The most common side effect associated with the use of clozapine is hypersalivation (sialorrhea).

Clozapine is an atypical antipsychotic often reserved for treatment-resistant schizophrenia due to its unique efficacy profile. While it has a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia compared to typical antipsychotics, it is notorious for other side effects.

- Hypersalivation (sialorrhea): Clozapine frequently causes increased salivation, often most noticeable at night. This is thought to be due to its anticholinergic effects combined with selective muscarinic receptor activity, which paradoxically increases saliva production. This side effect can be distressing and socially embarrassing for patients.

- Extrapyramidal symptoms (EPS): Unlike typical antipsychotics, clozapine has a very low risk of causing EPS because of its weak dopamine D2 receptor antagonism.

- Tardive dyskinesia: Clozapine is also associated with a lower risk of tardive dyskinesia compared to first-generation antipsychotics and other atypicals.

- Weight loss: On the contrary, clozapine is more commonly associated with weight gain and metabolic disturbances rather than weight loss.

In clinical practice, while monitoring for serious adverse effects like agranulocytosis and myocarditis is essential in patients taking clozapine, clinicians should also counsel and manage hypersalivation as one of the frequent and bothersome side effects.

Reference: Katzung BG, Basic & Clinical Pharmacology, 15th Edition, Chapter 16: Drugs Used in Psychotic Disorders, p. 329-335