Clozapine Prescribing Research Articles

Differences between physicians' and nurse practitioners' viewpoints on reasons for clozapine underprescription

IntroductionClozapine (CLZ) is the only proven effective therapy for treatment‐resistant schizophrenia, but it is underutilized across the globe. Previous findings suggest a lack of experience with CLZ prescription and concerns about CLZ's pharmacological characteristics are the prime reasons for CLZ underutilization. To our knowledge, it is currently unknown whether the reasons for underutilization and suggested solutions differ between physicians and nurse practitioners. Such differences are important as nurse practitioners are becoming increasingly involved in prescribing CLZ.MethodsTo examine to what degree physicians and nurse practitioners differ with regard to their take on reasons for CLZ underutilization and suggested solutions, an online questionnaire was distributed to physicians and nurse practitioners. The primary outcome was to compare the patient‐related and prescriber‐related reasons for CLZ underprescription between physicians and nurse practitioners, while secondary outcome measures included the potential solutions to prevent this underprescription.ResultsPhysicians (N = 112) and nurse practitioners (N = 41) agreed that the two most common reasons for underprescription (patient‐related and prescriber‐related) were refusal to undergo regular blood tests and side‐effect concerns. They also agreed that the third most common prescriber‐related reason was medical complications. Physicians rated patients' unwillingness to switch medication as the third most common reason for CLZ underprescription, whereas nurse practitioners rated refusal to undergo baseline bloodtests as the third most common reason. The solutions to reduce underprescription largely corresponded between both groups.ConclusionsWe conclude that slight differences exist between physicians' and nurse practitioners' viewpoints on patient‐related and prescriber‐related reasons for CLZ underprescription. Future research projects should involve patients to elucidate whether the patient‐related factors put forward by prescribers align with the patients' opinions.

Off-Label Use of Clozapine in Children and Adolescents-A Literature Review.

Clozapine is a second-generation antipsychotic typically used for refractory schizophrenia or otherwise psychotic pathology. There are no FDA or manufacturer guidelines for use of clozapine in pediatric population. We investigated the current state of research concerning the use of clozapine in pediatric patients. We describe consistent calls for more research into the long-term and short-term effects of clozapine use in a young patient population. Despite the strongly supported efficacy, questions concerning clear indications for use and risk-benefit analysis persist. We acknowledge that a more comprehensive meta-analysis would greatly benefit the field. However, this is the first article of its kind for clozapine in recent history, and therefore, serves as a focus and reference point for future, more in-depth analyses. We conducted a search of PubMed, ClinicalKey, PsycINFO, and MEDLINE databases. Keywords used included, in varying combinations: clozapine, off-label, indications, children and adolescent, pediatric, behavioral, suicidality, psychosis, early and very-early onset schizophrenia, side-effect profile, and long-term use. Further criteria and selection are described in Methods below. We describe the documented efficacy of clozapine for the management of refractory psychotic and nonpsychotic symptoms in the pediatric population. The authors highlight the risk of unmanaged early-onset schizophrenia, aggressive or suicidal behavior, and severe nonpsychotic pathology. Unfortunately, these studies are generally small. There is little consistency in when clozapine is prescribed, how long it is administered, and how long patients are followed. Despite the lack of FDA and manufacturer guidelines, clozapine continues to be used for the benefit of young patients. Indications for prescription of clozapine should be revisited, given the data presented in this manuscript of a low risk-benefit ratio for properly chosen patients. Larger studies should be conducted to provide more statistical power and determine clear guidelines for use, risk of side effects, and long-term adverse events that may arise.

Clozapine prescription pattern in patients with schizophrenia in Asia: The REAP survey (2016)

Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P < 0.001), less frequent first admission in the sample (OR = 0.6, P < 0.001), more severe negative symptoms (OR = 1.4, P = 0.001) and less first generation antipsychotics (FGAs) (OR = 0.2, P < 0.001) were independently and significantly associated with clozapine prescription. Clozapine is frequently and increasingly prescribed for schizophrenia in Asia, with large variation across countries and territories. Given the diverse prescription patterns of clozapine found in Asian countries/territories, the clinical rationale of clozapine prescription needs careful consideration in Asia with more local input.

Clozapine-induced agranulocytosis and leukopenia: Incidence, associated factors, and rate of hematologic adverse-effects monitoring in psychiatric out-patient services in Thailand.

The present study aimed to investigate the incidence of agranulocytosis and leukopenia and its associated factors in Thai schizophrenia patients treated with clozapine and the rate of hematologic adverse events monitored in clinical practice. Data were collected from the medical records of 641 outpatients at two hospitals. The results showed no cases of agranulocytosis and 20 cases of leukopenia (3.1%), 85% of which were observed after 1 year of prescription. The associated factors were female (p = 0.019) and duration of clozapine prescription (p = 0.026). According to the guideline for safety monitoring, 23.6% of cases had neutrophils count monitoring.

Psychiatric pharmacist's role in overcoming barriers to clozapine use and improving management.

Clozapine is an antipsychotic that exhibits superior efficacy and effectiveness for those with schizophrenia and other serious mental illness. However, its side-effect profile and administrative burdens present challenges to its use. In the United States, the medication is grossly underused even though it may improve outcomes and reduce costs. Current barriers to use include lack of prescriber knowledge and confidence, negative prescriber attitudes, special monitoring requirements, administrative factors, lack of clozapine on formularies, lack of support and infrastructure to use the medication within many health systems, and inadequate understanding or acknowledgement of clozapine prescribing and risks by policy makers and payers. Approaches using interprofessional models of care, which include pharmacists specializing in psychiatric care, can help meet the needs of patients receiving clozapine. This article lays out the big picture of barriers to clozapine and how psychiatric pharmacists could play a role in improving access.

A mixed methods analysis of clozapine errors reported to the National Reporting and Learning System.

To review and analyse medication errors related to clozapine, an atypical antipsychotic, that were reported to the National Reporting and Learning System (NRLS). Following extraction of one year of clozapine related errors from the NRLS, a qualitative analysis (thematic analysis and re-classification) and quantitative analysis was performed. An incident was considered a clozapine error if there was a failure in its medication process (i.e. an error in the prescribing, dispensing, preparing, administering, monitoring or advising of clozapine). "Issues with stock/supply/ordering" was the most common theme derived from the qualitative thematic analysis (n=338), followed by wrong dose/strength/frequency (n=221) and medication omissions (n=202). Most errors occurred in the "administration/supply" medication stage. Over half of reported clozapine incidents involved people 26 to 55years old (n=830) and 82% of errors were reported by mental health services (n=1270). Only 1.5% of reports were classed as moderate/severe harm. Issues with availability, stock, and supply were found to be the most common causes. This usually entailed a lack of stock to fulfil a patient's dose/supply. Such incidents could potentially be reduced by improved management of the supply process, and liaison between pharmacy and clinical staff. The implementation of emergency drug cupboards at the discretion of an on-call pharmacist may prove to be a preventative measure for such errors. Despite the potential adverse effects associated with clozapine, very few incidents led to moderate/severe harm. Encouragement of NRLS reporting is recommended for incidents of all degrees of harm.

Differences between counties in the prescribing of clozapine.

Norwegian national guidelines recommend that clozapine be offered to patients with schizophrenia after two failed attempts with other antipsychotic drugs. One of the main objectives for the introduction of clinical pathways in mental health care is to provide an equal service to patients irrespective of where in the country they live. We wished to investigate the prescribing level of clozapine in various Norwegian counties. We retrieved aggregated data from the Norwegian Prescription Database, the Norwegian Patient Registry and Statistics Norway on prescribing of clozapine, number of patients in contact with the specialist health service with the diagnosis schizophrenia, and population figures for 2016. Nationwide in 2016, there were 50 users of clozapine per 100 000 inhabitants (95% confidence interval (CI) 48-52). The number of users was highest in Troms county (76 (95% CI 63-89) per 100 000 inhabitants) and lowest in Akershus county (38 (95% CI 33-43) per 100 000 inhabitants). We found no significant correlation between the prescribing rate for clozapine and the proportion of the population in the county who were undergoing treatment for schizophrenia in the specialist health service. Prescribing of clozapine varies among Norwegian counties and is not correlated with the proportion of the population who are undergoing treatment for schizophrenia in the specialist health service. Different levels of implementation of the national guidelines constitute a possible explanation for the geographic differences.

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care.

Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients).Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH).Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8–34.7% (mean: 23.0%), type 2: 0–8.2% (mean: 3.5%), type 3: 1.7–15.6% (mean: 6.9%), type 4: 1.8–16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0–90.9% (mean: 68.8%). These figures were lower in early intervention teams.Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher.Registration number: NTR5135 http://www.trialregister.nl/trialreg/index.asp

Meta-analysis examining the epidemiology of clozapine-associated neutropenia.

Clozapine is associated with life-threatening neutropenia. There are no previous meta-analyses of the epidemiology of clozapine-associated neutropenia. To determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine. A systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis]. Random effects meta-analysis to determine event rates and longitudinal incidence of events per 100 person-years of exposure. A total of 108 studies were included. The incidence of clozapine-associated neutropenia was 3.8% (95% CI: 2.7-5.2%) and severe neutropenia 0.9% (95% CI: 0.7-1.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01-0.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6-2.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment. Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine-associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.

Long-term follow-up of clozapine prescribing.

Clozapine is uniquely effective for treatment-resistant schizophrenia, and so treatment continuation is essential. We aimed to identify factors associated with an increased likelihood of clozapine discontinuation in a cohort of patients in South East London. We gathered demographic and treatment information such as duration of illness and antipsychotic treatment history. t-tests, chi-square tests and binary logistic regression were used to compare patients who continued and discontinued clozapine during the study and to identify predictor variables for discontinuation. Out of the study population of 133 patients, 48 discontinued clozapine at least once during the study period. The majority of these (75%) stopped treatment within the first 4 years of clozapine therapy. Age, ethnicity, diagnosis and antipsychotic treatment history were not predictive of the risk of clozapine discontinuation. However, male patients were more likely to stop taking clozapine (χ2 = 6.81, p = 0.009). The odds of discontinuing clozapine were 2.15 times higher for male patients. The most common reason for discontinuation was patient refusal of treatment. We found that patients who discontinue clozapine are more likely to be male, but no other demographic variable was found to predict treatment cessation. Discontinuation usually occurred due to patient refusal of treatment.

T228. VARIABILITY AND UNDERUTILISATION OF CLOZAPINE IN SPAIN

BackgroundThe analysis of the information available in many countries on the use of clozapine, systematically indicates low prescription, underdosing and delay in the start of treatment. But as striking as this underutilization is the great variability between territories studied, which are related to multiple factors, and have led to various initiatives to improve its use. We do not have studies that evaluate these aspects in the Spanish population, so we have considered a first approximation through samples from four territories.MethodsThe authors analyzed the prescription data of clozapine in Castilla y León, the Basque Country, Catalonia and a Southern Madrid Area.ResultsThe patients diagnosed with schizophrenia who receive treatment in the territories studied oscillate around 0.3%; the treatments with clozapine / 10000 inhabitants between 33.0 and 57.0; and patients diagnosed as schizophrenia receiving clozapine account for between 13.7% and 17.9% of those treated. The coefficient of variation between centers and prescribers is frequently higher than 50%.DiscussionThe global clozapine prescription data in the territories studied are in the range of countries in our environment. The variability in the prescription is very high and increases as we analyze smaller territories, until a great heterogeneity of the individual prescription.

T222. EARLY TREATMENT RESISTANCE IN A LATIN-AMERICAN COHORT OF PATIENTS WITH SCHIZOPHRENIA

BackgroundFailure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195patients with schizophrenia from a Latin-American cohort, to explore the timing of treatment resistance during the course of the disease and possible subgroup differences.MethodsWe used survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward.ResultsEchoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093–0.13), compared to 0.018 (0.012–0.024) between years 1 and 5, and 0.006 (0–0.019) after 5 years. There were no differences in age at psychosis onset or gender related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis.DiscussionOur results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.

41. RECONSIDERING THE EVIDENCE FOR CLOZAPINE FOR TREATMENT REFRACTORY SCHIZOPHRENIA

Overall : The superiority of clozapine for treatment refractory schizophrenia was, until very recently, seen as one of the few unshakeable truths in psychiatry. But the pre-eminence of clozapine has recently been called into question by meta-analyses. What are we to make of the fact that meta-analyses of clinical trials, supposedly the pinnacle of evidence based medicine, fail to show an effect which seems clearly evident to most clinicians, and on which many of our guidelines are based? Have we believed in a fairytale for the past three decades? Or do biases in RCTs and methodological limitations of meta-analyses explain the results? These questions will be discussed by Dan Siskind.Another way to address the question of efficacy is to examine the pharmaco-epidemiological evidence using population-based registers. Jari Tiihonen will present data from his seminal studies of mortality and readmission rates under clozapine treatment versus other antipsychotics, as well as other data. These data seem to show powerful positive effects of clozapine at the population level. Furthermore, more recent evidence suggests a role for clozapine in reducing rates of violent offending, with new data presented for the first time by Vishal Bhavsar.Finally, despite clinical guidelines recommending the use of clozapine, the actual rates of clozapine use are much lower than expected, with large regional and international variations. There is evidence that the burden of blood monitoring deters physicians from prescribing clozapine. Yvonne van der Zalm will present new data from a cluster randomised trial testing the efficacy and safety of an intervention to increase rates of clozapine prescribing by employing nurse practitioners trained in the initiation and monitoring of clozapine.John Kane, author of the first, seminal RCT of clozapine in 1988, will lead the discussion.

Early treatment resistance in a Latin-American cohort of patients with schizophrenia

BackgroundFailure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. MethodsSurvival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. ResultsEchoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093–0.13), compared to 0.018 (0.012–0.024) between years 1 and 5, and 0.006 (0–0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. ConclusionsOur results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.

Assessing prescribing practices of clozapine before and after the implementation of an updated risk evaluation and mitigation strategy.

Introduction:Clozapine is an atypical antipsychotic medication approved for treatment-resistant schizophrenia and suicidal behavior in schizophrenia or schizoaffective disorders. Despite its therapeutic efficacy, clozapine is associated with several adverse effects, including agranulocytosis. In late 2015, the Food and Drug Administration updated the risk evaluation and mitigation strategy (REMS) for clozapine with new requirements for monitoring, prescribing, and dispensing. The purpose of this study was to evaluate clozapine prescribing practices at a Kentucky state psychiatric hospital before and after the implementation of the updated REMS program.Methods:The primary outcome of this study was to evaluate clozapine prescribing practices by identifying the number of patients on clozapine therapy in the 6 months pre and post updated REMS implementation. Included in the study were patients at a Kentucky state psychiatric hospital on clozapine therapy for the 24 months before the updated REMS implementation and in the 6-month study period after the implementation. The secondary objective of this study examined psychiatrist comfort level of prescribing clozapine.Results:Since the implementation of the updated REMS program, there has been an increased percentage of patients that were prescribed clozapine at a Kentucky state psychiatric hospital. This increase was not statistically significant (P = .2610).Discussion:The prescribing practices of clozapine within this facility did not differ significantly comparing pre- and post-REMS change in terms of number of patients prescribed clozapine, patient's dose, and therapy duration. Data from this study contributes to the body of knowledge evaluating this new standard of practice under the updated REMS.

Validation of an algorithm-based definition of treatment resistance in patients with schizophrenia

Large-scale pharmacoepidemiological research on treatment resistance relies on accurate identification of people with treatment-resistant schizophrenia (TRS) based on data that are retrievable from administrative registers. This is usually approached by operationalising clinical treatment guidelines by using prescription and hospital admission information. We examined the accuracy of an algorithm-based definition of TRS based on clozapine prescription and/or meeting algorithm-based eligibility criteria for clozapine against a gold standard definition using case notes. We additionally validated a definition entirely based on clozapine prescription. 139 schizophrenia patients aged 18–65years were followed for a mean of 5years after first presentation to psychiatric services in South-London, UK. The diagnostic accuracy of the algorithm-based measure against the gold standard was measured with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A total of 45 (32.4%) schizophrenia patients met the criteria for the gold standard definition of TRS; applying the algorithm-based definition to the same cohort led to 44 (31.7%) patients fulfilling criteria for TRS with sensitivity, specificity, PPV and NPV of 62.2%, 83.0%, 63.6% and 82.1%, respectively. The definition based on lifetime clozapine prescription had sensitivity, specificity, PPV and NPV of 40.0%, 94.7%, 78.3% and 76.7%, respectively. Although a perfect definition of TRS cannot be derived from available prescription and hospital registers, these results indicate that researchers can confidently use registries to identify individuals with TRS for research and clinical practices.

Clozapine and Gastrointestinal Hypomotility.

Gastrointestinal hypomotility (GIH) is an under-reported but highly prevalent and potentially dangerous side effect of clozapine. In a comprehensive meta-analysis of clozapine-treated patients, the prevalence of GIH was 32%. In general, GIH has consistently been reported to have a negative impact on quality of life, and there is no reason to believe this will be different in clozapine-treated patients with therapy-resistant schizophrenia. GIH is dangerous; in a comparative review of lethal side effects of clozapine, the mortality of agranulocytosis was 2.2-4.2% compared with 15.0-27.5% for GIH. The mortality rate in our review of all published case reports of ileus was 43.7%. (Co-)Prescription of anticholinergic drugs in patients treated with clozapine should be avoided as anticholinergics are associated with increased incidence and fatality of ileus. Prevention of GIH can best be obtained by frequent and targeted questioning by the mental healthcare providers of the patients' defecation pattern and this is therefore strongly recommended for timely detection and treatment of treatment-emergent GIH throughout clozapine treatment. Treatment approaches can be either preventive laxative prescription with every clozapine prescription in all clozapine-treated patients or targeted treatment of treatment-emergent GIH. First-line treatments of GIH are the osmotic laxative macrogol, stool softener docusate and bowel stimulant senna. As the occurrence of severe cases of GIH is not restricted to a certain treatment duration, alertness for and/or treatment of GIH is required for the whole duration of clozapine treatment.

Real-World Effectiveness of Clozapine for Borderline Personality Disorder: Results From a 2-Year Mirror-Image Study.

While some second-generation antipsychotics have shown efficacy on patients with borderline personality disorder (BPD), limited data exist regarding the effect of clozapine. Thus, we aimed to investigate the effects of clozapine on naturalistic outcomes in BPD patients with a 2-year mirror-image model. Among 25,916 patients with BPD, 1,107 redeemed ≥ 1 clozapine prescription. Of these, 18,188 were "specific" BPD patients, and 102 redeemed ≥ 1 clozapine prescription. During a mean observation period of 598.51 days, in all BPD patients, clozapine was associated with a significant reduction in psychiatric admissions from 2.52 (95% CI [2.31, 2.78]) to 2.00 (95% CI [1.77, 2.23]) admissions (p < .001) and a significant reduction in psychiatric bed-days from 190.08 (95% CI [176.84, 203.33]) to 65.95 (95% CI [58.27, 73.66]) bed-days (p < .001). Similar findings were found for "specific" BPD patients. The number of patients with intentional self-harm or overdose decreased significantly from 189 to 114 individuals (p < .001) after clozapine initiation. Randomized trials evaluating the risk- benefit ratio of clozapine in patients with severe BPD are warranted.

Changing prescribing patterns in an Irish community mental health service.

Medication is an important component of the treatment of many mental illnesses. Very little information is available about the particular medications that are being prescribed by community mental health services and how this has changed over time. We set out to obtain details of psychiatric medications being prescribed by one Irish community mental health service. All prescribing by the Cluain Mhuire Community Mental Health Service became electronic during 2004. Using Business Intelligence software, we obtained details of all psychiatric medications prescribed from 2005 to 2016. We compared numbers of prescriptions written in the first 6 years (2005-2010) with the following 6 (2011-2016). Olanzapine was the most commonly prescribed medication throughout but its use declined by one-quarter over the study period. Clozapine, quetiapine, aripiprazole and haloperidol prescribing increased. Prescriptions for mood stabilisers and antidepressants fell by 25%. Sedative prescriptions declined by almost 50%. Absolute numbers of prescriptions written for methylphenidate and pregabalin were small but increased dramatically over the time period. This community mental health service prescribed less of most psychiatric medications in 2016, than had been the case in 2005. This is despite an increase in the numbers of patients seen over the same period. It is not clear if this pattern is echoed in other services.

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study.

Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (β coefficient = 15.82; 95% confidence interval 10.88-20.75). Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries.