Drawbacks of Olanzapine Therapy: An Emphasis on Its Metabolic Effects and Discontinuation

Radical drug therapy for schizophrenia is usually hard to achieve with one currently available antipsychotic agent. Indeed, it is the negative symptoms of this morbidity that are a dilemma to neutralize. Most of the first-generation agents can deal with the positive symptoms of the disease to a convincing degree, but not with its negative symptoms. The creation of so-called second-generation agents aimed to treat the negative symptoms, as these invisible barriers are the real reasons that isolate psychotic individuals and hinder their integration into society. Unfortunately, these newly designed drugs, including OLZ, turned out to induce different categories of undesired effects; the most embarrassing among them are the metabolic drawbacks, such as insulin resistance, weight gain, and other subcategories of metabolic consequences. Antagonism induced at certain receptors, particularly 5-HT2C and histamine H1 receptors, is implicated particularly in these metabolic adverse effects. The choice of antipsychotics (APCs) should be tailored separately for each case, as each patient responds variably to each neuroleptic. This possibility exists due to the abundant alternatives within the currently available APC medications. This work aims to discuss the reasons behind these undesired metabolic effects, how to deal with them, how to choose the appropriate agent for each psychotic case, and how to manage intoxication using olanzapine. To address these inquiries, we carefully selected 154 relevant studies, including robust meta-analyses, from the past 20 years and analyzed them in this work.