Salivary Flow Rate in Patients With Schizophrenia on Clozapine

Praharaj, Samir Kumar; Jana, Anirban; Goswami, Kausik; Das, Poonam R.; Goyal, Nishant; Sinha, Vinod Kumar

doi:10.1097/wnf.0b013e3181e204e0

Cited by 24 publications

(20 citation statements)

References 9 publications

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“…Despite drooling in the groups of schizophrenic patients on clozapine in the studies of Ben‐Aryeh et al (1996) and Rabinowitz et al (1996), the mean salivary flow rate at rest was not different from that of controls. However, in the longitudinal study of Praharaj et al (2010), the salivary flow rate at rest was higher 2–3 weeks after the start of clozapine treatment than before. In the literature, many times the words sialorrhea and drooling are interchangeable used but strictly sialorrhea refers to an increase in saliva production, whereas drooling refers to involuntary spilling of saliva from the mouth (Laskawi and Ellies, 2011).…”

Section: Introductionmentioning

confidence: 77%

Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine‐induced sialorrhea

Godoy¹,

Riva²,

Ekström³

2012

Oral Diseases

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Section: Introductionmentioning

confidence: 77%

Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine‐induced sialorrhea

Godoy¹,

Riva²,

Ekström³

2012

Oral Diseases

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“…Preclinical studies may offer an explanation for the ‘clozapine‐induced sialorrhea’ that occurs in about one‐third of patients under treatment for schizophrenia, a phenomenon that may be particularly troublesome during the night, with choking sensations and the aspiration of saliva (Praharaj et al , 2006, 2010; Gardner and Teehan, 2011). Experiments, using the rat as an animal model, show that clozapine, and its metabolite N ‐desmethylclozapine, exerts dual and opposite actions on the salivation (Ekström et al , 2010a,b; Godoy et al , 2011): a direct excitatory action on muscarinic acetylcholine receptors of the M1 type evokes a low‐grade continuous flow of saliva from the parotid and submandibular glands, and a direct, and marked, inhibitory action on the parasympathetically and sympathetically nerve‐evoked secretion by muscarinic acetylcholine receptors of the M3 type and by α 1 ‐adrenergic receptors.…”

Section: Introductionmentioning

confidence: 99%

Salivary secretion effects of the antipsychotic drug olanzapine in an animal model

2012

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Oral Diseases (2012) Objective: Olanzapine, introduced as an alternative to clozapine in schizophrenia therapy, is thought to display a receptor affinity similar to that of clozapine. Antipsychotics are well‐known xerogenic drugs. However, clozapine exerts both antagonistic and agonistic salivary effects (‘clozapine‐induced sialorrhea’), the latter probably via muscarinic M1 type of receptor. We hypothesise that olanzapine also has dual salivary effects. Material and methods: Effects of intravenous olanzapine were examined in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). Secretion was evoked reflexly, and by intravenous methacholine and the tachykinin substance P. Results: At 0.01–1 mg kg−1, olanzapine dose dependently reduced secretion in response to methacholine or reflex stimulus but not that to substance P. At 10 mg kg−1, olanzapine evoked a long‐lasting secretion, independent of the autonomic innervation as well as of α‐ and β‐adrenergic receptors and muscarinic receptors. The secretion was reduced, but not abolished, by a substance P receptor antagonist. Conclusions: Like clozapine, olanzapine evoked secretion. The response to olanzapine was greater and, in contrast to clozapine, involved non‐traditional gland receptors (such as substance P receptors). The findings imply that olanzapine plays an excitatory role via tachykinin receptors in humans.

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“…The strategies suggested to abolish clozapine‐induced sialorrhoea include treatment with amisulpride, a substitute benzamide derivate (3, 4). Data from clinical studies which have measured the volume of saliva secreted, are few and contradictory (5–7). In fact, some authors relate the reported salivation associated with clozapine to a weakened swallowing reflex (8, 9).…”

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confidence: 99%

Clozapine-induced salivation: interaction with N-desmethylclozapine and amisulpride in an experimental rat model

Godoy

Riva

Ekström

2011

European Journal of Oral Sciences

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Many drugs (e.g. amisulpride) have been used to treat troublesome clozapine-induced salivation; however, varying success has been achieved in this respect, probably because, until recently, the salivatory action of clozapine has been largely unexplained. In the rat, clozapine and its main metabolite, N-desmethylclozapine, were found to exert mixed secretory actions: excitatory, through muscarinic acetylcholine M1-receptors giving rise to a long-lasting, low-level flow of saliva; and inhibitory, through muscarinic M3-receptors and α(1) -adrenoceptors reducing the parasympathetically and sympathetically nerve-evoked flow of saliva. The aim of the present study was to define the interactions between clozapine and N-desmethylclozapine, and clozapine and amisulpride, with respect to the excitatory response. Submandibular glands, sensitized by chronic parasympathetic preganglionic denervation, were studied in pentobarbitone-anaesthetized rats. To prevent clozapine from being metabolized to N-desmethylclozapine by hepatic enzymes, the liver was, under terminal anaesthesia, excluded from the circulation. The weak receptor-stimulating clozapine prevented the strong receptor-stimulating N-desmethylclozapine, at specific ratios in humans and in rats, from exerting its full agonistic action. In conclusion, the contribution of N-desmethylclozapine to the clozapine-induced sialorrhoea was, at most, only partly additive. Furthermore, the present experimental set-up failed to demonstrate any anti-salivatory action of amisulpride on the clozapine-induced flow of saliva.

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Salivary Flow Rate in Patients With Schizophrenia on Clozapine

Abstract: There was a significant increase in salivary flow rate from baseline after starting clozapine, with a significant increase from the second to the third week followed by a "plateau."

Cited by 24 publications

References 9 publications

Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine‐induced sialorrhea

Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine‐induced sialorrhea

Salivary secretion effects of the antipsychotic drug olanzapine in an animal model

Clozapine-induced salivation: interaction with N-desmethylclozapine and amisulpride in an experimental rat model

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