Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a growing global health burden closely linked to obesity, insulin resistance, and dietary patterns. Despite intense drug-development efforts, effective and widely approved pharmacological therapies remain limited. Methods: In this work, we systematically evaluated the quality of clinical evidence supporting currently proposed pharmacological treatments for MASLD/MASLD using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, focusing on phase III and IV clinical trials. Results: Our analysis demonstrates that overall quality of evidence for most pharmacological agents ranges from very low to moderate, primarily due to imprecision and suspected publication bias. Conclusions: Overall, our findings reinforce that, in the current therapeutic landscape, pharmacological therapies should be reserved for carefully selected patients and interpreted in the context of limited evidence certainty.