Clozapine In Patients Research Articles

Management of clozapine treatment during the COVID-19 pandemic.

Clozapine is the only available treatment for refractory schizophrenia but its use involves frequent physical contact with healthcare workers for the purpose of mandatory blood monitoring. During the COVID-19 pandemic, patients taking clozapine will be self-isolating to reduce the risk of infection, not least because these patients are at high risk of serious illness and fatality because of high rates of diabetes, obesity and pulmonary disease and an increased risk of pneumonia. Problems may also arise because both clozapine-induced myocarditis and neutropenic sepsis share signs and symptoms with COVID-19 (fever, chest pain, dyspnoea, etc.). We recommend decreasing the frequency of physical contacts by extending the blood monitoring interval to 12 weeks in those patients taking clozapine for more than 1 year. To distinguish COVID-19 from clozapine-related physical adverse effects, we suggest an urgent antigen test alongside a full blood count. In those taking clozapine who develop COVID-19, we suggest continuing with clozapine whenever possible (even during ventilation), reducing the dose if necessary in line with blood assay results. Blood monitoring should continue but clozapine should only cease if there is a significant fall in neutrophils (COVID-19 is linked to lymphopenia but not neutropenia). To protect against the likelihood and severity of respiratory infection, we recommend the use of vitamin D in all clozapine patients. Initiation of clozapine is likely to remain problematic while the risk of infection remains, given the degree of physical contact required to assure safety.

Clinical Issues to Consider for Clozapine Patients Who Vape: A Case Illustration.

Vaping uses an electronic nicotine delivery system (ENDS) for inhaling vaporized and aerosolized ingredients. A significant subset of the psychiatric patient population will use ENDS and may have concurrent cigarette usage. In the clinical case highlighted here, a patient with significant nicotine use is prescribed clozapine. He typically inhales vaporized nicotine solution, but during a chemical dependency treatment, he was provided cigarettes instead of ENDS to prevent him from consuming substances other than nicotine. Exposure to cigarette smoke led to clinically worsening psychotic symptoms that reversed when he was discharged from treatment, stopped cigarette use, and resumed ENDS use. However, his extremely high nicotine exposure then led to symptoms resembling an anxiety disorder, which resolved when ENDS use decreased. Psychiatrists must become familiar with patients' vaping and smoking habits and be alert to altered plasma drug levels in patients whose method of nicotine ingestion changes over time.

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.

A cross sectional study of impact and clinical risk factors of antipsychotic-induced OCD

A large proportion of schizophrenia patients treated with second generation antipsychotics will develop Obsessive Compulsive Disorder (OCD). However, there are few studies about the impact of this comorbidity and who is at higher risk. In this study of clozapine-treated patients, we aimed to determine the impact on outcome of clozapine-induced OCD, as well as the clinical and sociodemographic risk factors related to OCD-onset in clozapine patients. We had strict and novel inclusion criteria to minimise mis-identification of cases. The Obsessive-Compulsive Inventory-Revised (OCI-R) was used to divide 231 clozapine-treated patients into extreme cases of OCD (OCI ≥ 24 or checking subscale ≥6) versus non-OCD (OCI <15 and checking subscale <4). The Global Assessment of Functioning (GAF), short version of Warwick-Edinburgh Wellbeing scale and Clinical Global Impression for schizophrenia (CGI) scales were used to determine outcome. Socio-demographic information was used to identify the risk factors for OCD development. We found that schizophrenia patients with OCD symptoms had a significantly lower patient rated wellbeing scores (p < 0.001) only (no difference in clinician rated wellbeing scores), higher CGI positive (p < 0.01) and higher CGI depressive scores (p < 0.05). The only risk factors that reached significance level were higher treatment dose (p < 0.01) and younger paternal age at birth (p < 0.05). There is scope for future studies based on e.g. imaging and genetic studies to further investigate causality, and in improving clinician screening for OCD.

Glycopyrrolate in comparison to hyoscine hydrobromide and placebo in the treatment of hypersalivation induced by clozapine (GOTHIC1): a feasibility study

BackgroundClozapine-induced hypersalivation (CIH) is a common side effect of clozapine treatment and is disliked by clozapine patients, potentially threatening adherence to clozapine treatment. We proposed a trial of alternative medications, hyoscine and glycopyrrolate, for the treatment of CIH and the primary objective of the feasibility study was to assess the recruitment and retention of community clozapine patients as well as assess the metrics of the primary hypersalivation measure.MethodsThis 11-month trial took place in two NHS trusts in northwest UK. Participants were community-dwelling clozapine patients aged 18–65 years who were suffering from CIH, and were recruited from community mental health clinics. They were randomised using a telephone randomisation service to receive either hyoscine (1 week at 0.6 mg daily, 3 weeks at 0.9 mg daily), glycopyrrolate (1 week at 2 mg daily, 3 weeks at 3 mg daily) or placebo. Participants and investigators were blinded to which study arm the participants had been randomised to. We collected data on salivation levels and side effects on a weekly basis and also assessed cognition at the beginning and end of the trial. We also interviewed a sample of participants after the trial to gather information on their experience of having taken part.ResultsOne hundred and thirty-eight potential participants agreed to being contacted by researchers about participation in the trial and of these, 29 participants were randomised. Of these, four participants exited the trial before taking any trial medication, and two participants left the study owing to concerns of side effects. Data from four participants was missing, and complete data was available for 19 participants who completed the trial. The mean recruitment rate overall was 1.3 participants per site per month, and the overall retention rate was 76%. Interview data suggested that participants’ experiences of trial participation were overwhelmingly positive.ConclusionsThe feasibility study demonstrated that a trial of alternative medications in the treatment of CIH is feasible; patients were willing to be randomised to the trial and retention rate was high.Trial registrationClinicalTrials.gov, NCT02613494, registered 24 November 2015

S185. Treatment Response Trajectories in Treatment-Resistant Schizophrenia: A Chart Review Study

Although clozapine is the only antipsychotic indicated for treatment-resistant schizophrenia, 40-70% of clozapine patients have persistent psychosis (ultra-treatment-resistant schizophrenia, URS). Treatment response trajectories in patients on clozapine remain unclear; thus, we aimed to characterize treatment-resistant patients based on clozapine response and explore the clinicodemographic predictors of patients who were resistant to clozapine since its initiation.

Clinical correlates of sialorrhea in clozapine patients

Objective: Sialorrhea occurs more frequently in patients on clozapine than in those on other antipsychotics and has an adverse impact on the quality of life. We evaluated clinical correlates of sialorrhea. Method: 79 patients with schizophrenia (54 males, 25 females; mean age 43.3 years, SD=12.7) from an urban clozapine clinic participated. Their total daily 24 hour dose of clozapine ranged from 100 to 650mg with the average at 341.8, SD=133.1). The part administered at nighttime ranged from 25 to 600mg, with the average at 258.7, SD=106.7. Results: The scores on Nocturnal Hypersalivation Rating Scale (NHRS) ranged from 0 to 4 with the average at 1.7, SD=1.2. The symptom was absent in 17.7%, minimal in 36.7%, mild in 15.2%, moderate in 21.5%, and severe in 8.9% of patients. The intensity of sialorrhea was not significantly correlated to the daily clozapine dose, or its nighttime part, or duration of clozapine treatment, age, and gender. The presence of concurrent other antipsychotics slightly increased the NHRS scores (r=.37) and the presence of antihypertensive medication slightly reduced these sialorrhea scores (r=-.25). Discussion and Conclusions: About a half of the patients reported mild to severe nocturnal hypersalivation, but its intensity seems unrelated to the clozapine dose or to its nighttime administration. No gender or age differences in hypersalivation were found. Concurrent use of other antipsychotics could lightly intensify the sialorrhea.

M107 - IDENTIFICATION OF CLINICAL FEATURES THAT PREDICT FUTURE WEIGHT TRAJECTORY IN A NOVEL COHORT OF CLOZAPINE-TREATED PATIENTS

There is a lack of genetic and epidemiological studies specific to weight gain among individuals receiving clozapine treatment for established psychosis. Knowing if patients have factors that predispose them to weight gain trajectory or a weight constant trajectory would enable more effective targeting of weight loss programs to avoid problematic weight gain. This study aims to assess the trajectory of weight gain using data routinely collected by Clozapine Therapeutic Monitoring Services in a novel longitudinal cohort of clozapine patients from the United Kingdom and Ireland. We use genetic, clinical and demographic data to determine the influence of these variables on trajectory membership. A total of 3500 individuals had clinical and candidate/proven gene data available. Weight trajectory was calculated from individuals who had at least two weight records over a period of 24 months from the first available record. Trajectories were developed utilising K-Means for Longitudinal data (KML), an algorithm that assigns individuals to a user-defined number of trajectories based on their similarity. There are three distinct trajectories patients take within the first 2 years of clozapine treatment, which are influenced by age, starting weight and clozapine plasma level. Weight gain is more likely to be seen in individuals with younger age, lower plasma levels and lower starting weight. Individuals under the age of 25 with lower starting weight were more likely to be in the weight gain trajectory, whereas older people with higher starting weights were more likely to be in the weight loss trajectory. This could be due to individuals in the weight loss trajectory actively reducing weight after prior weight gain from other antipsychotics. Clozapine plasma levels were also lower in the weight gain trajectory, possibly reflecting incorrect dosage or non-compliance. Clozapine levels were more likely to be in the normal range for individuals in the weight-constant or weight -loss trajectory, reflecting a stable maintenance dosage and increased compliance.

A pilot study examining the profile of older people on clozapine.

The primary aim was to comprehensively describe the characteristics of a cohort of older people taking clozapine. Participants aged ⩾ 60 had a geriatric assessment including full medical, medication and social history. Standardized screening tools for cognition, function, comorbidity and antipsychotic side effects were administered and descriptive statistics utilized. Thirteen patients were eligible to participate and 10 were assessed. The mean age was 69 years. The mean clozapine dose was 309 mg/day and mean duration of use was 10 years. All participants had executive dysfunction, and half had cognitive impairment. The mean number of co-morbid conditions was five. Seven people met the criteria for polypharmacy. Eight people experienced moderate-severe antipsychotic-related side-effects. The majority demonstrated impaired physical functioning. This cohort of older people taking clozapine experienced considerable morbidity, functional and cognitive impairment. We suggest routine screening of cognition and function in clozapine patients aged ⩾ 60 years. Those screening positive should be considered for further assessment by Older Person's Mental Health Services and/or a Geriatric Medicine service.

S92. DISTINCT RISK FACTORS FOR OBSESSIVE AND COMPULSIVE SYMPTOMS IN SCHIZOPHRENIA

BackgroundObsessive-compulsive disorder (OCD) is common in schizophrenia patients treated with antipsy-chotics with significant anti-serotoninergic action. Clozapine was the first drug reported and is still the medication more frequently associated with OCD, along with olanzapine. The aim of this study was to study the OCD prevalence, clinical profile and associated severity factors, using electronic records of a large cohort of clozapine-medicated schizophrenic patients. Patients were routinely screened for OCD using standardised scales as well as relevant clinical, psychometric and demographic data.MethodsThe electronic records of a large cohort of clozapine-medicated schizophrenia patients routinely screened for OCD using standard measures were used. The Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118 cases and a 21 points cut-off threshold for OCD was defined.ResultsOCD prevalence was 47% and significantly higher in patients on several medications including clozapine than on clozapine monotherapy (64% vs 31%; p=.001). Two OCI-R factors had significantly higher scores in these patients and were associated with distinct risk factors: checking behaviour (mean=5.1; SD=3.6), which correlated with length on clozapine treatment (r=.21; p=.026), and obsessing factor (mean=4.8; SD=3.6), which correlated with psychosis severity (r=.59; p=.001). However, these factors along with total OCI-R, did not correlate with either clozapine dose or plasma levels, after correcting for psychosis severity.DiscussionWe propose an imbalance between impaired goal-directed behaviour and habit formation in favour of the latter in clozapine-OCD as a potential theoretical framework for our results. Compulsion in clozapine-medicated schizophrenia patients could be understood as a long-term by-product of the psychosis (even after remission) perpetuated by clozapine’s potent antiserotoninergic properties. Screening for OCD in clozapine patients, and probably in those treated with structurally similar drugs like olanzapine, should be widely adopted by clinicians.

31.2 CAN WE IMPROVE FUNCTIONAL OUTCOME AND ADHERENCE IN OPTIMISE PARTICIPANTS WITH A PSYCHOSOCIAL INTERVENTION?

BackgroundWe hypothesised that a multi-modal psychosocial intervention (PSI) after first episodes of non-affective psychosis would increase antipsychotic adherence, improve functioning and prevent readmission in a multi-centre, blind-rated, randomised controlled trial.MethodsFollowing treatment of first episode non-affective psychosis with amisulpride, olanzapine or clozapine (those remitting after phases 1–3 of the OPTIMISE program or dropping-out but willing to enter the adherence trial) patients with DSM-IV schizophreniform disorder, schizophrenia, or schizoaffective disorder were eligible for allocation to PSI or treatment as usual (TAU).PSI involved: i) e-learning via a psychoeducational website; ii) mHealth intervention with 3 months SMS medication reminders configured by participants; iii) motivational interviewing targeting adherence over 6 weeks.Primary outcome measures at 3 and 12 month follow-up were Compliance Rating Scale (score 1–7 worst to best), and Social and Occupational Function Assessment Scale (SOFAS; 0–100). Secondary outcomes included remission, Drug Attitudes Inventory (DAI), and EuroQoL quality of life scale. We present interim analyses of 3 month data with general linear and logistic regression models, clustered by centre and adjusted for baseline scores and demographics.ResultsRecruitment time, now finished, was extended to reach target sample size, so 12 month data are incomplete. 258 were allocated to PSI or TAU. 18 dropped-out before baseline assessment: 240 entered the modified intention to treat analysis (PSI 121, TAU 119). After PSI, 71% were followed-up at 3 months; after TAU, 80%. No baseline variable significantly predicted this attrition.Webpages covering illness and treatment had 244–290 hits each. Only 24% of the PSI group set up SMS text reminders. At least 70% attended motivational interviewing, 77% of these for all sessions. Mean California Patient Alliance Scale item score was 5.2 (95% Confidence Interval, CI, 5.0, 5.3; score 1–7 poor-good).Mean baseline SOFAS (SD) for the PSI group was 62 (14); for TAU 62 (15). General linear modelling of 12 week data included baseline CRS and drug attitudes: marginal mean SOFAS after PSI was 65.3 (CI 62.6, 68.0) and after TAU 61.4 (CI 59.3, 63.4; p0.025; standardised effect size Glass’ Δ=0.41). Median (IQR) compliance score was 6 (5,7) at baseline for PSI and 6 (6,7) for TAU; and 6 (5,7) at 3 months in both groups (ordinal logistic regression, p0.36).In secondary analyses 3 month DAI did not differ significantly between PSI and TAU (marginal means 13.5 v 11.5, bootstrapped p0.164). EuroQoL wellbeing score was significantly better after PSI (marginal means 76.0 v 69.1, bootstrapped p0.003) and remission was significantly commoner (72 v 54%, binary logistic regression p0.007). No analysis result was sensitive to probability weighted adjustment for drop out.DiscussionInterim analyses indicate that immediately after PSI social function and wellbeing improved significantly and remission was commoner. Adherence and DAI did not differ significantly. Either PSI’s immediate benefits were non-specific or adherence measures failed to capture its effect. Longer term effects are unclear until definitive analyses planned before 2018.

The Clozapine Clinic: A Model of Integrated Care

Introduction: A significant proportion of individuals with psychotic illness are either refractory to, or intolerant of, standard antipsychotic pharmacotherapy. There is currently only one medication available with proven effectiveness in this population. Clozapine while providing a superior response rate requires significant physical health care monitoring both before and during treatment. The medication requires weekly hematologic monitoring and intensive metabolic screening. Methods: A site was selected for establishment of a new Clozapine Clinic to provide services for individuals with treatment refractory psychotic symptoms or individuals with medication side effects deemed to be related to standard antipsychotic medications. Individuals were selected without predetermined exclusion criteria such as age or physical comorbidity. Patients were accepted into the Clozapine Clinic with a combination of physical health and mental health assessments. The Clozapine Clinic was fortunately located in close proximity to a County Primary Care Clinic and County Tertiary Care Hospital, both of which were helpful in obtaining baseline physical health assessments and diagnostic tests and concurrent hematologic and metabolic laboratory monitoring Results: A new Clozapine Medication Support service line was established using a collaborative care model with existing County facilities. At total of 10 new and established individuals were enrolled into the Clozapine Clinic, with weekly, biweekly and monthly psychiatric and physical health monitoring. The Clozapine Clinic continues to receive referrals for individuals in need of complex care with this unique psychopharmacologic agent. Conclusions: Clozapine pharmacotherapy for treatment resistant psychotic symptoms provides a model for integrated care in this population. Using a collaborative relationship and employing integrated care principles as the model, the complex care of new and established Clozapine patients was provided at an existing County Mental Health Clinic. Weekly hematologic and metabolic monitoring was achieved by partnering with the affiliated hospital laboratory in order to provide rapid, same day results. A dedicated Clozapine Clinic Nurse was employed to provide the coordination of physical health assessments, psychiatric evaluations and laboratory monitoring. In less than a year, the Clozapine Clinic services at this clinical site were expanded to approximately 10 individuals, with additional individuals awaiting entry. Clozapine pharmacotherapy for treatment refractory psychiatric illness is vastly underutilized in large part due to the complexity in coordination of physical health and mental health needs. This underutilization leads to high levels of morbidity and mortality in the psychiatric population. Implications for Integrated Care Practice: Since a significant percentage of patients with chronic psychotic illness are either intolerant or refractory to standard antipsychotic medications, Clozapine remains the only effective agent available. However, with its significant need for monitoring of physical health side effects, integrated care models of treatment provide the most cost effective, efficient and comprehensive model for addressing the whole person health care needs of this special population. Integrated Care models represent the solution to the underutilization of Clozapine pharmacotherapy in treatment resistant populations.

Clozapine Patients at the Interface between Primary and Secondary Care.

Patients receiving clozapine must undergo routine blood monitoring to screen for neutropenia, and to monitor for potential agranulocytosis. In Cork University Hospital, Cork, Ireland, clozapine is dispensed in the hospital pharmacy and the pharmacists are not aware of co-prescribed medicines, potentially impacting upon patient safety. The aim of this study was to examine the continuity of care of patients prescribed clozapine. A retrospective audit was conducted on patients attending the clozapine clinic at Cork University Hospital and assessed patients’ (i) independent living, (ii) co-prescribed medicines and (iii) knowledge of their community pharmacists regarding co-prescribed clozapine. A list of prescribed medicines for each patient was obtained, and potential drug-drug interactions between these medicines and clozapine were examined using Lexicomp® and Stockley’s Interaction checker. Secondary outcomes included patients’ physical health characteristics, and a review of co-morbidities. Data were collected between the 29 May 2017 and 20 June 2017. Local ethics committee approval was granted. Patients were eligible for inclusion if they were receiving clozapine treatment as part of a registered programme, were aged 18 years or more, and had the capacity to provide written informed consent. Microsoft Excel was used for data analysis. Of 112 patients, (33% female; mean age (SD) 43.9 (11.3) years; 87.5% living independently/in the family home) 86.6% patients reported that they were taking other prescribed medicines from community pharmacies. The mean (SD) number of co-prescribed medicines in addition to clozapine was 4.8 (4) per patient. Two thirds of community pharmacists were unaware of co-prescribed clozapine. Interactions with clozapine were present in all but 3 patients on co-prescribed medicines (n = 97). Lexicomp® reported 2.9 drug-drug interactions/patient and Stockley’s Interaction Checker reported 2.5 drug-drug interactions/patient. Secondary outcomes for patients included BMI, total cholesterol, and HbA1c levels, which were elevated in 75%, 54% and 17% respectively. Patients prescribed clozapine did not receive a seamless service, between primary and secondary care settings. Community pharmacists were not informed of clozapine, prescribed for their patients, in two thirds of cases. Patients in this study were exposed to clozapine-related drug-drug interactions and hence potential adverse effects. This study supports reports in the literature of substandard management of the physical health of this patient group. This study shows that there is an opportunity for pharmacists to develop active roles in the management of all clozapine-related effects, in addition to their traditional obligatory role in haematological monitoring. This study supports the need for a clinical pharmacist to review inpatients commencing on clozapine, monitor for drug-drug interactions and provide counselling.

Distinct risk factors for obsessive and compulsive symptoms in chronic schizophrenia.

Obsessive-compulsive disorder (OCD) is common in clozapine-treated patients although the actual prevalence, phenomenology and risk factors remain unclear. The aim of the present study was to address the three aforementioned questions. The electronic records of a large cohort of clozapine-medicated schizophrenia patients routinely screened for OCD were used. The Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118 cases and a 21 points cut-off threshold for OCD was defined. OCD prevalence was 47%, higher in patients on poly-pharmacy than on monotherapy (64% vs 31%; p = 0.001). Two OCI-R factors had significantly higher scores and distinct risk factors: checking behaviour (mean = 5.1; SD = 3.6) correlated with length of clozapine treatment (r = 0.21; p = 0.026), and obsessing factor (mean = 4.8; SD = 3.6) correlated with psychosis severity (r = 0.59; p = 0.001). These factors along with total OCI-R, did not correlate with either clozapine dose or plasma levels, after correcting for psychosis severity. Screening for OCD in clozapine patients, and probably in those treated with structurally similar drugs with potent antiserotoninergic properties, should be widely adopted by clinicians. Further research is needed to understand the pathophysiology underlying repetitive behavior onset in clozapine-treated patients.

Collaborative Effort Among Stakeholders Can Reduce Barriers to Clozapine Use

Challenges surrounding prescribing clozapine may seem intimidating to clinicians with little or no training in use of the drug, but working with primary care physicians and more experienced prescribers can reduce the burdens.

GI, Pulmonary Illnesses: Most Cited for Hospitalizing Clozapine Patients

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessGI, Pulmonary Illnesses: Most Cited for Hospitalizing Clozapine PatientsVabren WattsVabren WattsSearch for more papers by this authorPublished Online:17 Jan 2017https://doi.org/10.1176/appi.pn.2017.1a22AbstractA chart review reveals that the primary reasons for the hospitalization of patients taking clozapine were not related to conditions listed in the medication’s FDA boxed warnings.When prescribing clozapine—the only antipsychotic that has been FDA-approved for treatment-resistant schizophrenia—clinicians are required by an FDA boxed warning to closely monitor patients’ blood to reduce the risk of agranulocytosis and other adverse events. A study published online on November 18, 2016, in Psychosomatics now suggests pulmonary and gastrointestinal illnesses may be the most likely reason for patients taking clozapine to be hospitalized.“The new study gives a clear profile of medical vulnerabilities faced by some patients treated with clozapine,” said Mark Olfson, M.D., M.P.H., a professor of psychiatry at Columbia University Medical Center, who was not involved in the study. Jonathan Leung, Pharm.D., believes that vigilant monitoring for pulmonary and gastrointestinal-related issues may help to prevent adverse events from developing into life-threatening complications.Jonathan Leung, Pharm.D. For the study, Jonathan Leung, Pharm.D., of the Mayo Clinic in Minnesota and colleagues conducted a retrospective chart review of patients with schizophrenia or schizoaffective disorder who were taking clozapine and admitted to an inpatient medical unit at the Mayo Clinic for nonpsychiatric illness between January 1, 2003, and August 1, 2005. A total of 104 adults aged 18 and older was included in the analysis. They were admitted into the hospital a total of 248 times, and the mean clozapine dose prescribed at the index admission was 407.2 mg. Pulmonary illness and gastrointestinal illness were the most common reasons for hospitalizations at 32.2 percent and 19.8 percent, respectively. The most common pulmonary diagnosis was pneumonia, accounting for 58 percent of pulmonary admissions. The most common reason for gastrointestinal diagnosis was hypomotility, at 61.2 percent. The authors noted that clozapine was discontinued due to neutropenia in two patients; there were no patients admitted for myocarditis. (Agranulocytosis can lead to neutropenia when the bone marrow fails to make enough neutrophils.)“In our sample, the primary reasons for admission were not related to the FDA boxed warnings, but rather to pulmonary and gastrointestinal illnesses,” the authors wrote. “This is not unexpected given that clozapine-related neutropenia and myocarditis have the highest incidence within several months after first exposure and are likely to be discovered through vigilant monitoring. Discovery then allows for early clozapine discontinuation and resolution of the adverse event, potentially avoiding medical hospitalization.” Psychiatric consultation was obtained in 25 percent of the hospitalizations, “most frequently for ‘clozapine management,’ retitration recommendations, or possible clozapine toxicity. Clozapine dosage adjustment infrequently occurred, and complete discontinuation was rare,” the authors wrote. In an interview with Psychiatric News, Leung said that current findings are congruent with other published information and highlight two important aspects of clozapine therapy. First, all clinicians should vigilantly monitor bowel function in order to prevent potentially fatal complications; and second, pneumonia associated with clozapine is an underappreciated event. Leung continued that it will be important for future investigations to include control populations such as patients on other antipsychotics to understand the proportion of adverse events potentially attributable to clozapine. “We can then focus on developing improved monitoring procedures and interventions that can minimize morbidity and mortality associated with pulmonary and gastrointestinal complications.”No financial support was received for this study. ■An abstract of “Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine” can be accessed here. ISSUES NewArchived

A Reasonable Alternative to Clozapine in the Chronically Relapsing Smoking Patient? A Retrospective Analysis.

Background: Clozapine levels are severely decreased by cigarette smoke hydrocarbons. A new agent that is unaffected by smoking is paliperidone palmitate. Objective: The purpose of this study is to retrospectively evaluate hospital readmission and time until readmission for patients prescribed paliperidone palmitate intramuscular injection (PP) as an alternative to oral clozapine for patients with severe schizophrenia who resume smoking following discharge. A secondary analysis was performed to determine whether smoking status alone affects hospital readmission rates in both smoking and nonsmoking clozapine-treated patients. Methods: This was a retrospective analysis of all patients who were positive for smoking at admission and readmission who were prescribed clozapine and PP. Smokers were identified by concurrent orders for nicotine replacement. Readmission rates and time until readmission were determined. Data were analyzed utilizing nonparametric statistical methods. Results: A total of 133 subjects were identified, including 108 smokers in PP group, 18 smokers in clozapine group, and 7 nonsmoking clozapine patients. Readmission rates were statistically significant between smokers in the clozapine and PP groups, with significantly lower readmission rates in the PP group (p = .004). In the sub-analysis, hospital readmissions between smokers and nonsmokers in the clozapine group were statistically significant (p = .027). Results may be influenced by use of a single hospital site, limits of a retrospective analysis, and variation in pharmaceutical preparation. Conclusion: PP may be a reasonable alternative to clozapine in severe schizophrenia for patients who continually resume smoking following discharge. Smoking may also be an important predictor of decompensation in smokers prescribed clozapine. A further prospective study is warranted.

Management of cardiovascular risk in clozapine patients: how can we optimise it?

Management of cardiovascular risk in clozapine patients: how can we optimise it?

Comparative study of the side-effect profile between clozapine and non-clozapine patients

IntroductionFor resistant schizophrenia, the only approved treatment is clozapine. However, clozapine is underused, mainly due to its wide range of side-effects. Secondary effects differ amongst antipsychotics (Leucht et al., 2009). Despite that there is no good evidence that combined antipsychotics offer any advantage over the use of a single antipsychotic, combination increases the frequency of adverse events (Maudsley guidelines).ObjectivesTo compare the side-effect profile between clozapine and non-clozapinepatients.AimsTo provide evidence that clozapine patients do not show a worse side-effects profile.MethodsWe cross-sectionally analysed all patients from a Spanish long-term mental care facility (n = 139). Schizophrenic/schizoaffective patients were selected (n = 118) and their treatment was assessed, 31 patients used clozapine. We paired clozapine and non-clozapine patients by sex and age and assessed antipsychotic side effects and possible confounder variables.ResultsOur sample was 27 clozapine patients and 29 non-clozapine patients. 67,9% were male with a mean age of 51.3 (SD 9.6) years. For continuous variables: age, BMI, waist/hip, cholesterol, TG, glucose, prolactin, heart-rate, blood pressure, sleeping hours, the only statistical differences found were lower heart-rate (P = 0.001) in clozapine group and higher salivation subscale of SAS (P = 0.002) in clozapine group. For discrete variables: monotherapy, obesity, overweight, metabolic syndrome or possible confounders as propranolol, laxative, diet, antiglycemiant or insulin, fibrates or statins, antihypertensive or anticholinergic, no statistical differences were found.ConclusionsWe did not find differences in cardiometabolic parameters, which are the main barrier to prescribing clozapine, probably due to the concomitant use of other drugs in both groups.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Study of the contributory factors to metabolic abnormalities in resistant schizophrenia

IntroductionSchizophrenia is a developmental disorder that includes non-psychiatric abnormalities [2]. Metabolic abnormalities prior to antipsychotic treatment exist. The clozapine metabolic profile causes clozapine underuse in resistant schizophrenia [1].ObjectivesTo correlate metabolic profile with psychiatric severity and compare the correlations between clozapine/non-clozapine patients.AimsTo determine possible contributory factors to metabolic abnormalities in schizophrenia.MethodsWe cross-sectionally analyzed all patients from a Spanish long-term mental care facility (n = 139). Schizophrenic/schizoaffective patients were selected (n = 118). N = 31 used clozapine. We paired clozapine and non-clozapine patients by sex and age and assessed metabolic and psychopathologic variables.We compared psychopathologic variables between patients with/without cardiometabolic treatment and the differences between clozapine/non-clozapine groups.ResultsWe analyzed: 27 clozapine/29 non-clozapine patients. A total of 67,9% males with a mean age of 51.3 (SD 9.6) years. In the whole sample TG negatively correlated with Negative-CGI (r: −0,470, P: 0.049) and HDL-cholesterol correlates with Global-CGI(r: 0,505, P: 0.046). Prolactin correlated with the number of antipsychotics (r: 0.581, P: 0.023) and IMC (r: 0.575, P: 0.025). Clozapine group took less antipsychotics [Fisher (P: 0.045)] and had higher scores in total BRPS scale [t-Student (P: 0.036)]. They did not use more cardiometabolic treatment. There were no psychopathological differences between cardiometabolic treated/non-treated patients. In the non-cardiometabolic treated group (n = 35/62,5%), IMC negatively correlated with positive and total BPRS, positive, cognitive and global-CGI. We found negative correlations between metabolic parameters and psychopathology in clozapine (40%) and non-clozapine subgroups (60%). In the cardiometabolic treated group (n = 21/37,5%), we did not find these correlations in either of clozapine (61.9%) or non-clozapine (38.1%) subgroups.ConclusionsSeverity [2], prolactine [3] and treatment [1] could play a role in metabolic parameters. In our sample we found negative correlations between psychopathological and metabolic parameters.References not available.Disclosure of interestThe authors have not supplied their declaration of competing interest.