The sublingual use of atropine in the treatment of clozapine‐induced sialorrhea: A systematic review

Poorten, T van der; Hert, Marc De

doi:10.1002/ccr3.2431

Cited by 19 publications

(16 citation statements)

References 38 publications

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“…hyoscine hydrobromide, atropine 1% drops, pirenzepine), and substitute benzamide derivatives (e.g. amisulpride, sulpiride, metoclopramide) [ 15 – 18 ]. There is no licensed medication for CIH and treatment recommendations are limited by the insufficient available evidence and the risk of bias in the published studies [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH)

et al. 2022

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Objective The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. Method This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. Results Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. Conclusion Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.

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Section: Discussionmentioning

confidence: 99%

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH)

et al. 2022

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“…Despite the absence of an adapted galenic form and robust safety data using this route, sublingual administration is regularly used off-label, is documented for the treatment of drooling even in children, and is still studied in clinical trials [24][25][26][27][28][29]. As used for the management of sialorrhea, one or two drops (0.5 to 1 mg) of 1% atropine eye drops every 4 to 6 h (<10 mg/day) are described as being tolerable with low frequency, and with reversible side effects [27,30]. This cheap molecule has a quick start of action, with effects observable after 15 to 30 min [31].…”

Section: Discussionmentioning

confidence: 99%

Sublingual Atropine Administration as a Tool to Decrease Salivary Glands’ PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [68Ga]Ga-PSMA-11

et al. 2022

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Prostate Specific Membrane Antigen (PSMA)-directed radionuclide therapy has gained an important role in the management of advanced castration-resistant prostate cancer. Although extremely promising, the prolongation in survival and amelioration of disease-related symptoms must be balanced against the direct toxicities of the treatment. Xerostomia is amongst the most common and debilitating of these, particularly when using an alpha emitter. It is therefore of main importance to develop new preventive strategies. This preclinical study has evaluated the effect of α-adrenergic and anticholinergic drugs on [99mTc]TcO4− Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET/CT). Methods: The effects of phenylephrine, scopolamine, atropine, and ipratropium on salivary glands uptake were evaluated in non-tumor-bearing mice by [99mTc]TcO4− microSPECT/CT. The most efficient identified strategy was evaluated in non-tumor-bearing and xenografted mice by [68Ga]Ga-PSMA-11 PET/CT. Results: Scopolamine and atropine showed a significant decrease in the parotid glands’ uptake on SPECT/CT whereas phenylephrine and ipratropium failed. Atropine premedication (sublingual route), which was the most effective strategy, also showed a drastic decrease of [68Ga]Ga-PSMA-11 salivary glands’ uptake in both non-tumor-bearing mice (−51.6% for the parotids, p < 0.0001) and human prostate adenocarcinoma xenografted mice (−26.8% for the parotids, p < 0.0001). Conclusion: Premedication with a local administration of atropine could represent a simple, safe, and efficient approach for reducing salivary glands’ uptake.

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“…Moreover, systemically acting drugs such as pirenzepine increase the overall anticholinergic load, raising the risk for CIGH 212,213,261 . Sublingual administration of atropine eye drops 72,262 and regular botulinum toxin injections into the parotid and submandibular glands can avoid this problem 263,264 . Importantly, CIH increases the risk of clozapine-associated pneumonia via salivary aspiration 265 .…”

Section: Hypersalivation and Pneumoniamentioning

confidence: 99%

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

Qubad¹,

Bittner²

2022

Preprint

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Despite its continued relevance as the single most effective and important evidence-based treatment for schizophrenia, the degree of underutilization of clozapine across health systems remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to use clozapine due to its relatively large side-effect burden and its comparatively complex dosing and monitoring requirements. This underscores the necessity for continued education of clinicians in the intricacies of clozapine use and in the still growing case in favor of this vital treatment option. Consequently, this narrative review provides a comprehensive outline of all lines of evidence, which support clozapine’s wide-ranging superior efficacy, and of the current knowledge regarding the prevalence and diagnosis of treatment resistance. The distinct neurobiological and clinical characteristics of this condition makes the swift initiation of clozapine indispensable. Moreover, we review the extensive literature regarding clozapine’s side effect profile and current recommendations for optimal treatment and monitoring algorithms including for particularly vulnerable populations such as elderly patients and pregnant women and for potential re-challenges after myocarditis and neutropenia. We also discuss established approaches to increase treatment response as well as augmentation strategies for patients with partial or full clozapine resistance. We argue for a clear focus on early and consistent detection and management of side effects, which can ensure patient safety and reduce permanent all-cause discontinuation. This strategy needs to be combined with a long-term approach acknowledging the late onset of clozapine’s full advantageous effects, which – in cases like reduced mortality rates – even then may not be easily discernible. Our aim is to encourage a safer, more frequent, and timely use of clozapine to maximize patients’ short- and long-term benefits. Even now, the extent of these benefits as well as patient’s satisfaction with treatment still clearly set clozapine apart from all other available treatment options.

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The sublingual use of atropine in the treatment of clozapine‐induced sialorrhea: A systematic review

Cited by 19 publications

References 38 publications

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH)

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH)

Sublingual Atropine Administration as a Tool to Decrease Salivary Glands’ PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [68Ga]Ga-PSMA-11

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

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