Monotherapy with antidepressants and any use of tricyclic AD and venlafaxine still has a considerable prevalence in bipolar depression, but this is controversial due to the reported risk of treatment emergent affective switches. Triple and quadruple therapy is not evidence-based but increasingly used in clinical practice. This may reflect an attempt to overcome treatment failure, and further studies should evaluate efficacy and safety of this common practice.

In order to improve medication safety, more epidemiological data on the prevalence and clinical relevance of drug interactions are required. We developed an interface for mass analysis using the Clinical Decision Support Software (CDSS) MediQ and a multidimensional classification (Zurich Interaction System (ZHIAS)) incorporating the Operational Classification of Drug Interactions (ORCA). These were applied to 359,207 cross-sectional prescriptions from 84,607 psychiatric inpatients collected through the international AMSP program. MediQ issued 2,308 "high" and 71,112 "average" danger interaction alerts. Among these, after ORCA reclassification, there were 151 contraindicated and 4,099 provisionally contraindicated prescriptions. The ZHIAS provided further detailed categorical information on recommended management and specific increased risks (QTc prolongation being the most frequent one) associated with interactions. We developed a highly efficient solution for the identification and classification of drug interactions in large prescription data sets; this solution may help to reduce the frequency of overalerting and improve acceptance of the efficacy of CDSS in reducing the occurrence of potentially harmful drug interactions.

BACKGROUND: Clinical decision support software (CDSS) solutions can automatically identify drug interactions and thereby aim to improve drug safety. However, data on the comparative performance of different CDSS to detect and appropriately classify interactions in real-life prescription datasets is limited. OBJECTIVE: The aim of this study was to compare the results from two different CDSS analysing the pharmacotherapy of a large population of psychiatric inpatients for drug interactions. METHODS: We performed mass analyses of cross-sectional patient-level prescriptions from 84,625 psychiatric inpatients using two CDSS -MediQ and ID PHARMA CHECK(®). Interactions with the highest risk ratings and the most frequent ratings were reclassified according to the Zurich Interaction System (ZHIAS), a multidimensional classification that incorporates the OpeRational ClassificAtion of Drug Interactions (ORCA) and served as a reference standard. RESULTS: MediQ reported 6,133 unique interacting combinations responsible for 270,617 alerts affecting 63,454 patients. ID PHARMA CHECK(®) issued 5,400 interactions and 157,489 alerts in 48,302 patients. Only 2,154 unique interactions were identified by both programmes, but overlap increased with higher risk rating. MediQ reported high-risk interactions in 2.5 % of all patients, compared with 5 % according to ID PHARMA CHECK(®). The positive predictive value for unique major alerts to be (provisionally) contraindicated according to ORCA was higher for MediQ (0.63) than for either of the two ID PHARMA CHECK(®) components (0.42 for hospINDEX and 0.30 for ID MACS). MediQ reported more interactions, and ID PHARMA CHECK(®) tended to classify interactions into a higher risk class, but overall both programmes identified a similar number of (provisionally) contraindicated interactions according to ORCA criteria. Both programmes identified arrhythmia as the most frequent specific risk associated with interactions in psychiatric patients. CONCLUSIONS: CDSS can be used for mass-analysis of prescription data and thereby support quality management. However, in clinical practice CDSS impose an overwhelming alert burden on the prescriber, and prediction of clinical relevance remains a major challenge. Only a small subset of yet to be determined alerts appears suitable for automated display in clinical routine. DOI: https://doi.org/10.1007/s40264-013-0027-9Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-76756 Accepted Version Originally published at: Zorina, Olesya I; Haueis, Patrick; Greil, Waldemar; Grohmann, Renate; Kullak-Ublick, Gerd A; Russmann, Stefan (2013). Comparative performance of two drug interaction screening programmes analysing a cross-sectional prescription dataset of 84,625 psychiatric inpatients. Drug Safety, 36(4):247-258.

CDSS showed major differences in the identification and grading of interactions, and many interactions were only identified by one of the two CDSS. For both programs, only a small proportion of all identified interactions appeared clinically relevant, and the selected display of alerts that imply management changes is a key issue in the further development and local setup of such programs.

Patients on levodopa therapy frequently require additional antipsychotic pharmacotherapy. However, consideration must be given to antagonistic interactions on dopamine receptors between levodopa and antipsychotics, and efficacy and safety of such combinations. We therefore aimed to explore the practice and rationale of coprescription between levodopa and antipsychotics in psychiatric patients.A descriptive retrospective study based on cross-sectional prescription data repeatedly collected from psychiatric inpatients through the international Drug Safety in Psychiatry (AMSP) program between 1994 and 2008 was undertaken.Within a population of 84 596 psychiatric patients the prevalence of levodopa therapy was 1.0% (n=886). Among those patients on levodopa therapy 59.6% (n=528) also received antipsychotics. Quetiapine coprescription increased after its first marketing in 2000 to 45.9% in 2008. Coprescription of clozapine and olanzapine decreased from up to 25 and 22%, respectively, before to less than 10% after the introduction of quetiapine. Coprescribing of other antipsychotics remained approximately stable with average prevalences between 6 and less than 1%.Quetiapine has now replaced clozapine as the most frequently coprescribed neuroleptic in psychiatric patients with levodopa therapy. This is in accordance with recent data indicating a low potential for clinically relevant interactions with levodopa and efficacy against psychosis in levodopa-treated patients. The combined use of antipsychotics other than quetiapine and clozapine with levodopa is less common and generally not supported by appropriate evidence.