When clozapine fails: Augmentation strategies in the management of clozapine-resistant schizophrenia

Schizophrenia is a chronic and debilitating illness affecting about 0.5% of the population. Antipsychotics are the mainstay of the pharmacological treatment of such burdensome condition, although documented that roughly 20% up to 60% of the patients with schizophrenia do not respond sufficiently to conventional treatments. These patients may have a good response when clozapine is introduced with a great efficacy often seen in everyday clinical practice. However, it has been estimated that around 40–70% of patients with ascertained treatment-resistant schizophrenia receiving clozapine may have an incomplete remission and are referred to as “ultra-resistant” or “refractory.” Clozapine-resistant schizophrenia represents a challenge for the clinician and a misfortune for the patients, and several strategies have been proposed to overcome this problem, yet, to date, it remains high-bar goal. The aim of this chapter was to provide an overview of the managing strategies of clozapine-resistant schizophrenia with a particular focus on augmentation strategies aimed to improve efficacy on schizophrenia symptoms.