Adverse Effects Of Clozapine Research Articles

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug.

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms "Clozapine indications", "Clozapine adverse effects", "Clozapine regenerative effects", and "Clozapine neuroplasticity" with the aim of reviewing the scientific literature on Clozapine's treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management.

Patient safety: adverse effects of Clozapine and their management at the Psychiatric Hospital Ghrasia in Yogyakarta, Indonesia.

Clozapine is an atypical antipsychotic indicated for treating patients resistant to antipsychotic therapy when other medications in this class have no therapeutic effect. Clozapine has greater efficacy but more side effects than other atypical antipsychotics (e.g., agranulocytosis, seizures, sedation, and weight gain). Side effects can cause discomfort to patients and can affect patient compliance, interfering with therapeutical outcomes. This study aims to identify the side effects of clozapine use in patients at the Psychiatric Hospital Grhasia, in Yogyakarta, Indonesia. Using a cross-sectional design, this research provides a retrospective descriptive analysis using medical records of patients at the Psychiatric Hospital Ghrasia Yogyakarta. Inpatient and outpatient medical records of patients who had received a clozapine prescription from January to December 2019 were analyzed. In the 336 patients that met the inclusion criteria, the incidence of side effects from clozapine use was 16.07% (95%, CI:2.2-4.1), with the most frequent being dizziness, vomiting, diarrhea, and hypersalivation. There was no effect of age, gender, profession, or patient's disease on their incidence. The management of side effects is classified into three aspects: the drug is stopped, the patient is given additional therapy, and the patient is not given therapy. The results showed that the use of clozapine at the Psychiatric Hospital Ghrasia Yogyakarta was relatively safe. Identification of side effects is necessary to determine the follow-up treatment.

Effect of taxifolin on clozapine-induced experimental oxidative and inflammatory heart damage in rats

AimClozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (3,5,7,3’,4’-pentahydroxy flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data. Material and methodThe rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin+clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-▪B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically. ResultsTroponin I, CK-MB, MDA, TNF-α, NF-▪B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin+clozapine groups (P<0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (P>0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin+clozapine group, while they were significantly lower than the clozapine group (P<0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin+clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin+clozapine group (TLC group), myofibrils generally showed a regular morphology. ConclusionWe found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury.

Urinary Retention as a Rare Adverse Effect of Clozapine.

Urinary Retention as a Rare Adverse Effect of Clozapine.

A network meta-analysis of efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia

ObjectiveClozapine is considered as the standard treatment for this subgroup, but the evidence is not unequivocal. There are several potential alternatives being used because of the possible adverse effects of clozapine. We aimed to examine the efficacy and adverse events of different antipsychotics in treatment-resistant schizophrenia by performing a network meta-analysis.MethodsWe searched the Cochrane Schizophrenia Group register for randomized-controlled trials (up to March 06, 2022) and MEDLINE (up to January 20, 2023). We included blinded and open studies and participants with a broad definition of treatment resistance. The primary outcome was overall symptoms of schizophrenia; secondary outcomes were response to treatment, positive and negative symptoms of schizophrenia, discontinuation, side effects, quality of life, and functioning. The study was registered in Open Science Framework (https://osf.io/9nf2y/).ResultsWe included 60 studies involving 6838 participants in the network meta-analysis. In the primary outcome, clozapine and olanzapine were more efficacious than risperidone, haloperidol, fluphenazine, sertindole, chlorpromazine, and quetiapine (range of mean SMDs, − 0.11 to − 0.48). The difference between clozapine and olanzapine was trivial and uncertain (SMD − 0.05, 95% CI, − 0.21 to 0.11). The result of other efficacy outcomes as well as subgroup and sensitivity analyses were consistent with the primary analysis. Clozapine and olanzapine were associated with more weight gain, and clozapine was associated with more sedation events compared to many other antipsychotics.ConclusionsClozapine remains the gold standard for patients with treatment-resistant schizophrenia. Olanzapine seems to be second-best and could be tried before switching to clozapine.

Rarer adverse effect of clozapine

Introduction: Clozapine is an atypical anti-psychotic drug widely used in the treatment of schizophrenia. It reduces suicidal ideations in schizophrenics and hence the mortality. Agranulocytosis is one among the most known serious complication of this drug. However, it can also cause life-threatening complications like necrotizing enterocolitis. Case Report: We report a case of a 31-year-old male with past history of schizophrenia and seizure disorder on 300 mg clozapine and phenytoin 300 mg daily for 10 years. He was admitted for the evaluation of altered sensorium. Blood routine investigations and radioimaging were normal. Electroencephalogram (EEG) showed non-convulsive status epilepticus which was managed with anti-epileptic drugs. His sensorium did not improve. He started to develop fever and loose stools, later developed abdominal distension and pain. On evaluation it was found to have ischemic colitis with secondary bacterial peritonitis. Clozapine was stopped, managed conservatively. The patient recovered completely. Conclusion: Clozapine can cause seizures. The anti-cholinergic effect of this drug can induce focal intestinal necrosis, which when unrecognized progress to transmural ischemia and perforation. Such cases need surgical intervention and is associated with high mortality. A high index of suspicion for early diagnosis, prompt correction of risk factors and early intervention prevents mortality.

Management of sedation due to clozapine

SUMMARYSedation is one of the most common adverse effects of clozapine. Although tolerance develops to some extent, a significant proportion of patients continue to experience sedation and associated negative consequences on their quality of life. Sedation is also one of the most common reasons for the discontinuation of clozapine and it is therefore important to proactively manage it. This article provides brief guidance for clinicians.

Factors Associated With Poor Response to Clozapine in Schizophrenia: A Study From Northern India.

Limited numbers of studies have assessed the predictors of clozapine nonresponse. This study aimed to assess the demographic and clinical factors associated with an inadequate response to clozapine in patients with treatment-resistant schizophrenia (TRS). Two hundred eighty-seven outpatients with TRS receiving clozapine for more than 1 year were divided into 2 groups based on the need for a second antipsychotic medication and/or electroconvulsive therapy after receiving clozapine in the maximum tolerable dose for at least 3 months. One hundred two patients (35.4%) were considered to be clozapine nonresponders. Compared with responders, clozapine nonresponders were more often unemployed at the time of starting clozapine (P = 0.04), had a longer duration of untreated psychosis (P = 0.007), had received significantly higher number of adequate antipsychotic trials in the past (P = 0.02), had received antipsychotic polypharmacy in the past (P = 0.01), had experienced adverse effects with first- (P < 0.001) and second-generation antipsychotics (P = 0.01), and had more medical comorbidities (P = 0.03). The nonresponders more frequently had visual hallucinations (P = 0.001), and feelings/acts or impulses attributed to some external source (P = 0.03) in the lifetime, and had a significantly higher Clinical Global Impression severity score at the time of starting of clozapine (P < 0.001). While on clozapine, nonresponders received significantly higher dose of clozapine (P = 0.001) and higher proportion of them experienced constipation (P = 0.04), hypersalivation (P = 0.002), and obsessive-compulsive symptoms (P = 0.05) as adverse effects of clozapine. The present study shows that approximately one-third of patients with TRS do not respond to clozapine. However, clozapine nonresponders, although broadly similar in sociodemographic profile to clozapine responders, differ from clozapine responders on past treatment profile.

Recognition and management of clozapine adverse effects: A systematic review and qualitative synthesis.

Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute strongly to treatment reluctance. The aim of this systematic review was to provide clinicians with a comprehensive information source regarding clozapine ADEs. PubMed and Embase databases were searched for English language reviews concerned with clozapine ADEs; publications identified by the automated search were manually searched for additional relevant citations. Following exclusion of redundant and irrelevant reports, pertinent information was summarized in evidence tables corresponding to each of six major ADE domains; two authors reviewed all citations for each ADE domain and summarized their content by consensus in the corresponding evidence table. This study was conducted in accordance with PRISMA principles. Primary and secondary searches identified a total of 305 unique reports, of which 152 were included in the qualitative synthesis. Most clozapine ADEs emerge within 3months, and almost all appear within 6months, after initiation. Notable exceptions are weight gain, diabetic ketoacidosis (DKA), severe clozapine-induced gastrointestinal hypomotility (CIGH), clozapine-induced cardiomyopathy (CICM), seizures, and clozapine-induced neutropenia (CIN). Most clozapine ADEs subside gradually or respond to dose reduction; those that prompt discontinuation generally do not preclude rechallenge. Rechallenge is generally inadvisable for clozapine-induced myocarditis (CIM), CICM, and clozapine-induced agranulocytosis (CIA). Clozapine plasma levels >600-1000μg/L appear more likely to cause certain ADEs (e.g., seizures) and, although there is no clear toxicity threshold, risk/benefit ratios are generally unfavorable above 1000μg/L. Clozapine ADEs rarely require discontinuation.

The disquietude of clozapine continuation during the COVID-19 pandemic.

The disquietude of clozapine continuation during the COVID-19 pandemic.

Clozapine Once-Daily Versus Divided Dosing Regimen: A Cross-sectional Study in Japan.

Clozapine is generally recommended to be prescribed in a divided dosing regimen based on its relatively short plasma half-life. However, there has been little evidence to support the superiority of divided dosing of clozapine over once-daily dosing. To our knowledge, there have been no studies examining differences in actual plasma concentrations or adverse effects between the 2 dosing strategies of clozapine. We aimed to compare actual plasma concentrations of clozapine between once-daily and divided dosing regimens, and to examine the relationships of these regimens with psychiatric symptoms and adverse effects of clozapine. We analyzed data from 108 participants of a previous study conducted in 2 hospitals in Japan. A population pharmacokinetic model was used to estimate the peak and trough plasma concentrations of clozapine based on actual plasma concentrations. We evaluated psychiatric symptoms with the Brief Evaluation of Psychosis Symptom Domains and adverse effects of clozapine with the Glasgow Antipsychotic Side-effects Scale for Clozapine. The estimated peak and trough plasma concentrations of clozapine did not differ significantly between once-daily and divided dosing regimens. There were no significant differences in psychiatric symptoms except for depression/anxiety or subjective adverse effects of clozapine between the 2 dosing strategies. Our findings tentatively support the feasibility and clinical utility of once-daily dosing of clozapine in clinical practice. Further studies are needed to replicate these findings and determine causality between dosing strategies and clinical outcomes.

The Effect of Clozapine on Self-reported Duration of Sleep and Its Interaction With 23 Other Medications: A 5-Year Naturalistic Study.

Sedation is a common and incapacitating clozapine adverse effect, but the factors associated with sedation and its pharmacological management remain poorly studied. We conducted a retrospective cohort study based on deidentified electronic clinical records of clozapine-treated patients from the secondary mental health care provider for Cambridgeshire and Peterborough, United Kingdom. We first evaluated cross-sectionally the influence of clozapine dose, clozapine, and norclozapine plasma levels on self-reported hours slept, as a proxy for sedation, using bivariate correlation and then the longitudinal effect of changes in clozapine dose and other 23 medications using linear mixed effect models. We followed 241 clozapine-treated patients for 56 months on average, with 2237 face-to-face assessments in total. Patients slept for a mean of 9.35 h/d, with 46% reporting 10 h/d or more. Cross-sectionally, sleep duration did not correlate with clozapine dose (r = 0.14, P = 0.106), but with clozapine plasma levels (r = 0.38, P < 0.0001) and norclozapine plasma levels (r = 0.25, P = 0.005). Longitudinally, the final mixed-effects model revealed 4 pharmacological variables that had a significant impact on hours slept: clozapine, risperidone augmentation, and atenolol were associated with increased sleep, whereas aripiprazole augmentation was associated with decreased sleep. We found that 20 other psychotropic medications measured were not associated with changes in sleep when added to clozapine. Excess sleep is a clozapine level-dependent adverse effect. The impact of different augmentation strategies might help clinicians decide on the most adequate strategy, albeit further studies should confirm our results.

Constipation: A potentially serious adverse effect of clozapine that’s often overlooked

Constipation: A potentially serious adverse effect of clozapine that’s often overlooked

Alcohol intake potentiates clozapine adverse effects associated to CYP1A2*1C in patients with refractory psychosis.

Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation-dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, were included in the analysis by linear regression. Overall, CYP variants showed no effect on CLZ pharmacokinetics. The rs2069514 variant in homozygous genotype (also known as CYP1A2*1C/*1C) was associated with CLZ adverse reactions in Mexican patients with refractory psychosis (OR=3.55 CI95 = 1.041-12.269, p=.043) and demonstrated that this effect is doubled by concomitant alcohol consumption (OR=7.9 CI95 =1.473-42.369, p=.016). Clinicians should be aware of this information before starting CLZ use, when treating patients with refractory psychosis, who are alcohol drinkers and carriers of this genetic variant in order to prevent CLZ-related adverse reactions. Nevertheless, our findings should be replicated in larger samples.

The side effect profile of Clozapine in real world data of three large mental health hospitals.

Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. A better understanding of how drugs work in the real world can complement clinical trials.

Bioactivation of clozapine by mitochondria of the murine heart: Possible cause of cardiotoxicity

The mechanism of clozapine-associated cardiotoxicity has not been elucidated. The formation of a reactive nitrenium ion from the drug has been suggested as the cause, however, the reason why the heart is a target remains unknown. The heart is one of the most perfused organs; therefore, it contains a large number of mitochondria per cell; these organelles are responsible for both oxygen metabolism and energy production due to high energy expenditure. Given that mitochondria play critical roles in cellular homeostasis and maintenance, this study tested the hypothesis that cardiac mitochondria are both a target and initiator of clozapine-induced cardiotoxicity through activating the drug. We investigated whether murine heart receives a relatively high amount of systemically administered drug (20 mg/kg, i.p., Wistar albino rats) and whether cardiac mice (Swiss albino) and rat (Wistar albino) mitochondria locally activate clozapine (100 μM) to a reactive metabolite. We observed a relatively large distribution of clozapine to heart tissue as well as the formation of reactive metabolites by cardiac mitochondria in situ. Mitochondrial cytochrome P450 enzymes (CYP) in cardiac tissue responsible for biotransformation of clozapine were also characterized. CYP3A4 has been found to be the major enzyme catalyzes CLZ bioactivation, while CYP1A largely and CYP3A4 partially catalyzes the formation of stable metabolites of CLZ. At 100 μM concentration, clozapine caused a significant decline in mitochondrial oxygen consumption rate in vitro as much as positive control (antimycin A), while it did not induce mitochondrial permeability transition pore opening. These data provide an explanation as to why the heart is a target for clozapine adverse effects.

Mental Health Nurses' Knowledge of Clozapine

Clozapine, sold under the brand name Clozaril, is an antipsychotic medication prescribed since the 1970s as an effective treatment for individuals with treatment resistive schizophrenia. Medical experts have produced extensive literature on the need for close monitoring as this medication can cause life threatening adverse effects. Mental health nurses play a vital role in the management of clozapine, however to date just one study specifically examines psychiatric/mental health nurse’s knowledge of this medication. Nurses need to be aware of the adverse effects and be able to provide psychoeducation to help support and inform clients prescribed this medication. This study used a survey questionnaire. A clozapine knowledge questionnaire with 18 questions was developed by De Hert et al. to explore psychiatric/mental health nurse’s knowledge on the adverse effects of clozapine. We distributed a shortened version of this knowledge questionnaire (12-multi-choice questions) to 209 mental health nurses working within one Irish Mental Health Service. One hundred and twenty-nine (n = 129) nurses completed the questionnaire with a response rate of 62%. Our results indicated that over 40% of mental nurses had not received sufficient education on clozapine medication during their formal education. We found that just 50% of participants scored over six correct questions out of 12 questions on various areas of knowledge related to clozapine medication. We identified gaps in knowledge on clozapine medication in relation to on myocarditis, epilepsy and metabolic syndrome. We highlighted gaps in mental health nurses’ knowledge of clozapine medication that need to be improved in order to help clients. We advocate additional education on clozapine medication at undergraduate education and through educational packages at the service level.

M202. SEX-RELATED DIFFERENCES IN CLOZAPINE SIDE EFFECTS IN PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA

BackgroundTreatment resistant schizophrenia (TRS) affects up to 30% of patients with psychosis and is a major cause of disability. Although clozapine is the only indicated drug for TRS, it is largely underused, partially due to its life-threatening adverse effects (AEs) as agranulocytosis and myocarditis. However, clozapine treatment is also burdened by other AEs as constipation, hypersalivation, postural hypotension, tachycardia, metabolic abnormalities and weight gain. In recent years many efforts have been made to outline clinical and neurobiological characteristics of TRS. Although sex is one of the most relevant factors accountable for the clinical variability of schizophrenia, literature on sex differences in clozapine’s tolerability is still limited. Studies showed that women experience more often than men weight gain, hyperglycemia and constipation. Conversely, hypertension and dyslipidemia seem more frequent in men. Based on these premises, our study aimed to investigate sex differences in prevalence of clozapine’s chronic AEs in TRS patients.MethodsWe performed an observational cross-sectional study with TRS on 147 patients, 93 males and 54 females with at least two-year clozapine treatment. We assessed metabolic status and AEs by interviews, collection of clinical data (BMI, waist circumference, blood pressure and heart rate) and blood tests including lipid profile, fasting glucose and HbA1c.Chi-square analysis was used to investigate the association between sex and clozapine AEs (tachycardia, postural hypotension, constipation, hypersalivation and metabolic syndrome). Multiple logistic regression analyses were performed to further analyze the relationship between sex and AEs considering the role of possible confounding factors as plasmatic concentration, oral dosage, number of daily administration, age and duration of therapy.ResultsWe found a higher prevalence of tachycardia in males (p=0.034, χ2=4.49) and of orthostatic hypotension (p=0.01, χ2=6.70) and constipation (p=0.01, χ2=6.45) in females. Logistic regressions showed that male sex was the only significant predictor of tachycardia (p=0.01), while female sex predicted hypotension (p=0.04) and constipation (p=0.03). Although no differences emerged for hypersalivation and metabolic syndrome (MetS), Chi-square showed significant differences in prevalence for two MetS criteria: hypertriglyceridemia (56.94% in men, 29.79% in women, p=0.003, χ2=8.43) and central obesity (83.33% in men, 97.44% in women, p=0.03, χ2=4.69).DiscussionConsistent with previous literature, our study showed sex differences in prevalence of chronic clozapine’s AEs. Although perceived as minor AEs, hypotension, constipation and tachycardia could affect patient’s quality of life, cause treatment discontinuation or increase mortality. In particular, postural hypotension and tachycardia have been associated with an increased risk of all-cause death and cardiovascular events in the general population.Clozapine-related constipation can develop into full-blown ileus in up to 2.1% of cases, a higher, more durable and more dangerous risk than agranulocytosis. Finally, hypertriglyceridemia and central obesity are well known cardiovascular risk factors.Our study suggests clinicians should carefully monitor for clozapine’s AEs also considering sex, in order to early detect them, promptly treat them and prevent severe complications.Literature suggest some of the sex differences reported in schizophrenia may be due to the protective role of estrogens. Further studies, with a particular attention to hormonal status, could contribute to better understand the pathophysiology of sex differences in TRS and define a personalized therapeutic approach.

Constipation screening in people taking clozapine: A diagnostic accuracy study

ObjectiveClozapine is the favoured antipsychotic for treatment-refractory schizophrenia but its safe use requires careful adverse-effect management. Clozapine-induced gastrointestinal hypomotility (CIGH or ‘slow-gut’) is one of the most common and serious of clozapine's adverse effects. CIGH can lead to paralytic ileus, bowel obstruction, gastrointestinal ischaemia, toxic megacolon, and death. Enquiring about constipation is a simple and commonly used screening method for CIGH but its diagnostic accuracy has not previously been assessed. MethodsFirst, we examined the reliability of asking about constipation compared with asking about Rome constipation criteria in inpatients treated with clozapine (n = 69). Second, we examined the diagnostic accuracy of (1) self-reported constipation and (2) the Rome criteria, compared with the reference standard of gastrointestinal motility studies. ResultsAfter 30 motility tests, it was clear constipation screening had very poor diagnostic properties in this inpatient group and the study was terminated. Although 73% of participants had objective CIGH on motility testing, only 26% of participants self-reported constipation, with sensitivity of 18% (95% CI: 5–40%). Specificity and positive predictive values were higher (95% CI: 63–100% and 40–100%, respectively). Adding in Rome criteria improved sensitivity to 50% (95% CI: 28.2–71.8%), but half the cases were still missed, making this no more accurate than tossing a coin. ConclusionsCIGH is often silent, with self-reported constipation having low sensitivity in its diagnosis. Treating CIGH based on self-reported symptoms questions will miss most cases. However, universal bowel motility studies are impractical. In the interests of patient safety, prophylactic laxatives are suggested for people taking clozapine.

Rare serious adverse effects of clozapine

Rare serious adverse effects of clozapine