Four patients were prescribed doses 100% above the licensed maximum, all of which involved amisulpride and high-dose quetiapine combinations. The use of high-dose quetiapine is not an isolated finding. Recently the suggestion that high doses of quetiapine is necessary for therapeutic effect has led to prescribers disregarding guidelines, despite the fact that Inhibitors,research,lifescience,medical the only available evidence to support this theory is from case reports [Sparshatt et al. 2008]. Adverse effects were common and occurred equally amongst patients prescribed medication within daily defined limits and those on high-dose combinations.

Both serious adverse events (QTc prolongation and arrhythmia) occurred in high-dose patients, which is not altogether unexpected considering risk of cardiac events is dose related [Taylor et al. 2009]. Extrapyramidal side effects (EPSEs) affected the greatest number of patients in this sample, all of whom were Inhibitors,research,lifescience,medical receiving two atypical antipsychotics or atypical–typical combinations. This finding supports the theory that combining atypical with typical antipsychotics results in loss of atypicality, probably due to additional inhibition of

striatal dopamine receptors [Kapur et al. 2001]. Clinical outcome was variable where documented, with Inhibitors,research,lifescience,medical the majority of benefit being observed for nonpsychotic symptoms. A reduction in psychotic symptoms was documented in a quarter of all patients. Inhibitors,research,lifescience,medical However, differentiating between whether the effect

observed is due to the combination of drugs or the addition of the second drug is a major problem inherent to polypharmacy studies. In this study, the original antipsychotic was gradually removed to observe the effects of the added antipsychotic in two patients only. In both cases, trial discontinuation did result in a significant increase in psychotic symptoms, Inhibitors,research,lifescience,medical suggesting the effectiveness of the polypharmacy regimen as opposed to the added drug only. However, these findings must clearly be interpreted with caution. Documented improvements in adverse effects were uncommon. In a patient with risperidone-induced hyperprolactinaemia and galactorrhoea, the addition of aripiprazole resulted in a reduction in prolactin levels (and associated symptoms) definitely without necessitating a reduction in risperidone dosage. This positive finding has also been reflected in a large RCT [Kane et al. 2009], indicating the potential value of aripiprazole in a subset Entinostat of patients suffering from antipsychotic- induced hyperprolactinaemia. A significant proportion of prescribers considered stopping polypharmacy, possibly reflecting lack of efficacy, tolerability or concerns over long-term safety implications of coprescription. However, the practice continued in the majority of cases, mainly because of patient refusal to medication changes. Some prescribers also expressed fears that reverting to monotherapy would result in relapse and the worsening of psychotic symptoms.