QT interval prolongation related to psychoactive drug treatment:a comparison of monotherapy versus polytherapy

Background - Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method - We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results - Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). Conclusions - No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents.

The pharmacist's contribution towards monitoring and reporting adverse drug reactions

The activities and function of the West Midlands Adverse Drug Reaction Study Group are described. The impact of the Group on the reporting of adverse drug reactions to the CSM by the yellow card system has been evaluated in several ways including a comparison with the Trent Region. The role of the pharmacist in the Group is highlighted. A nationwide survey of the hospital pharmacist's involvement in adverse drug reaction reporting and monitoring is described, the results are reported and discussed. The available sources of information on adverse drug reactions, both primary and secondary, are critically reviewed. A checklist of necessary details for case reports is developed and examples of problems in the literature are given. The contribution of the drug information pharmacist in answering enquiries and encouraging reporting is examined. A role for the ward pharmacist in identifying, reporting, documenting and following up adverse drug reactions is proposed. Studies conducted to support this role are described and the results discussed. The ward pharmacist's role in preventing adverse drug reactions is also outlined. The reporting of adverse drug reactions in Australia is contrasted with the U.K. and particular attention is drawn to the pharmacist's contribution in the former. The problems in evaluating drug safety are discussed and examples are given where serious reactions have only been recognised after many patients have been exposed. To remedy this situation a case is made for enhancing the CSM yellow card scheme by further devolution of reporting, increasing the involvement of pharmacists and improving arrangements at the CSM. It is proposed that pharmacists should undertake the responsibility for reporting reactions to the CSM in some instances.

Comparison of hydrophilic and hydrophobic active molecules release from polymer-phospholipid complexes

Hypercoiling polymers can be suited for application to living systems because they are similar in structure to the protein-based lipid assemblies found at fluid interfaces within the body. This leads to a range of exciting possibilities, not only in membrane transport applications but also in biosensors, drug delivery and mechanistic studies of biological membrane function. This study is focused in the study of the stability and suitability of nanostructures made of a hypercoiling polymer for drug delivery applications. The polymer poly (styrene-maleic acid) (PSMA) was combined with the phospholipid dimyristoylphosphatidylcholine (DMPC) to form amphiphilic nanostructures. The stability and suitability of these polymer-phospholipid nanocarriers for hydrophobic and hydrophilic molecules load and release was analyzed by several techniques. It was found that several of the studied molecules had a substantial effect on the surface charge and stability of the nanocarrier. It was also demonstrated that two types of nanocarriers, chemically modified and unmodified, were able to control the release of the molecules, especially in the case of hydrophobic compounds. In addition, as the hydrophobicity increased the release slowed down. These clear nanocarriers have the potential to behave very favorably at interfaces such as the tear lipid film were transparency is a requirement, giving a new way of controlled drug release in the eye.

Pathway to clozapine use:a comparison between a patient cohort from New Zealand and a cohort from the United Kingdom

Background and Objective: Clozapine has been available since the early 1990s. Studies continue to demonstrate its superior efficacy in treatment-resistant schizophrenia. Despite this, numerous studies show under-utilisation, delayed access and reluctance by psychiatrists to prescribe clozapine. This retrospective cross-sectional study compared the prescribing of clozapine in two adult cohorts under the care of large public mental health services in Auckland (New Zealand) and Birmingham (United Kingdom) on 31 March 2007. Method: Time from first presentation to clozapine initiation, prior antipsychotics trialled and antipsychotic co-prescribing were compared. Data included demographics, psychiatric diagnosis, co-morbid conditions, year of first presentation, admissions and pharmacological treatment (clozapine dose, start date, prior antipsychotics, co-prescribed antipsychotic). Results: Overall, 664 people were prescribed clozapine (402 Auckland; 262 Birmingham); mean daily dose of 384 mg (Auckland) and 429 mg (Birmingham). 53 % presented after 1990 and the average duration of time before starting clozapine was significantly longer in the Birmingham cohort (6.5 vs. 5.3 years) but this reduced in both cohorts to a 1-year mean in those presenting within the last 3 years. The average number of antipsychotics trialled pre-clozapine for those presenting since 1990 was significantly higher in the Birmingham cohort (4.3 vs. 3.1) but in both cohorts this similarly reduced in those presenting within the last 3 years. Antipsychotic co-prescribing was significantly higher in the Birmingham cohort (22.9 vs. 10.7 %). Conclusions: There is evidence that access to clozapine has improved over time in both cohorts, with a reduction in the duration between presentation and initiation of clozapine and number of different antipsychotics trialled pre-clozapine. These are very positive findings in terms of optimising outcomes with clozapine and are possibly due to the impact of guideline recommendations, increasing clinician, consumer and carer knowledge, and experience with clozapine and funding changes. © 2014 Springer International Publishing.

On the drug adsorption capacity of SBA-15 obtained from various detemplation protocols

The effect of the mild detemplation method, based on Fenton chemistry (with and without previous solvent extraction), and calcination was evaluated by the drug uptake capacity of SBA-15 materials. A number of characterization techniques were applied for evaluation and comparison of the materials properties such as TGA, CNH, N2 physisorption and 29Si NMR. The mild Fenton detemplation method rendered a nearly pristine SBA-15 without structural shrinkage, low residual template, improved surface area, pore volume and silanol concentration. The drug (ibuprofen) adsorption experiments were carried out by solution immersion in powdery form. The mild detemplated samples experienced an enhanced uptake that could be explained by the enhanced density of silanols (mmol/g), originated from the absence of calcination in the Fenton approaches. © 2014 Elsevier B.V.