Glycopyrrolate 1 mg was not superior to placebo, whereas 2 mg showed a significant clinical improvement of nocturnal sialorrhea compared with placebo. Glycopyrrolate seemed to be a tolerable anticholinergic agent in the treatment of clozapine-associated sialorrhea.

We read with great interest the recent Therapeutic Advances in Psychopharmacology article by Maher and colleagues entitled 'Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life'. 1 The authors evaluated the prevalence of clozapine-induced hypersalivation (CIH) in a population of psychiatric patients in a specialized clozapine clinic. In addition, they assessed and quantified the severity of CIH, using the Nocturnal Hypersalivation Rating Scale (NHRS) and the Drooling Severity and Frequency Scale, and its impact on global functioning. They reported that CIH was the most prevalent adverse effect negatively impacting the quality of life in patients treated with clozapine.The NHRS is a validated five-item scale used to determine patient-reported hypersalivation. Owing to their subjective nature, individual differences exist in patient-reported treatment satisfaction and perceived burden of hypersalivation. With regard to the extent to which changes in NHRS score affect patients' perceived burden and treatment satisfaction, we here report an association between NHRS and, firstly, the Patient Global Impression of Severity (PGI-S) five-point scale (regarding CIH specifically), which has similar anchors for scoring as the Clinical Global Impression-Severity scale, and, secondly, the Medication Satisfaction Questionnaire (MSQ) seven-point scale among patients experiencing CIH before and after treatment with the anticholinergic agent glycopyrrolate.We included 32 psychiatric patients experiencing nocturnal CIH in a double-blind crossover study (EudraCT number: 2012-002299-15) and investigated the association between NHRS score, perceived burden of CIH (PGI-S), and participants' satisfaction (MSQ) with clozapine treatment, comparing before intervention (baseline) and after intervention with glycopyrrolate 1 mg and 2 mg. 2 Thus, further to the study of Maher and colleagues 1 we investigated the effect of treatment of CIH on severity and perceived burden within patients.All participants (n = 32) received glycopyrrolate 1 mg once daily for 6 days consecutively. This treatment was followed by a washout week and eventually by an optional open-label treatment with glycopyrrolate 2 mg once daily (n = 23) for 6 days consecutively. Only patients who were willing to continue and who met the eligibility criteria participated in the open-label treatment. We calculated Spearman's rank correlation coefficients to assess the association between the different patient-reported outcome scales.A decrease in NHRS score after intervention with glycopyrrolate 1 mg once daily was significantly associated with a decrease in PGI-S score (r s (30) = 0.747, p < 0.001), but with a nonsignificant change in MSQ score (r s (30) = −0.165, p = 0.366). A decrease in NHRS score after intervention with glycopyrrolate 2 mg once daily was not significantly associated with a change in either PGI-S (r s (21) = 0.264, p = 0.224) or MSQ (r s (21) = 0.052, p = 0.814) score. This indicates that clozapine users perceive...