Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature

Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug-drug interactions

Factors associated with first- versus second generation long-acting antipsychotics prescribed un-der ordinary clinical practice in Italy.

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network \u201cDepot\u201d Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAI

A simple approach to manage dosages in drug-epidemiology research

In the study of the beneficial and adverse effects of psychotropic drugs, in addition to experimental studies (Barbui et al., 2007), epidemiological studies may provide interesting insights. A key methodological aspect in drug utilization studies is how drug consumption should be measured. Specifically, the need is to end up with a single variable that may be reliably used to indicate the overall consumption, for each patient included in a certain survey, of one specific drug (for example one antipsychotic, say haloperidol) or a specific drug class (for example second-generation antipsychotics) or a group of drugs (for example psychotropic drugs, including antipsychotics plus antidepressants plus benzodiazepines). Not only such a variable has to accommodate the problem that actual doses cannot be directly compared, but also that many patients often receive more than one drug, belonging to different or to the same pharmacological class. A methodology is therefore needed to convert each medication dosage into a standardised measure that allows to calculate, for each patient, a cumulative index of drug consumption. Standardised measures of drug consumption are also beneficial for national and international comparisons, for the evaluation of time trends in drug use, and for assessing the public health impact of specific events (for example a change in reimbursement status).</jats:p

Do antidepressants prolong the QT interval?

According to a recent cross-sectional study, some antidepressants, including amitriptyline, citalopram and escitalopram, are associated with QTc prolongation. However, the magnitude of this association is relatively small, and the clinical implications uncertain. In this article, the main strengths and weaknesses of this cross-sectional study are briefly analysed alongside recent warnings issued by regulatory authorities. Implications for research and practice are discussed

Generating psychotropic drug exposure data from computer-based medical records

Purpose: To develop a methodology for extracting psychotropic drug exposure data from computer-based medical records and for generating drug exposure variables suitable for secondary use. Methods: In South-Verona, Italy, a registry including every patient receiving psychotropic medications is operating since 2004. The basic structure of the registry is the medication record. Each record stores data on a specific prescription, and patients with more than one prescription have more than one record. Results: The longitudinal history of drug use was described identifying consecutive prescriptions of a specific drug, concomitant prescriptions of a specific drug and distinct prescriptions of a specific drug. Consecutive prescriptions implies that the beginning of the second prescription coincides with the end of the first prescription, concomitant prescriptions implies that the beginning of the second prescription precedes the end of the first prescription, distinct prescriptions implies that a gap of at least 1 day exists between prescriptions. Using this framework of drug representation, we identified episodes of drug therapy, where each episode is constituted of consecutive and/or concomitant prescriptions. Within each episode, prescriptions were categorised into theoretical phases, where the beginning of the new phase always coincides with the end of the previous phase. On the basis of this data representation, a module operating in Access and using Visual Basic for Applications was developed for creating episodes and phases on a routine basis (available from authors). A graphical representation of this conceptual model is presented. Conclusion: The development of a simple methodology for extracting and generating drug exposure data suitable for secondary use will allow a better understanding of the beneficial and adverse consequences of psychotropic drug use in ordinary practice. \ua9 2006 Elsevier Ireland Ltd. All rights reserved

Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial

BACKGROUND: Long-term studies for patients with resistant schizophrenia are necessary to assess the effectiveness of combination strategies on persisting positive symptoms.AIMS AND METHODS:This multicenter, naturalistic, randomized, superiority study (ClinicalTrials.gov identifier: NCT00395915) aimed to compare clinical efficacy and tolerability of haloperidol versus aripiprazole as combination treatment with clozapine in patients with resistant schizophrenia.RESULTS:One hundred six patients were followed up for 12 months. After 12 months, the proportion of patients who discontinued treatment was not significantly different between aripiprazole and haloperidol (37% vs 28%, respectively; P = 0.431). The change in the Brief Psychiatric Rating Scale score was similar in the aripiprazole and haloperidol groups (-7.0 vs -7.9, respectively; P = 0.389), whereas the tolerability total score decreased significantly more in the aripiprazole group (-7.2 vs -2.3; P = 0.008).CONCLUSIONS:While the effectiveness of clozapine augmentation with a second antipsychotic agent is not clearly demonstrated yet, results from this study suggest that augmentation with aripiprazole offers no substantial benefit over haloperidol in efficacy. Aripiprazole was perceived more tolerable than haloperidol, but it is uncertain how this finding may translate into the real world of clinical practice

Adverse effects of antipsychotic drugs: survey of doctors' versus patients' perspective.

AIMS: Almost no data are available on whether patients and doctors have similar or dissimilar opinions on the presence and level of distress due to antipsychotic adverse effects. The aim of this survey is to compare doctors' versus patients' perspective on the presence and level of distress due to antipsychotic adverse effects in a sample of patients under the care of the South-Verona mental health services. METHODS: All patients exposed to antipsychotic drugs during a census period of 6\ua0months were identified. For each included subject, socio-demographic, clinical and treatment data were extracted. Patients' perspective on antipsychotic adverse effects was measured by means of the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The LUNSERS was similarly employed to measure doctors' perspective on antipsychotic adverse effects. RESULTS: During the recruitment period, 243 patients taking antipsychotic drugs were enrolled. The correlation between the total LUNSERS score reported by patients and doctors was very low (correlation coefficient 0.22, 95\% confidence interval 0.15-0.30). On average, patients perceived more adverse effects and with a significant higher distress than doctors. Multivariate analyses found no factors simultaneously associated with both patient and doctor ratings of adverse effects. CONCLUSION: Our study suggests that doctors, researchers and health care providers should increasingly consider patient and doctor perspectives as two complementary dimensions that may provide different insights in the evaluation of antipsychotic drugs. Integrating different points of view may represent a way to develop a better therapeutic alliance that might decrease the likelihood of nonadherence

Drug treatment modalities in psychiatric inpatient practice: a 20-year comparison

Objectives: The present study investigated whether the increased number of psychotropic agents available in Italy in the last 20 years increased the proportion of inpatients being treated with individual medication classes and the proportion receiving combined treatments with agents of the same class or of different classes. Methods: This study was conducted in South-Verona, Italy. From the local Psychiatric Case Register (PCR) all patients consecutively admitted to the inpatient unit during the years 1981/1982, 1991/92 and 2001/02 were extracted. Drug use at discharge was derived from clinical records, while service use data were extracted from the PCR. Results: During the six years surveyed 160 patients were admitted in 1981/82, 139 in 1991/92 and 228 in 2001/02. An increasing proportion of subjects receiving antipsychotic, antidepressant and benzodiazepine treatment at discharge was observed. In addition, we found an increasing proportion of patients receiving two or more psychotropic drugs at discharge, which accounted for almost 80% of cases in 2001/02. The number of psychotropic agents prescribed at hospital discharge was positively correlated with the total consumption of psychotropic drugs. A relevant proportion of patients were also dispensed agents for medical conditions, yielding an average number of 3.2 prescriptions in 2001/02. The Lavik score, a summary index of service use, indicated that subjects admitted in 1981/82 were moderate users of psychiatric services, while those admitted in 1991/92 and in 2001/02 were high users of psychiatric services. Conclusion: This study documented emerging trends toward polypharmacotherapy and higher total doses. Additional pharmacoepidemiological research is needed to clarify both the beneficial and, potentially, adverse effects associated with these trends in psychiatric pharmacotherapy