The Evidence Based Medicine paradigm (EBM), in which the evidence from randomised controlled clinical trials drives treatment protocols to optimise health while maximising economic efficiency, has revolutionised treatment is many fields of medicine. Treatment resistant psychosis carries a very high social and economic burden, but I will argue that EBM has failed to improve the lives of people with treatment resistant psychosis. The first problem has been the concept of treatment resistant psychosis itself. While it is a clinically recognisable syndrome, it is poorly defined and validated, and is unattractive to pharmaceutical companies as it is imbued with a sense of therapeutic pessimism. Secondly, I will argue that the model of EBM overvalues the findings of randomised clinical trials (RCTs). However, RCTs have several drawbacks which are accentuated in TRP. These include selection bias, short time horizons and outcome measures that are poorly measured, can fail to detect clinically meaningful effects and do not align with patient priorities. Thirdly, non-RCT evidence for the efficacy of clozapine in this population, while compelling, is undervalued by the EBM paradigm. After presenting these arguments, I will make suggestions as to how we can move forward with research in this field.
Evidence-based treatment guidelines for the management of difficult-to-treat schizophrenia recommend clozapine since many years due to its superior efficacy for treatment-resistant positive symptoms.According to different guidelines, achieving plasma clozapine levels of ≥350 ng/ml constitutes a minimum threshold requirement for establishing clozapine non-response in treatment-resistant schizophrenia (TRS). In the context of optimal dose finding, both external factors (i.e. Cytochrome P450 1A2 (CYP1A2) modulating comedication, tobacco smoking, caffeine intake)and internal factors (i.e. age, gender, ethnicity) have to be taken into consideration to guarantee optimal safety and efficacy of clozapine treatment. Several studies have consistently shown the need of continued clozapine maintenance treatment, where safely tolerated, due to its superior efficacy in TRS. Nevertheless, clozapine is associated with potentially burdensome or even life-threatening side-effects and in up to 60% of patients with TRS, clozapine fails to be effective. The aim of my talk is to summarize the current evidence regarding optimization of clozapine monotherapy as well as pharmacological and non-pharmacological strategies (i.e. ECT) for clozapine-resistance.
Abstract: Clozapine is the most effective medication for treatment refractory schizophrenia (TRS). However, there is a significant burden of adverse drug reactions. Safe and quality prescribing of clozapine requires a fine balance between management of psychotic symptoms and amelioration of the adverse drug reactions our consumers bear.
To provide updates regarding:
an understanding of the use of clozapine among people with complex and difficult to treat psychosis
increased awareness of the management strategies for serious clozapine adverse effects, notably constipation, pneumonia and myocarditis
guidance on how to use metformin at the time of clozapine initiation for prevention of weight gain.
Methods: The presenters will present clinical data and review the current literature on quality and safe use of clozapine. We will focus on complex psychosis, management of adverse drug effects and how to prevent clozapine-associated weight gain.
Findings: Clozapine is significantly more effective than other anti-psychotics for treatment of TRS; however, practitioners must be vigilant for adverse drug reactions, notably constipation, pneumonia and constipation, and be proactive in prevention of weight gain to reduce the risk of cardiometabolic illness.
Conclusions: At the end of this session, practitioners will be proficient in the quality and safe use of clozapine.