Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013

Abstract

Background Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome. Methods This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients. Results A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine. Conclusions Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.

QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson’s Disease Psychosis: A Narrative Review

“… 54 Analysis of a database encompassing Austria, Germany, and Switzerland reported a QTc prolongation frequency of 0.006% among patients treated with clozapine or quetiapine and 0% with aripiprazole, olanzapine, and risperidone. 55 …”

“…Aripiprazole was mentioned in 6 systematic reviews and meta-analyses, 30 , 31 , 56–59 13 prospective or observational studies, 33 , 47 , 55 , 60–69 and 4 case reports. 70–73 The literature consistently showed that aripiprazole is associated with small reductions in QTc interval.…”

“…The effect of clozapine on QTc interval was described in 1 systematic review, 59 13 studies, 33 , 45 , 50 , 51 , 55 , 61 , 67 , 77–82 and 6 case reports. 71 , 73 , 83–86 One study found no significant change from baseline in mean QTc interval or the incidence of QTc prolongation, 79 but this is inconsistent with findings from other researchers.…”

Effects of neuroleptics and antidepressants on the cardiovascular system: literature review

“…Ap ra ðo mi pa vieniai ðios vais tø gru pës su kel ti kli ni ki niai at ve jai þur na luo se ir FDA ða lu ti niø po vei kiø re gist ro duo me nø ba zë je [32,33]. Ty ri muo se su svei kais sa va no riais di dþiau sià QTc pail gë ji mà ið ati pi niø neu ro lep ti kø su ke lia zip ra zi do nas, ly gi nant já su olan za pi nu, ris pe ri do nu, kve tia pi nu, ta èiau jo arit mo ge ni nis po vei kis në ra di de lis [30,34]. Ne pai sant keliø su di de lë mis olan za pi no do zë mis sie ja mø ap ra ðy tø QTc pail gë ji mo at ve jø [35], au to riai ðá vais tà sie ja su ne di de le arit mi jø ri zi ka [36].…”

Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs—Influence of Smoking Behavior and Inflammation on Pharmacokinetics

“…In particular, schizophrenia, a complex and heterogeneous mental disorder, which is often difficult to treat, is associated with a higher risk of polypharmacotherapy and trialand-error treatment choices [5,[14][15][16]. Antipsychotic drugs, used to treat psychosis and thus schizophrenia (among other mental disorders), are further reported to show a high interindividual variability in drug serum concentration [17][18][19] and cause a vast array of serious ADRs (such as agranulocytosis, extrapyramidal motor symptoms, or malignant neuroleptic syndrome), justifying consequent drug monitoring [20][21][22][23][24][25][26].…”