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Addressing clozapine under-prescribing and barriers to initiation: a psychiatrist, advanced practice provider, and trainee survey
Abstract
Clozapine use has declined, despite its superior antipsychotic efficacy in treatment-resistant schizophrenia. Implications for clozapine underutilization include suboptimal treatment outcomes and increased hospitalizations. Many barriers preventing the use of clozapine have been described in the literature, including suboptimal knowledge and poor perceptions. The aim of this study was to assess psychiatry prescribers' perception and knowledge of clozapine. A survey was distributed to advanced practice providers, psychiatrists, and trainees (i.e. residents and fellows) at 10 medical centers within the US and Canada. The survey asked respondents about their perception of clozapine use and assessed their pharmacotherapeutic knowledge of clozapine. Two hundred eleven individual submitted completed surveys of a possible 1152; a response rate of 18.3%. There were no statistically significant differences between the advanced practice provider plus psychiatrist groups and the trainee group for most perception (eight of nine) and knowledge (eight of nine) questions. The knowledge questions with the lowest scores pertained to clozapine reinitiation and myocarditis. The majority of all respondents (144, 68.2%) felt that clozapine prescribing was a burden. Findings of this study support the need for continued clozapine education regardless of a prescriber's age/experience. Future studies to assess barriers to clozapine prescribing should extend beyond academic centers.
... Numerous survey studies have identified gaps in prescribers' and psychiatric trainees' knowledge, unfounded negative perception of clozapine, and a general discomfort with clozapine prescribing. [15][16][17] Prescribers' concerns around the complexities of monitoring clozapine perpetuate what has been described in the literature as "clozaphobia." 18 Beyond concern for these clinical barriers, such as ADRs and patient adherence, there are known administrative barriers that decrease clozapine prescribing. 1 The hematologic monitoring requirements and process for reporting have changed several times in the US since the FDA approval of clozapine. ...
... At Mayo Clinic-Rochester, the clozapine clinic alternative collects blood samples via finger capillary sampling, which still may be viewed as less invasive as compared with venipuncture. 15,126 Samples collected are still processed by the onsite laboratory with results available in 5 to 15 minutes. 15 Rapid immunoassays for clozapine serum concentrations have been developed, and a recent study has been found to have fewer false positives than the liquid chromatography/tandem mass spectrometry but other comparative studies are needed. ...
... 15,126 Samples collected are still processed by the onsite laboratory with results available in 5 to 15 minutes. 15 Rapid immunoassays for clozapine serum concentrations have been developed, and a recent study has been found to have fewer false positives than the liquid chromatography/tandem mass spectrometry but other comparative studies are needed. 127 In the US, the FDA has approved a rapid clozapine immunoassay and in Europe point-of-care technology is available for antipsychotic concentrations. ...
Purpose: Although clozapine was Food and Drug Administration (FDA) approved more than 3 decades ago by the FDA, major barriers and gaps in knowledge continue to prevent its effective and safe use. We review modern-day problems encountered with clozapine in the United States (US).
Methods: Information surrounding current administrative, clinical, research, and technological gaps or barriers related to clozapine use in the US was reviewed.
Findings: The history of how clozapine became FDA approved likely contributes to gaps in knowledge. The frequency of safety warnings added to the FDA prescribing information may add to fears about clozapine, as evidence by numerous published survey studies. The clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been modified several times in the last decade, causing access and safety issues for patients, which are discussed. Evidence may suggest that the FDA REMS requirements for hematologic monitoring are too cumbersome, and there may be ability to safely loosen requirements. The COVID-19 pandemic brought forth the ability for extended interval monitoring but also greater awareness of the clozapine-inflammation interaction. Newer guidelines published describe considerations in personalizing clozapine titration based on principles of ethnopsychopharmacology. Emerging technologies to support the use of clozapine are not widely available.
Implications: Clozapine is a unique life-saving drug but it is underused in the US, despite its established efficacy. The 2021 REMS changes led to significant difficulties for providers and patients. We highlight the importance of the clozapine-inflammation interaction, therapeutic drug monitoring, and the ability for individual care based on patient-specific factor. There is an urgent need for advancing technology used for clozapine monitoring, evaluating barriers created by REMS, and establishing consistent practices throughout the US.
... The results were consistent with the leading concerns highlighted in surveys of practitioners in the United Kingdom, India, and Israel; practitioners in the latter two countries further described concerns about the patient's nonadherence to clozapine as a barrier to its prescription. [15][16][17]21 Health system factors were also identified as key areas to focus on. These include the need for more resources in terms of outpatient clinic support (where clozapine initiation least occurs) and the provision of adequate resources for monitoring the frequent blood testing needed for clozapine treatment. ...
... One such solution would be the simplification of blood monitoring through the use of point-of-care testing devices instead of venipuncture. 21,25 Some European countries have also proposed an easing of the frequency of blood monitoring to a quarterly basis in mentally competent and adequately informed patients after the first 6 months of clozapine treatment. 6,26 Given that the risk of clozapine-induced agranulocytosis is minimal after the first 18 weeks of treatment, 27,28 and as blood monitoring is no longer costeffective after 6 months, this proposal may have its merits. ...
... e6 J Clin Psychiatry 83:4, July/August 2022 nurses, and allied health professionals to manage the multiple needs of patients on clozapine and aid in the provision of psychoeducation, monitoring of medication adherence, management of adverse effects, and review of stable patients. 21,37,38 These multidisciplinary approaches have been beneficial in increasing patient health literacy related to clozapine, improving clozapine continuation rates and patient/caregiver satisfaction, reducing resource utilization, and increasing service cost savings. 21,38 Such models of care may serve as references for the development of similar services within our regions. ...
Objective: This study aimed to survey clinicians' attitudes in Singapore and Hong Kong toward clozapine and elucidate the barriers to its prescription in patients with treatment-resistant schizophrenia.
Methods: All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants' characteristics, their experience with clozapine initiation, perceived usefulness of clozapine, barriers to clozapine initiation, and factors that might improve clozapine use. Data collection took place between December 2018 and March 2019 in Singapore and September 2019 and February 2020 in Hong Kong.
Results: A total of 261 clinicians (156 in Singapore, 105 in Hong Kong) responded to the survey. The majority of participants believed that clozapine was an effective and satisfactory treatment for schizophrenia. Clinicians were most concerned about the need for frequent blood monitoring (84.5% in Singapore; 87.5% in Hong Kong), clozapine's tolerability (51.9% in Singapore; 61.6% in Hong Kong), and medical complications (54.8% in Singapore; 49.1% in Hong Kong). Compared to Hong Kong, more clinicians in Singapore endorsed an underutilization of clozapine (67.9% in Singapore; 51.4% in Hong Kong) and a greater need for outpatient resources in terms of clinic and administrative support (74.4% in Singapore; 59.0% in Hong Kong) to improve clozapine prescription.
Conclusions: The underutilization of clozapine in treatment-resistant schizophrenia remains a concern in both regions. An integrated clozapine service that addresses the system barriers and clinicians' confidence in prescribing clozapine and managing its adverse effects would greatly improve the utilization of clozapine.
... [3] The most frequent barriers to prescribing were blood monitoring, limited experience, and side effects. [3] In addition to presenting the most common clozapine prescription barriers mentioned above, Leung et al, [22] Verdoux et al, [23] and Rubio and Kane [9] also highlighted administrative and healthcare systems-level barriers affecting clozapine monitoring and utilization. Verdoux et al [23] conducted a systematic review exploring prescribing practices of mental health professionals, including psychiatrists and psychiatry trainees, institutional factors affecting prescription, and interventions to improve clozapine prescription. ...
... [23] Rubio and Kane [9] completed a narrative review of clozapine use and found that the most common barriers to clozapine prescription were prescribers' lack of experience with clozapine, their perceived treatment barriers on patients, and systems-level factors. Leung et al [22] administered a survey assessing clozapine knowledge and perception to psychiatrists, advanced practice providers, and psychiatry trainees (including residents and fellows) in the US and Canada; they noted the following prescribing barriers: lack of clozapineeligible patients, lack of REMS registration, too much trouble, too many side effects, or other (more than 1 barrier). [22] In addition to replicating the above findings regarding prescriber-related barriers, data from multiple studies show the impact of patients, resources, communities, and logistical and administrative healthcare systems barriers affecting clozapine prescription and utilization. ...
... Leung et al [22] administered a survey assessing clozapine knowledge and perception to psychiatrists, advanced practice providers, and psychiatry trainees (including residents and fellows) in the US and Canada; they noted the following prescribing barriers: lack of clozapineeligible patients, lack of REMS registration, too much trouble, too many side effects, or other (more than 1 barrier). [22] In addition to replicating the above findings regarding prescriber-related barriers, data from multiple studies show the impact of patients, resources, communities, and logistical and administrative healthcare systems barriers affecting clozapine prescription and utilization. [17,19,20,24,25] Thien and O'Donoghue [19] noted that additional patient-level and systems-level barriers include the complexities of initiating clozapine, difficulties convincing patients/family to start trials, lack of community support, and shortage of hospital beds to initiate clozapine. ...
Background
Treatment-resistant schizophrenia is prevalent and difficult to manage, as patients fail multiple antipsychotic trials before being considered as treatment-resistant. Currently clozapine is the only Food and Drug Administration-approved pharmacotherapy for treatment-resistant schizophrenia but remains under-prescribed. The purpose of this study is to investigate recent literature on clozapine in order to identify barriers to prescribing clozapine and categorize the recommended solutions.
Methods
We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using free text and the medical subject headings, we searched MEDLINE/PubMed electronic bibliographic database from 2017 until 2020. Eligible studies included peer-reviewed English language articles with multiple methodologies aiming to identify clozapine barriers in treatment-resistant schizophrenia. We used search terms combining clozapine AND treatment OR treatment-resistant schizophrenia AND barriers AND prescribing OR prescription OR prescriber. We merged search results in a citation manager software, removed duplicates, and screened the remaining articles based on the study eligibility criteria.
Results
We retrieved 123 studies, however, only 10 articles exclusively met the study inclusion criteria for full text review. These studies represented 20 countries; 6 were exclusively conducted in the US. The top barriers delineated by the studies include: providers’ lack of knowledge and training (n = 7), concern about side effects (n = 8), and poor adherence (n = 7). All studies described more than 1 barrier. Other barriers included prescriber-perceived barriers (n = 4), administrative barriers (n = 5), and other healthcare systems-related barriers (n = 3). Top recommendations to overcome clozapine prescription barriers included improving prescriber clozapine education/training, utilizing interdisciplinary teams and providing integrated care via clozapine clinics, and simplifying blood test monitoring.
Conclusion
Clozapine remains under-prescribed for patients with treatment-resistant schizophrenia due to multiple barriers related to the individual prescriber, system of care, and technology. It is recommended that by improving prescriber knowledge and training, use of integrated care, and use of technology that can enable continuous, real-time blood test monitoring, these barriers may be overcome.
... Studies have demonstrated that clozapine may benefit a person's quality of life, satisfaction with treatment, overall mood, and social abilities (Qurashi et al., 2015;Waserman & Criollo, 2000) as well as reduce aggressive behavior (Krakowski et al., 2006). Most prescribers believe clozapine to be the most effective antipsychotic (Leung et al., 2019). ...
... Physicians who have never prescribed clozapine tend to overestimate the significance of barriers to prescribing in comparison to current prescribers (Kelly et al., 2018). A lack of prescriber comfort with clozapine may postpone a trial in favor of antipsychotic polypharmacy or other treatment options that are not supported by the evidence (Leung et al., 2019). ...
Considerable variation in clozapine utilization exists across the United States, and little is known about the perspective of psychiatrists in states with low clozapine use. To better understand clozapine practices, attitudes, and barriers, a survey was administered to a group of southeastern state conference attendees (SSCA; N = 86). The same survey was administered to psychiatrists belonging to a national community psychiatry organization (AACP; N = 57), and differences were analyzed across the two samples. In comparison to the AACP, the SSCA group felt less comfortable, perceived clozapine as less safe and effective, had fewer patients on clozapine, and were more likely to prefer antipsychotic polypharmacy to clozapine use. Across the sample, use of a myocarditis screening protocol was rare (N = 14/76; 18%) and less than half used plasma antipsychotic levels to guide dosage (N = 60/129; 47%). Continuing professional education on clozapine are needed for psychiatrists who see individuals with psychotic disorders.
... Access to expertise, such as a "hub and spoke" model, may also help clinicians with clozapine management 3 . This is supported by evidence that most clinicians view clozapine prescribing as a burden 39 . Reducing the perceived cumbersome nature of clozapine monitoring by minimising the degree of physical health monitoring (whilst maintaining safety standards) through evidence-based guidelines alongside use of POC testing could reduce barriers to clozapine use, improve patient satisfaction and overall increase clozapine utilisation 40 . ...
Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians’ views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% ( n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.
... Consequently, under-use of clozapine may emerge. The frequency of clozapine prescription and less than 5 under-treated patients has been reported (78 and 56%, respectively) in Leung et al. 's study [30]. Strategies to enhance patients' adherence, including follow-up teams and increasing patients' and families' literacy about treatment with clozapine, can effectively increase the number of under-treated patients and clozapine prescriptions. ...
Background:
Clozapine has the greatest efficacy for treatment-resistant schizophrenia (TRS), even though its underutilization is not uncommon across different countries. This study aimed to investigate the knowledge and attitude of Iranian psychiatrists toward clozapine use.
Method:
In this cross-sectional study, a questionnaire was distributed among psychiatrists registered with the Iranian Psychiatrists Association (including its provincial branches) to assess their knowledge and attitude towards clozapine use. A total of 282 psychiatrists completed the questionnaire. Descriptive analysis was used to describe demographic information, and Chi-square tests were conducted to determine if there is an association between academic position and work experience. All statistical analyses were performed using SPSS® version 25.0 for Windows, and a significance level of 0.05 was used.
Results:
Most respondents (93%) acknowledged that they prescribed clozapine for their patients, and 74% believed that clozapine was more effective than other antipsychotic drugs. However, 43.3% of the respondents said they did not believe in the safety of clozapine. Difficulty initiating and having no firsthand experience in the superiority of clozapine were reported by 81.2 and 80% of the respondents, respectively. Our results also showed an association between having an academic position and access to appropriate facilities for the control and management of patients treated with clozapine and believing in the safety of clozapine (p < 0.05). Longer work experience (more than 15 years) was associated with a higher prescription of clozapine, belief in greater effectiveness of clozapine, and its safety (p < 0.0001).
Conclusion:
Iranian psychiatrists had a good self-perception of knowledge about the efficacy of clozapine for patients with TRS, but concerns about serious side effects are common. Psychiatrists with longer work experience and academic positions were more optimistic towards clozapine use than the younger ones with no academic position. Considering the results in planning the strategies to decrease concerns about clozapine use is recommended.
... 11,12,26 Surveys of prescribers have consistently demonstrated a lack of confidence or expertise in clozapine prescribing, negative perceptions, insufficient knowledge about its adverse effects and their management, as key limiting factors in limiting prescribing, and consequently, increased preference for less evidence-based prescribing of other antipsychotics in high dose and combinations. 26,27 Prescribers also express concerns about patient compliance with clozapine treatment and monitoring, 28 the presence of co-morbid medical conditions 12 and a reluctance about initiating clozapine in the community. 29 Where clozapine is more widely prescribed, there is often increase in experience and the development of expertise that serve to drive up prescribing standards. ...
Background
Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing.
Methods
We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of Severe Mental Illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries.
Findings
There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries.
Interpretation
There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.
Purpose of review:
Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). Although the evidence base for its wide-ranging, unique efficacy continues to expand, clozapine remains alarmingly underutilized in industrialized countries. Analyzing the causes and consequences of this problem is crucial for substantially improving the quality of care for TRS patients.
Recent findings:
Clozapine is the most effective antipsychotic for reducing all-cause mortality in TRS. In most cases, treatment resistance emerges during the first psychotic episode. Delaying clozapine treatment has a negative impact on long-term outcome. Patients' experience with clozapine treatment is largely positive despite a comparatively high rate of side effects. Patients prefer clozapine, while psychiatrists regard it as a burden due to concerns regarding safety and side effect management. Shared decision-making (SDM), which increases the likelihood of a clozapine recommendation, is not routinely used, possibly due to stigmatization of TRS patients.
Summary:
The mortality-reducing effects of clozapine alone warrant its regular use. Therefore, psychiatrists must not exclude patients from the decision regarding a clozapine trial by not even offering it. Rather, they have a clear obligation to align their actions more closely with the existing evidence and patients' needs and to facilitate the timely initiation of clozapine.
A still expanding body of evidence unequivocally supports the superior efficacy of clozapine compared to other antipsychotics for a considerable number of outcome measures in the treatment of schizophrenia including positive symptoms, negative symptoms, aggression and suicidality. Therefore, clozapine remains the gold standard not only for treatment-resistant schizophrenia but also for a larger number of patients with a poor course of illness. Furthermore, recent meta-analytical evidence clearly demonstrates the superiority of clozapine for reducing all-cause mortality. This finding indicates that clozapine is one of the most potent means to reduce the outrageous mortality gap faced by patients with schizophrenia. Despite its unmatched and wide-ranging efficacy as well as its cost effectiveness, clozapine remains alarmingly underutilized throughout the industrialized world even though patients’ acceptance of clozapine treatment is surprisingly high. While limited, existing evidence indicates that this is primarily due to psychiatrists’ concerns regarding safety and side effect management possibly resulting from insufficient clinical training in using clozapine. This would imply that many patients are never offered clozapine in the first place despite a clear indication. We argue that psychiatrists have an urgent obligation to address this issue and ensure sufficient availability of this vital treatment option. If our fields’ commitment to shared decision-making is to be genuine, we must not exclude patients from the potentially life-changing decision to initiate clozapine treatment. Therefore, concerted research and mental-health policy efforts should focus on identifying barriers for clozapine utilization and effective measures to overcome them. On the one hand, this will require structural changes to clinical training and care systems. On the other and hand – and at least as important – it will require a continued commitment of individual psychiatrists to align their attitudes and clinical practices more closely with the existing evidence and patient preference. The benefits for patients, their families, clinical psychiatry and society will be substantial.
Unlike with smoking cigarettes, electronic nicotine delivery systems do not cause CYP450 1A2 induction as there is a lack of combustion and polycyclic aromatic hydrocarbon production. Changing to the use of an electronic nicotine delivery system from cigarettes can result in the deinduction of CYP450 1A2 and the increase of certain medication serum concentrations, including clozapine. A case is reported in which the switch from smoking to an electronic nicotine delivery system resulted in increased clozapine serum concentration and constipation, necessitating pharmacologic management. The patient ultimately transitioned back to cigarettes, which resulted in the emergence of psychiatric symptoms. An evaluation of longitudinal serum concentrations and clinical correlation is provided. It is important that patients and health care professionals have knowledge not only about the impact of smoking cigarettes on clozapine metabolism, but also the effects of switching to or from an electronic nicotine delivery system.
The current suicide public health crisis and advances in clinical practice have increased the need for clear, evidence-informed guidance on suicide prevention in healthcare. This clinical suicide prevention handbook is an essential resource for mental health and primary care professionals, and any practitioner aiming to ensure their practice is up-to-date, patient-centred and consistent with the most current standards of care. Starting with a summary of the science and public health model of suicide, the book offers quick tips for suicide screening, risk assessment, interventions, and follow-up communication. It discusses medicolegal risk management, how health systems can prevent suicide and provides highly specialized guidance for clinicians following the loss of a patient to suicide. Focused sections include incorporating social media into care plans, telemedicine, issues related to culture and race/ethnicity, and working with specific populations. It introduces an integrated, prevention-oriented approach to suicide prevention, incorporating realistic supports, foreseeable changes, and strategies.
Background:
Clozapine is the only medication with Food and Drug Administration approval for treatment-resistant schizophrenia. However, it is underutilized in the United States because of several life-threatening adverse effects, including clozapine-associated myocarditis (CAM), and a limited understanding of how to manage these complications. To date, recommendations for rechallenging patients with CAM that incorporate the cardiac literature or cardioprotective medications have not been developed.
Findings:
In this article, we outline a protocol developed with cardiologists and guided by the cardiac literature that provides direction on how to monitor for the initial development of CAM and how to rechallenge patients with CAM. Furthermore, we present 2 successful cases of clozapine rechallenge that were managed using this protocol.
Conclusions:
In both cases, the patients showed marked improvement in their psychiatric symptoms and functioning, demonstrating the importance of considering rechallenge in patients after CAM.
Introduction:
In an effort to establish clinical support for providers prescribing clozapine and to help reverse the national decline in clozapine utilization, a clinical pharmacist began seeing half the clozapine clinic patients, preceding the psychiatrist, at this facility in July 2017. The other half of the clozapine clinic patients continued being seen by the psychiatrist only. The purpose was to determine the impact of the pharmacist on clozapine management and identify barriers to clozapine use to potentially increase its utilization.
Methods:
Baseline data (clozapine dose, number of antipsychotics and other psychotropics, A1c, lipids, pulse, body mass index, weight, blood pressure, and number of medications for adverse effects) were collected via chart review from the first clinic visit and each follow-up visit. A provider survey was used to identify barriers and solutions to prescribing clozapine.
Results:
There were no statistically significant differences from baseline in patient outcomes between the collaborative and psychiatrist-only group. In the prepharmacist to postpharmacist analysis, there was a decrease in number of antipsychotics (-0.27 ± 0.65), number of other psychotropics (-0.18 ± 0.41), A1c (-0.04% ± 0.25%), clozapine dose (-7.96 mg ± 19.58 mg), and total cholesterol (-15.73 mg/dL ± 42.31 mg/dL). There were more pharmacologic (71 vs 19) and nonpharmacologic (154 vs 3) interventions documented in the collaborative group compared to the psychiatrist-only group. Eleven providers (69%) completed the survey. Providers' perception of patient refusal of monitoring was the barrier that received the most responses (54%). A pharmacist seeing every clozapine clinic patient was the solution that received the most responses (90%).
Discussion:
Trends were seen for decreasing the number of antipsychotics, other psychotropics, A1c, and total cholesterol as well as an increased number of nonpharmacologic and pharmacologic interventions documented in the collaborative group. Providers identified that pharmacists seeing every clozapine clinic patient would be a solution to clozapine underutilization, which demonstrates the perceived value of pharmacist involvement.
Clozapine is the only antipsychotic with evidence for efficacy in treatment of resistant schizophrenia but it carries a high side effect burden. Patient information is provided but may be poorly retained. This study aims to examine the impact of pharmacist counselling upon patient knowledge of clozapine. Outpatients, aged 18 years and over, attending St. Patrick’s University Hospital, Dublin, participated in this study between June and August 2015. The intervention consisted of pharmacist counselling on two occasions one month apart. Knowledge was assessed using a 28-point checklist devised from the currently available clozapine patient information sources, at baseline and after each counselling session. Ethics approval was obtained. Twenty-five participants (40% female; mean age 45.1 years, SD 9.82; 64% unemployed, 28% smokers) showed an improvement in knowledge scores of clozapine from baseline to postcounselling on each occasion with an overall improvement in knowledge score, from baseline to postcounselling at one month, of 39.43%; p<0.001 . This study adds to the evidence that interventions involving pharmacist counselling can improve patient knowledge, whilst the specific knowledge gained relating to recognition of side effects may help patients towards more empowerment regarding their treatment.
Objective:
To describe the pattern of antipsychotic drug prescribing in patients with first episode psychosis, with more emphasis in the use of clozapine in this group of patients.
Method:
A cross-sectional survey involving six early intervention service (EIS) teams in the West Midlands was conducted. Data was extracted from case notes and electronic records by clinicians working in each participating team. The pattern of antipsychotic prescribing and the changes that took place after being accepted in EIS, including the use of clozapine, was established. Clinicians involved in the treatment of patients in each team rated the overall clinical response to treatment based on the presence or absence of positive psychotic symptoms.
Result:
431 patients with FEP were included in the final analysis. Low antipsychotic discontinuation rate was observed, with the majority (88.2%) still being prescribed antipsychotics. Most (77.3%) were prescribed second-generation antipsychotic drugs, with olanzapine (21.8%) and aripiprazole (19.7%) being the most frequently prescribed antipsychotics. There was low rate use of antipsychotic combinations (7.4%), high dose antipsychotic regime (3.9%), low depot antipsychotic prescribing (9.3%), and clozapine use was low (9.7%). On average, three antipsychotics were tried before clozapine was initiated and it took on average 19.5 months from being accepted into EIS to clozapine being initiated.
Conclusion:
The majority of patients were prescribed antipsychotics within the guidelines. EIS was associated with an overall low antipsychotic discontinuation. There was also a short waiting time before clozapine was initiated following patients being accepted into EIS.
Background: Clozapine is an antipsychotic medication used in treatment resistant schizophrenia. However, clozapine is associated with a significant adverse effect profile and extensive monitoring is required to optimise consumer safety. Traditionally, clozapine can only be prescribed by a psychiatrist and dispensed at a hospital or hospital affiliated pharmacy in Australia. These restrictions could result in significant treatment burden for consumers taking clozapine.
Objective: To identify (1) the different models of supply that exist for people living in the community taking clozapine in Australia and compare to those in New Zealand and the United Kingdom, and (2) explore how these supply models may impact on consumer burden from the perspective of professionals involved in the supply of clozapine.
Method: Key informants were interviewed (n=8) from Australia, New Zealand and the United Kingdom regarding how consumers, who lived in the community, accessed clozapine. Data were analysed and led to the development of four clozapine supply models. These four models were further validated by an online survey of a wider sample (n=30). Data were analysed thematically and via simple descriptive statistics.
Results: Clozapine supply varied depending on location. A secondary care model was utilised in the United Kingdom compared to a community based (primary care) model in New Zealand; Australia utilised a mixture of both secondary and primary care. A key theme from all study participants was that community pharmacy should be utilised to dispense clozapine to consumers living in the community, provided adequate training and safeguards are in place. It was noted that the utilisation of community pharmacies could improve access and flexibility, thereby reducing treatment burden for these consumers.
Conclusion: There are predominately two models for supply of clozapine to consumers living in the community in Australia, New Zealand and the United Kingdom. One model utilises secondary care facilities and the other community services. Community pharmacy is ideally placed to increase access to clozapine for consumers living in the community, provided appropriate training and support is given to pharmacists providing this professional service.
The authors developed and validated a clozapine-specific side-effects scale capable of eliciting the subjectively unpleasant side-effects of clozapine.
Questions from the original Glasgow Antipsychotic Side-effects Scale (GASS) were compared to a list of the most commonly reported clozapine side-effects and those with a significant subjective burden were included in the GASS for Clozapine (GASS-C). The original authors of the GASS and a group of mental health professionals from the UK and Ireland were enlisted to comment on the questions in the GASS-C based on their clinical experience. 110 clozapine outpatients from two sites completed the GASS-C, the original GASS and a repeat GASS-C. Statistical analyses were performed using SPSS for Windows version 19.
The GASS-C was shown to have construct validity, in that Spearman's correlation coefficient was 0.816 (p<0.001) with the original GASS, whilst Cohen's kappa coefficient was >0.77 (p<0.001) for one question and >0.81 (p<0.001) for remaining relevant questions. GASS-C was also shown to have strong test-retest reliability, in that Cronbach's alpha coefficient was >0.907 (p<0.001), whilst Cohen's kappa coefficient was >0.81 (p<0.001) for 12 questions and >0.61 (p<0.001) for the remaining four questions.
The GASS-C is a valid and reliable clinical tool to enable a systematic assessment of the subjectively unpleasant side-effects of clozapine. Future research should focus on how the scale can be utilised as a clinical tool to improve real-world outcomes such as adherence to clozapine therapy and quality of life.
Copyright © 2015 Elsevier B.V. All rights reserved.
Clozapine is the most effective antipsychotic drug for schizophrenia treatment, however it is currently underused. In order to understand the barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine levels, we developed a psychiatrist survey and began and integrative approach of designing a point-of-care device that could eventually have real-time monitoring with immediate results.
We ascertained barriers related to clozapine management and the acceptance of possible solutions by sending an anonymous survey to physicians in psychiatric practice (N=860). In parallel we tested clozapine sensing using a prototype point-of-care monitoring device.
255 responses were included in the survey results. The two barriers receiving mean scores with the highest agreement as being a significant barrier were patient nonadherence to blood work and blood work's burden on the patient (out of 28). Among nine solutions, the ability to obtain lab results in the physician's office or pharmacy was top-ranked (mean±sd Likert scale (4.0±1.0)). Physicians responded that a point-of-care device to measure blood levels and WBCs would improve care and increase clozapine use. Residents ranked point-of-care devices higher than older physicians (4.07±0.87 vs. 3.47±1.08, p<0.0001). Also, the prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3μg/mL buffered solutions.
Survey results demonstrate the physician's desire for point-of-care monitoring technology, particularly among younger prescribers. Prototype sensor results identify that clozapine can be detected and integrated for future device development. Future development will also include integration of WBCs for a complete detection device.
Patients prescribed clozapine were surveyed to assess (a) the effects, both positive and adverse, and overall satisfaction with clozapine in comparison to previously prescribed antipsychotics and (b) the relative significance of effects experienced, both positive and adverse, in terms of impact on subjective well-being.
A total of 56 male patients prescribed clozapine at a forensic psychiatric hospital were surveyed using a 27-item questionnaire. All patients had been prescribed clozapine for a minimum of 3 months. Respondents were asked to rate effects and satisfaction with clozapine treatment in comparison with previously prescribed antipsychotic medication on a five-point scale. Respondents were also asked to rate effects experienced with clozapine treatment in terms of impact on subjective well-being on a five-point scale.
A total of 89% of respondents reported greater satisfaction with clozapine than with previously prescribed antipsychotic medication. A majority of patients reported positive effects in terms of an improvement in their quality of life (68%) and social abilities (52%) with clozapine in comparison with previously prescribed antipsychotics. Nocturnal hypersalivation (84%) and weight gain (57%) were the most common adverse effects. Hedonic responses were assessed for each effect in order to determine the associated subjective experiences. The most positive hedonic responses were for quality of life, mood and alertness. In terms of adverse impact on subjective well-being, nocturnal hypersalivation ranked highest.
Patients in a UK forensic sample are largely satisfied with clozapine treatment. The subjective effects of clozapine treatment should be taken into account by clinicians when assessing response. This may provide an opportunity to highlight the positive changes and prioritize management of the most undesirable adverse effects, which is likely to promote compliance and improve longer term treatment outcomes.
It has been repeatedly shown that clozapine is underutilized and there is delayed use of it in clinical practice.
An online survey was sent to 2771 consultant psychiatrists registered with the Royal College of Psychiatrists in the UK. A total of 243 responded to this survey. The survey elicited their views and experiences in using clozapine as well as to identify what may be the underlying causes for its underutilization.
Over 75% acknowledged that they had good training in using clozapine and about 56% had clozapine-dedicated service. However, 40.5% preferred to use several other antipsychotics prior to considering clozapine. A third felt it was not safe to start clozapine in the community and 42% had less than five patients on clozapine. Eleven possible reasons for clozapine underutilization were identified including concerns about side effects, patients not wanting to have blood tests and lack of experience or knowledge. Knowledge deficiency in certain aspects of clozapine use were identified, e.g. a third of respondents did not know that the risk of agranulocytosis changes with time, 42.7% did not think that clozapine can reduce substance use, while 20% were not aware of its benefit in reducing suicidal risk.
Important areas of concern such as managing side effects and deficiency in evidence-based use of clozapine were identified. These can be targeted in training and professional development programme.
These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia published in 2006. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful. They are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F) and five levels of recommendation (1-5) ( Bandelow et al. 2008a ,b, World J Biol Psychiatry 9:242, see Table 1 ). This second part of the updated guidelines covers long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication and other pharmacological treatment options) of adults suffering from schizophrenia.
Due to computer technology, a forced-response can be easily achieved in online questionnaires and is frequently used to gather complete datasets. An Internet-based quasi-experiment was conducted on the student server at the University of Vienna to study the influence of forced-response on dropout, demographic reports, and the content of the results. Forced-response was shown to substantially increase dropout. In addition, forced-response interacted with reported sex in eliminating a naturally occurring sex difference in dropout that was observed for the questionnaire whenever responses did not need to be enforced. Also reported sex turned out to have a mediating effect on time of dropout: Men dropped out earlier than did women. Further analyses revealed a reactance effect, as predicted by reactance theory. It is concluded that data from online questionnaires with forced-response designs are in danger of being hampered by dropout and reactance.
To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009.
Analyses were performed on IMS Brogan's Canadian Disease and Therapeutic Index (CDTI). The CDTI is a national physician panel study consisting of a representative sample of physicians both geographically and by specialty. Weighting adjustments are made to estimate national drug recommendations. Quarterly, panel physicians record all therapeutic recommendations during a 2-day period, including patient age, sex, and indication. Antipsychotic recommendations were estimated using CDTI data in which schizophrenia was listed as the indication.
First-generation antipsychotic (FGA) recommendations for adults with schizophrenia increased by 38% between 2005 and 2009, from 329 380 to 454 960 recommendations. There were notable increases in recommendations for chlorpromazine, loxapine, zuclopenthixol, and flupentixol. Second-generation antipsychotic (SGA) recommendations increased to a much lesser extent (9%), which was mostly attributable to an increase in recommendations for clozapine. Drug recommendations for olanzapine decreased by 9%.
The rate of increase of FGA use is now greater than that of SGAs. This may be due to data from recent comparative trials, which suggest that clinical efficacy, and the rate of neurological side effects is similar between FGAs and SGAs. The decreasing use of olanzapine may be due to metabolic adverse effects. The increased use of clozapine may be due to data on its superiority in patients who are treatment resistant.
Although common in psychiatric practice, reasons for antipsychotic polypharmacy (APP) have remained unclear.
Single-site, semi-structured interview study of prescribers at a psychiatric teaching hospital inquiring about APP attitudes and behaviors, including frequency, preferred combinations, rationale and concerns.
Forty-four prescribers reported using APP in 17.0 ± 10.0% of antipsychotic-treated patients. Although clinicians themselves initiated APP in only 23.3 ± 27.0% of cases, they did not attempt conversion to antipsychotic monotherapy in 40.9 ± 37.7%, despite reported successful conversion in 28.0 ± 30.8% of cases. The following reasons justified most APP (0-10): cross-titration (9.2 ± 1.4), failed clozapine trial (8.2 ± 2.2), randomized controlled evidence (8.0 ± 2.0), and clozapine intolerance (7.7 ± 2.6). Prescribers felt "moderately" (5.0 ± 1.9) concerned about APP (0-10), mostly due to chronic side effects (7.6 ± 2.0), lack of evidence (7.1 ± 2.2), non-adherence risk (6.7 ± 2.3) and mortality risk (6.7 ± 3.2), while increased cost (4.9 ± 2.5) and higher total antipsychotic dose (4.2 ± 2.9) ranked lowest. Comparing high with low APP prescribers (>10% vs. ≤ 10% of patients; mean: 36.1 ± 19.8 vs. 3.4 ± 3.4, p<0.0001), no differences emerged on 25/26 ratings regarding APP justification and 9/9 ratings regarding concerns. In a multivariate analyses, only attending status (OR=10.3, p=0.0043) and endorsing a specific APP preference (OR=21.4, p=0.011) predicted APP use >10% (r(2):0.35, p<0.0001), yet no uniformly preferred APP strategy emerged.
High APP prescribers had more clinical experience, less concerns about APP and more likely a preferred APP choice, although no overall preferred strategy emerged. Otherwise, high and low APP prescribers shared attitudes toward APP. Both had inherited most of their APP cases and were reluctant to convert patients to antipsychotic monotherapy.
Background Clozapine is very effective for treatment-resistant schizophrenia, but its use has been limited due to the risk of agranulocytosis. From July 2015, clozapine has been accessible from Australian community pharmacies following regulatory changes, but pharmacists’ attitudes towards these changes remain unknown. Objective To explore pharmacists’ perspectives and experiences in supplying clozapine. Setting Australian community pharmacists. Methods A cross-sectional study with a mixed methods approach involving two phases. An online survey containing Likert-type and open-response questions was distributed to community pharmacists (n = 134) via ClopineCentral™ (clozapine monitoring system). Participants were then invited to participate in semi-structured telephone interviews (n = 12) regarding clozapine supply. Quantitative data were statistically analysed, while qualitative responses were thematically content-analysed. Main outcome measures Pharmacists’ responses to surveys and interviews. Results Community pharmacists were supportive towards supplying clozapine as it increased access for consumers. Better patient-pharmacist relationships and holistic care approach were identified to benefit both consumers and pharmacists. Pharmacists reported to be confident (89.6%), have adequate support (73.1%), knowledge (86.6%) and skills (93.3%) in dispensing clozapine. Training and support received facilitated pharmacists’ roles, whereas administrative issues, especially in obtaining valid haematology results, posed challenges. Educational and technical improvements were suggested to improve service provision. Conclusion Community pharmacists welcomed the regulatory changes positively and were confident in supporting consumers taking clozapine. Despite challenges present, benefits and facilitators identified supported the feasibility of this service in community pharmacies. Future research should explore other aspects of clozapine supply, such as attitudes of other stakeholders, to improve current supply systems.
Although clozapine has demonstrated unique efficacy for the treatment of seriously ill patients with refractory psychosis, its real-world use presents challenges to clinicians in a variety of settings, leading to its underutilization in the United States. The barriers include a lack of prescriber knowledge and confidence, negative prescriber attitudes, special monitoring requirements, administrative burden, unprepared health systems, and inadequate appreciation of clozapine's unique nature by policy makers and payers. In 2016, the National Association of State Mental Health Program Directors (NASMHPD) gathered a national team of expert clinicians and researchers to identify and address barriers to clozapine use. NASMHPD has since expanded the work group, which convenes monthly to continue addressing specific recommendations. This Open Forum describes the deliberations of the work group and urges practitioners, administrators, local and state governments, researchers, families, and patients to join similar efforts to promote better access to clozapine and improve the treatment management for patients receiving clozapine.
Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended.
Aim:
To assess the attitude of psychiatrists towards clozapine and also to evaluate the prescription practices of psychiatrists for clozapine.
Methodology:
An email survey was sent to 3381 psychiatrists from India, of whom 548 (16.2%) responded.
Results:
Mean number of years in clinical practice was 12.59 (SD-10.1) for participating psychiatrists. Majority of the participants rated their knowledge about clozapine to be good (61.5%)/very good (34.5%). The primary indication for use of clozapine for almost all the participants was treatment resistance and most of the psychiatrists initiated clozapine either in the dose of 25mg OD (44.3%) or 12.5mg OD (37%). Half (51.8%) of the psychiatrists preferred to use clozapine as BD dosing schedule, and median doses required to stabilize the patients ranged from 137.5 to 400mg/day. Once the clozapine dose had been stabilized, about half (51%) of the psychiatrists advised blood monitoring at monthly intervals. Almost all psychiatrists rated effectiveness of clozapine to be better than other antipsychotics. In terms of tolerability, 45.3% of the psychiatrists rated it as 'same as other antipsychotics' and 15.9% rated it as better than other antipsychotics. Most common patient and therapist related factors associated with reluctance to start clozapine were history of poor medication compliance and need for monitoring, respectively. Upon reviewing the prescription of other psychiatrists, participating psychiatrists reported that in about 28.46% of patients clozapine was not prescribed though indicated.
Conclusions:
This survey suggests that clozapine is underused in India, although psychiatrists have adequate knowledge about the drug but many psychiatrists have negative attitude towards clozapine.
Clozapine is often referred to as the gold standard for the treatment of schizophrenia and yet has also been described as the most underutilized treatment for schizophrenia supported by solid evidence-based medicine. In 2008, it was used to treat only 4.4% of patients with schizophrenia in the U.S., which is ∼10-20% of those with approved indications for clozapine for which there is no alternative of equal efficacy. Its use is much higher in Scandinavian countries and China. The primary indications for clozapine are: 1) treatment-resistant schizophrenia or schizoaffective disorder, defined as persistent moderate to severe delusions or hallucinations despite two or more clinical trials with other antipsychotic drugs; and, 2) patients with schizophrenia or schizoaffective disorder who are at high risk for suicide. Concerns over a number of safety considerations are responsible for much of the underutilization of clozapine: 1) agranulocytosis; 2) metabolic side effects; and, 3) myocarditis. These side effects can be detected, prevented, minimized and treated, but there will be a very small number of fatalities. Nevertheless, clozapine has been found in two large epidemiologic studies to have the lowest mortality of any antipsychotic drug, mainly due to its very large effect to reduce the risk for suicide. Other reasons for limited use of clozapine include the extra effort entailed in monitoring white blood cell counts to detect granulocytopenia or agranulocytosis and, possibly, minimal efforts to market it now that it is largely generic. Awareness of the benefits and risks of clozapine is essential for increasing the use of this lifesaving agent.
This study aimed to assess the delay in initiation of clozapine, number of adequate antipsychotic trials prior to starting clozapine and practice of polypharmacy prior to starting clozapine. A retrospective study design was followed. Treatment records of 200 patients started on clozapine during the period of January 2006 to June 2014 were reviewed. The mean delay in clozapine initiation was 1.93 (SD 1.82) years and median was 1.5 years. Mean of 3 (SD 1.18) adequate antipsychotic trials were given prior to considering clozapine and 27.5% patients had received polypharmacy prior to clozapine. Factors related to delay in starting of clozapine included higher age, longer duration of illness, age more than 20 years of age, polypharmacy, use of an adequate trial of typical antipsychotic medication, patients from urban locality and those with onset of illness prior to introduction of clozapine into Indian market. Findings of the present study suggest that there is a delay of 1.5 to 2 years in starting of clozapine and about one-fourth of patients receive polypharmacy prior to receiving clozapine. These finding suggests that there is a need to change the prescribing habits to reduce the delay in starting of clozapine.
AimTo compare sole nurse and doctor-led multidisciplinary team delivery of community clozapine services for people with treatment-resistant schizophrenia.Background
Around 20% of people with schizophrenia are treatment resistant and fail to respond to front line medications. Clozapine, a second-line treatment, has potentially serious side effects requiring regular monitoring. Different models of community clozapine services are emerging in the British National Health Service, but there is little evidence about which is best.DesignQuestionnaire survey of service users.Methods
All patients on the lists of seven clozapine clinics (four sole nurse, three multidisciplinary team) in one trust were invited to participate, 2009–2010. Forward stepwise regression was used to investigate associations between patient well-being, functioning, self-efficacy and satisfaction, and clinic model attended, controlling for socio-demographic and health characteristics and processes of care. Use (and costs) of other health and social services accessed was compared between models.ResultsSixty-six service users (35% participation rate) responded. Well-being and functioning were associated with patient characteristics and processes of care, not clinic model. Patients managed by sole nurses reported, over 3 months: more community psychiatric nurse visits and hospital psychiatrist appointments. Clinic list size affects costs per patient.Conclusions
Multidisciplinary team delivery may reduce use of other services. Although multidisciplinary team delivery is regarded as best practice, sole nurses can effectively provide clozapine services and may be warranted in areas of low population density.
Psychosis is relatively common, with schizophrenia being the most prevalent form of psychotic disorder, affecting about seven in 1000 adults, with onset typically occurring between the ages of 15 and 35.1 These disorders, which are characterised by distressing hallucinations and delusions, disturbed behaviour, and memory and motivation problems, present a major personal,2 social,3 clinical,4 and financial5 challenge. Moreover, poor physical health is strongly associated with schizophrenia, with men dying 20 years earlier than the general population and women dying 15 years earlier,6 7 mainly from illnesses such as cardiovascular disease, diabetes, chronic obstructive pulmonary disease, HIV infection, hepatitis C, and tuberculosis.8 Difficulties in people with severe mental illness accessing general medical services in primary and secondary care contribute to reduced life expectancy.9
Although many people with psychosis and schizophrenia respond to antipsychotic drugs initially, around 80% relapse within five years, partly because they discontinue medication,10 which for many people has unacceptable side effects. However, although around 75% of people with schizophrenia recurrently relapse and have continued disability,10 there is a moderately good long term global outcome in over half.11
This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on managing psychosis and schizophrenia in adults.12
NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.
### Care across all phases—physical health
Objective
The authors sought to develop a model educational clinic and curriculum for psychiatric residents, to increase knowledge and comfort about clozapine prescribing. This matters because clozapine is an important evidence-based treatment for refractory schizophrenia that remains underutilized in clinical practice.
Methods
This is a description of how the Clozapine Clinic of the Massachusetts General Hospital (MGH) Schizophrenia Program was integrated into the curriculum of the MGH-McLean Adult Psychiatric Residency.
Results
PGY-II residents participated in a weekly clozapine clinic with direct patient contact and accompanying curriculum-based instruction for a 6-week period. The method of teaching by participating in a dedicated Clozapine Clinic received favorable feedback. Residents’ knowledge about clozapine increased.
Conclusion
Residency programs should determine whether their trainees receive sufficient training in the use of clozapine and consider setting up clozapine clinics where feasible.
The atypical antipsychotic clozapine can have profound clinical benefits for patients with severe schizophrenia and schizoaffective disorder when alternative agents have been ineffective.[1][1] In 2009, the Department of Veterans Affairs (VA) Pharmacy Benefits Management and Office of Mental Health
The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.
Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.
Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between clozapine vs perphenazine, and p<0.0001 for all other antipsychotic drugs). Long-term cumulative exposure (7-11 years) to any antipsychotic treatment was associated with lower mortality than was no drug use (0.81, 0.77-0.84). In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted (HR for trend per exposure year 0.991; 0.985-0.997).
Long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use. Second-generation drugs are a highly heterogeneous group, and clozapine seems to be associated with a substantially lower mortality than any other antipsychotics. Restrictions on the use of clozapine should be reassessed.
Annual EVO Financing (Special government subsidies from the Ministry of Health and Welfare, Finland).
Clozapine is, in most countries, underutilized and the initiation of clozapine is often delayed. The purpose of this study is to investigate the reasons for the delay and the underutilization of clozapine. One hundred psychiatrists were interviewed by phone. The interview was a structured interview with questions regarding attitude to, knowledge of and experiences with clozapine. Forty-eight (48%) psychiatrists had treatment responsibility of fewer than five patients treated with clozapine and 31 of the interviewed psychiatrists (31%) had started clozapine within the last 3 months. Seven psychiatrists (7%) had never prescribed clozapine despite the fact that they had been working more than five years in general psychiatry. Sixty-four psychiatrists (64%) would rather combine two antipsychotics than use clozapine. Sixty-six psychiatrists (66%) believed that patients treated with clozapine were less satisfied with their treatment when compared with those treated with other atypical antipsychotics. Many psychiatrists are reluctant to use clozapine and this might be due to less experience and knowledge of clozapine. A reason for the low awareness of clozapine's properties might be that clozapine is now a generic drug, and therefore, the marketing and education in using the drug is sparse.
Research on the impact of nicotine on schizophrenia and antipsychotic medications was reviewed to determine ways to improve treatment planning for patients with schizophrenia who smoke and to evaluate smoking cessation programs for this population.
All major research databases were searched. The review focuses on reports published since 1990.
Smoking improves processing of auditory stimuli (sensory gating) by patients with schizophrenia and may lessen negative symptoms by increasing dopamine in the nucleus accumbens and the prefrontal and frontal cortex. Use of traditional antipsychotics may result in patients' smoking more, whereas patients taking atypical antipsychotics may smoke less. Patients who smoke metabolize antipsychotics faster than nonsmoking patients. Smoking cessation programs for outpatients with schizophrenia report a success rate of about 12 percent after six months. No studies of cessation programs for chronically ill inpatients with schizophrenia have been published. Several hospitals have implemented smoking bans with equivocal results.
Nicotine affects both schizophrenia and antipsychotic medications. Neurobiological and psychosocial factors reinforce the high use of nicotine by patients with schizophrenia
A 37-item survey covering a variety of somatopsychic domains was constructed to explore patients' subjective response to treatment with clozapine. The survey was administered to 130 patients with diagnoses of chronic schizophrenic or schizoaffective disorders who were on a stable clozapine regimen. The majority reported improvement in their level of satisfaction, quality of life, compliance with treatment, thinking, mood, and alertness. Most patients reported worsening in nocturnal salivation, and smaller numbers reported worsening in various gastrointestinal and urinary symptoms and weight gain. This general health survey highlights the patients' positive regard for clozapine, despite adverse bodily experiences. Subjective reports are a useful component of outcome measures of drug treatment.
Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.
To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.
Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).
Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).
Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.
Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.