficient to allow a reliable prediction of the clinical effects of specific drug combinations.

Anticonvulsants↗

An evaluation of community pharmacy records in the development of pharmaceutical care in The Netherlands.

An electronic patient database linking prescribes with a Dutch community pharmacy consortium was evaluated in a subset of the population of Noordwijk (11,760 patients out of a total of 25,600). The pharmacy database (a file of 41 disease contra-indications representing a subset of the prescribers' medical diagnosis) was studied in order to assess its value for the accurate discrimination of target patient groups within the community and for support to the pharmaceutical care of individual patients. The aim was to examine the application of the pharmacy records to pharmaceutical care, tested by measuring the accuracy of the pharmacy database to predict the community public health profile; and, more specifically, the accuracy to identify three potential target groups for pharmaceutical care. The records of patients with angina, chronic respiratory disease and diabetes (n = 1116), representing 65% of the total pharmacy morbidity records, were studied in detail and verified by the files and texts of the prescriber's individual patient records. From samples of patients (n = 273) from the three patient groups, the extent and nature of co-morbidity, polypharmacy (drug entities prescribed annually) and drug therapy instability (prescription changes to dose or dose form annually) were characterised. Angina patients showed the most comorbidity, 46% having three or more additional diseases; chronic respiratory disease patients showed most drug therapy instability; and insulin-dependent diabetic patients received most polypharmacy per disease. The pharmacy database predicted the prevalence of 10 of 23 relevant disease categories (representing 51% of the total morbidity on the medical records). However, the prevalences of eight categories were underestimated and of five categories overestimated. Of the three patient groups, 73% of patients appeared on both the pharmacy and the medical database. Of the total co-morbidity recorded for these patients, 68% of records were common to both databases. The database discrepancies (32%) were due to morbidity omitted (12%) and morbidity unverified (10%) on the pharmacy database, together with morbidity omitted from the medical database (10%). The current pharmacy database provides a limited view of morbidity. A strategic approach to pharmaceutical care requires pharmacists and prescribers to verify and share patient information if patient groups and individuals within a group are to be usefully targeted.

Cardiovascular Diseases↗

Pharmacotherapy of inpatients with bipolar depression.

The pharmacotherapy of bipolar depression has not been well studied. Controlled studies support the efficacy of some antimanic and antidepressant drugs, but these studies usually exclude patients typically seen in nonresearch settings. The purpose of this study was to examine the pharmacotherapy of 69 inpatients with bipolar depression. More than 90% of the patients received at least one antimanic drug, and lithium was used most frequently. Only one-half of the patients received antidepressants. Three-quarters of antidepressant-treated patients received serotonin reuptake inhibitors or other nontricyclic drugs. There were few differences between antidepressant- and non-antidepressant-treated patients. Psychotic patients were more likely to receive lithium, neuroleptics, and anticholinergics, whereas nonpsychotic patients tended to receive anticonvulsants more often. Psychotic patients were also more likely to receive polypharmacy. These results suggest that polypharmacy of inpatients with bipolar depression is common, and that psychosis is an important variable in the choice of pharmacotherapy.

Adult↗

[Pharmacokinetics and pharmacodynamices in the elderly].

Pharmacokinetic and dynamic alterations, the appearance of multiple illnesses which are treated with polypharmacy and, possibly as a consequence of polypharmacy, impaired compliance with drug therapy are associated with a higher incidence of drug-drug interactions and adverse drug reactions in geriatric patients. The most important among these alterations are discussed and possible solutions are presented.

Adult↗

Self-reported medication use for older people in England and Wales.

OBJECTIVES: To describe the patterns of self-reported medication use, including both prescription and non-prescription drugs, for older people in five areas in England and Wales, and to identify the effects of socio-demographic features on medication use. DESIGN: A cross-sectional survey on population random samples of people aged 65 and over. The survey is a part of the screening interviews at the first stage of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) carried out between 1991 and 1994. The sample was stratified to provide equal numbers in the 65-74 years and 75 years and over age groups. SETTING: Three urban (Newcastle, Nottingham and Oxford) and two rural (Cambridgeshire and Gwynedd) centres. Older people living in both the general community and institutions were included. PARTICIPANTS: 12489 older people whose medication data were collected among the 13009 participants of the CFAS, of which the participation rate is 80%. RESULTS: Overall prevalence of medication use was 75% (95% confidence interval 74-76%) for people aged 65-74 and 84% (83-85%) for people aged 75 and over, with a mean number of 2.03 (standard deviation 1.95) and 2.47 (2.02) drugs reported per respondent in each group, respectively. Concurrent use of five or more drugs (polypharmacy) was found in 11% (10-12%) of people in the 65-74 age group and in 15% (14-16%) in the 75 and over age group. People aged 75 and over were more likely to be taking at least one drug than people aged 65-74 (OR=1.69, 1.54-1.85), and women were more likely to be so compared with men (OR=1.43, 1.30-1.56). Centre variation was found but none of the centres consistently showed higher or lower usage of medications across the major drug categories. People living in institutions were more likely to be taking gastrointestinal drugs, central nervous system drugs and experience polypharmacy. The use of respiratory and central nervous system drugs (except hypnotics and anxiolytics) increased in lower social class and decreased in people attending full-time education for 10 years or more. The use of haematology/dietetic drugs (85% of which were vitamin and mineral preparations) decreased in lower social class. CONCLUSION: This study provides representative estimates of medication usage among older people in England and Wales and identified associated factors and regional variations for medication use in a category-specific manner. The findings, suggesting the existence of centre variation and the association between type of accommodation, social class and medication use warrant further investigation.

Age Factors↗

Divalproex sodium: migraine treatment and monitoring.

Divalproex sodium is an effective drug for the treatment of migraine. Most adverse drug events are transient and not of great clinical concern. Although rare, well-documented examples of liver toxicity have been reported in children under 2 years of age on polypharmacy. Additional cases occur in children under 10 who are receiving polypharmacy, particularly those who have intractable seizures and degenerative central nervous system disease. Clinicians who treat migraineurs with divalproex sodium do not need to be overly preoccupied with monitoring of drug levels and liver function tests. The most valuable test is clinical observation of the patient.

Adolescent↗

Changing patterns of psychotropic medications prescribed by child psychiatrists in the 1990s.

The active (1994) and closed (1988 to 1992) outpatient records of youths seen in four separate community mental health centers (CMHC) in Baltimore County, Maryland were reviewed in mid-1994 to document recent changes in the medication-prescribing practices of local child psychiatrists. Inpatient summaries of previously hospitalized CMHC youths were also reviewed to supplement the outpatient medication assessment with hospital data. This regional survey of medication treatments in child psychiatry revealed that, during the half decade before 1994, there was an increase in overall psychotropic medication treatment, multiple concurrent medication treatments (polypharmacy), and antidepressant treatment with serotonin reuptake inhibitors (SRIs). Inpatient youths were consistently prescribed more psychotropic medications and diagnosed more frequently with major depressive disorder than outpatients. Medications typically used to first treat mood disorders became the predominant medication prescribed for both outpatients and inpatients by child psychiatrists in 1994, leading to a proportional decline in prescribed stimulant treatment. The shift from tricyclic antidepressants to SRI antidepressants in the 1990s by child psychiatrists matches the same recent practice shift by adult psychiatrists. Likewise, the increased prescription of drugs to treat mood disorders and the increased rate of polypharmacy notable of late among child psychiatrists now also mirrors adult psychiatry practice. Wide geographic variations in neuroleptic and antidepressant medication patterns were noted, even among facilities in the same metropolitan region. After psychiatric hospitalization, most youths who continued treatment at a CMHC outpatient clinic discontinued their inpatient medications within 3 months; the sole exception were children who had been placed on psychostimulants.

Adolescent↗

Factors predictive of outcome on admission to an acute geriatric ward.

AIM: To investigate which factors predict outcome of elderly patients on discharge and at 6 months. METHODS: A prospective study in an acute geriatric ward. Within 48 h of admission, patients were assessed for social factors, geriatric problems, admission diagnoses, medication, function and mental ability. Outcome measures were mortality, length of stay, institutionalization, readmissions and attendance at accident and emergency within 6 months. RESULTS: 353 patients were studied, with a mean age of 81.8 years. Logistic regression analyses showed that variables predicting hospital mortality were Barthel index on admission, pre-morbid disability and polypharmacy. The only variable independently predictive of prolonged stay in hospital was a Barthel score of <45 on admission. Functional disability on admission was predictive of institutionalization on discharge. Variables predicting mortality within 6 months of discharge were Barthel index on admission <65, presence of pressure sores, malnutrition and polypharmacy. Variables independently predictive of institutionalization were mental state and a low pension. Those who took more than five drugs on admission were more likely to attend accident and emergency and be readmitted. CONCLUSION: Limited activities of daily living and geriatric problems on admission are the strongest predictive factors of outcome, independent of diagnoses.

Aged↗

Medication management at home: medication-related risk factors associated with poor health outcomes.

BACKGROUND: Some patients may have medication-related risk factors only identified by home visits, but the extent to which those risk factors are associated with poor health outcomes remains unclear. OBJECTIVE: To determine the association between medication-related risk factors and poor patient health outcomes from observations in the patients' homes. DESIGN: Cross-sectional study. SETTING: Patients' homes. SUBJECTS: 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. METHODS: Medications and medication-related risk factors were identified in the patients' homes by community pharmacists and general practitioners (GPs). The medication-related risk factors were examined as determinants of patients' self-reported health related quality of life (SF-36) and their medication use, as well as physicians' impression of patient adverse drug events and health status. RESULTS: Key medication-related risk factors associated with poor health outcomes included: Lack of any medication administration routine, therapeutic duplication, hoarding, confusion between generic and trade names, multiple prescribers, discontinued medication repeats retained and multiple storage locations. Older age and female gender were associated with some poorer health outcomes. In addition, expired medication and poor adherence were also associated with poor health outcomes, however, not independently. CONCLUSION: The findings support the theory that polypharmacy and medication-related risk factors as a result of polypharmacy are correlated to poor health outcomes.

Adult↗

Screening for hospitalization and nutritional risks among community-dwelling older persons.

BACKGROUND: The potential for the use of nutritional screening to identify older persons at risk of hospitalization has not been contrasted with the use of tools developed for predicting hospital admissions. OBJECTIVE: Our goal was to compare the associations of items from the Level II Nutrition Screen (LII) and the Probability of Repeated Admissions (P(ra)) questionnaire with the outcome of hospitalization. DESIGN: This was a cohort study of participants in a Medicare managed-risk health plan who completed both the LII and P(ra) (n = 386). All hospitalizations within 1 y of screening were recorded. Hierarchical multivariate logistic regression was used to model associations with hospitalization. RESULTS: P(ra) items that retained significant associations with hospitalization were self-reported health, hospitalization in the past year, and >6 doctor visits in the past year (positive predictive value: 20%; sensitivity: 53.1; specificity: 69.7). LII items that retained significant associations with hospitalization were eating problems and polypharmacy (positive predictive value: 17.9%; sensitivity: 58.0; specificity: 56.3). Those persons designated by the P(ra) score as being at high risk of hospitalization (P(ra) > or = 0.30, 75th percentile) were also more likely to report weight loss, polypharmacy, consumption of a special diet, and functional limitation on the LII. CONCLUSIONS: Retained items from the P(ra) and the LII were comparable in identifying participants at risk of hospitalization. These observations suggest that nutritional risk factors such as eating problems, weight loss, and consumption of special diets should be considered in the management of older persons at risk of hospitalization, irrespective of the screening approach selected.

Aged↗

Predicting mortality and length of stay of geriatric patients in an acute care general hospital.

Three-hundred-eight geriatric patients (mean age = 76.7 yr, range = 70-94 yr) consecutively admitted to an acute care general hospital were followed up to identify the predictors of in-hospital mortality and long stay. Sociodemographic, medical, and functional data were collected within 24 hours from admission and their correlation with the outcomes assessed by logistic regression analysis. The following variables were shown to be independent predictors of death: use of more than 6 drugs (odds ratio = 3.04, confidence limits = 1.05-8.76); abnormal Mini-Mental State score (o.r. = 1.72, c.l. = 1.05-1.83); low ADL score (o.r. = 2.4, c.l. = 1.07-5.56). Extended stay was significantly and independently predicted by polypharmacy (o.r. = 1.94, c.l. = 1.18-3.2) and comorbidity (o.r. = 2.06, c.l. = 1.24-3.38). The mortality rates of patients with cognitive impairment and polypharmacy with or without functional impairment were 40% and 22%, respectively. The proposed method allows identification of high-risk geriatric inpatients by a simple medical and functional assessment on admission.

Activities of Daily Living↗

Clinical trials to study pain in patients with advanced cancer: practical difficulties.

Cancer is a common cause of death in our society and associated pain is prevalent in cancer patients. Despite this, pain is often not treated optimally. Although education (patient and caregiver) might improve the situation, many difficulties remain in carrying out clinical trials of new drugs or therapies in this particular group of patients. Appropriate controlled clinical trials need to be designed to maximise validity (randomised, blinding, quality of collected data, enough evaluable patients, statistical analyses) and effectiveness. Patient numbers are often small, the diseases and mechanisms of pain non-homogenous, and assessment techniques and analgesic requirements (and tolerance) may be variable. Furthermore, pain may be unstable, polypharmacy is often involved, behavioral and other cognitive factors may change, patient compliance may be suspect, and side effect profiles may be difficult to interpret (disease, patient status, polypharmacy). Strategies that may increase validity constrain the feasibility of the study and the generalisability of the study results obtained.

Clinical Trials as Topic↗

Anabolic steroid use in weightlifters and bodybuilders: an internet survey of drug utilization.

PURPOSE: Dietary supplements and ergogenic agents, including anabolic steroids, are common components of present-day bodybuilder and weightlifter training regimens. Prior reports of anabolic steroid use suggest polypharmacy and high doses of injectable agents. HYPOTHESIS: To provide an updated description of anabolic steroid regimens employed by weightlifters and bodybuilders and to determine the extent to which anabolic steroid-associated behaviors are consistent with substance dependence. STUDY DESIGN: Web-based survey. METHODS: Links to the Web-based survey instrument were established from leading bodybuilding and fitness web pages. The questionnaire included demographic information, anabolic drug use history, adverse effects, information sources, and steroid use behavior consistent with criteria for a substance dependence disorder. RESULTS: A total of 207 subjects provided a detailed anabolic steroid drug history. Steroid regimens included a mean of 3.1 agents, involved cycles ranging from 5 to 10 weeks, and often included doses 5 to 29 times greater than physiologic replacement doses. Behavior consistent with a substance dependence disorder was endorsed by 33% of respondents. CONCLUSIONS: These findings suggest that anabolic steroid use among weightlifters and bodybuilders continues, generally involving multiple steroids and additional dietary supplementary agents. The adverse effects, polypharmacy, large dosages, and risk of substance abuse are all major health care concerns that require further study. CLINICAL RELEVANCE: The survey findings provide sports medicine practitioners a reasonable estimate of the expected drug history among bodybuilders and weightlifters for the use of performance-enhancing agents.

Adolescent↗

Patterns of drug treatment of schizophrenic patients in Estonia, Spain and Sweden.

1. Patterns of drug treatment and the use of polypharmacy in schizophrenic in-patients were compared and evaluated in the University Teaching Hospitals of Psychiatry in Badajoz, Spain, Huddinge, Sweden, and Tartu, Estonia. 2. The medical records of up to 100 consecutively admitted patients were retrospectively reviewed using a standardized data form. 3. The male patients were significantly younger than females in all study locations, but there were no age differences between the locations. The length of stay was equal for the two series in the same hospital, but considerably longer in Tartu than in Badajoz and Huddinge. 4. The neuroleptic drugs used most commonly in Badajoz and Tartu were similar in prescription frequency and in the doses prescribed, but different from those used in Huddinge. Haloperidol was the most frequently prescribed neuroleptic in Badajoz and Tartu, accounting for one third of all neuroleptic prescriptions. In Huddinge the choice of neuroleptics was more evenly spread over several compounds. Intramuscular injections other than depot preparations were commonly used in Tartu and Badajoz, but not in Huddinge. 5. At least two neuroleptics were prescribed simultaneously on 73% of treatment days in Badajoz and 46% in both Huddinge and Tartu. The average cumulative daily doses of concomitant multiple neuroleptic treatment, expressed in chlorpromazine equivalents, were lower in Huddinge than in the other study locations and higher for male patients in Badajoz and Tartu. 6. Anticholinergics were used together with neuroleptics in 42% of treatment days in Badajoz and 30% in Huddinge as compared with 75% in Tartu. The use of anticholinergics increased in parallel to the increase in the number and the cumulative dose of concomitant neuroleptics in all study locations. 7. About 15% of patients in Badajoz and Tartu, but only 1% in Huddinge, received concomitant treatment with antidepressant drugs. The simultaneous use of antidepressants and benzodiazepines was inversely related to the number and the cumulative dose of neuroleptics in Badajoz and Tartu. In contrast, the cumulative dose and number of neuroleptics were greater, when additional benzodiazepines were prescribed in Huddinge. 8. The study in schizophrenic in-patients revealed that polypharmacy with concomitant multiple neuroleptics, additional anticholinergics and other psychotropics is an international phenomenon.

Adult↗

Antipsychotic drug prescription for schizophrenia in East Asia: rationale for change.

The purpose of this international collaborative study was to investigate the prescription patterns of antipsychotic drugs for schizophrenia in East Asia and to analyze factors that affect these patterns. Prescription patterns for patients admitted for treatment of schizophrenia were surveyed using a standardized protocol from six East-Asian region/countries: China, Hong Kong, Japan, Korea, Singapore and Taiwan. Patients' social and clinical characteristics, psychiatric symptoms, course of illness, and adverse effects of medications were systematically assessed and recorded. Prescriptions of the first- and second-generation antipsychotic drugs were compared. A total of 2399 patients were recruited. The second-generation drugs comprised 28.1% of all prescribed antipsychotics, and 46% of the antipsychotic prescriptions were in the context of polypharmacy. The mean dosage of antipsychotics for the whole sample was 675.3 + 645.1 mg chlorpromazine equivalents. Japan had a high frequency of prescribing high doses and polypharmacy; Singapore had a high utilization of depot injections while China had a higher prescription of clozapine. Using multiple logistic regression analysis, distinctions in the prescription patterns of antipsychotic drugs were found: first-generation drugs were mainly for controlling aggressive behavior, while second-generation drugs were targeted at the alleviation of positive, negative psychotic symptoms as well as disruptive behavior in schizophrenia. The present collaborative study highlighted differences in the prescription patterns, especially the under-utilization of second-generation antipsychotic drugs in East Asia. The pattern of antipsychotic medication use varied from country to country and is likely to be influenced by the prevailing health-care system, the availability and cost of the drugs.

Adult↗