clozapine and Sialorrhea

Clozapine, an atypical antipsychotic used to treat people with schizophrenia, has been proposed as a possible treatment for salivary gland hypofunction. This scoping review investigated the available literature on clozapine's impact on salivary flow, in order to determine whether it could be used by dental practitioners in low doses as a treatment for dry mouth.. An electronic search was completed using Ovid MEDLINE (1996 to Nov 2021). Key MeSH search terms included "clozapine," "Clozaril," "salivation," "salivary flow rate," "sialorrhea," "hypersalivation," and "drooling." Two reviewers independently reviewed eligible articles and extracted the data based on the inclusion and exclusion criteria.. The initial search identified 129 studies, six of which were included in this review. Four of them (one cross-sectional and three interventional) described salivary flow rates in schizophrenic patients taking clozapine, while one of those and two others focused on the mechanism of clozapine-induced sialorrhea, with one study covering both. There were mixed findings, with one study observing a moderate association between clozapine dose and salivary flow, and the others reporting no differences. Findings on the putative mechanisms for clozapine-induced sialorrhea (CIS) were inconclusive.. There is insufficient high-quality information to justify using low-dose clozapine to increase salivary flow in dental patients with salivary gland hypofunction. Well-designed interventional studies and randomized control trials are required.

Topics: Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Dentists; Humans; Professional Role; Sialorrhea; Xerostomia

Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation.. Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment », « hypersalivation », « induced », « drug », « clozapine »). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study.. Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63).. In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.

Topics: Amisulpride; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Female; Humans; Male; Quality of Life; Scopolamine; Sialorrhea

Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea.. We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm.. 19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1).. Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.

Topics: Antidepressive Agents; Antipsychotic Agents; Clozapine; Histamine Antagonists; Humans; Medicine, Chinese Traditional; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Salivation; Schizophrenia; Sialorrhea

In patients taking clozapine, about 30% experience sialorrhoea, with its related potentially important medical and psychosocial implications. Until now, systemic treatments have been unsuccessful and also have unfavourable side-effects.
AIM: To examine the current evidence regarding the use of local atropine in clozapine-induced sialorrhoea (cis), as well as for sialorrhoea of other etiology.
METHOD: PubMed and Google Scholar were searched using the keywords 'sialorrhea', 'clozapine' and 'atropine' to investigate the use of sublingual atropine for cis, as well as for sialorrhoea of other etiology. Two patients are described and discussed.
RESULTS: Of 24 identified patients, 21 experienced a beneficial effect on cis with sublingually administered atropine eye drops or 1% ipratropium bromide nasal spray (0.03%). Side-effects, such as a dry mouth, unpleasant taste and short duration of action of the eye drops, were reported. Of the 67 patients treated with local atropine for sialorrhoea of other etiology, generally a beneficial effect and few side-effects were reported.
CONCLUSION: The sublingual administration of atropine appears to be effective in the treatment of cis, as well as in sialorrhoea of other etiology. The dose is usually 1-2 eye drops, two to three times per day.

Topics: Administration, Sublingual; Atropine; Clozapine; Humans; Sialorrhea

This article reviews four of the milder but still bothersome side effects of clozapine that are fairly frequent and may have a negative impact on patients' compliance with the treatment regime. We reviewed the available literature on the rate and management of four non-life-threatening side effects of clozapine, including hypersalivation, constipation, tachycardia, and nocturnal enuresis. We found a variety of pharmacological and behavioral strategies to manage these four side effects. There is, however, no consensus on a preferred strategy to control these distressing side effects and there are no guidelines. Psychiatrists should be aware of the relatively high rate of hypersalivation, constipation, tachycardia, and nocturnal enuresis in clozapine-treated patients, of the impact that these side effects may have on patients' quality of life, and should be able to suggest management strategies to the patients.

Topics: Antipsychotic Agents; Clozapine; Constipation; Humans; Nocturnal Enuresis; Sialorrhea; Tachycardia

To provide an understanding of the underlying pathophysiology and current treatment options for clozapine-induced sialorrhea.. Literature was retrieved through MEDLINE (1977-February 2011) using the key search terms clozapine, sialorrhea, hypersalivation, drooling, and treatment. In addition, reference citations from identified publications were reviewed.. All articles published in English identified from the data source were evaluated and included in the review.. Sialorrhea is a common and disabling adverse effect of clozapine use. Current treatment options include topical and oral antimuscarinic medications and α-adrenergic agents. New areas of investigation include glycopyrrolate, botulinum toxin, and substitute benzamide derivatives. Thirteen clinical trials (2 retrospective, 5 open-label, 6 double-blind) and 13 case reports were reviewed. Overall, there are weak data on use of antimuscarinic agents, consisting mostly of small open-label or retrospective studies. Glycopyrrolate, however, demonstrated significant reduction of hypersalivation in a randomized controlled trial. Medications with activity at α-adrenergic receptors have shown positive results in case reports, retrospective evaluations, and an open-label trial, but have not been investigated in a double-blind, controlled fashion. Botulinum toxin also significantly improved sialorrhea in both a case report and double-blind study, although the trial included hypersalivation from other etiologies in addition to clozapine. Substitute benzamide derivatives have demonstrated significant improvements in randomized controlled trials; however, they are not available in the US. Overall, few treatment strategies have been evaluated in controlled settings, warranting further randomized controlled trials to identify more effective treatment options.. Current pharmacologic treatment options for clozapine-induced sialorrhea are limited in number and efficacy. Although few randomized controlled trials have been conducted, this review identifies potential treatment alternatives for this common and sometimes severe adverse effect.

Topics: Adrenergic alpha-Agonists; Clinical Trials as Topic; Clozapine; Double-Blind Method; Humans; Muscarinic Antagonists; Retrospective Studies; Sialorrhea

Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%).. To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation.. We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.. We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation.. We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data.. Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7).. There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.

Topics: Antipsychotic Agents; Clozapine; Drugs, Chinese Herbal; Muscarinic Antagonists; Phenylpropionates; Randomized Controlled Trials as Topic; Sialorrhea

Topics: Antipsychotic Agents; Astemizole; China; Clozapine; Doxepin; Histamine Antagonists; Humans; Medicine, Chinese Traditional; Muscarinic Antagonists; Placebo Effect; Propantheline; Randomized Controlled Trials as Topic; Sialorrhea; Treatment Outcome

Clozapine-induced hypersalivation (CIH) is a significant side effect affecting about one-third of patients treated with clozapine. CIH can be stigmatizing, can affect quality of life, and can result in discontinuation of clozapine treatment. The purpose of this review is to provide an understanding of CIH, specifically, its pathophysiology, measurement, and the evidence for CIH treatment alternatives.. We searched MEDLINE from 1980 to June 2006 for all reported pharmacologic treatment studies related to CIH. We identified additional references by a manual search of the bibliographies of retrieved articles.. Several studies reported improvement of CIH with both selective and nonselective anticholinergic medications. However, with the exception of local anticholinergic agents such as ipratropium bromide and atropine eye drops, potential systemic adverse effects limit the effectiveness of this class of medications. Open-label studies of clonidine, an alpha2 antagonist, suggest that it may be beneficial in managing CIH. Other pharmacologic treatments, such as amisulpride and botulinum toxin, may be useful in refractory CIH cases.. Although few randomized controlled trials were found in the literature, this review highlights potential treatment alternatives for this common and disabling cause of hypersalivation. Prompt and effective treatment of CIH may assist with treatment tolerability, adherence, and outcomes in patients with treatment-refractory schizophrenia. Information on funding and support and author affiliations appears at the end of the article.

Topics: Clozapine; Humans; Psychotic Disorders; Sialorrhea; Stereotyping

Clozapine is an atypical antipsychotic agent with proven efficacy in refractory schizophrenia, but its widespread use is limited by adverse effects such as agranulocytosis, seizures, sedation, weight gain, and sialorrhea. Clozapine-induced sialorrhea (CIS) is bothersome and has socially stigmatizing adverse effects, which result in poor treatment compliance. The pathophysiology of this condition is poorly understood and the treatment options available are based mostly on case reports and open-label studies.. To review the available studies on CIS.. All relevant studies available through PUBMED search supplemented with manual search were undertaken.. The clinical features, complications, assessment, pathophysiology, and management of CIS are discussed.. Although the studies evaluating the therapeutic options has limitations and no drug has been found to be superior, judicious use of pharmacological agents along with behavioral methods will reduce this troublesome side effect and enhance compliance.

Topics: Adrenergic alpha-Agonists; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Humans; Sialorrhea

Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.. A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters.. A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%).. Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.

Topics: Antipsychotic Agents; Clozapine; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Sialorrhea; Treatment Outcome

Hypersalivation is frequently observed in patients treated with clozapine. Current strategies to counteract sialorrhea include the introduction of antimuscarinergic (anticholinergic) and alpha(2)-agonistic treatment. However, the use of these substances is limited in part by lack of efficacy and by adverse side effects. In cases of intractable sialorrhea, the application of botulinum toxin may be a new and safe therapeutic option. We here present an overview on current treatment strategies for sialorrhea and describe a patient who received botulinum toxin B for clozapine-induced hypersalivation.

Topics: Adult; Botulinum Toxins; Botulinum Toxins, Type A; Clozapine; Humans; Male; Muscarinic Antagonists; Practice Guidelines as Topic; Practice Patterns, Physicians'; Schizophrenia; Sialorrhea

To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials.. A computerized Medline search supplemented by an examination of cross-references and reviews was performed.. Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more 'tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment.. Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Delirium; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Risk; Risperidone; Schizophrenia; Schizophrenic Psychology; Sialorrhea; Treatment Outcome

Clozapine has demonstrated superior efficacy in relieving positive and negative symptoms in treatment-resistant schizophrenic patients; unlike other antipsychotics, it causes minimal extrapyramidal side effects (EPS) and has little effect on serum prolactin. Despite these benefits, the use of clozapine has been limited because of infrequent but serious side effects, the most notable being agranulocytosis. In recent years, however, mandatory blood monitoring has significantly reduced both the incidence of agranulocytosis and its associated mortality. The occurrence of seizures appears to be dose-related and can generally be managed by reduction in clozapine dosage. Less serious and more common side effects of clozapine including sedation, hypersalivation, tachycardia, hypotension, hypertension, weight gain, constipation, urinary incontinence, and fever can often be managed medically and are generally tolerated by the patient. Appropriate management of clozapine side effects facilitates a maximization of the benefits of clozapine treatment, and physicians and patients alike should be aware that there is a range of benefits to clozapine use that is wider than its risks.

Topics: Agranulocytosis; Antipsychotic Agents; Cardiovascular Diseases; Clozapine; Drug Monitoring; Humans; Respiration Disorders; Seizures; Sialorrhea; Weight Gain

To review underlying pathophysiology and possible treatments for clozapine-induced hypersalivation.. Primary literature was accessed through MEDLINE (1966-May 1999). Key search terms included clozapine, hypersalivation, sialorrhea, and treatment.. Hypersalivation occurs in up to 54% of patients receiving clozapine. An evaluation of studies and case reports focusing on management of clozapine-induced hypersalivation was conducted.. It is unclear whether clozapine increases salivation through its muscarinic M4 receptor activation and/or blockade of alpha2-adrenoceptors, or by causing a distortion in swallowing reflex. Treatment options include chewing gum, reducing the dosage of clozapine, or prescribing pharmacologic agents such as anticholinergics or alpha2-adrenoceptor agonists.

Topics: Adrenergic Agonists; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Drug Monitoring; Humans; Sialorrhea

Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induced sialorrhea is predominantly based on case reports. Due to its elusive mechanism, physicians have attempted to treat this side effect with agents that counteract clozapine's adrenergic and muscarinic properties. We evaluated reported treatment options and other possible strategies from a pharmacologic standpoint. Antimuscarinic agents and alpha-receptor agonists are both viable options but must be administered and monitored cautiously in patients with psychiatric disorders. Although not yet available in the United States, pirenzepine, a selective muscarinic receptor antagonist, has the most promising mechanism. Other selective, peripherally acting agents must be investigated in controlled clinical trials to determine their efficacy as possible alternatives.

Topics: Adrenergic Agents; Antipsychotic Agents; Cholinergic Agents; Clozapine; Humans; Receptors, Adrenergic; Receptors, Muscarinic; Sialorrhea

Compliance with conventional antipsychotic medication is often poor, with many patients discontinuing treatment only a few months after commencing therapy. The side effects of treatment, which are not necessarily restricted solely to motor symptoms, are often considered to be responsible for this noncompliance. In contrast to conventional antipsychotics, clozapine is associated with only minimal extrapyramidal symptoms, and in most patients, its use results in significant improvements in compliance. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. Clozapine therapy is associated with a beneficial risk/benefit ratio in the majority of treatment-resistant schizophrenic patients. With careful hematologic control, the risk of agranulocytosis can be minimized. The marked increase in the well-being of patients receiving clozapine should stimulate psychiatrists to broaden its use and not limit it to severely treatment-resistant individuals.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Fatigue; Humans; Patient Compliance; Risk Assessment; Schizophrenia; Schizophrenic Psychology; Seizures; Sialorrhea; Tachycardia; Treatment Outcome

Hypersalivation and drooling are commonly reported in clozapine-treated patients. Current management strategies have been evaluated using subjective measures. Many case reports describe the successful use of atropine in the treatment of the condition.. To measure the effect and safety of sublingual atropine on nocturnal unstimulated saliva secretion. Secondary aims were to evaluate the patient's satisfaction with the atropine effect on hypersalivation (or sialorrhea), drooling, and sleep.. Twenty-one clozapine-treated patients with hypersalivation, or drooling, were randomised to take a single 600-μg dose of sublingual atropine drops or a matching placebo. The saliva secretion was measured over 5 min at baseline and 2 h after the administration of the study medication.. Sublingual atropine reduced the saliva secretion significantly more than the placebo (mean difference = - 57.21%, 95% CI: - 104.30, - 10.11, P = 0.02). A significant decrease in standing pulse rate was recorded in the participants in the atropine group (- 5.8 (- 9.54, - 2.15), P = 0.002). Subjectively, more patients in the atropine group found their pillow to have less saliva the following morning and found their sleep to be better.. Sublingual atropine drops significantly reduces nocturnal unstimulated clozapine-induced saliva secretion. More research is required to compare the effect of sublingual atropine with other anticholinergic medications and different dosage forms.. ACTRN12618000051246.

Topics: Administration, Sublingual; Adult; Antipsychotic Agents; Atropine; Clozapine; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Saliva; Salivation; Sialorrhea; Treatment Outcome

Clozapine is the only evidence-based antipsychotic for treatment-resistant schizophrenia. However, it has considerable side effects, limiting its usability and reducing patients' adherence. One of the most common and distressing side effects is hypersalivation, which can be debilitating, stigmatizing and potentially dangerous through its association with aspiration pneumonia. There is a paucity of evidence guiding possible treatment strategies for hypersalivation. This study aims to examine the efficacy of hyoscine (scopolamine) for clozapine-induced hypersalivation. Fourteen inpatients diagnosed with treatment-resistant schizophrenia, treated with clozapine and suffering from hypersalivation were randomized to receive hyoscine 0.3 mg and placebo daily for 4 weeks each in a randomized, double-blind, placebo-controlled cross-over trial. The primary outcome was improvement in the Toronto Nocturnal Hypersalivation Scale. The secondary outcomes were change in the mass of the pillowcase, anxiety, depression and quality of life. Hypersalivation improved significantly with hyoscine over placebo when measured by the Toronto Nocturnal Hypersalivation Scale (odds ratio=0.21, 95% confidence interval: 0.16-0.28, P<0.001). No significant difference was observed in any of the secondary outcomes. This study showed a beneficial effect of hyoscine over placebo for clozapine-induced hypersalivation.

Topics: Adult; Antipsychotic Agents; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Schizophrenia; Scopolamine; Sialorrhea

This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine-induced hypersalivation.. The patients enrolled in this study consisted of 10 clozapine-treated schizophrenia patients and 10 healthy adult men. A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed.. A total of 10 patients and 10 healthy adult men completed the study. No significant reduction in the saliva production of the clozapine-treated patients was observed; however, that of the healthy adult men decreased significantly.. Scopolamine ointment was not effective against clozapine-induced hypersalivation. A further study is necessary for confirming its effect.

Topics: Adult; Aged; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Outcome Assessment, Health Care; Pilot Projects; Prospective Studies; Schizophrenia; Scopolamine; Sialorrhea; Young Adult

Nocturnal sialorrhea is one of the most frequent adverse events in clozapine treatment. Symptomatic management of sialorrhea usually consists of off-label treatment with anticholinergic agents. The aim of the current study is to evaluate the efficacy and safety of glycopyrrolate in patients using clozapine that experience sialorrhea.. In a double-blind randomized crossover trial, patients with nocturnal sialorrhea (n = 32) were randomized to treatment with glycopyrrolate 1 mg or placebo. This double-blinded phase was followed by an optional open label extension phase with glycopyrrolate 2 mg. Exposure periods consisted of 6 consecutive days and were separated with 1 washout week. The primary outcome was clinical improvement of nocturnal sialorrhea assessed by the Patient Global Impression of Improvement (PGI-I).. The proportion of patients with a clinical improvement according to PGI-I did not significantly differ between 1 mg and placebo (18.8% vs 6.3%, P = 0.289); however, in patients using glycopyrrolate 2 mg once daily versus placebo, it did (43.5% vs 6.3%, P = 0.039). Glycopyrrolate was not associated with severe adverse events or worsening of cognitive adverse events.. 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.

Topics: Adult; Antipsychotic Agents; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Glycopyrrolate; Humans; Male; Mental Disorders; Middle Aged; Muscarinic Antagonists; Outcome Assessment, Health Care; Sialorrhea

Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

Topics: Adult; Antipsychotic Agents; Clozapine; Dopamine D2 Receptor Antagonists; Double-Blind Method; Humans; Metoclopramide; Middle Aged; Schizophrenia; Sialorrhea; Young Adult

Clozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK. Although efficacious, a common and unpopular side effect of clozapine treatment is clozapine-induced hypersalivation (CIH), which can contribute to non-adherence. The standard treatment for CIH in the UK is hyoscine hydrobromide but this may aggravate cognitive deficits in patients with schizophrenia while glycopyrrolate may be an effective alternative with a more tolerable side effect profile. There is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH.. This is a multicentre randomised, double-blind, placebo-controlled feasibility study of glycopyrronium bromide (glycopyrrolate) and hyoscine hydrobromide (hyoscine) in patients with clozapine-induced hypersalivation. We aim to recruit 42 patients who have been prescribed clozapine and are experiencing hypersalivation, and randomise them to one of three study arms (either hyoscine, glycopyrrolate or placebo). The primary outcome measures will be the participant recruitment and attrition rates, and the secondary outcome will be the metrics of the daytime hypersalivation measure. After a 1-week washout period (discontinuing CIH medication, if any), there will be a 4-week treatment period where participants will be titrated up to the maximum tolerated dose of hyoscine, glycopyrrolate or placebo. Measurements of daytime salivation, nocturnal salivation, cognition and side effects will be taken during home visits in week 2 and week 5. Information on salivation and side effects will also be taken through telephone calls in week 3 and week 4. To gather information on the experience of study participants, exit interviews will also be requested with all participants who drop out of the study and a sample of participants who complete the study.. There is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH. There is promising evidence that glycopyrrolate may be more successful in the treatment of CIH causing fewer cognitive side effects. We propose to conduct a randomised placebo-controlled feasibility study of glycopyrrolate and hyoscine in the treatment of clozapine-induced hypersalivation to inform the design of a future efficacy trial.. Clinicaltrials.gov NCT02613494 , 23 November 2015.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Clinical Protocols; Clozapine; Double-Blind Method; Feasibility Studies; Female; Glycopyrrolate; Humans; Male; Middle Aged; Muscarinic Antagonists; Research Design; Salivation; Schizophrenia; Scopolamine; Sialorrhea; Time Factors; Treatment Outcome; United Kingdom; Young Adult

Previous publications demonstrated substitute benzamides as effective agents in treatment of clozapine-induced sialorrhea (CIS). The aim of this study was to compare efficacy of amisulpride and moclobemide (both from the substitute benzamide group) in controlling, or at least minimizing, CIS.. The study was designed as a 6-week, two-center, fixed-dose, comparison study of 400 mg/day of amisulpride versus 300 mg/day of moclobemide as an adjunctive treatment in 53 schizophrenia and schizoaffective disorder patients (diagnosed according to DSM-IV) suffering from CIS. The patients were treated with each medication during 2 weeks, followed by a washout period of 2 weeks. Primary outcome measures included the reduction in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Secondary outcomes included the Positive and Negative Syndrome Scale (PANSS), Manic State Assessment Scale, and Extrapyramidal Symptom Rating Scale (ESRS).. Both amisulpride and moclobemide were very effective in reducing CIS. Almost 74% of patients treated with amisulpride and 83% of patients treated with moclobemide showed some level of improvement on NHRS. Only in one patient treated with amisulpride, CIS worsened.. Both medications were safe and effective as treatment of CIS. Although moclobemide exceeded amisulpride in antisalivation activity, treatment of CIS with amisulpride leads to improvement in psychotic symptoms.

Topics: Adult; Aged; Amisulpride; Antipsychotic Agents; Clozapine; Cross-Over Studies; Female; Humans; Male; Middle Aged; Moclobemide; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Sialorrhea; Sulpiride

It is reported that 30% to 80% schizophrenia patients suffered from hypersalivation when taking clozapine. Some investigations of the use of formulas of traditional Chinese medicine (TCM) to treat clozapine-induced hypersalivation suggested their potential treatment effects. In these formulas, Suoquan Pill (SQP) and Wuling Powder (WLP) were suggested to have therapeutic effects in improving clozapine-induced hypersalivation.. A prospective, double-blind, randomized, placebo-controlled study will be conducted to test the therapeutic effects of SQP and WLP in relieving hypersalivation in patients taking clozapine. A total of 45 patients will be enrolled into this study with 15 in each treatment group. Patients will receive medication according to their assigned group. Either SQP 10 g per oral dose twice daily, WLP 10 g per oral dose twice daily or placebo powder 10 g per oral dose twice daily will be prescribed to the patients for 8 weeks. The Drooling Severity Scale, Nocturnal Hypersalivation Rating Scale and sialoscintigraphy will be used as the primary outcome measures; the Clinical Global Impressions Severity, the Positive and Negative Syndrome Scale, the Abnormal Involuntary Movement Scale, the Simpson-Angus Scale and the TCM constitutional scale will be used as the secondary outcome measures. It is hypothesized that SQP and WLP will have a beneficial effect in controlling clozapine-induced hypersalivation symptoms. It may also improve the life quality of psychotic patients by improving their mental status.. ClinicalTrials.gov (Identifier: NCT01045720).

Topics: Clozapine; Double-Blind Method; Drugs, Chinese Herbal; Humans; Phytotherapy; Placebos; Prospective Studies; Research Design; Schizophrenia; Sialorrhea

Clozapine-induced sialorrhea (CIS) is a subjective distressing adverse effect and occurs in 31%-57% of schizophrenic patients receiving clozapine therapy. Current pharmacotherapy on CIS has focused on anticholinergic agents, even though they may impair cognitive function. Previous case reports have suggested the benefit of glycopyrrolate or biperiden in treating this condition, but no randomized controlled trial has provided evidence. The objective of our study was to evaluate the efficacy and impact on cognition of glycopyrrolate and biperiden treatments for schizophrenic patients suffering from CIS.. Patients who satisfied the inclusion criteria entered a 12-week, randomized, double-blind, crossover, fixed-dose trial. The study consisted of two 4-week crossover phases, which were separated by a 4-week washout period. Sialorrhea and global cognitive function were assessed by using a Drooling Rating Scale (DRS) and the Mini Mental State Examination (MMSE), respectively.. Throughout the study, patients treated with glycopyrrolate or biperiden had significantly reduced DRS scores. Moreover, the DRS scores were significantly lower with glycopyrrolate treatment than with biperiden. In other respects, there were no significant differences in MMSE scores in patients treated with glycopyrrolate. However, we found a significant reduction in MMSE scores in patients treated with biperiden.. We provide evidence, for the first time, of the efficacy of glycopyrrolate and biperiden in the treatment of CIS. Furthermore, glycopyrrolate displays less impact on cognitive function. Consequently, glycopyrrolate can become a valid option for treating CIS. Observations from our study serve as a springboard for additional large-scale prospective trials.

Topics: Adult; Antipsychotic Agents; Biperiden; Clozapine; Cognition; Cross-Over Studies; Double-Blind Method; Female; Glycopyrrolate; Humans; Male; Mental Status Schedule; Middle Aged; Muscarinic Antagonists; Schizophrenia; Sialorrhea; Taiwan

Clozapine-induced hypersalivation (CIH) occurs in up to 57% of treated patients and can be the source of considerable subjective distress. Previous open-label studies suggest that sublingual ipratropium bromide may be effective in treating CIH.. We conducted a randomized, double-blind, placebo-controlled crossover trial to evaluate the efficacy of ipratropium in 20 individuals with CIH between September 2006 and August 2007. This study was 5 to 6 weeks in duration, based on the participants' clozapine blood-monitoring schedule, and it consisted of two 2-week crossover phases separated by a 1- or 2-week washout period. Primary outcome measures included the reduction in the Toronto Nocturnal Hypersalivation Scale (TNHS) and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Secondary outcomes included visual analog scales assessing hypersalivation severity (VAS-S) and distress (VAS-D).. No significant reduction in CIH was found on the TNHS (P = .379), CGI-S (P = .266), or CGI-I (P = .599). Moreover, no difference was noted between study groups on the VAS-S (P = .969) and VAS-D (P = .527). There was no difference in the number of CIH responders at the conclusion of the 2-week placebo (40%, n = 8) and ipratropium (45%, n = 9) study phases (45%, n = 9) according to the TNHS. Randomization order did not have a significant effect on TNHS, CGI-S, or CGI-I scores. Tolerability was comparable between groups, with dry mouth occurring in 1 placebo group subject and 2 ipratropium group subjects.. Despite the reports of some preliminary studies that ipratropium is an efficacious treatment for CIH, ipratropium failed to demonstrate significant clinical effect in comparison to placebo. Further research should explore the efficacy of other locally acting anticholinergic agents or other classes of medications.. clinicaltrials.gov Identifier: NCT00381589.

Topics: Adolescent; Adult; Aged; Cholinergic Antagonists; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Humans; Ipratropium; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Sialorrhea; Surveys and Questionnaires; Treatment Outcome

The second generation antipsychotics clozapine and olanzapine frequently induce weight gain. Randomized studies investigating abnormal eating behavior (food craving, binge eating) possibly associated with weight gain are lacking. Thirty patients with schizophrenia, schizophreniform, or schizoaffective disorder were included in this randomized, double-blind, parallel study comparing abnormal eating behavior using a standardized scale, clinical efficacy using the Brief Psychiatric Rating Scale 0-6 and Clinical Global Impression-Severity scale, and tolerability of clozapine and olanzapine. In both treatment groups, the number of patients reporting food craving, binge eating, or both increased over time. The likelihood to experience food craving at any time during drug treatment showed a trend (P = 0.068) to be higher in the olanzapine group (48.9%) compared with the clozapine group (23.3%). The likelihood to experience binge eating at any time during drug treatment was numerically but not statistically significantly higher in the olanzapine group (16.7%) than in the clozapine group (8.9%). In both groups, significant baseline-to-end point improvements of clinical symptoms (Brief Psychiatric Rating Scale 0-6: clozapine, 36.6 +/- 8.8 to 15.9 +/- 13.7; olanzapine, 36.7 +/- 9.9 to 19.1 +/- 13.8) and severity of illness (Clinical Global Impression-Severity scale: clozapine, 4.7 +/- 0.6 to 2.5 +/- 1.5; olanzapine, 4.5 +/- 0.6 to 2.3 +/- 1.2) were observed. These improvements did not differ significantly between groups. Olanzapine was more tolerable than clozapine; adverse events occurred significantly (P < 0.01) less frequently than in the clozapine group. These results suggest that both clozapine and olanzapine can induce food craving and binge eating, however, olanzapine possibly to a greater extent. Findings on clinical efficacy and safety are in accordance with previous reports.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Blood Pressure; Body Mass Index; Bulimia; Clozapine; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Heart Rate; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Sialorrhea; Treatment Outcome; Weight Gain

The beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Placebos; Schizophrenia; Sialorrhea; Sulpiride

Clozapine has shown superior efficacy in treatment of refractory schizophrenia, but its use is limited by emergent side-effects. Among other adverse effects, sialorrhea is a troublesome side-effect, its stigmatizing nature results in poor treatment compliance. Several hypotheses have been put forward in the etiology of clozapine-induced sialorrhea. 2 adrenergic antagonism is hypothesized to be involved in its pathophysiology, based on the response to clonidine and lofexidine. Oral clonidine (50 to 100 g/day) was tried on 12 stable outpatients of schizophrenia maintained on clozapine. Wet area over the pillow as reported by the patients was recorded at baseline and at 4 weeks of treatment along with the subjective response after the treatment. Most of the patients reported a decrease in sialorrhea without any adverse events. We describe encouraging results in an open case series of oral clonidine for clozapine-induced sialorrhea.

Topics: Adrenergic alpha-Agonists; Adult; Antipsychotic Agents; Clonidine; Clozapine; Female; Humans; Male; Middle Aged; Schizophrenia; Sialorrhea

Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded.. In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC with UV detection before and after addition of pirenzepine for 3 days.. Significantly fewer patients reported hypersalivation after addition of pirenzepine (69 % vs. 34.5 %, P = 0.002). No significant differences of clozapine and N-desmethylclozapine serum levels before (329 +/- 181 ng/ml and 218.0 +/- 123.4 ng/ml, respectively) and 3 days after (336 +/- 215 ng/ml and 235.9 +/- 164.4 ng/ml, respectively) addition of pirenzepine were found. In three patients, however, clozapine serum levels increased; this was probably unrelated to pirenzepine.. In conclusion, treatment of clozapine-induced hypersalivation with pirenzepine is a recommendable combination with low risk of additional side effects.

Topics: Adult; Antipsychotic Agents; Chromatography, High Pressure Liquid; Clozapine; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Pilot Projects; Pirenzepine; Schizophrenia; Sialorrhea; Spectrophotometry, Ultraviolet

The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4-muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo-controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor.

Topics: Adult; Antipsychotic Agents; Clozapine; Cross-Over Studies; Double-Blind Method; Humans; Muscarinic Antagonists; Pirenzepine; Sialorrhea

Sialorrhea is reported by 31% of patients taking clozapine. Anticholinergic agents and adrenergic agonists are used for its treatment based on empirical evidence. In the present study, 10 patients who failed to respond to anticholinergic or adrenergic agents received intranasal ipatropium bromide (IPB) to minimize anticholinergic systemic absorption. Intranasal IPB was given to 10 patients for clozapine-induced sialorrhea who failed to respond to benztropine or clonidine. Pre-, post- and 6 month follow-up values were recorded on a single-item, 5-point Hypersalivation Rating Scale. The sign test was used for statistical comparison (P < 0.05). Eight patient reported initial improvement in sialorrhea values. Two patients reported no change and two patients discontinued IPB. At 6 months, six patients maintained improvement. Side-effects for IPB were minor. A significant trend was observed in the values pre- and post-treatment with IPB (P < 0.004). Improvement was maintained at 6 month follow-up (P < 0.008). This case series demonstrates the possible utility of intranasal IPB for clozapine-induced sialorrhea. Intranasal IPB lacks significant systemic anticholinergic effects when prescribed along with clozapine. This study shows only qualitative differences in salivation values and large controlled-comparative trials are needed.

Topics: Adult; Antipsychotic Agents; Benztropine; Cholinergic Antagonists; Clozapine; Female; Humans; Ipratropium; Male; Middle Aged; Muscarinic Antagonists; Psychiatric Status Rating Scales; Schizophrenia; Sialorrhea

The objective of this study was to investigate the efficacy of the anticholinergic agent trihexyphenidyl in the treatment of clozapine-induced hypersalivation. Fourteen chronic schizophrenic patients who exhibited nocturnal hypersalivation during clozapine treatment were coadministered trihexyphenidyl (5-15 mg/day, at bedtime) for 15 days. Salivation was assessed by a single-item 5-point scale. A reduction of 44% in the reported nocturnal hypersalivation was observed after trihexyphenidyl treatment. These results indicate that at least some chronic schizophrenic patients with clozapine-induced nocturnal hypersalivation may benefit from anticholinergic treatment.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Muscarinic Antagonists; Schizophrenia; Sialorrhea; Trihexyphenidyl

This study examined the effect of clozapine on saliva flow rate. Unstimulated whole saliva was collected from 9 patients taking clozapine (dose range = 50-400 mg/day) and from 8 controls who had never used clozapine. There was no significant difference between the average saliva flow rates in the two groups (p > .10), nor was there significant correlation between saliva flow rate and daily clozapine dose (p > .10). Alternative explanations for observations or complaints of excessive salivation, drooling, or a choking feeling while taking clozapine are proposed.

Topics: Antipsychotic Agents; Clozapine; Humans; Pilot Projects; Salivation; Sialorrhea

The extent of hypersalivation was evaluated in a group of 25 schizophrenic patients on clozapine. A high prevalence of the complaint was detected by a questionnaire; up to 80% of the patients complained of hypersalivation at night. Salivary flow-rate and composition was examined in 17 patients who agreed to participate and in a matched group of healthy controls. No significant differences were detected in composition or flow-rates of resting and stimulated saliva. The salivary flow-rates in the schizophrenic patients on clozapine did not correlate with the subjective complaint of hypersalivation. Because the severity and prevalence of the complaint was higher at night, a possibility of an altered circadian rhythm of salivation might be suggested in these patients.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Potassium; Saliva; Schizophrenia; Sialorrhea; Sodium; Taste

Clozapine is an atypical neuroleptic with superior efficacy in severely ill, treatment-resistant inpatients with schizophrenia. To determine if clozapine's differential efficacy generalizes to less ill, outpatients populations, the authors examined the effects of clozapine on positive and negative symptoms in outpatients with schizophrenia.. Outpatients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospective 6-week trial of fluphenazine participated in a 10-week, double-blind, parallel-groups comparison of clozapine and haloperidol. Thirteen men and six women were given clozapine, and 15 men and five women were given haloperidol. Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed. Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day (SD = 45.8) and 24.8 mg/day (SD = 5.5), respectively.. Clozapine was superior to haloperidol for treating positive symptoms. In addition, eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria. Clozapine was also superior to haloperidol for treating negative symptoms, although these effects were relatively minor. Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia. Overall, clozapine was well tolerated.. Clozapine has superior efficacy for treating positive symptoms in partially responsive outpatients with chronic schizophrenia, suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill.

Topics: Adult; Ambulatory Care; Chronic Disease; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sialorrhea; Tachycardia

In order to assess the safety and some efficacy aspects of clozapine under UK conditions, 54 in-patients with severe treatment-resistant schizophrenic disorders were evaluated using several scales before and during treatment. Of the 54 evaluated, 26 completed the 26-week study. Of these patients, 20 showed improvement in psychopathology, often to a marked degree, involving both positive and negative symptoms. Some oral-facial extrapyramidal side-effects decreased as well. Two patients developed neutropenia, but recovered on discontinuation of clozapine. The most frequent adverse event was hypersalivation, and five patients suffered from seizures. It is concluded that clozapine is worth considering for the treatment of severe treatment-resistant patients in the UK.

Topics: Adult; Chronic Disease; Clozapine; Drug Resistance; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neutropenia; Schizophrenia; Schizophrenic Psychology; Sialorrhea; Treatment Outcome; United Kingdom

40 Schizophrenic inpatients with clozapine induced salivation were divided into two groups randomly. They were treated with Suo Quan pill and a control study of the placebo (neutral pill) for reducing clozapine induced salivation. These cases were also classified by TCM Syndrome Differentiation and laboratory examinations were performed.. There was a significant difference in effect on salivation between the therapeutic group (21 cases) and the controlled group (19 cases), P < 0.01. According to their TCM subtypes two subtypes (Stagnation of Phlegm-Dampness and Yin Deficiency) showed the best results. No correlation between the peripheral clozapine level and salivation was found. No side effect was recorded.

Topics: Adult; Clozapine; Double-Blind Method; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Schizophrenia; Sialorrhea

Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied.. To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life.. We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed.. Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (B = 0.417; p = 2.1e - 6, R. The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended.. Clinical Trials ( https://clinicaltrials.gov ) under reference NCT04197037.

Topics: Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Humans; Prevalence; Quality of Life; Sialorrhea

Clozapine-induced sialorrhea (CIS) is one of the most common side effects of clozapine use, while the mechanism remains unclear.. A total of 51 schizophrenia patients taking clozapine were selected. Among them, 32 had sialorrhea, and 19 had no sialorrhea. Saliva metabolites were identified using ultra-high-performance liquid chromatography-MS/MS (UHPLC-MS/MS), and the differences in saliva metabolites in each group were analyzed through qualitatively searching HMDB, KEGG, and self-built databases, combined with multivariate statistics. After further evaluation by receiver-operating characteristic curve (ROC) analysis, the screened differential metabolites were enriched and topologically analyzed.. The biomarkers potentially related to CIS included 37 differential metabolites involving 17 metabolic pathways, mainly histidine metabolism (p < 0.05, impact = 0.50), pyrimidine metabolism (p < 0.05, impact = 0.08), and β-alanine metabolism (p < 0.05, impact = 0.06).. Our study indicates that histidine metabolic pathway may contribute to the mechanism of CIS.

Topics: Antipsychotic Agents; Biomarkers; Clozapine; Histidine; Humans; Metabolic Networks and Pathways; Sialorrhea; Tandem Mass Spectrometry

Topics: Amitriptyline; Antipsychotic Agents; Clozapine; Humans; Schizophrenia; Sialorrhea

The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH.. This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust.. 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.. 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.

Topics: Antipsychotic Agents; Clozapine; Humans; Metoclopramide; Retrospective Studies; Schizophrenia; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Humans; Schizophrenia; Sialorrhea; Sulpiride

Hypersalivation is a common, clozapine-related adverse drug reaction with a serious impact on quality of life. Pharmacokinetic correlates of clozapine-related hypersalivation have evaded attention. The purpose of this study was to compare pharmacokinetic parameters between clozapine-treated patients with vs. without hypersalivation from a large therapeutic drug monitoring database.. Out of a large therapeutic drug monitoring dataset of clozapine-treated patients, we compared a group of patients with hypersalivation (n = 72) and a control group of patients without any adverse reactions in this regard (n = 323). Comparisons included plasma concentrations and concentrations-by-dose as well as demographic characteristics between groups. Post-hoc analyses were performed separately in smokers and non-smokers. We used the non-parametric Mann-Whitney U test and the chi-square test, while effects of confounders were assessed using a bootstrapping analysis of covariance.. Patients with hypersalivation had higher clozapine plasma concentrations and concentrations-by-dose (p < 0.001 for the Mann-Whitney U test in both cases). Groups did not differ regarding demographic characteristics except for clozapine daily dose and percentage of smokers (p = 0.005 for the Mann-Whitney U test and p = 0.028 for the chi-square test, respectively). There were fewer smokers across patients with hypersalivation compared with patients without and daily doses were higher in patients with hypersalivation. After analysis of covariance, differences remained for both plasma concentrations and concentrations-by-dose (p < 0.001 for both). Post hoc analyses in smokers and non-smokers separately reported similar findings.. Elevated clozapine plasma concentrations and higher concentrations-by-dose were observed in patients with hypersalivation. A potential role for therapeutic drug monitoring in the prevention or management of clozapine-related hypersalivation is suggested.

Topics: Antipsychotic Agents; Clozapine; Drug Monitoring; Humans; Quality of Life; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Humans; Schizophrenia; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Humans; Sialorrhea

Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia. Despite all this effectiveness, it has side effects that can be serious and bothersome. Sialorrhea is the most common adverse drug reaction that occurs during clozapine treatment. It is usually persistent, may impair the patient's quality of life and reduce treatment compliance. However, there is limited evidence to guide possible treatment strategies for sialorrhea. N-Acetylcysteine (NAC) is a powerful antioxidant. It acts directly as a scavenger of free radicals, in particular oxygen radicals. The antioxidant NAC also modulates glutamatergic, neurotrophic and inflammatory pathways. The first time we examined and reported the effect of NAC (1200-2400 mg/day) on clozapine-induced sialorrhea in a patient group of five patients. After four weeks of follow-up, the severity of sialorrhea decreased significantly with NAC augmentation. There were no significant side effects of NAC as measured by the UKU scale.

Topics: Acetylcysteine; Adult; Clozapine; Female; Humans; Male; Middle Aged; Schizophrenia; Sialorrhea

Topics: Agammaglobulinemia; Antipsychotic Agents; Betacoronavirus; Clozapine; Contraindications, Drug; Coronavirus Infections; COVID-19; Drug Monitoring; Drug Prescriptions; Humans; Pandemics; Parkinson Disease; Pneumonia, Aspiration; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2; Schizophrenia; Sialorrhea

Topics: Anticonvulsants; Antipsychotic Agents; Betacoronavirus; Clozapine; Coronavirus Infections; COVID-19; Delayed-Action Preparations; Drug Resistance; Drug Therapy, Combination; Humans; Immunologic Factors; Lithium Carbonate; Male; Middle Aged; Paliperidone Palmitate; Pandemics; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2; Sialorrhea; Treatment Outcome; Valproic Acid

Topics: Acetylcholine Release Inhibitors; Antipsychotic Agents; Botulinum Toxins; Clozapine; Female; Humans; Middle Aged; Neurotoxins; Sialorrhea; Young Adult

Side Effects of Smoking Cessation Abstract. We present the case of a clozapine intoxication associated with aspiration pneumonia due to smoking cessation. Clozapine is mainly metabolized by CYP1A2. CYP1A2 is induced by cigarette smoking, which may change the plasma level of clozapine, especially if consuming habits change.. Zusammenfassung. Wir präsentieren den Fall einer Clozapin-Intoxikation mit konsekutiver Aspirationspneumonie nach einem Rauchstopp. Clozapin wird hauptsächlich über CYP1A2 metabolisiert, Zigarettenkonsum führt zu einer Induktion von CYP1A2 und kann hierdurch den Plasmaspiegel von Clozapin relevant beeinflussen, insbesondere, wenn sich die Konsumgewohnheiten ändern.

Topics: Clozapine; Confusion; Cytochrome P-450 CYP2A6; Humans; Male; Middle Aged; Pneumonia, Aspiration; Risk Factors; Schizophrenia, Paranoid; Sialorrhea; Smoking Cessation

Clozapine is the drug of choice for treatment-resistant schizophrenia. While pediatric clozapine use is not contraindicated, the literature describing its clinical application is limited. The primary objective of this study was to assess the use of clozapine in a child and adolescent population by characterizing the documented safety and clinical benefits of the medication.. A multicenter retrospective study at sites in the United States and Australia included children and adolescents admitted to a psychiatric unit who were administered at least one dose of clozapine. Information related to demographics, patient history, past treatments, clozapine, and adverse events was collected.. Eighty-two patients from eight sites were included in this study. Patients were predominantly clozapine naive (76.8%), and most had a discharge diagnosis of a primary psychotic disorder (61%) or bipolar disorder (25.6%). Four clozapine discontinuations occurred during hospitalization due to severe neutropenia, ileus, need for diagnostic clarification, and significant psychomotor retardation. The remainder (n = 78) were discharged on a mean clozapine dose of 218.1 ± 142.2 mg. Sedation (26.8%) and sialorrhea (17.1%) were the most common documented adverse events. The mean number of previously trialed antipsychotics before clozapine was 3.5 ± 1.4 (range 1-10). Improvement with clozapine was documented as significant (31.7%), moderate (32.9%), minimal (12.2%), no improvement (2.4%), and not described (20.7%).. In this cohort, 95% of pediatric patients admitted with or started on clozapine during an acute psychiatric hospitalization were discharged on the medication. The high incidence of adverse events should reinforce to clinicians the need for vigilant monitoring. Pediatric guidelines recommend clozapine for refractory schizophrenia but stress the critical need to ensure an accurate diagnosis. Limited data exist for the use of clozapine in pediatric patients with other diagnoses.

Topics: Adolescent; Antipsychotic Agents; Australia; Bipolar Disorder; Child; Clozapine; Female; Humans; Male; Neutropenia; Psychiatric Department, Hospital; Psychotic Disorders; Retrospective Studies; Sialorrhea

Topics: Administration, Sublingual; Adult; Antipsychotic Agents; Atropine; Clozapine; Humans; Male; Middle Aged; Muscarinic Antagonists; Psychotic Disorders; Schizophrenia; Sialorrhea

Topics: Adult; Cholinergic Antagonists; Clozapine; Female; Humans; Ointments; Schizophrenia, Paranoid; Scopolamine; Sialorrhea

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pneumonia, Aspiration; Schizophrenia, Paranoid; Sialorrhea

Clozapine is an antipsychotic drug recommended for resistant schizophrenia, but its widespread use is limited by adverse effects. Sialorrhea is a common and troublesome adverse effect seen with clozapine which leads to poor compliance. Several treatment strategies are advocated, no single treatment is considered superior. Amitriptyline, a tricyclic antidepressant, has been found to be useful for clozapine-associated sialorrhea at 87-100 mg per day. We report the effect of very low dose amitriptyline (10 mg per day) in a patient with clozapine-associated sialorrhea. There was rapid and complete resolution of sialorrhea after three days without any emergent adverse effect.

Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Clozapine; Humans; Male; Schizophrenia; Sialorrhea; Young Adult

Topics: Antipsychotic Agents; Clozapine; Humans; Metoclopramide; Schizophrenia; Sialorrhea

The clinical records of 190 patients with schizophrenia who discontinued clozapine between 1990 and 2012 in the county of Northamptonshire were examined, in an attempt to answer the following questions. Why do patients stop clozapine? What do physicians prescribe as an alternative? What is the mortality in this patient group?. Patients' data were extracted using their electronic records, then analysed using descriptive statistical methods.. Non-compliance with treatment, or with the mandatory white blood cell monitoring, was the most common reason (55.3%) for clozapine cessation, followed by neutropaenia and other adverse effects (25.2%). Death (mean age 48 years) was the third most common reason (10%), with respiratory infections accounting for more than a quarter of the deaths. 13% of the patients had died (mean age 49 years) at some point following clozapine discontinuation. In terms of the alternative antipsychotic prescribing, olanzapine was the most commonly prescribed (37.1%) drug in patients who were still under the care of the local psychiatric service (n=121), at the time of data extraction. Clozapine had been reinstated in 19% of these patients.. Our findings are generally consistent with previous studies, and they demonstrate the need for physicians to address their patients' concerns regarding clozapine treatment, and to effectively manage any adverse effects. Sialorrhea and constipation seem to be particularly of concern, as they may be linked to clozapine- related mortality. Olanzapine was the most commonly prescribed alternative to clozapine, which suggests that it may possibly have a role in refractory schizophrenia.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Constipation; Electronic Health Records; Female; Humans; Male; Middle Aged; Olanzapine; Prescription Drugs; Retrospective Studies; Schizophrenia; Sialorrhea

The parasympathetic transmitter vasoactive intestinal peptide (VIP) increases salivary gland blood flow and evokes protein secretion and, in some species, such as rats, a small fluid secretion. It interacts synergistically with muscarinics for protein and fluid output. Human salivary acini are supplied with VIP-containing nerves. We hypothesise that VIP and clozapine, acting together, evoke a volume of saliva greater than the sum of those induced by each drug given separately. It was further considered whether, in the current test situation, circulatory events influenced the magnitude of the secretory response.. Saliva from parotid glands deprived of their autonomic innervation, and saliva and blood from innervated submandibular glands were collected in adrenoceptor antagonist-pretreated pentobarbitone-anaesthetised rats. Initially, the individual and then the combined effects of intravenous doses of VIP and clozapine were established.. The submandibular volume response to the combination was 2-3 times higher, while blood pressure and glandular blood flow did not differ from those to VIP alone. The synergism occurred independent of nerves as shown in denervated parotid glands.. From the current preclinical data, we speculate that VIP of parasympathetic origin, by its synergistic interaction with clozapine, may contribute to the clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.

Topics: Animals; Antipsychotic Agents; Clozapine; Female; Parasympathetic Nervous System; Parotid Gland; Rats; Rats, Sprague-Dawley; Sialorrhea; Submandibular Gland; Vasoactive Intestinal Peptide

Clozapine is the drug of choice for patients with an unsatisfactory response to routine antipsychotic treatment. Side effects such as sedation, weight gain, hypotension and hypersialorrhea are frequently reported whereas clozapine-induced parotitis is a less known complication.. We report the case of a 32-year-old woman with a refractory schizoaffective disorder, bipolar type. The failure to respond to at least two well-conducted antipsychotic trials with flupentixol and risperidone, led clinicians to prescribe clozapine, which was started three years earlier. Since its introduction, clozapine induced sialorrhea, which has been managed until now with anticholinergic medication. Recently, Mrs B. was hospitalized for a new relapse. Once treatment compliance checked (good level of plasmatic dosage), we decided to increase the dose of clozapine from 350 mg/d to 500 mg/d. Twenty days later, Mrs B. exhibited improvement of symptoms but complained of acute bilateral auricular pain and odynophagia. The bilateral and comparative clinical exam displayed a bilateral filling of the retromandibular depression, the painful swelling of the parotid gland, along with ptyalism and a slight inflammatory oedema of the Stenon duct orifice. Mrs B. was apyretic, with physiological constants within the limits of normal values. The biological analyses displayed a discrete inflammatory syndrome (mild hyperleucocytosis and anemia), a negative mumps IgM test and positive mumps IgG test, and a 1050 ng/mL clozapine blood level. Once viral parotitis was ruled out, the involvement of clozapine was evoked. Symptomatic medication was prescribed with per os analgesic (paracetamol) and antiseptic mouthwash (Éludril). Clozapine dosage was lowered to 400 mg/d. A week later, clinical examination confirmed improvement of the medical and psychiatric conditions.. We report the case of a patient who developed a parotitis following clozapine dose adjustment. Clozapine induced parotitis was retained once the infectious and other organic etiologies had been ruled out. Previous cases of clozapine-induced parotitis have already been reported and we have some arguments to suspect this etiology in our case. First, Mrs B. experienced more hypersialorrhea with the increase in clozapine dosage. Second, the anticholinergic medication was interrupted 3 days before the episode of parotitis. Two main pathophysiological hypotheses, immune and inflammatory, have already been proposed to explain clozapine-induced parotitis. In the former, the immunomodulating properties of clozapine may sensitize the mononuclear blood cells, leading to the sialadenitis. The latter hypothesis is the more documented and proposes that clozapine-induced hypersialorrhea may be responsible for a chronic inflammatory state that can lead to the formation of a parotid lithiasis and consequently parotitis. This case report illustrates clozapine induced-parotitis, a poorly known complication of this compound. Clinicians should be aware of its hypersialorrhea and inflammatory consequences in order to better prevent the occurrence of this complication.

Topics: Adult; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Parotitis; Psychotic Disorders; Recurrence; Sialorrhea

Topics: Adult; Antipsychotic Agents; Clozapine; Glycopyrrolate; Humans; Male; Muscarinic Antagonists; Schizophrenia, Paranoid; Sialorrhea; Treatment Outcome

Four cases in which glycopyrrolate was used to treat clozapine-induced sialorrhea (CIS) are reported.. Glycopyrrolate is an antimuscarinic agent that can be used preoperatively to inhibit drooling and excessive secretions of the respiratory tract. The outcomes of four patients who received glycopyrrolate for the treatment of CIS are described. The Thomas-Stonell and Greenberg Drooling Severity and Frequency Scale (DSFS) was used retrospectively to rate patients' drooling. Glycopyrrolate was effective in alleviating CIS in cases 1-3. Two patients (cases 1 and 4) exhibited severe drooling, which caused their clothing, hands, and objects to consistently become wet. One patient (case 1) responded well to glycopyrrolate and was restarted on the medication when CIS returned after discontinuation of the drug. While another patient (case 3) displayed a similar response to therapy for CIS as the patient described in case 1, this patient did not experience the psychosocial complications as did the patient in case 1, possibly due to the use of glycopyrrolate as the initial treatment of choice. The patient in case 2 experienced moderate but frequent drooling. Thioridazine's high anticholinergic potential may have contributed to this patient's lower baseline DSFS score compared with the scores of the other three patients, or it could have augmented initial symptom improvement. CIS continued in the patient described in case 4 despite treatment with glycopyrrolate, with only mild improvement in the severity and frequency of drooling.. Glycopyrrolate was effective in alleviating symptoms in three of four patients with CIS. In a fourth patient, the degree of improvement was unknown due to documentation discrepancies; however, mild improvement was noted initially.

Topics: Adult; Antipsychotic Agents; Clozapine; Glycopyrrolate; Humans; Male; Middle Aged; Muscarinic Antagonists; Psychotic Disorders; Schizophrenia; Sialorrhea; Young Adult

Clozapine-induced sialorrhea (CIS) is a common, inconvenient and socially stigmatizing adverse effect. The pathophysiology of CIS may be related to the effect of clozapine on the muscarinic and adrenergic receptors as well as the disruption of the circadian rhythms. The aim of this study was to find out if polymorphisms in muscarinic M1 and M3 receptor genes (CHRM1 and CHRM3), adrenoceptor alpha 2A gene (ADRA2A) or clock circadian regulator gene (CLOCK) are associated with CIS.. Two hundred and thirty-seven clozapine-treated Finnish schizophrenia patients were genotyped for CHRM1, CHRM3, CLOCK and ADRA2A polymorphisms, and their salivary dysfunction was assessed with two questions. Twenty-six of these patients had previously been on medication to treat CIS. Comparisons of the genotypes between patients with excessive versus non-excessive salivation were analysed. Genotype distributions between patients and control group and haplotypes were also studied.. CHRM1, CHRM3 and CLOCK polymorphisms and haplotypes were not associated with CIS. ADRA2A (rs1800544) genotype was associated with CIS (p = 0.029). In patients with CIS, CC genotype (n = 103) was more common than in G-allele carriers (n = 79) (p = 0.013, OR 2.13, 95% CI: 1.17-3.88). No differences were found in the distributions of genotypes between patients and controls.. ADRA2A genotype was associated with CIS.

Topics: Adult; Alleles; Antipsychotic Agents; CLOCK Proteins; Clozapine; Female; Finland; Genetic Predisposition to Disease; Genotyping Techniques; Haplotypes; Humans; Logistic Models; Male; Polymorphism, Single Nucleotide; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Receptors, Adrenergic, alpha-2; Receptors, Muscarinic; Schizophrenia; Sialorrhea

Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5-10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Constipation; Diabetes Mellitus; Eosinophilia; Humans; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Schizophrenia; Sialorrhea; Tachycardia; Weight Gain

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Dopamine D4; Sialorrhea

Topics: Administration, Sublingual; Antipsychotic Agents; Atropine; Clozapine; Dose-Response Relationship, Drug; Drug Resistance; Humans; Male; Middle Aged; Muscarinic Antagonists; Schizophrenia; Scopolamine; Sialorrhea; Treatment Outcome

Amisulpride is suggested for treatment of clozapine-induced sialorrhea. However, objective measurements of its effectiveness are lacking and, preclinically, amisulpride has no effect. We currently hypothesise that amisulpride acts by reducing the nervous- rather than the clozapine-driven salivary secretion.. Effects of intravenous amisulpride (as well as of clozapine and raclopride, a dopamine D2/D3 antagonist) were investigated in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). In duct-cannulated glands, secretion was evoked reflexly, at low and maximum flow rates, and by electrical stimulation of the parasympathetic and sympathetic innervations, and administration of autonomimetics (including substance P).. Unlike clozapine, amisulpride had no effect on the reflexly evoked secretion at maximum rate. With respect to reflex secretion at low rate and to the secretion evoked by muscarinic, α-adrenergic, β-adrenergic and substance P receptors, amisulpride (in contrast to raclopride) dose dependently potentiated the responses. Amisulpride had no effect on gland blood flow.. No support for any inhibitory influence of amisulpride was found. Conversely, amisulpride universally enhanced secretion, suggesting that amisulpride is a potential drug for dry-mouth treatment. The mechanism behind the potentiation is currently unknown.

Topics: Amisulpride; Amylases; Animals; Antipsychotic Agents; Autonomic Agents; Bethanechol; Clozapine; Denervation; Female; Isoproterenol; Methacholine Chloride; Parasympathetic Nervous System; Parotid Gland; Raclopride; Rats; Rats, Sprague-Dawley; Saliva; Salivation; Sialorrhea; Submandibular Gland; Substance P; Sulpiride; Sympathetic Nervous System

Clozapine induced sialorrhea is a common and troublesome adverse effect leading to poor treatment compliance. Although there are various treatment options, none has been demonstrated to be superior. In our case study, amisulpride 150 mg/d significantly reduced troublesome daytime sialorrhea along with minimal improvement in nocturnal sialorrhea.

Topics: Antipsychotic Agents; Clozapine; Dopamine Antagonists; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Sialorrhea; Sulpiride

Topics: Adult; Antipsychotic Agents; Clozapine; Constipation; Drug Utilization; Female; Humans; Hyperlipidemias; Inpatients; Male; Polypharmacy; Schizophrenia; Sialorrhea

To describe a case of clozapine-induced sialorrhea alleviated by immediate-release oxybutynin.. A 53-year-old female with schizoaffective disorder-bipolar type was admitted to a psychiatric unit and initiated on clozapine. During titration to a dose of 300 mg daily and despite taking concomitant oral benztropine 1 mg twice daily, the patient began to experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose reached 400 mg daily, and the patient was routinely seen with a saliva-soaked shirt. Additionally, she had become self-conscious and wanted to stop clozapine therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in significant reduction of the sialorrhea within 24 hours. The patient was discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate-release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only mild sialorrhea.. It is unknown why clozapine induces sialorrhea. One speculation is that clozapine interrupts muscarinic receptor homeostasis. Immediate-release oxybutynin is an anticholinergic agent with high affinity for salivary gland M₃ receptors that may have restored muscarinic receptor imbalance in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is largely responsible for oxybutynin's anticholinergic activity. The activity of oxybutynin and its metabolite may result in dry mouth in over 80% of patients taking the immediate-release formulation, while producing dry mouth in only 40% and 7.5% of patients taking the extended-release and topical formulations, respectively.. To our knowledge, this is the first report of immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea. If oxybutynin is considered for this indication, use of the immediate-release formulation seems prudent. Additional data, including randomized controlled trials, are needed to confirm whether immediate-release oxybutynin has a significant role in the management of this stigmatizing adverse effect.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Psychotic Disorders; Sialorrhea

Individuals receiving clozapine treatment for schizophrenia complain of drooling. Reports on salivary flow measurements are contradictory in humans and lacking in animals. Clozapine has affinity for several different receptor types and may, hypothetically, both stimulate and inhibit salivary secretion. In rats, intravenous clozapine evoked a long-lasting secretion, being more prominent from submandibular than from parotid glands. Chronic denervation enhanced the responses. Clozapine acted on muscarinic (M1-) receptors of acinar cells, independent of central nervous mechanisms, pre-synaptic intraglandular events, or circulating catecholamines. A fraction of the methacholine- and parasympathetic-nerve-evoked secretion was abolished by clozapine at doses below those evoking secretion. Sympathetic-nerve-evoked secretion was partially reduced by clozapine, due to antagonistic action on alpha-adrenoceptors; the beta-adrenoceptor-mediated response persisted. Subsecretory doses of clozapine enhanced secretion induced by the beta-adrenoceptor agonist isoprenaline. The overall actions of clozapine suggest that, in clozapine-treated humans, salivation is increased during sleep and at rest, but is decreased during meals.

Topics: Animals; Antipsychotic Agents; Autonomic Denervation; Cholinergic Agents; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Parotid Gland; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Receptors, Muscarinic; Saliva; Salivation; Sialorrhea; Submandibular Gland

To assess the change in salivary flow rate in patients with schizophrenia on clozapine and whether the change in salivary flow rate was dose related.. Twenty male inpatients with a diagnosis of schizophrenia according to the International Statistical Classification of Diseases, 10th Revision diagnostic criteria for research who were started on clozapine were recruited for the study. Unstimulated salivary flow rate was assessed at baseline and then weekly for 4 weeks using cotton swab method in 17 patients.. Repeated-measures analysis of variance showed a significant increase in salivary flow rate over time (F [2.37/37.94] = 3.134, P = 0.047, Greenhouse-Geisser correction, eta = 0.16). Also, there was a significant increase in salivary flow rate between weeks 2 and 3 (P < 0.05). There was no correlation between salivary flow rate and mean clozapine dose.. 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."

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Prospective Studies; Salivation; Schizophrenia; Sialorrhea; Young Adult

Clozapine-induced sialorrhea (CIS) is a frequently occurring debilitating adverse effect. Although various treatment options exist, none has been proved to be distinctly superior to others. We report a case of CIS that responded to low dose of trihexyphenidyl (2 mg/day).

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Muscarinic Antagonists; Sialorrhea; Treatment Outcome; Trihexyphenidyl

Topics: Adult; Amisulpride; Antipsychotic Agents; Clozapine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Humans; Male; Receptors, Dopamine D3; Schizophrenia, Paranoid; Sialorrhea; Sulpiride

(1) Sialorrhoea is the production of saliva that patients perceive as excessive; (2) Saliva accumulation is either due to a reduction in swallowing frequency or to an increase in saliva production; (3) Patients who drool may be ostracized, and there is also an increased risk of aspiration pneumonia; (4) Sialorrhoea can be caused by buccal, gastrointestinal or neurological disorders, or by drugs; (5) Sedatives such as benzodiazepines, neuroleptics, cholinesterase inhibitors and pilocarpine carry a dose-dependent risk of sialorrhoea; (6) In practice, the role of a drug should be borne in mind when a patient presents with sialorrhoea or excessive saliva accumulation. The parents of children treated with sedative drugs should be informed of this risk.

Topics: Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Clozapine; Deglutition Disorders; Donepezil; Galantamine; Humans; Hypnotics and Sedatives; Indans; Phenylcarbamates; Pilocarpine; Piperidines; Quality of Life; Risperidone; Rivastigmine; Sialorrhea

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bupropion; Clozapine; Humans; Male; Mental Disorders; Middle Aged; Sialorrhea

Topics: Amitriptyline; Antipsychotic Agents; Clozapine; Humans; Male; Muscarinic Antagonists; Nocturnal Enuresis; Schizophrenia; Sialorrhea; Trihexyphenidyl; Young Adult

Clozapine is an atypical and novel antipsychotic medication useful for patients with schizophrenia who are refractory to treatment. Its use is often associated with troublesome side effects like sialorrhea, sedation, weight gain, enuresis, dizziness, besides life threatening side effects like agranulocytosis. Drug treatments used for Clozapine induced sialorrhea (CIS) like anticholinergic drugs and alpha 2 receptor antagonists have their own added side effects. A case of CIS responding to low dose of Amisulpride is reported.

Topics: Adult; Amisulpride; Antipsychotic Agents; Clozapine; Female; Humans; Sialorrhea; Sulpiride

The aim of this case study was to report preliminary data on the effectiveness and tolerability of glycopyrrolate for the treatment of clozapine-induced sialorrhea, or excessive flow of saliva, in an adolescent population.. Three adolescent females (age 13-16), who developed sialorrhea secondary to clozapine treatment, received an open-label trial of glycopyrrolate (4-8 mg) during inpatient hospitalization for treatment-resistant psychotic illness.. The target symptom of sialorrhea was improved in all three cases, with patient self-reports of decreased production of saliva confirmed by staff observation. Glycopyrrolate was generally well tolerated by the patients. One patient reported constipation, which improved with symptomatic treatment. A second patient reported dry mouth, which improved with a reduction in dose of glycopyrrolate.. These three cases provide support for the potential effectiveness and tolerability of glycopyrrolate for clozapine-induced sialorrhea in adolescents. Further controlled studies are required to determine the safety, efficacy and tolerability of glycopyrrolate in this age group and in adults for clozapine-induced sialorrhea.

Topics: Adolescent; Antipsychotic Agents; Clozapine; Female; Glycopyrrolate; Humans; Male; Sialorrhea

To describe the treatment pathway and patterns of clozapine use in patients with schizophrenia, including coprescribed psychotropic medications, and compare the extent of coprescribing of clozapine with that of non-clozapine schizophrenia treatment in community mental health services in the Auckland and Northland regions of New Zealand.. A retrospective chart review was conducted for adult outpatients receiving care from community mental health services on October 31, 2004. Data collected for all patients prescribed an antipsychotic included demographics (sex, age, ethnicity); principal diagnosis (Diagnostic and Statistical Manual of Mental Disorders, 4th edition); comorbid conditions; duration of mental illness; psychiatric admissions; and treatment information (psychotropic medications, with dose and route of administration). If clozapine had been started after the introduction of full government prescription subsidy (February 1999), additional data, including year of initiation and prior antipsychotic history, were collected. Analysis included all outpatients with a diagnosis of schizophrenia (including schizoaffective disorder).. Antipsychotics were prescribed for 2796 schizophrenia patients; 32.8% were prescribed clozapine, with a mean dose of 372 mg/day and an average duration of illness of 9.7 years before starting clozapine. Patients who had started treatment after clozapine was funded by the government (59.3%) had received a median of 3 antipsychotic drugs prior to starting clozapine; most of the treatment regimens included 1 second-generation antipsychotic (91.2%). Clozapine patients were less likely to be coprescribed another antipsychotic compared with non-clozapine patients (11.7% vs 17.6%; p < 0.001). Both the clozapine and non-clozapine groups had a low total number of psychotropic medications prescribed (median 2); for clozapine patients, the second drug was most likely to be for treatment of hypersalivation.. Outpatients with treatment-resistant schizophrenia were prescribed clozapine at expected rates; however, treatment was delayed longer than recommended. There is some evidence that access to clozapine for treatment-resistant schizophrenia has improved, possibly as the result of the introduction of government subsidy, guideline dissemination, or increasing experience of clinicians with use of clozapine. In this real-world environment, the number of concomitant psychotropic medications for outpatients with schizophrenia was found to be low; when used concomitantly with clozapine, they were most commonly used to manage adverse effects.

Topics: Adolescent; Adult; Ambulatory Care; Antipsychotic Agents; Clozapine; Community Mental Health Services; Cross-Sectional Studies; Female; Financing, Government; Health Services Accessibility; Humans; Information Dissemination; Male; Middle Aged; New Zealand; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Schizophrenia; Sialorrhea; Treatment Outcome

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Humans; Male; Nocturnal Enuresis; Sialorrhea

Clozapine is associated with non-neurological side effects that can be subjectively unpleasant and/or clinically serious. We sought to: (i) assess the nature and prevalence of side effects experienced by patients receiving maintenance treatment with clozapine and (ii) explore the relationship between clozapine plasma concentration and side effect burden. Patients were receiving clozapine maintenance treatment. Open questioning followed by systematic enquiry using the Antipsychotic Non-neurological Side Effects Rating Scale were used to assess side effects. Trough plasma clozapine and norclozapine concentrations were measured. One hundred and three patients participated. On open questioning, 61 patients reported a total of 117 side effects, whereas systematic enquiry identified an additional 649 side effects, with each patient reporting at least one. Clozapine plasma concentrations were significantly but weakly correlated with total Antipsychotic Non-neurological Side Effects Rating Scale score (Pearson correlation=0.29, P<0.004). Patients with a plasma clozapine concentration >0.25 mg/l were significantly more likely to have moderate/severe side effects than patients with lower plasma concentrations (63/76 vs. 12/23, chi=9.07, d.f.=1, P<0.01). The side-effect burden associated with maintenance clozapine treatment is high and the true extent can only be ascertained by systematic inquiry. The use of target plasma concentrations below those used for acute treatment should be explored as a strategy for minimizing side effects.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Clozapine; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Prevalence; Psychotic Disorders; Schizophrenia; Sexual Dysfunction, Physiological; Sialorrhea

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Clozapine; Fluphenazine; Glycopyrrolate; Humans; Male; Muscarinic Antagonists; Psychotic Disorders; Sialorrhea; Valproic Acid

Side effects from a high-dose clozapine treatment for a schizophrenic patient led to massive compliance problems. The dose of clozapine could be halved without recurrence of an acute psychotic symptomatology by concomitantly administering amisulpride. The side effects, especially hypersalivation, disappeared almost entirely, which in turn led to good compliance. In a short review we would like to present the pathophysiology and therapeutic options of clozapine-induced hypersalivation.

Topics: Adult; Amisulpride; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Humans; Male; Schizophrenia, Paranoid; Sialorrhea; Sulpiride

Hypersalivation is a common, troublesome side effect of clozapine treatment. It occurs in 31-54% of clozapine treated patients. Management of this stigmatizing side effect may reduce noncompliance. Reports in the literature have shown beneficial clinical effects of combined clozapine-sulpiride therapy as measured by the Brief Psychiatric Rating Scale, and we found that this treatment combination also has very strong antisalivatory activity for clozapine-induced hypersalivation.. 18 patients (12 female, 6 male) with clozapine-induced hypersalivation received sulpiride (150-300 mg/day) in addition to ongoing clozapine treatment (from 100 mg/d to 800 mg/d). Baseline, 7 day and 21 day follow-up values were recorded for the 5-point Nocturnal Hypersalivation Rating Scale.. At the end of the trial only 3 patients complained of minimal sialorrhea, and the mean Nocturnal Hypersalivation Rating Scale scale values showed a significant reduction in sialorrhea (delta baseline-endpoint -.2.78 +/- 0.87).. Our findings support reports of the beneficial effect of clozapine-sulpiride combination therapy and suggest that sulpiride addition may contribute to the amelioration of clozapine-induced hypersalivation.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Clozapine; Female; Follow-Up Studies; Humans; Male; Schizophrenia; Sialorrhea; Sulpiride

Topics: Administration, Intranasal; Administration, Sublingual; Aerosols; Bipolar Disorder; Clozapine; Drug Administration Schedule; Female; Humans; Ipratropium; Male; Schizophrenia; Sialorrhea; Treatment Outcome

Hypersalivation is a common and frequently disabling side effect of atypical neuroleptics such as clozapine. Current treatment options of this adverse advent are limited by lack of efficacy or additional side effects. Botulinum toxin (BTX) injections into the parotid glands have been shown to be very effective in treating sialorrhea in the context of various neurological disorders, such as Parkinson's and motor neuron disease. Surprisingly, BTX treatment of drug-induced sialorrhea has not yet been described. We here report a patient with clozapine-induced hypersalivation and a good response to BTX injections lasting for more than 12 weeks, resulting in a marked reduction of the hypersalivation and consequently of his social withdrawal. Our patient serves to alert clinicians to the frequent problem of drug-induced sialorrhea and suggests that BTX injections should be considered as an effective and safe treatment for hypersalivation in psychiatric patients treated with clozapine.

Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Clozapine; Follow-Up Studies; Humans; Male; Middle Aged; Sialorrhea; Treatment Outcome

Topics: Administration, Cutaneous; Adult; Antipsychotic Agents; Clozapine; Female; Humans; Scopolamine; Sialorrhea; United States

Topics: Administration, Oral; Antipsychotic Agents; Atropine; Clozapine; Humans; Male; Middle Aged; Muscarinic Antagonists; Ophthalmic Solutions; Schizophrenia, Paranoid; Sialorrhea

Topics: Adult; Clozapine; Female; Guanfacine; Humans; Sialorrhea

Topics: Administration, Intranasal; Administration, Sublingual; Atropine; Clozapine; Humans; Ipratropium; Sialorrhea

Topics: Adult; Antipsychotic Agents; Biperiden; Clozapine; Humans; Hyperhidrosis; Male; Muscarinic Antagonists; Schizophrenia; Sialorrhea; Treatment Outcome

Monitoring plasma clozapine concentrations may play a useful role in the management of patients with schizophrenia, but information on the relationship between the plasma levels of the drug and response is still controversial.. The purpose of this study was to assess the relationship between plasma concentrations of clozapine and its weakly active metabolite norclozapine and clinical response in patients with schizophrenia resistant to conventional neuroleptics.. Forty-five patients, 35 males and ten females, aged 19-65 years, were given clozapine at a dosage up to 500 mg/day for 12 weeks. Steady-state plasma concentrations of clozapine and norclozapine were measured at week 12 by a specific HPLC assay. Psychopathological state was assessed at baseline and at week 12 by using the Brief Psychiatric Rating Scale, and patients were considered responders if they showed a greater than 20% reduction in total BPRS score compared with baseline and a final BPRS score of 35 or less.. Mean plasma clozapine concentrations were higher in responders (n=18) than in non-responders (n=27) (472+/-220 versus 328+/-128 ng/ml, P<0.01), whereas plasma norclozapine levels did not differ between the two groups (201+/-104 versus 156+/-64 ng/ml, NS). A significant positive correlation between plasma levels and percent decrease in total BPRS score was found for clozapine (r(s)=0.371, P<0.02), but not for norclozapine (r(s)=0.162, NS). A cutoff value at a clozapine concentration of about 350 ng/ml differentiated responders from non-responders with a sensitivity of 72% and a specificity of 70%. At a cutoff of 400 ng/ml, sensitivity was 67% and specificity 78%. The incidence of side effects was twice as high at clozapine concentrations above 350 ng/ml compared with lower concentrations (38% versus 17%).. These results suggest that plasma clozapine levels are correlated with clinical effects, although there is considerable variability in the response achieved at any given drug concentration. Because many patients respond well at plasma clozapine concentrations in a low range, aiming initially at plasma clozapine concentrations of 350 ng/ml or greater would require in some patients use of unrealistically high dosages and imply an excessive risk of side effects. Increasing dosage to achieve plasma levels above 350-400 ng/ml may be especially indicated in patients without side effects who failed to exhibit amelioration of psychopathology at standard dosages or at lower drug concentrations.

Topics: Adult; Aged; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Conscious Sedation; Constipation; Dizziness; Dose-Response Relationship, Drug; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Sialorrhea; Tachycardia; Treatment Outcome; Weight Gain

Topics: Adult; Citalopram; Clozapine; Confusion; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Fatigue; Humans; Male; Psychotic Disorders; Sialorrhea; Sleep Wake Disorders

Topics: Adult; Atropine; Chronic Disease; Clozapine; Female; Humans; Ophthalmic Solutions; Schizophrenia; Sialorrhea

Topics: Antipsychotic Agents; Atropine; Clozapine; Humans; Mydriatics; Parasympatholytics; Sialorrhea; Treatment Outcome

Topics: Antipsychotic Agents; Clozapine; Humans; Sialorrhea

Topics: Adult; Clozapine; Deglutition; Humans; Male; Mouth Breathing; Nasal Septum; Schizophrenia, Paranoid; Sialorrhea

Topics: Adult; Benztropine; Clozapine; Edema; Female; Humans; Obsessive-Compulsive Disorder; Parotid Diseases; Sialorrhea

Enuresis is an adverse event of clozapine treatment. The occurrence of nocturnal functional enuresis in two schizophrenic patients during the initial phase of clozapine therapy is reported. Beneficial effect of trihexyphenidyl administration (5 mg at 21.00 h) on clozapine-induced enuresis is clearly demonstrated in one patient. Trihexyphenidyl discontinuation and subsequent readministration in this patient led to corresponding recurrence and then disappearance of enuresis. Involvement of the cholinergic system has been proposed as one of the possible pathophysiological mechanisms of clozapine-induced enuresis.

Topics: Adult; Antipsychotic Agents; Clozapine; Enuresis; Humans; Male; Muscarinic Antagonists; Sialorrhea; Trihexyphenidyl

Topics: Antipsychotic Agents; Brain; Clozapine; Humans; Receptors, Adrenergic, alpha-2; Receptors, Dopamine D2; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Middle Aged; Pneumonia, Aspiration; Sialorrhea

Topics: Antipsychotic Agents; Clozapine; Humans; Muscarinic Antagonists; Pirenzepine; Sialorrhea

Topics: Antipsychotic Agents; Chronic Disease; Clonidine; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Middle Aged; Receptors, Adrenergic, alpha-2; Schizophrenia; Sialorrhea

Topics: Adult; Clozapine; Humans; Male; Parotitis; Schizophrenia, Paranoid; Sialorrhea

Topics: Adult; Clozapine; Deglutition Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Esophageal Motility Disorders; Humans; Male; Psychotic Disorders; Sialorrhea

Topics: Adult; Airway Obstruction; Circadian Rhythm; Clozapine; Deglutition Disorders; Humans; Male; Psychotic Disorders; Sialorrhea; Sleep Wake Disorders

Topics: Adult; Clonidine; Clozapine; Female; Humans; Male; Middle Aged; Sialorrhea

Topics: Clozapine; Humans; Male; Middle Aged; Schizophrenia; Sialorrhea

Topics: Amitriptyline; Clozapine; Drug Administration Schedule; Humans; Schizophrenia; Sialorrhea

Topics: Adult; Clozapine; Drug Synergism; Female; Humans; Lorazepam; Male; Middle Aged; Sialorrhea; Sleep Stages