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Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India
Accepted Manuscript Title: Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India Authors: Prasad Rao Gundugurti, Rajesh Nagpal, Ashit Sheth, Prashant Narang, Sonal Gawande, Vikram Singh PII: DOI: Reference:
S1876-2018(17)30541-5 http://dx.doi.org/doi:10.1016/j.ajp.2017.08.002 AJP 1211
To appear in: Received date: Accepted date:
3-8-2017 4-8-2017
Please cite this article as: Gundugurti, Prasad Rao, Nagpal, Rajesh, Sheth, Ashit, Narang, Prashant, Gawande, Sonal, Singh, Vikram, Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India.Asian Journal of Psychiatry http://dx.doi.org/10.1016/j.ajp.2017.08.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India Running title: Oral versus long-acting antipsychotics: A psychiatrists’ survey in India
Authors Prasad Rao Gundugurti1, Rajesh Nagpal2, Ashit Sheth3, Prashant Narang4, Sonal Gawande4, Vikram Singh4 1
Division of Schizophrenia and Psychopharmacology, Asha Hospital, Hyderabad, India
2
Manobal Klinik, New Delhi, India
3
Unlimited Potentialities, Mumbai, India
4
Medical Affairs, Johnson & Johnson India Private Limited, Mumbai, India
Corresponding author Dr. Prashant Narang Medical Affairs, Johnson & Johnson India Private Limited, Arena Space, JVLR, Jogeshwari East, Mumbai, 400060, India Email: [email protected]
Previous Presentation: Presented at 7th ISPOR Asia Pacific conference, 3rd - 6th September 2016
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Highlights
First Indian survey to evaluate psychiatrists’ prescription practices in schizophrenia
Oral antipsychotics were the treatment of choice for acute and chronic cases
LAI therapy perceived to offer assurance of medication adherence and reduced relapses
Owing to perceived high costs, LAIs were not preferred treatment
A conservative approach and sparing use of LAIs observed in India
ABSTRACT Background: Schizophrenia is associated with functional challenges for patients; relapses in schizophrenia may lead to increased treatment costs and poor quality of life. Objective: This SUSTAIN-I study was conducted to establish psychiatrists’ perspective on impact of long-acting injectables (LAIs) antipsychotics on the socio-economic and functional burden of schizophrenia. Methods: This cross-sectional, survey-based study was conducted in 5 cities in India. Psychiatrists (≥ 5 years of experience) working in clinics, psychiatric, government hospitals and rehabilitation centers were included and administered a specially designed questionnaire to elicit information on their clinical practice and prescription patterns. Perceived treatment costs for LAI versus oral antipsychotic treatments (OATs) and relapse rates were assessed. Descriptive statistics were used to summarize results. Results: Total 31 physicians completed this survey. In acute phase, OAT prescription was higher whereas chronic patients were treated with either OATs or LAIs. Treatment with LAIs was the preferred treatment in 9% of chronic cases. Reduced relapse rates
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were observed with LAI treatment: 12% patients on LAIs relapsed as compared with 60% patients on OATs. Monthly medication cost for oral medications was lower ($8$17) than short-acting injectables ($22-$50). For chronic cases, atypical antipsychotics cost (oral: $11.7-25, LAI: $150-167) was higher than typical antipsychotics (oral: $4-5, LAI: $5-25). Of total expenses incurred, cost for hospital admissions was the largest component (78%). Conclusion: Despite enhanced treatment adherence and potential to lower risk of rehospitalizations from relapse, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Keywords: antipsychotics, functional burden; long-acting injectables; psychiatrists’ survey; schizophrenia; relapse
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1. INTRODUCTION Schizophrenia is a chronic relapsing mental disorder that profoundly affects an individual’s emotional regulation and social behavior (Tandon et al., 2009). It is associated with enormous functional challenges for both, patients as well as their caregivers (Gupta et al., 2015). Relapses in schizophrenia are associated with increased symptoms recurrences, increased hospitalization costs and poor quality of life (Almond et al., 2004). Although antipsychotic medications are effective in preventing relapse, this goal is often hindered by poor adherence to treatment (Bruijnzeel et al., 2014). Currently, pharmacotherapy of schizophrenia includes first-generation or typical antipsychotics and second-generation or atypical antipsychotics (Tandon and Halbreich, 2003). Poor adherence to oral antipsychotic therapy (OAT) led to the development of first and subsequently second generation antipsychotic long-acting injectables (LAIs) in 1960s and 1990s respectively (Brissos et al., 2014). LAIs, which are to be administered once every 2-12 weeks, provide assurance of adherence; numerous studies have established their efficacy, safety and cost effectiveness with benefits on a range of outcome measures- lesser relapse rates, reduced frequency of hospitalizations, shorter hospital stays and better overall functioning (Castillo and Stroup, 2015; Sreeraj et al., 2017; Stevens et al., 2016; Yoshimura et al., 2015). Despite their established advantages, treating pyschiatrists tend to reserve LAIs only for severe and chronic conditions (Heres, 2014). Since data from India about the challenges of appropriate utilization of LAIs are sparse, a cross sectional study, “Study to Understand Schizophrenia Treatment Approach- physician and caregiver INsights on social, economic and functional benefits of LAI in India (SUSTAIN-I) was conducted to
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ascertain and characterize psychiatrists’ perspective on impact of LAIs on the socioeconomic and functional burden of schizophrenia on patients and their caregivers.
2. METHODS 2.1 Study design and participants This observational and epidemiological survey, funded by Janssen, India was conducted in two phases across India, between October 2015 and March 2016. In phase 1, experienced psychiatrists (≥ 5 years of experience) who worked in clinics, private and government hospitals and rehabilitation centers were included. A broad range of psychiatrists prescribing high and low proportions of LAI, those with substantial practice in management of schizophrenia and who agreed to provide sufficient time for the survey, were included in this survey. Here we present the findings of the phase 1 study. 2.2 Assessment A questionnaire was designed to elicit information on the categories of patients visited and their disease conditions (acute or chronic cases), demographics of patients, preferred antipsychotics, commonly prescribed treatment regimes, etc. Physician’s prescription practices were assessed to establish the treatment patterns for patients suffering from acute and chronic schizophrenia. Currently prescribed oral and LAI medications were classified as 1st (typical) or 2nd generation (atypical) antipsychotics based on the conventional classification (Table 1). Attendance of schizophrenia patients in the outpatient department (OPD) were collected and analyzed to establish patterns in patient profiles. Annual relapse rates and relapse rates leading to hospitalization, average length of stay in hospital, treatment discontinuation and treatment adherence
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were calculated based on data obtained from the survey questionnaire. Data collection protocol was approved by an Independent Ethics Committee. Psychiatrist participants received written and verbal information regarding the study. Consent was deemed implicit if they returned a completed questionnaire. Perceived costs of treatment for LAIs and OATs were assessed based on the psychiatrist’ survey. All costs presented in this study were strictly related to the treatment of schizophrenia.
Direct costs: These included medication costs- unit costs for all prescribed (for schizophrenia) and supportive medications per month, not inclusive of dispensing fee. Medication acquisition cost was considered for prescribed trade names and in cases of generic names, price of the cheapest brand was included for calculations.
2.3 Statistical Analysis Responses to the verbal questionnaire were noted and statistically analyzed. Data were analyzed to detect the patterns in prescription practices, comparison of ratios/ percentages and development of standard scores. Descriptive statistics were used to summarize psychiatrists’ prescription preferences.
3. RESULTS 3.1 Profiles and characteristics of Psychiatrist surveyed This survey-based study was conducted among treating senior psychiatrists with extensive experience in the management of Schizophrenia from five of the 7 most populous cities across India (Hyderabad, Bengaluru, Mumbai, Pune and Delhi).
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Physician survey respondents included 31 psychiatrists (clinics=18, psychiatry hospitals=6, government or charitable hospitals=5, rehabilitation centers=2). 3.2 Psychiatrists’ perceptions on patient profiles Outpatient department attendance of schizophrenia patients Nearly 10-20% (median 25%) of all the OPD attendees comprised of schizophrenia patients. About 25% of all schizophrenia cases were reported as new cases while the rest were old or relapsed cases. Psychiatrists experienced that on an average 42% of the cases were aged between 20-30 years of age and 21% were aged between 30-40 years. About 17% of all cases were adolescents aged between 15-20 years. The number of cases with age > 40 years (20%) was low. 3.3 Psychiatrists’ prescription preferences Physician prescription practices were based on the phases (acute or chronic) of schizophrenia, Table 2. In this study, for the sake of comparison of oral versus LAI treatment, patients receiving oral atypical antipsychotics (i.e., amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone) were assigned to the oral medication group and patients receiving atypical antipsychotic injections (i.e., risperidone and paliperidone) were assigned to the LAI group. Acute phase: In acute cases/phase, patients were initiated on either 1st or 2nd generation OAT or short-acting second generation injectables or on a combination of 1st and 2nd generation agents. First generation OATs were primarily prescribed in government facilities (20%) as compared with private facilities (5%). Second generation OATs were prescribed in 80% and 90-95% of patients in government and private facilities respectively. Injectable preparations (1st generation) were prescribed in rare cases, to
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control acute symptoms. Short-acting second generation injectables were prescribed to control acute symptoms, especially in hospital settings. Chronic phase: Patients in chronic phase were predominantly on 2nd generation OATs or LAIs [1st or 2nd generation] with/without education and psycho-social counseling. First generation OATs were rarely prescribed for chronic patients in both private and hospital setups. Nearly 80% of chronic patients hospitalized and 90% of chronic cases in private facilities were treated with 2nd generation OAT. Second generation LAIs were the preferred treatment regimen in approximately 9% of the chronic schizophrenia cases. 3.4 Psychiatrists’ perceptions on impact of relapses on hospitalization The psychiatrists’ opinion on hospital admissions suggested that nearly 15% patients suffering a relapse, required hospital admission. About 50% of patients admitted in government setting required more than 14 days hospital stay versus 15% in private set up. The average length of hospital stay was >14 days in government hospitals; as for private hospitals, the average length of stay was between 7 to 14 days. 3.5 Average relapse rate per year Relapse rates for patients based on the psychiatrists’ survey suggested that proportion of patients who were without relapse was greater in patients on LAIs (78%) as compared with patients on OAT (40%). Also, more number of patients on oral antipsychotic regimen had greater number (2-3) of relapses as compared with patients on the LAI maintenance therapy, Fig.1.
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3.6 Psychiatrists’ perceptions on economic cost associated with schizophrenia Medication costs Psychiatrists reported that monthly medication expenditure for patients with acute schizophrenia ranged between $8-17 (Indian Rs. 500-1,000) when oral medication was prescribed and $22-50 (Indian Rs. 1,300-3,000) for short-acting injectables. The LAIs although rarely prescribed in acute cases, would account to $22 - $50 (Indian Rs. 1,3253000) per month. For patients with chronic conditions receiving long-term treatment, the monthly medication expenses for typical antipsychotics was comparatively lower (oral: $4-5 [Indian Rs. 250-300], LAIs: $5- 25 [Indian Rs. 300-1500]) when compared with the atypical antipsychotics (oral: $11.7-25 [Indian Rs. 700-1,500], LAI: $150-167 [Indian Rs. 9,000-10,000]). Hospitalization costs Psychiatrists perceived that costs pertaining to hospitalizations varied depending upon the category of hospital and services. In the majority of cases, patients were treated on OPD basis and hospital admissions were recommended only after gauging the severity of symptoms, extent of patient care required at home or till the acute symptoms subsided. Daily inpatient-care costs were perceived to be highest in corporate hospitals ($75-117 [Indian Rs. 4,500-7,000]), followed by private hospitals ($33-117 [Indian Rs. 2,000-7,000]) and lowest for government institutions ($0 - 12.5 [Indian Rs. 0-750]). Duration of hospitalization was extended in certain cases due to initiation of rehabilitation and counseling to help patients and caregivers acclimatize to domestic settings post-hospitalization. Cost for hospital admissions (room charges, nursing fees, food etc.) was the largest component (78%) of total expenses incurred in nursing homes or private setups followed by doctor’s fees (20%) and medications (2%).
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3.7 Rehabilitation, caregiver and day costs Psychiatrist suggested that, rehabilitation programs were recommended for about 5% to 30% patients and the duration of rehabilitation program varied from a minimum of 2 weeks to 3 months, with more frequent and longer stays observed for patients with comorbidities. The cost of rehabilitation varied according to the class of facilities opted for government aided and charitable daycare centers offer free services, whereas private services are paid. On an average, the monthly rehabilitation costs ranged from $2501700 (Indian Rs. 15,000-1,00,000). Among the psychiatrists interviewed, 50% were in favor of daycare services for patients with schizophrenia. Such services were considered as a rare requisite by 25% psychiatrists and the remaining 25% were unaware of the nature and requirement of these services. Personal caregivers were employed for daily or episodic home-based care in 5% to 10% cases and their monthly salary was estimated to be $100-250 (Indian Rs. 6,000-15,000). 3.8 Post treatment reported reasons on treatment discontinuation and adherence Treatment discontinuation Psychiatrists recounted that treatment-emergent adverse events (TEAEs) were a major contributing factor for poor adherence and treatment discontinuation. The TEAEs reported were similar between the two treatment formulations and the total number of treatment discontinuations due to TEAEs were comparable (LAIs=32%, OAT=25%). Drowsiness, extrapyramidal symptoms, weight gain, metabolic derailments and erectile dysfunction were reported in both treatment groups; however, more number of patients on OATs reported these TEAEs as compared with LAIs. Other contributing factors to treatment discontinuation (LAIs= 30%, OAT= 50%) were cost of medications, feeling
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of wellness and recovery, family/ peer pressure and poor insight of the patient about the illness. Treatment adherence Analysis of treatment adherence between OATs and LAIs revealed that 78% patients on LAIs and 50% patients on oral medications were treatment adherent in the past six months. Psychiatrists’ opinion on treatment adherence suggested that patients on OAT are more likely to discontinue in the first six months owing to TEAEs as compared to patients on LAIs (Fig.2).
4. DISCUSSION This survey attempted to provide an overview of the psychiatrists’ prescription practices for the use of LAIs versus OATs for the management of schizophrenia, in India. This study is the first of its kind to evaluate the psychiatrists’ prescription perception and assess the impact of available treatment options on treatment cost. Overall analyses of the prescription practices highlighted that OATs were the treatment of choice for acute schizophrenia and psychiatrists reserved LAIs for a limited number of chronic and severe cases. Based on extended evaluation to identify the reasons for this trend, high acquisition cost of LAIs perceived by the psychiatrists was found to primarily impact their prescribing decisions. It is important to note that in their perception of costeffective healthcare, psychiatrists did not account for additional costs of relapses, hospitalization and caregiving that are commonly associated with OATs. Thus, a comprehensive account of total treatment costs, inclusive of costs of relapses, chronic hospitalization associated with relapse and caregiver costs would provide a holistic picture of the complete expenditure associated with both treatments. In addition, a head-
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to-head comparison of all costs associated with schizophrenia management (OATs versus LAIs) provides a better understanding of the economic impact of treatment. In the present study, psychiatrists reported that a majority of patients attending their OPDs had chronic schizophrenia (75%) and were less than 40 years of age (80%) i.e., the most productive years of their lives. These high incidence rates of chronic schizophrenia particularly in patients from the productive age group, warrant studies that understand the barriers which impede the use of reliable treatment strategies such as the LAIs which are capable of improving their overall quality of life. Similar prescription trends and prescriber attitudes have been reported from across the world; for example, a study conducted with 891 healthcare professionals found that 90% of them selected LAIs only for chronic patients and for patients with a history of multiple relapses (Geerts et al., 2013). Conversely, there is strong evidence supporting the use of LAIs as early intervention for effective symptom remission in schizophrenia (Heres et al., 2014; Patel et al., 2010; Stevens et al., 2016; Suzuki et al., 2017). In addition, it is vital to consider that newly diagnosed schizophrenia patients tend to be more responsive to antipsychotic treatment; however, delay in effective treatment and/ or issues with adherence to treatment lead to higher relapse rates, increasing chronicity and refractoriness to treatment (Emsley et al., 2013).These aspects underscore the need for a reliable treatment with improved adherence as early as possible in the treatment of acute schizophrenia. Additional factors contributing to the suboptimal use of LAIs in the treatment of schizophrenia include psychiatrists’ faulty presumption of ‘sufficient adherence’ with oral antipsychotic treatment (Heres et al., 2011), psychiatrists’ belief that LAIs have a
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stigmatizing and negative image among patients (Potkin et al., 2013), and psychiatrists’ fear of an adverse impact on their therapeutic relationships (Iyer et al., 2013). Contrary to the psychiatrist perceptions highlighted in this study and elsewhere, patients generally report a more favorable attitude to use of LAIs. Therefore, there seems to be a gap between reality and psychiatrists’ perceptions of patients' apprehensions and acceptance of LAIs, which also contribute to the low prescription rates. This gap informs us that preference for LAIs is dependent on both the treating psychiatrists and the patients’ experiences. Increasing awareness about LAIs with information on positive experiences in patients may improve attitudes among the psychiatrists and facilitate the prescribing process of LAI. In this survey, the proportions of TEAEs were comparable and TEAEs were a major contributor to premature treatment discontinuation for both treatment groups as reported by the physicians. This observation is analogous to that observed in large clinical studies that evaluated the safety of LAIs vis-à-vis the OATs (Chue et al., 2005). Psychiatrists opinion in our study suggests that patients on OATs are likely to discontinue treatment in the first six months owing to TEAEs while patients on LAIs are believed to taper use after six months due to a burden of cost and a feeling of ‘wellness’. However, these observations cannot be substantiated as the data was limited to 6 months, which may not be sufficient to provide conclusive evidences. Another important observation from the current physician’s survey was a higher rate of hospitalization due to relapse among patients on OATs, as compared with those receiving LAIs. A similar observation was reported by Emsley et al; 97% of the patients on LAIs who achieved early symptom remission, maintained remission at 2 years
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(Emsley et al., 2008) as opposed to only 24% patients on oral risperidone or haloperidol and for relatively shorter period of 6 months.(Emsley et al., 2007) An analysis of the patients from a claims database with schizophrenia either on LAI or OATs reported that initiating LAI versus OAT treatment (n=2,610) had significant (P<0.001) reductions in number of schizophrenia-related hospitalizations, including length of hospital stay during the 12- month follow-up period.(Offord et al., 2013) Thus, as compared with OATs, LAIs, by providing prolonged remission may potentially lower the risk of rehospitalization from relapse, thereby improving the overall outcome of schizophrenia management. Further, though poor adherence causing relapses is perceived as an established fact, yet psychiatrists viewed LAIs as an impractical treatment options due to the high costs (direct costs of LAIs ($150-167[Indian Rs.9000-10,000) vs. OATs ($12-$25 [Indian Rs. 700-1500]) and inconveniences associated with frequent clinic appointments (Iyer et al., 2013). As a result, psychiatrist chose to reserve the LAIs for severe and chronic conditions thereby leading to underutilization of LAIs. However, increased hospitalization rates and longer hospital stay due to relapses may cumulatively incur much more cost than the medication acquisition cost, eventually considerably impacting overall direct cost. This is supported by the results of a real-world medication study that analyzed the impact of LAI treatment versus OATs on healthcare costs. The study reported that though the direct medication costs were reportedly higher with LAI use, the total in-patient and out-patient healthcare costs were significantly (P<0.001) lower with LAIs, as compared with oral treatment (Lin et al., 2013). Limitations of the study include a modestly sample size and self-reporting; the survey responses could reflect some bias contributing to measurement errors. With no formal 14
statistical analyses performed, conclusive evidence on perceived better treatment adherence with LAIs could not be drawn. Further, this survey was conducted largely in an urban population, thus limiting generalization to the population across the country including rural regions. A comparatively large and diverse study, spread across the geography of India, with quantifiable and statistically conclusive results would be beneficial to objectively identify and help psychiatrists make appropriate and more informed treatment decisions. Although, the SUSTAIN-I study is associated with considerable limitations, it is the first structured survey conducted in India that assessed the physician attitudes and prescription practices in schizophrenia with reference to LAIs; a study about prescriber attitudes to use of clozapine has previously been reported (Grover et al., 2015). Of note, suboptimal use of the most effective treatment options in schizophrenia appears to be principally driven by prescriber misperceptions.
5. CONCLUSION This study demonstrates that despite enhanced treatment adherence, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Considering the complete cost analysis (direct medication costs, cost due to hospitalization and other treatment related expenses), treatment nonadherence with OAT leading to relapses, are associated with high overall costs in the management of schizophrenia. Our findings shed light on the Indian scenario wherein despite the identified advantages of LAIs, practicing psychiatrist have a conservative approach for LAI prescription. The study provides implications on the sparing use of LAIs and aims to support the healthcare providers to make informed and
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judicious treatment decisions in order to improve the socioeconomic and functional benefits in patients with schizophrenia and also to ease the burden of caregivers.
AUTHOR AGREEMENTS Funding sources: This study was funded by Johnson & Johnson India Private Limited, Mumbai, India
Conflicts of interest: Vikram Singh, Prashant Narang and Sonal Gawande, are employees of Johnson & Johnson India. Drs. Prasad Rao Gundugurti, Rajesh Nagpal and Dr. Asit Sheth are consultants for Johnson & Johnson India Private Limited.
Author contributions: Drs. Gundugarti, Nagpal, Sheth, Narang, Gawande, and Singh were all involved in conception and design of the study. Drs. Narang and Singh were involved in data acquisition. Drs. Gawande and Narang were involved in data analysis. All authors were involved in the interpretation of data and contributed to manuscript development and critical revision. All authors approved the final manuscript for submission. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publications.
6. ACKNOWLEDGEMENTS Authors thank Ms. Shweta Pitre, ISMPP CMPP™ for providing writing assistance and Dr. Madhavi Patil for editorial support (both SIRO Clinpharm Pvt. Ltd., India) during
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the development of this manuscript. The authors also thank all participating psychiatrist, for their time and inputs, without whom this study would not have been accomplished. .
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Iyer, S., Banks, N., Roy, M.A., Tibbo, P., Williams, R., Manchanda, R., Chue, P., Malla, A., 2013. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: part II-physician perspectives. Can J Psychiatry. 58 (5 Suppl 1) 23s-29s.
Lin, J., Wong, B., Offord, S., Mirski, D., 2013. Healthcare cost reductions associated with the use of LAI formulations of antipsychotic medications versus oral among patients with schizophrenia. J Behav Health Serv Res 40 (3) 355-366.
Offord, S., Wong, B., Mirski, D., Baker, R.A., Lin, J., 2013. Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral. J Med Econ. 16 (2) 231-239.
Patel, M.X., Haddad, P.M., Chaudhry, I.B., McLoughlin, S., Husain, N., David, A.S., 2010. Psychiatrists' use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years. J Psychopharmacol. 24 (10) 1473-1482.
Potkin, S., Bera, R., Zubek, D., Lau, G., 2013. Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia. BMC Psychiatry. 13 261.
Sreeraj, V.S., Shivakumar, V., Rao, N.P., Venkatasubramanian, G., 2017. A critical appraisal of long acting injectable antipsychotics: Translating research to clinics. Asian J Psychiatr. 28 57-64.
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Stevens, G.L., Dawson, G., Zummo, J., 2016. Clinical benefits and impact of early use of long-acting injectable antipsychotics for schizophrenia. Early Interv Psychiatry. 10 (5) 365-377.
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Yoshimura, B., Shinkawa, I., Konishi, A., 2015. Hospitalization risk in patients with schizophrenia before and after initiation of risperidone long-acting injection in Japan. Asian J Psychiatr. 14 67-68.
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FIGURES Figure Legends Figure 1: Average Relapse Rates per Year LAIs: Long acting injectables; OATs: oral antipsychotic therapies Figure 2: Trends for treatment discontinuation in patients on oral versus LAI antipsychotics LAIs: Long acting injectables; OATs: oral antipsychotic therapies
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Fig.1
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Fig.2
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TABLES Table 1: Available treatment regimens for OATs and LAIs First generation Typical OATs
Atypical antipsychotics: LAIs
Chlorpromazine
Haloperidol decanoate
Trifluoperazine
Flupenthixol decanoate
Haloperidol
Zuclopenthixol decanoate
Flupentixol
Fluphenazine decanoate
Second generation Atypical OATs
Atypical antipsychotics: LAIs
Amisulpride Aripiprazole
Risperidone Paliperidone
Clozapine
Olanzapine*
Olanzapine Quetiapine Risperidone Ziprasidone *Olanzapine LAI has not been included in the study group due to lack of sufficient data in practical settings; LAI: Long-acting injectable; OATs: oral antipsychotic therapies
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Table 2: Antipsychotic prescription practices of psychiatrists in India
st
1 generation OATs 2nd generation OATs
Acute Phase
Chronic Phase
Private setup:<5% Government setups: 20% Private setup: 90-95% Government setups: 80% Negligible
Government setups: 10%
Private setup: 90-95% Government setups: 80% 1st generation LAIs Government setups:15% in non-compliant and nonaffording patients nd 2 generation LAIs Rarely used 9% patients to achieve better compliance and outcome LAIs: Long acting injectables; OATs: oral antipsychotic therapies
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S1876-2018(17)30541-5 http://dx.doi.org/doi:10.1016/j.ajp.2017.08.002 AJP 1211
To appear in: Received date: Accepted date:
3-8-2017 4-8-2017
Please cite this article as: Gundugurti, Prasad Rao, Nagpal, Rajesh, Sheth, Ashit, Narang, Prashant, Gawande, Sonal, Singh, Vikram, Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India.Asian Journal of Psychiatry http://dx.doi.org/10.1016/j.ajp.2017.08.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists’ survey in India Running title: Oral versus long-acting antipsychotics: A psychiatrists’ survey in India
Authors Prasad Rao Gundugurti1, Rajesh Nagpal2, Ashit Sheth3, Prashant Narang4, Sonal Gawande4, Vikram Singh4 1
Division of Schizophrenia and Psychopharmacology, Asha Hospital, Hyderabad, India
2
Manobal Klinik, New Delhi, India
3
Unlimited Potentialities, Mumbai, India
4
Medical Affairs, Johnson & Johnson India Private Limited, Mumbai, India
Corresponding author Dr. Prashant Narang Medical Affairs, Johnson & Johnson India Private Limited, Arena Space, JVLR, Jogeshwari East, Mumbai, 400060, India Email: [email protected]
Previous Presentation: Presented at 7th ISPOR Asia Pacific conference, 3rd - 6th September 2016
1
Highlights
First Indian survey to evaluate psychiatrists’ prescription practices in schizophrenia
Oral antipsychotics were the treatment of choice for acute and chronic cases
LAI therapy perceived to offer assurance of medication adherence and reduced relapses
Owing to perceived high costs, LAIs were not preferred treatment
A conservative approach and sparing use of LAIs observed in India
ABSTRACT Background: Schizophrenia is associated with functional challenges for patients; relapses in schizophrenia may lead to increased treatment costs and poor quality of life. Objective: This SUSTAIN-I study was conducted to establish psychiatrists’ perspective on impact of long-acting injectables (LAIs) antipsychotics on the socio-economic and functional burden of schizophrenia. Methods: This cross-sectional, survey-based study was conducted in 5 cities in India. Psychiatrists (≥ 5 years of experience) working in clinics, psychiatric, government hospitals and rehabilitation centers were included and administered a specially designed questionnaire to elicit information on their clinical practice and prescription patterns. Perceived treatment costs for LAI versus oral antipsychotic treatments (OATs) and relapse rates were assessed. Descriptive statistics were used to summarize results. Results: Total 31 physicians completed this survey. In acute phase, OAT prescription was higher whereas chronic patients were treated with either OATs or LAIs. Treatment with LAIs was the preferred treatment in 9% of chronic cases. Reduced relapse rates
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were observed with LAI treatment: 12% patients on LAIs relapsed as compared with 60% patients on OATs. Monthly medication cost for oral medications was lower ($8$17) than short-acting injectables ($22-$50). For chronic cases, atypical antipsychotics cost (oral: $11.7-25, LAI: $150-167) was higher than typical antipsychotics (oral: $4-5, LAI: $5-25). Of total expenses incurred, cost for hospital admissions was the largest component (78%). Conclusion: Despite enhanced treatment adherence and potential to lower risk of rehospitalizations from relapse, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Keywords: antipsychotics, functional burden; long-acting injectables; psychiatrists’ survey; schizophrenia; relapse
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1. INTRODUCTION Schizophrenia is a chronic relapsing mental disorder that profoundly affects an individual’s emotional regulation and social behavior (Tandon et al., 2009). It is associated with enormous functional challenges for both, patients as well as their caregivers (Gupta et al., 2015). Relapses in schizophrenia are associated with increased symptoms recurrences, increased hospitalization costs and poor quality of life (Almond et al., 2004). Although antipsychotic medications are effective in preventing relapse, this goal is often hindered by poor adherence to treatment (Bruijnzeel et al., 2014). Currently, pharmacotherapy of schizophrenia includes first-generation or typical antipsychotics and second-generation or atypical antipsychotics (Tandon and Halbreich, 2003). Poor adherence to oral antipsychotic therapy (OAT) led to the development of first and subsequently second generation antipsychotic long-acting injectables (LAIs) in 1960s and 1990s respectively (Brissos et al., 2014). LAIs, which are to be administered once every 2-12 weeks, provide assurance of adherence; numerous studies have established their efficacy, safety and cost effectiveness with benefits on a range of outcome measures- lesser relapse rates, reduced frequency of hospitalizations, shorter hospital stays and better overall functioning (Castillo and Stroup, 2015; Sreeraj et al., 2017; Stevens et al., 2016; Yoshimura et al., 2015). Despite their established advantages, treating pyschiatrists tend to reserve LAIs only for severe and chronic conditions (Heres, 2014). Since data from India about the challenges of appropriate utilization of LAIs are sparse, a cross sectional study, “Study to Understand Schizophrenia Treatment Approach- physician and caregiver INsights on social, economic and functional benefits of LAI in India (SUSTAIN-I) was conducted to
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ascertain and characterize psychiatrists’ perspective on impact of LAIs on the socioeconomic and functional burden of schizophrenia on patients and their caregivers.
2. METHODS 2.1 Study design and participants This observational and epidemiological survey, funded by Janssen, India was conducted in two phases across India, between October 2015 and March 2016. In phase 1, experienced psychiatrists (≥ 5 years of experience) who worked in clinics, private and government hospitals and rehabilitation centers were included. A broad range of psychiatrists prescribing high and low proportions of LAI, those with substantial practice in management of schizophrenia and who agreed to provide sufficient time for the survey, were included in this survey. Here we present the findings of the phase 1 study. 2.2 Assessment A questionnaire was designed to elicit information on the categories of patients visited and their disease conditions (acute or chronic cases), demographics of patients, preferred antipsychotics, commonly prescribed treatment regimes, etc. Physician’s prescription practices were assessed to establish the treatment patterns for patients suffering from acute and chronic schizophrenia. Currently prescribed oral and LAI medications were classified as 1st (typical) or 2nd generation (atypical) antipsychotics based on the conventional classification (Table 1). Attendance of schizophrenia patients in the outpatient department (OPD) were collected and analyzed to establish patterns in patient profiles. Annual relapse rates and relapse rates leading to hospitalization, average length of stay in hospital, treatment discontinuation and treatment adherence
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were calculated based on data obtained from the survey questionnaire. Data collection protocol was approved by an Independent Ethics Committee. Psychiatrist participants received written and verbal information regarding the study. Consent was deemed implicit if they returned a completed questionnaire. Perceived costs of treatment for LAIs and OATs were assessed based on the psychiatrist’ survey. All costs presented in this study were strictly related to the treatment of schizophrenia.
Direct costs: These included medication costs- unit costs for all prescribed (for schizophrenia) and supportive medications per month, not inclusive of dispensing fee. Medication acquisition cost was considered for prescribed trade names and in cases of generic names, price of the cheapest brand was included for calculations.
2.3 Statistical Analysis Responses to the verbal questionnaire were noted and statistically analyzed. Data were analyzed to detect the patterns in prescription practices, comparison of ratios/ percentages and development of standard scores. Descriptive statistics were used to summarize psychiatrists’ prescription preferences.
3. RESULTS 3.1 Profiles and characteristics of Psychiatrist surveyed This survey-based study was conducted among treating senior psychiatrists with extensive experience in the management of Schizophrenia from five of the 7 most populous cities across India (Hyderabad, Bengaluru, Mumbai, Pune and Delhi).
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Physician survey respondents included 31 psychiatrists (clinics=18, psychiatry hospitals=6, government or charitable hospitals=5, rehabilitation centers=2). 3.2 Psychiatrists’ perceptions on patient profiles Outpatient department attendance of schizophrenia patients Nearly 10-20% (median 25%) of all the OPD attendees comprised of schizophrenia patients. About 25% of all schizophrenia cases were reported as new cases while the rest were old or relapsed cases. Psychiatrists experienced that on an average 42% of the cases were aged between 20-30 years of age and 21% were aged between 30-40 years. About 17% of all cases were adolescents aged between 15-20 years. The number of cases with age > 40 years (20%) was low. 3.3 Psychiatrists’ prescription preferences Physician prescription practices were based on the phases (acute or chronic) of schizophrenia, Table 2. In this study, for the sake of comparison of oral versus LAI treatment, patients receiving oral atypical antipsychotics (i.e., amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone) were assigned to the oral medication group and patients receiving atypical antipsychotic injections (i.e., risperidone and paliperidone) were assigned to the LAI group. Acute phase: In acute cases/phase, patients were initiated on either 1st or 2nd generation OAT or short-acting second generation injectables or on a combination of 1st and 2nd generation agents. First generation OATs were primarily prescribed in government facilities (20%) as compared with private facilities (5%). Second generation OATs were prescribed in 80% and 90-95% of patients in government and private facilities respectively. Injectable preparations (1st generation) were prescribed in rare cases, to
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control acute symptoms. Short-acting second generation injectables were prescribed to control acute symptoms, especially in hospital settings. Chronic phase: Patients in chronic phase were predominantly on 2nd generation OATs or LAIs [1st or 2nd generation] with/without education and psycho-social counseling. First generation OATs were rarely prescribed for chronic patients in both private and hospital setups. Nearly 80% of chronic patients hospitalized and 90% of chronic cases in private facilities were treated with 2nd generation OAT. Second generation LAIs were the preferred treatment regimen in approximately 9% of the chronic schizophrenia cases. 3.4 Psychiatrists’ perceptions on impact of relapses on hospitalization The psychiatrists’ opinion on hospital admissions suggested that nearly 15% patients suffering a relapse, required hospital admission. About 50% of patients admitted in government setting required more than 14 days hospital stay versus 15% in private set up. The average length of hospital stay was >14 days in government hospitals; as for private hospitals, the average length of stay was between 7 to 14 days. 3.5 Average relapse rate per year Relapse rates for patients based on the psychiatrists’ survey suggested that proportion of patients who were without relapse was greater in patients on LAIs (78%) as compared with patients on OAT (40%). Also, more number of patients on oral antipsychotic regimen had greater number (2-3) of relapses as compared with patients on the LAI maintenance therapy, Fig.1.
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3.6 Psychiatrists’ perceptions on economic cost associated with schizophrenia Medication costs Psychiatrists reported that monthly medication expenditure for patients with acute schizophrenia ranged between $8-17 (Indian Rs. 500-1,000) when oral medication was prescribed and $22-50 (Indian Rs. 1,300-3,000) for short-acting injectables. The LAIs although rarely prescribed in acute cases, would account to $22 - $50 (Indian Rs. 1,3253000) per month. For patients with chronic conditions receiving long-term treatment, the monthly medication expenses for typical antipsychotics was comparatively lower (oral: $4-5 [Indian Rs. 250-300], LAIs: $5- 25 [Indian Rs. 300-1500]) when compared with the atypical antipsychotics (oral: $11.7-25 [Indian Rs. 700-1,500], LAI: $150-167 [Indian Rs. 9,000-10,000]). Hospitalization costs Psychiatrists perceived that costs pertaining to hospitalizations varied depending upon the category of hospital and services. In the majority of cases, patients were treated on OPD basis and hospital admissions were recommended only after gauging the severity of symptoms, extent of patient care required at home or till the acute symptoms subsided. Daily inpatient-care costs were perceived to be highest in corporate hospitals ($75-117 [Indian Rs. 4,500-7,000]), followed by private hospitals ($33-117 [Indian Rs. 2,000-7,000]) and lowest for government institutions ($0 - 12.5 [Indian Rs. 0-750]). Duration of hospitalization was extended in certain cases due to initiation of rehabilitation and counseling to help patients and caregivers acclimatize to domestic settings post-hospitalization. Cost for hospital admissions (room charges, nursing fees, food etc.) was the largest component (78%) of total expenses incurred in nursing homes or private setups followed by doctor’s fees (20%) and medications (2%).
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3.7 Rehabilitation, caregiver and day costs Psychiatrist suggested that, rehabilitation programs were recommended for about 5% to 30% patients and the duration of rehabilitation program varied from a minimum of 2 weeks to 3 months, with more frequent and longer stays observed for patients with comorbidities. The cost of rehabilitation varied according to the class of facilities opted for government aided and charitable daycare centers offer free services, whereas private services are paid. On an average, the monthly rehabilitation costs ranged from $2501700 (Indian Rs. 15,000-1,00,000). Among the psychiatrists interviewed, 50% were in favor of daycare services for patients with schizophrenia. Such services were considered as a rare requisite by 25% psychiatrists and the remaining 25% were unaware of the nature and requirement of these services. Personal caregivers were employed for daily or episodic home-based care in 5% to 10% cases and their monthly salary was estimated to be $100-250 (Indian Rs. 6,000-15,000). 3.8 Post treatment reported reasons on treatment discontinuation and adherence Treatment discontinuation Psychiatrists recounted that treatment-emergent adverse events (TEAEs) were a major contributing factor for poor adherence and treatment discontinuation. The TEAEs reported were similar between the two treatment formulations and the total number of treatment discontinuations due to TEAEs were comparable (LAIs=32%, OAT=25%). Drowsiness, extrapyramidal symptoms, weight gain, metabolic derailments and erectile dysfunction were reported in both treatment groups; however, more number of patients on OATs reported these TEAEs as compared with LAIs. Other contributing factors to treatment discontinuation (LAIs= 30%, OAT= 50%) were cost of medications, feeling
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of wellness and recovery, family/ peer pressure and poor insight of the patient about the illness. Treatment adherence Analysis of treatment adherence between OATs and LAIs revealed that 78% patients on LAIs and 50% patients on oral medications were treatment adherent in the past six months. Psychiatrists’ opinion on treatment adherence suggested that patients on OAT are more likely to discontinue in the first six months owing to TEAEs as compared to patients on LAIs (Fig.2).
4. DISCUSSION This survey attempted to provide an overview of the psychiatrists’ prescription practices for the use of LAIs versus OATs for the management of schizophrenia, in India. This study is the first of its kind to evaluate the psychiatrists’ prescription perception and assess the impact of available treatment options on treatment cost. Overall analyses of the prescription practices highlighted that OATs were the treatment of choice for acute schizophrenia and psychiatrists reserved LAIs for a limited number of chronic and severe cases. Based on extended evaluation to identify the reasons for this trend, high acquisition cost of LAIs perceived by the psychiatrists was found to primarily impact their prescribing decisions. It is important to note that in their perception of costeffective healthcare, psychiatrists did not account for additional costs of relapses, hospitalization and caregiving that are commonly associated with OATs. Thus, a comprehensive account of total treatment costs, inclusive of costs of relapses, chronic hospitalization associated with relapse and caregiver costs would provide a holistic picture of the complete expenditure associated with both treatments. In addition, a head-
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to-head comparison of all costs associated with schizophrenia management (OATs versus LAIs) provides a better understanding of the economic impact of treatment. In the present study, psychiatrists reported that a majority of patients attending their OPDs had chronic schizophrenia (75%) and were less than 40 years of age (80%) i.e., the most productive years of their lives. These high incidence rates of chronic schizophrenia particularly in patients from the productive age group, warrant studies that understand the barriers which impede the use of reliable treatment strategies such as the LAIs which are capable of improving their overall quality of life. Similar prescription trends and prescriber attitudes have been reported from across the world; for example, a study conducted with 891 healthcare professionals found that 90% of them selected LAIs only for chronic patients and for patients with a history of multiple relapses (Geerts et al., 2013). Conversely, there is strong evidence supporting the use of LAIs as early intervention for effective symptom remission in schizophrenia (Heres et al., 2014; Patel et al., 2010; Stevens et al., 2016; Suzuki et al., 2017). In addition, it is vital to consider that newly diagnosed schizophrenia patients tend to be more responsive to antipsychotic treatment; however, delay in effective treatment and/ or issues with adherence to treatment lead to higher relapse rates, increasing chronicity and refractoriness to treatment (Emsley et al., 2013).These aspects underscore the need for a reliable treatment with improved adherence as early as possible in the treatment of acute schizophrenia. Additional factors contributing to the suboptimal use of LAIs in the treatment of schizophrenia include psychiatrists’ faulty presumption of ‘sufficient adherence’ with oral antipsychotic treatment (Heres et al., 2011), psychiatrists’ belief that LAIs have a
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stigmatizing and negative image among patients (Potkin et al., 2013), and psychiatrists’ fear of an adverse impact on their therapeutic relationships (Iyer et al., 2013). Contrary to the psychiatrist perceptions highlighted in this study and elsewhere, patients generally report a more favorable attitude to use of LAIs. Therefore, there seems to be a gap between reality and psychiatrists’ perceptions of patients' apprehensions and acceptance of LAIs, which also contribute to the low prescription rates. This gap informs us that preference for LAIs is dependent on both the treating psychiatrists and the patients’ experiences. Increasing awareness about LAIs with information on positive experiences in patients may improve attitudes among the psychiatrists and facilitate the prescribing process of LAI. In this survey, the proportions of TEAEs were comparable and TEAEs were a major contributor to premature treatment discontinuation for both treatment groups as reported by the physicians. This observation is analogous to that observed in large clinical studies that evaluated the safety of LAIs vis-à-vis the OATs (Chue et al., 2005). Psychiatrists opinion in our study suggests that patients on OATs are likely to discontinue treatment in the first six months owing to TEAEs while patients on LAIs are believed to taper use after six months due to a burden of cost and a feeling of ‘wellness’. However, these observations cannot be substantiated as the data was limited to 6 months, which may not be sufficient to provide conclusive evidences. Another important observation from the current physician’s survey was a higher rate of hospitalization due to relapse among patients on OATs, as compared with those receiving LAIs. A similar observation was reported by Emsley et al; 97% of the patients on LAIs who achieved early symptom remission, maintained remission at 2 years
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(Emsley et al., 2008) as opposed to only 24% patients on oral risperidone or haloperidol and for relatively shorter period of 6 months.(Emsley et al., 2007) An analysis of the patients from a claims database with schizophrenia either on LAI or OATs reported that initiating LAI versus OAT treatment (n=2,610) had significant (P<0.001) reductions in number of schizophrenia-related hospitalizations, including length of hospital stay during the 12- month follow-up period.(Offord et al., 2013) Thus, as compared with OATs, LAIs, by providing prolonged remission may potentially lower the risk of rehospitalization from relapse, thereby improving the overall outcome of schizophrenia management. Further, though poor adherence causing relapses is perceived as an established fact, yet psychiatrists viewed LAIs as an impractical treatment options due to the high costs (direct costs of LAIs ($150-167[Indian Rs.9000-10,000) vs. OATs ($12-$25 [Indian Rs. 700-1500]) and inconveniences associated with frequent clinic appointments (Iyer et al., 2013). As a result, psychiatrist chose to reserve the LAIs for severe and chronic conditions thereby leading to underutilization of LAIs. However, increased hospitalization rates and longer hospital stay due to relapses may cumulatively incur much more cost than the medication acquisition cost, eventually considerably impacting overall direct cost. This is supported by the results of a real-world medication study that analyzed the impact of LAI treatment versus OATs on healthcare costs. The study reported that though the direct medication costs were reportedly higher with LAI use, the total in-patient and out-patient healthcare costs were significantly (P<0.001) lower with LAIs, as compared with oral treatment (Lin et al., 2013). Limitations of the study include a modestly sample size and self-reporting; the survey responses could reflect some bias contributing to measurement errors. With no formal 14
statistical analyses performed, conclusive evidence on perceived better treatment adherence with LAIs could not be drawn. Further, this survey was conducted largely in an urban population, thus limiting generalization to the population across the country including rural regions. A comparatively large and diverse study, spread across the geography of India, with quantifiable and statistically conclusive results would be beneficial to objectively identify and help psychiatrists make appropriate and more informed treatment decisions. Although, the SUSTAIN-I study is associated with considerable limitations, it is the first structured survey conducted in India that assessed the physician attitudes and prescription practices in schizophrenia with reference to LAIs; a study about prescriber attitudes to use of clozapine has previously been reported (Grover et al., 2015). Of note, suboptimal use of the most effective treatment options in schizophrenia appears to be principally driven by prescriber misperceptions.
5. CONCLUSION This study demonstrates that despite enhanced treatment adherence, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs. Considering the complete cost analysis (direct medication costs, cost due to hospitalization and other treatment related expenses), treatment nonadherence with OAT leading to relapses, are associated with high overall costs in the management of schizophrenia. Our findings shed light on the Indian scenario wherein despite the identified advantages of LAIs, practicing psychiatrist have a conservative approach for LAI prescription. The study provides implications on the sparing use of LAIs and aims to support the healthcare providers to make informed and
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judicious treatment decisions in order to improve the socioeconomic and functional benefits in patients with schizophrenia and also to ease the burden of caregivers.
AUTHOR AGREEMENTS Funding sources: This study was funded by Johnson & Johnson India Private Limited, Mumbai, India
Conflicts of interest: Vikram Singh, Prashant Narang and Sonal Gawande, are employees of Johnson & Johnson India. Drs. Prasad Rao Gundugurti, Rajesh Nagpal and Dr. Asit Sheth are consultants for Johnson & Johnson India Private Limited.
Author contributions: Drs. Gundugarti, Nagpal, Sheth, Narang, Gawande, and Singh were all involved in conception and design of the study. Drs. Narang and Singh were involved in data acquisition. Drs. Gawande and Narang were involved in data analysis. All authors were involved in the interpretation of data and contributed to manuscript development and critical revision. All authors approved the final manuscript for submission. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publications.
6. ACKNOWLEDGEMENTS Authors thank Ms. Shweta Pitre, ISMPP CMPP™ for providing writing assistance and Dr. Madhavi Patil for editorial support (both SIRO Clinpharm Pvt. Ltd., India) during
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the development of this manuscript. The authors also thank all participating psychiatrist, for their time and inputs, without whom this study would not have been accomplished. .
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Iyer, S., Banks, N., Roy, M.A., Tibbo, P., Williams, R., Manchanda, R., Chue, P., Malla, A., 2013. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: part II-physician perspectives. Can J Psychiatry. 58 (5 Suppl 1) 23s-29s.
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FIGURES Figure Legends Figure 1: Average Relapse Rates per Year LAIs: Long acting injectables; OATs: oral antipsychotic therapies Figure 2: Trends for treatment discontinuation in patients on oral versus LAI antipsychotics LAIs: Long acting injectables; OATs: oral antipsychotic therapies
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Fig.1
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Fig.2
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TABLES Table 1: Available treatment regimens for OATs and LAIs First generation Typical OATs
Atypical antipsychotics: LAIs
Chlorpromazine
Haloperidol decanoate
Trifluoperazine
Flupenthixol decanoate
Haloperidol
Zuclopenthixol decanoate
Flupentixol
Fluphenazine decanoate
Second generation Atypical OATs
Atypical antipsychotics: LAIs
Amisulpride Aripiprazole
Risperidone Paliperidone
Clozapine
Olanzapine*
Olanzapine Quetiapine Risperidone Ziprasidone *Olanzapine LAI has not been included in the study group due to lack of sufficient data in practical settings; LAI: Long-acting injectable; OATs: oral antipsychotic therapies
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Table 2: Antipsychotic prescription practices of psychiatrists in India
st
1 generation OATs 2nd generation OATs
Acute Phase
Chronic Phase
Private setup:<5% Government setups: 20% Private setup: 90-95% Government setups: 80% Negligible
Government setups: 10%
Private setup: 90-95% Government setups: 80% 1st generation LAIs Government setups:15% in non-compliant and nonaffording patients nd 2 generation LAIs Rarely used 9% patients to achieve better compliance and outcome LAIs: Long acting injectables; OATs: oral antipsychotic therapies
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