Research on antipsychotics in India : Indian Journal of Psychiatry

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Research on antipsychotics in India

Avasthi, Ajit; Aggarwal, Munish; Grover, Sandeep; Khan, Mohd Khalid Rasheed1

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Indian Journal of Psychiatry 52(Suppl1):p S317-S340, January 2010. | DOI: 10.4103/0019-5545.69261
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Abstract

INTRODUCTION

When one looks at the history of psychiatric treatments, prior to availability of electroconvulsive therapy (ECT), measures like magic, restraints, blood letting, emetics, purgatives, surgical operations on various organs, removal of foci of infections, vaccines and endocrines were tried as treatment options for schizophrenia. Therapies like insulin coma and electroconvulsive therapy became available.[1] However, the era of pharmacotherapy for treatment of schizophrenia started with use of chlorpromazine by Delay and Deniker for the treatment of patients suffering from schizophrenia in early 1950’s. Over the next half century, a large number of drugs have been evaluated and marketed as antipsychotics. This class of drugs also helped in understanding the neurobiology of schizophrenia to some extent. This class of drug has also changed the attitude of the clinicians towards the expected outcome of the disorder.

India, as a country was not isolated from all these developments. Over the years many classes of antipsychotics have become available in India, some of which have stood the test of time and are still in use and some are no more marketed or are no more favorite of the clinicians. Research focusing on the usefulness of psychotics in India has more or less followed the trends in the West; however, some of the newer antipsychotic drugs which are currently marketed have not been evaluated as thoroughly as others. The pharmaceutical industry and the policy of the government have ensured that these medications are available at a reasonable price.

This review focuses on research done on various anti psychotics in India. For this a thorough internet search was done using key words like India, antipsychotics, name of each antipsychotic, efficacy, effectiveness, usefulness, tolerability, side effects, metabolic syndrome, weight gain, prescription, cost in various combinations. Various search engines like PUBMED, GOOGLE SCHOLAR, SCIENCEDIRECT, SEARCH MEDICA, SCOPUS, and MEDKNOW were used. In addition, a through search of all the issues of Indian Journal of Psychiatry available online was done. Hand search of some of the missing issues was also attempted and this yielded a few more articles. We have excluded review articles which we felt did not reflect the Indian scenario to a large extent or did not cover the available Indian data. Data from the animal studies that originated in the form of case reports and studies published only as abstract have not been included.

EFFICACY OF ANTIPSYCHOTICS IN SCHIZOPHRENIA

Efficacy of first generation antipsychotics in schizophrenia [Table 1]

Twenty eight studies which have evaluated the efficacy of first generation oral antipsychotics in schizophrenia have been published.[229] Of these, most have been open trials, some have been double blind randomized controlled trials and only a few have compared active drug with placebo. Some have also followed the cross over design with intermediate drug free period. Some of the initial trials included subjects who had not responded to previous pharmacological or somatic treatment and were suffering from chronic schizophrenia. Further, some studies have included treatment refractory subjects and others have recruited only those subjects who responded to some medication in the past. The sample size has varied from 15 to 145 subjects and the duration of trials have varied from eight days to six months, but most have evaluated the subjects in 4-12 weeks. Most of the trials included subjects with acute symptoms, however, one trial evaluated the efficacy of penfluridol and haloperidol in the maintenance phase and another included subjects who, on baseline, had shown at least 50% response on BPRS to the previous antipsychotic medication.[29]

T1-53
Table 1:
Efficacy of first generation antipsychotics in schizophrenia

Except for some of the trials in the 1960s and early 1970s, the efficacy and side effects were measured on some rating scales. All these trials have not used the dropouts in their final analysis of data. Data from all these trials can be summarized as: Typical antipsychotics are useful for treatment of schizophrenia, typical antipsychotics are more efficacious than placebo in the treatment of schizophrenia, improvement is seen more in paranoid and catatonic symptoms, aggression and less so in depressive symptoms; addition of trihexyphenidyl doesn’t reduce the efficacy of antipsychotic like trifluperazine and extrapyramidal symptoms are common with typical antipsychotics.

Efficacy of injectable depot first generation antipsychotics in schizophrenia [Table 2]

Nine trials have evaluated the efficacy of depot antipsychotics in schizophrenia.[3038] Some of these trials have just focused on short term outcome (2-4 weeks), whereas others have evaluated the outcome after six months. One trial followed up the subjects for 1-3 years.[37] In most of these trials subjects included were those who were non-complaint to oral medications and had frequent relapse. All these were open label and did not use a comparator group, except for the trial by Bagadia et al.[36] that compared subjects on fluphenazine decanoate with subjects who has been receiving either chlorpromazine or trifluperazine. All these studies have shown that depot antipsychotics are useful in the management of schizophrenia in acute phases and also for maintenance treatment.

T2-53
Table 2:
Efficacy studies of injectable depot antipsychotics in schizophrenia/psychosis

Efficacy studies of first generation antipsychotics vs. electroconvulsive therapy/electroconvulsive therapy and first generation antipsychotics in schizophrenia [Table 3]

Thirteen studies have compared typical antipsychotics with either electroconvulsive therapy (ECT) alone or a combination of ECT and typical antipsychotic medication.[13950] All studies have specified the diagnosis as schizophrenia, except for one study, in which the diagnosis was mentioned as functional psychosis.[45] A common theme which emerges from these studies is that typical antipsychotic, alone or when used in combination with ECT, produces similar response rate in short term, but addition of ECT leads to a faster response. The only study which evaluated the efficacy of ECT and chlorpromazine in treatment resistant schizophrenia (TRS) showed that augmentation with ECT in TRS may be a worthwhile option.[50]

T3-53
Table 3:
Comparative efficacy studies of first generation antipsychotics vs. electroconvulsive therapy/electroconvulsive therapy and first generation antipsychotic in schizophrenia

Efficacy of centbutindole [Table 4]

Centbutindole was developed by Central Drug Research Institute, Lucknow; it has been evaluated in four trials and has been compared with trifluperazine, haloperidol and risperidone (see Table 5 for this trial).[51525354] These studies have shown that centbutindole is as efficacious as haloperidol, trifluperazine and risperidone in the treatment of schizophrenia.

T4-53
Table 4:
Efficacy studies of centbutindole in schizophrenia

Efficacy studies of second generation antipsychotics in schizophrenia [Table 5]

Twenty studies have been published on evaluation of the efficacy/effectiveness of second generation antipsychotics in schizophrenia.[5473] Of these trials, 11 have reported the efficacy of risperidone, five of clozapine, two of olanzapine, two of aripiprazole and one of quetiapine. Some of these studies have also evaluated different doses of the same medications and some others have evaluated the dosing schedule. All these trials have included subjects diagnosed as schizophrenia on the basis of DSM-IV or ICD-10 except for Agashe et al.[58] who used DSM-IIIR criteria. All these trials have used standard instruments to assess the efficacy and side effects. The sample size has varied from 30 to 606 and the duration of these trials have been six weeks to four months except for one trial which evaluated the outcome on risperidone at one year[61] and two studies, which followed up subjects on clozapine for 20 months and three years respectively.[6669] All the studies on risperidone have shown that it is efficacious in short term. Studies which have compared risperidone with other antipsychotic have shown it to be more efficacious than quetiapine but as efficacious as haloperidol and centbutindole. Agarwal and Chadda[64] demonstrated that there was no difference in efficacy of once daily dose versus twice daily dose of risperidone. The study which followed up the subjects on risperidone for one year showed that compared to haloperidol, more subjects on risperidone had better social functioning, productivity and education and significantly fewer patients had suicidal ideation or attempts and needed rehospitalization.[61] Srivastava et al.[62] showed that half of the schizophrenia subjects in India require 3-4 mg/day of risperidone and another one-third improve with dose ranging from 1-2 mg/ day. All the studies which have evaluated clozapine have done so in TRS cases and have reported it to be useful in both short and long term. In the study by Avasthi et al.[65] olanzapine was found to be as efficacious as haloperidol on PANSS. Additionally olanzapine was found to be better than haloperidol in reducing associated depressive and anxiety symptoms. Sarin et al.[68] reported no difference in efficacy of 10 and 15 mg/day of aripiprazole.

T5-53
Table 5:
Efficacy studies of second generation antipsychotics in schizophrenia

Efficacy of antipsychotics in other disorders: mania [Table 6]

Some of the older studies included a few subjects with mania. Three studies in the early 60s included very few subjects in the open label design studies and reported efficacy of haloperidol, thioridazine and thioproperazine in the treatment of mania.[468] One study included only one case of treatment refractory mania and showed that oral fluphenazine was not useful in such subjects.[5] Another study evaluated the efficacy of zuclopenthixol in management of 25 cases of mania. This study did not specifically report the efficacy of zuclopenthixol in mania, but irrespective of the diagnosis the reported outcome suggests that zuclopenthixol for eight weeks was useful.[74]

T6-53
Table 6:
Efficacy studies of antipsychotics in mania

However, in the recent trials, atypical antipsychotics have been evaluated in large samples in double blind placebo control trials and the outcomes have been measured using standard instruments. In the study by Khanna et al.[75] risperidone was found to be significantly better than placebo at weeks 1 and 2 and 3 (total YMRS: P < 0.01). Another multicentric trial, which included subjects from India too, showed that both risperidone and haloperidol were better than placebo; however, there was no difference in the efficacy of risperidone and haloperidol.[76] At three weeks, more patients were treatment responders (>50% reduction in YMRS total scores) among those treated with risperidone (48%) or haloperidol (47%) than placebo (33%). The difference between risperidone and placebo was significant (P < 0.01). At 12 weeks, the response rate was maintained in almost all subjects who responded at three weeks and additionally more than 80% of the subjects who did not respond (reduction of >50% in the YMRS total score) to risperidone or haloperidol at three weeks but continued the medications responded at 12 weeks.

Acute psychosis [Table 7]

Four studies have reported the efficacy of antipsychotics in the management of acute psychosis, of which three have specified that the trials included subjects with acute and transient psychosis,[607477] while another trial mentioned the diagnostic category only as acute psychosis.[78] Trial by Agarwal and Sitholey[77] involved children and adolescents presenting with acute and transient psychosis and is discussed later. These studies suggest that thioproperazine is better than chlorpromazine and there is no difference in short term efficacy of risperidone and haloperidol in acute and transient psychosis. As mentioned earlier Fernandes et al.[74] did not specifically report the outcome in acute and transient psychosis, however, irrespective of the diagnosis the reported outcome suggests that zuclopenthixol for eight weeks was useful.

T7-53
Table 7:
Efficacy studies of antipsychotic in acute psychosis

Anxiety

Studies in 1970s and 1980s evaluated the efficacy of low dose haloperidol,[79] flupenthixol,[80] trifluperidol,[81] pimozide,[82] prochlorperazine,[83] trifluperazine[84] in various anxiety states and reported these to be efficacious. The study which used pimozide compared it with chlordiazepoxide and reported it to be useful, but inferior to chlordiazepoxide.[82] The study which compared trifluperazine and chlordiazepoxide combination with prochlorperazine reported the latter to be better.[83]

Agitation and violence

Two studies have evaluated the role of antipsychotic in violent and agitated subjects attending the psychiatry emergency settings. In a randomized controlled trial, Alexander et al.[84] compared the efficacy of injectable lorazepam and a combination of injectable haloperidol and promethazine and reported that after four hours of the injection, 96% of the subjects in both the groups were tranquil or asleep. However, in terms of being asleep, 76% of the subjects given haloperidol-promethazine were asleep compared to 45% of subjects in the lorazepam group. The haloperidol-promethazine combination also produced a faster onset of tranquillization/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints, subjects absconding, or adverse effects. In another randomized study from the same centre, Raveendran et al.[85] compared the efficacy of intramuscular olanzapine with intramuscular haloperidol plus promethazine in 300 subjects and reported that both treatments led to similar proportions of subjects being tranquilized or asleep at 15 minutes (olanzapine-87%, haloperidol plus promethazine-91%) and 240 minutes (olanzapine-96% and haloperidol plus promethazine-97%). However, compared to those given haloperidol plus promethazine, more subjects in the olanzapine group required additional drugs over four hours (21% vs. 43%). Adverse effects were uncommon with both treatments.

Delirium

Only a small case series of seven cases reported that risperidone is effective in the management of delirium and it is well tolerated by these subjects.[86]

Delusional disorders

Good response to antipsychotics like trifluperazine, haloperidol and chlorpromazine was reported in cases of delusional parasitosis.[87] In their study on delusional disorder, Grover et al.[88] found that best response was seen with risperidone, followed closely by pimozide. Of the 20 subjects treated with risperidone, six were considered to have good response (>75% reduction in symptoms) and nine were considered to have partial response (>25 but <75% reduction in symptoms). Of the 18 subjects treated with pimozide, four qualified for good response and six as partial responders.

Use of Antipsychotic in Children and Adolescents [Table 8]

Seven studies have evaluated the efficacy of various antipsychotics in childhood disorders or childhood/adolescent onset disorders. Studies done in 1960s and early 70s evaluated the role of antipsychotics primarily in the behavioral problems in children with epilepsy/epilepsy and mental retardation and have shown that trifluperazine, prothipendyl and trifluperidol are useful but fluphenazine is ineffective. One small study evaluated the usefulness of clozapine in childhood onset schizophrenia.[91] A study which evaluated the role of risperidone in autism showed promising results[92] and another study demonstrated the efficacy of olanzapine in childhood/adolescent onset acute and transient psychosis.[77] However, the studies which used olanzapine and risperidone showed that these drugs lead to reasonable weight gain, which may be cause of concern.

T8-53
Table 8:
Efficacy studies of antipsychotic in children and adolescents

RESEARCH ON OTHER TREATMENT RELATED ISSUES

Pharmacogenomics

With increasing interest in the role of genetic factors in treatment response and side effects of medications, studies from India have tried to address the genetic links of tardive dyskinesia, treatment response and severity of psychopathology.[9396] However, the findings are preliminary and inconclusive. Tiwari et al.[93] evaluated the role of six single nucleotide polymorphisms (SNP) in tardive dyskinesia and showed that CYP1A2 1545 C > T SNP was associated with TD (P = 0.03) and schizophrenia (P = 0.04), but the association was rendered insignificant after corrections for multiple comparisons. Vijayan et al.(2007)[94] studied various alleles, genotypes, haplotypes and their linkage disequilibrium and observed that H313HTT genotype was associated with schizophrenia and TaqIB1B1 genotype was significantly associated with higher psychopathology score. Subjects with H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. Distinct shift in the linkage disequilibrium pattern of responder and non responder group was observed. Thomas et al.[95] reported that average olanzapine dose, baseline weight and dopamine receptor D-4 (DRD4-120 bp) duplication marker have significant association with the efficacy index. Gupta et al.[96] reported significant allelic associations of two SNPs (rs4633 and rs4680) with drug response.

Predictors of Treatment Response

A study reported that subjects, who showed initial dysphoric response to a test dose of neuroleptic, later respond poorly to the neuroleptics.[97]

Prescription Patterns

A few studies have evaluated the antipsychotic prescription patterns from India. In one of the early studies, Khanna et al.[98] evaluated the psychotropics drug prescription pattern in chronic long stay patients at Ranchi and compared the prescription trends in 1984 and 1988. Most of the patients whose prescriptions were reviewed were suffering from schizophrenia. More than one antipsychotic medication was prescribed to 13% in 1984, which fell down to 7% in 1988. Further it was seen that very few patients received anticholinergic agents and the use of benzodiazepines increased over the years (4% in 1984 and 10% in 1988), which authors attributed to development of distressing tardive dyskinesias over the years. In an evaluation of prescriptions at discharge of patients with schizophrenia, Padmini Devi et al.[99] reported that risperidone was the most commonly prescribed antipsychotic (56.17%), followed by olanzapine (21.34%) and quetiapine (3.93%). Typical antipsychotics were used only in 15.73% of cases and polypharmacy (concurrent use of more than 1 antipsychotic) was seen in 9% of cases. In another study from Jammu, Shanwey et al.[100] evaluated the prescription of 270 outpatients, and reported that fixed dose formulation of trifluperazine, chlorpromazine and trihexyphenidyl (parkinforte) was used in 45.4% of cases followed by chlorpromazine[36.3%] and quetiapine [34.5%]. The authors also found that typical antipsychotics were used in 82.72% of cases and polypharmacy was seen in 72.72% of cases. Dutta et al.[101] evaluated the prescription patterns in 118 stable schizophrenia subjects and reported that on an average 2.8 medications were prescribed to each subject and olanzapine was the most commonly prescribed antipsychotic followed by haloperidol and risperidone. About half of the subjects were receiving more than one antipsychotic. All these findings suggest that antipsychotic prescriptions vary from centre to centre and possibly have changed over the years.

In a recently conducted survey, Grover and Avasthi[102] found that the three most commonly prescribed antipsychotics by Indian psychiatrists were risperidone, olanzapine and haloperidol. Typical antipsychotics comprise 25.15% of all prescriptions and in about 22.36% of cases the psychiatrists were using more than one antipsychotic in the same patient. Another survey specifically assessed the prescribing practices of clozapine; only 28% of psychiatrists reported that their prescription of clozapine was guided by their knowledge about the efficacy of clozapine. Majority of the psychiatrists opined that clozapine leads to symptom reduction to the extent of 40 to 70%, and the average dose required for stabilization was between 75 to 300 mg/day. Only 16% of psychiatrists preferred to combine clozapine with other antipsychotics. In terms of blood monitoring, 80% of the psychiatrists monitored the blood counts weekly in the first month of therapy and then once monthly for next 6 months and further monitoring was done as per the need.[103]

Treatment continuation, compliance and attitude towards treatment

Khanna et al.[104] reported that 31% of the subjects with schizophrenia do not keep their appointment for detail evaluation after initial evaluation in the walk-in clinic. The authors also reported that 32% of the subjects stop attending the clinic after initial detailed workup and diagnostic clarification. In another study from the same center, Kulhara et al.[105] reported that 25% of schizophrenia subjects do not come for follow-up after six months of detailed workup and diagnostic clarification and 23% of subjects with schizophrenia don’t seek any medical help in next five years. Murthy et al.[106] studied a mixed group of patients (which included subjects of psychosis also) and reported that duration of illness more than six months, residence at a distance of more than 50 kilometers from the hospital and psychiatric diagnosis other than functional psychosis favored treatment discontinuation. Ponnudurai et al.[107] evaluated the treatment adherence in 111 cases of psychotic illness (mostly schizophrenia) by Ferric Chloride reagent test to look for excretion of phenothiazine in urine and reported non-adherence in 19% of subjects. In another interesting study Srinivasan and Thara[108] reported that history of noncompliance with oral medication was seen in about 58% of patients during the course of their illness and half of these subjects were given oral medications at least once without their knowledge by the family members under the psychiatrist’s advice. It was seen that spurious administration of antipsychotic leads to reduction in symptoms in 91% of subjects given medications in this way and helps to convince the patient to take oral medications subsequently. Half of the caregivers who participated in the study felt that spurious administration of antipsychotic was the right action under the circumstances. In a recent study, Baby et al.[109] reported rates of non-compliance with medication to be 38.7% in subjects with schizophrenia. The authors also reported that a majority of the patients and family members had a positive attitude towards medication and treatment. Further, family members are able to identify the compliance status of the patients and the reasons for the noncompliance better than the patients. The factors which had significant influence on the medication compliance included perceived daily benefit from medication, positive relationship with the psychiatrist, pressure from the family and health system and positive family belief towards illness and treatment. The significant reasons for noncompliance are no perceived daily benefit from medications, difficulty in gaining access to treatment and medications, financial obstacles, embarrassment or stigma related to treatment and medications and medicines currently not perceived as necessary. Besides attitude, other factors which are significantly associated with noncompliance include lower educational status, rural area of stay, adjustment difficulty with family and spouse, previous history of non-compliance, poor insight into illness, higher positive PANSS score. Past history of hospitalization was associated with better compliance with medications.

Impact of antipsychotics on disability

A recently published study, which compared three groups of community dwelling subjects with schizophrenia, showed that mean disability scores remain virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated. The proportion of patients classified as ‘disabled’ declined significantly in the treated group, but remained the same in the untreated group.[110]

Costs

A few studies have evaluated the cost of antipsychotics per se and cost of management of schizophrenia. Girish et al.[111] found that antipsychotic drugs are affordable and comparable to drug treatment costs of other physical illnesses. They found the monthly cost of treatment with chlorpromazine was Rs.55, an equivalent dose of trifluperazine amounted to Rs.25/month, risperidone Rs.60 and clozapine Rs.225 per month. They also concluded that although antipsychotic drugs are affordable, the other costs associated with treatment make them more expensive, like co-prescribed antiparkinsonian agents, antidepressants, anxiolytics etc. Sarma[112] showed that cost of one outpatient visit was Rs.201 in which medications accounted for less than 10% of the total cost. Grover et al.[113] found that the total annual cost of care of schizophrenia amounted to Rs.13687.38, which was similar to cost of treatment of diabetes mellitus. Money spent by patients on buying drugs constituted about 18% of the total costs. A study from Chennai showed that despite the cost of blood tests, the total cost of treatment with clozapine came down by nearly 25% compared to the cost before clozapine was started.[114] In another study, Despande[115] reported that the cost of medication to the hospital which provided free medications to subjects with schizophrenia was Rs.288-less than the cost of medications for bipolar disorders.

Research on Tolerability and Side Effects of Antipsychotic [Table 9]

Besides the efficacy or usefulness studies, some studies have specifically evaluated the side effects and tolerability issues with antipsychotics.[116136] In one of the earliest studies, Sarada Menon and Ramachandran[116] reported side effects of subjects who participated in two of their drug trials and had received either trifluperazine or trifluperidol. Other studies have evaluated the rates of skin pigmentation with phenothiazines,[117] rise in prolactin levels with chlorpromazine and trifluperazine[119] and changes in serum electrolytes.[120] Studies have reported prevalence rate of akathesia (25-28%), tardive dyskinesia (5-25.5%) and dystonia (17%) in subjects receiving typical antipsychotic.[118121123] Studies have also evaluated the incidence of neuroleptic malignant syndrome[124134] and extrapyramidal side effects with risperidone.[125] Another study by Pandey et al.[136] compared the rate of neuroleptic - induced acute dystonia and reported that there was no difference in vulnerability to develop dystonias in subjects with mania or schizophrenia. With recent interest in weight gain and metabolic syndrome, some of the studies have shown that patients receiving atypical antipsychotics (Olanzapine or risperidone) gain more weight compared to haloperidol and treatment with antipsychotic leads to disturbance in metabolic syndrome parameters[131133] whereas others suggest contrary findings.[129130] Studies have also shown that use of typical antipsychotic leads to higher rates of sexual dysfunction[128] and among the atypical antipsychotic sexual desire is more frequently impaired in subjects on risperidone and erectile dysfunction is more prevalent in subjects on olanzapine.[135]

T9-53
Table 9:
Side effects of antipsychotics

CONCLUSION AND FUTURE DIRECTIONS

Reasonably good amount of data on the efficacy of antipsychotics in schizophrenia is available from India. In addition, studies also suggest usefulness of antipsychotics in mania, acute and transient psychosis, delusional disorders and agitation and violence. Older studies also suggest that typical antipsychotics have usefulness in anxiety states. Many of the recent studies followed double blind randomized controlled design and had a reasonable sample size. Further, many studies have been carried out at multiple sites throughout the country. To some extent, data is also available with regards to the tolerability of antipsychotics and it shows that extrapyramidal symptoms and NMS are more common with typical antipsychotics and weight gain is more common with antipsychotics like olanzapine and risperidone.

However, the major limitation of the research is that there are not many studies on the treatment of schizophrenia in elderly, in subjects with comorbid physical illnesses and in cases with comorbid substance abuse. Data on long term efficacy of antipsychotics is also meager. There is still a need to conduct long term comparative multicentric studies to evaluate the efficacy, effectiveness, tolerability and side effects of antipsychotics.

REFERENCES

1. Bagadia VN, Dave KP, Shah LP. A comparative study of physical treatments in schizophrenia Indian J Psychiatry. 1970;12:190–204
2. Doongaji DR, Bagadia VN, Vahia NS. Clinical experience with prothipendyl hydrochloride (dominal) -a new tranquiliser Indian J Psychiatry. 1961;3:228–34
3. Sarada Menon M. Prochlorperazine in the treatment of chronic withdrawn schizophrenia Indian J Psychiatry. 1961;3:157–9
4. Damania GB, Masani KR. Clinical evaluation of Melleril-a new tranquilizer Indian J Psychiatry. 1961;3:95–9
5. Kothari UC. Clinical experience with fluphenazine in psychotic patients Indian J Psychiatry. 1962;4:37–9
6. Bhaskaran K. Clinical trials with Thioproperazine (Majeptil) Indian J Psychiatry. 1964;6:123–30
7. Thomas G, Narayanan HS. Trifluoperazine (eskazine) in the treatment of chronic paranoid schizophrenics-(a comparative study with unichlor promazine) Indian J Psychiatry. 1965;6:175–80
8. Jetley SK. Haloperidol - a clinical trial Indian J Psychiatry. 1966;8:251–4
9. Dube K, Mathur RS. Clinical trial with melleril Indian J Psychiatry. 1966;8:277–90
10. Narayan HS, Natarajan CL, Saroja Bai BK. Stemetil in chronic schizophrenia Indian J Psychiatry. 1967;9:234–8
11. Teja JS. Thioproperazine: A trial in outpatient schizophrenics Indian J Psychiatry. 1967;9:61–72
12. Sarada Menon SM, Haneef Badsha M. Clinical trial of thiothixine (in hospitalized chronic schiziophrenia patient in Government Mental Hospital, Madras Indian J Psychiatry. 1968;10:57–63
13. Kishore B, Kumar R, Kaur A. Thiothixene in hospitalised chronic schizophrenic patients Indian J Psychiatry. 1970;12:225–37
14. Bagadia VN, Doshi S, Hebbar YV, Chawla R, Saraf KR, Shah LP, et al Flupenthixol in schizophrenia Indian J Psychiatry. 1972;14:24–30
15. Bagadia VN, Jeste DV, Chawla R, Shah LP, Saraf KR. Trifluoperidol in schizophrenia Indian J Psychiatry. 1972;14:31–7
16. Ramchandran V, Sarda Menon M. Trifluperidol-a controlled clinical trial on a group of schizophrenia patients Indian J Psychiatry. 1972;14:11–8
17. Vyas BK, Bapna G. Phase I clinical study of GO 3315 in acute schizophrenics Indian J Psychiatry. 1972;14:39–44
18. Kishore B, Jam KC, Bhatia AS. Trifluperidol: A butyprophenone in hospitalized chronic schizophrenia patients (a comparative study with thiothixine and prochlorperazine) Indian J Psychiatry. 1972;14:65–75
19. Kishore B, Dhillon AK. Clinical efficacy of pimozide in hospitalized chronic schizophrenics Indian J Psychiatry. 1973;15:311–8
20. Sarada Menon M, Ramachandran V, Kakaturriangan V. A controlled trial of pimozide (R 6238): A new neuroleptic Indian J Psychiatry. 1973;15:325–8
21. Bagadia VN, Chandiali HN, Pradhan PU, Shah LP. Pimozide (R 8238) in schizophrenia-a pilot study Indian J Psychiatry. 1973;15:319–24
22. DeSousa A, Nayani GR. A controlled trial of trifluperidol with trifluoperazine Indian J Psychiatry. 1973;15:290–3
23. Mahal AS, Janakiramiah N. A double-blind placebo controlled trial of pimozide (R6238) in 49 hospitalised chronic schizophrenics Indian J Psychiatry. 1975;17:45–55
24. Channabasavanna SM, Kaliaperumal VG, Embar P, Shariff IA. Clinical trial of trifluoperidol: Our experience Indian J Psychiatry. 1976;18:193–8
25. Sharma S, Dutta D. A double-blind study of pimozide in the treatment of schizophrenic patients Indian J Psychiatry. 1976;18:34–7
26. Bagadia VN, Bhat R, Ghandiali HH, Pradhan PU, Shah LP. A comparative double blind trial of pimozide and trifluperazine in maintenance treatment of schizophrenia Indian J Psychiatry. 1976;18:199–203
27. Dube S, Sethi BB. Efficacy of lithium in schizophrenia Indian J Psychiatry. 1981;23:193–9
28. Sethi BB, Bhirnan A. A clinical study of trifluperazine vs. trifluperazine-benzhexol combination Indian J Psychiatry. 1983;25:155–6
29. Channabasavanna SM, Michael A. Penfluridol maintenance therapy in schizophrenia: A controlled study Indian J Psychiatry. 1987;29:333–6
30. Iyer DS, Doongaji DR, Vahia NS. Preliminary clinical impressions with “Moditen”.A depot tranquilizer Indian J Psychiatry. 1968;10:78–80
31. Bagadia VN, Varaiya PG. Fluphenazine enanthate injections in schizo phrenia-a clinical trial in 50 cases Indian J Psychiatry. 1971;13:119–30
32. Bagadia VN, Shastri PS, Sule SM, Shah LP. Further experience with fluphenazine enathate injection Indian J Psychiatry. 1972;14:279–86
33. Jha BK, Bhaskaran K. Experience with fluphenazine enanthate in long stay hospitalized schizophrenia Indian J Psychiatry. 1972;14:263–78
34. Gehlot PS, Purohit DR, Garg AR, Mundhra RS. Experience with fluphenazine decanoate in chronic schizophrenia Indian J Psychiatry. 1977;19:74–8
35. Bagadia VN, Bhatt R, Pradhan PV, Shah LP. Piportil injection (19552RP)- a depot neuroleptic in schizophrenia Indian J Psychiatry. 1979;21:259–61
36. Bagadia VN, Abhaynbar RR, Gopalini JH, Jagadish R, Pradhan PV, Shah LP. Maintenance therapy of schizophrenia Indian J Psychiatry. 1979;21:106–8
37. Shukla GD. Fluphenazine decanoate in chronic schizophrenia Indian J Psychiatry. 1981;23:234–6
38. Varma VK, Kulhara P. Open drug trial with haloperidol decanoate injection in schizophrenia Indian J Psychiatry. 1989;31:144–50
39. Ray SD. Relative efficacy of electroconvulsive therapy and chlorpromazine in schizophrenia J Indian Med Assoc. 1962;38:332–3
40. Chatterjee AK, Bhusan V. Clinical trials with “Melleril” in psychiatric patients Indian J Psychiatry. 1963;5:140–6
41. Dutta Ray S, Kapur RL. Significance of some prognostic indices of schizophrenics treated with ECT or chlorpromazine Indian J Psychiatry. 1963;5:190–5
42. Janakiramaiah N, Subbakrishna DK. ECT-chlorpromazine combination compared with chlorpromazine only in schizophrenia Indian J Psychiatry. 1981;23:230–3
43. Janakiramaiah N, Channabasavanna SM, Narshima Murthy NS. ECT/chlorpromazine combination versus chlorpromazine alone in acutely ill schizophrenic patients Acta Psychiatr Scand. 1982;66:464–70
44. Natani GD, Gautam S, Gehlot PS. Comparison of three treatment regimes in schizophrenia Indian J Psychiatry. 1983;25:306–11
45. Gangadhar BN, Choudhary JR, Channabasavanna SM. ECT and drug induced parkinsonism Indian J Psychiatry. 1983;25:212–3
46. Bagadia VN, Abhyankar RR, Doshi J, Pradhan PV, Shah LP. A double blind controlled study of ECT vs. chlorpromazine in schizophrenia J Assoc Physicians India. 1983;31:637–40
47. Agarwal AK, Winny GC. Role of ECT-phenothiazine combination in schizophrenia Indian J Psychiatry. 1985;27:233–6
48. Abraham KR, Kulhara P. The efficacy o ECT in the treatment of schizophrenia. A comparative study Br J Psychiatry. 1987;151:152–5
49. Sarkar P, Andrade C, Kapur B, Das P, Sivaramakrishna Y, Harihar C, et al An exploratory evaluation of ECT in haloperidol-treated DSM IIIR schizophreniform disorder Convuls Ther. 1994;19:271–8
50. Goswami U, Kumar U, Singh B. Efficacy of electroconvulsive therapy in treatment resistant schizophrenia: A double-blind study Indian J Psychiatry. 2003;45:26–9
51. Doongaji DR, Sheth AS, Paul T, Parikh RM, Vahora SA, Apte JS, et al Clinical evaluation of centbutindole as an anti-psychotic agent Indian J Med Res. 1983;78:126–33
52. Doongaji DR, Satoskar RS, Sheth AS, Apte JS, Desai AB, Shah BR. Centbutindole vs. trifluoperazine: A double-blind controlled clinical study in acute schizophrenia J Postgrad Med. 1989;35:3–8
53. Singh H, Srivastava JS, Raghuvanshi C, Dalal PK, Asthana OP. A comparative efficacy study of centbutindole and haloperidol in schizophrenia Indian J Psychiatry. 1999;41:325–8
54. Chandra R, Singh H, Dalal PK, Asthana OP, Srivastava JS. Comparative efficacy of centbutindole and risperidone in schizophrenia Indian J Psychiatry. 2002;44:365–71
55. Agarwal AK, Sharma M, Srivastava S, Mullick M, Kumar A. An open clinical trial with clozapine in treatment resistant schizophrenics Indian J Psychiatry. 1997;39:70–5
56. Agarwal AK, Bsahyam VSP, Channabasvanna SM, Dhavale HS, Khan MA, Khanna S, et al Risperidone in Indian patients with schizophrenia Indian J Psychiatry. 1998;40:247–53
57. Bajaj P, Nihalani N, Shah N, Desai N, Shinde U, Raut N. Reemergence of positive symptoms of schizophrenia in course of treatment with risperidone Indian J Psychiatry. 1999;41:96–9
58. Agashe M, Dhawale DM, Cozma G, Mogre V. Risperidone in schizophrenia Indian J Psychiatry. 1999;41:54–9
59. Desai N, Jain V, Ghalsasi S, Delvi M, Kelkar S. An open study of clozapine in the treatment of resistant schizophrenia Indian J Psychiatry. 1999;41:336–40
60. Chaudhuri BP, Bhagabati D, Medhi D. Risperidone versus haloperidol in acute and transient psychotic disorder Indian J Psychiatry. 2000;42:280–90
61. Shrivastava A, Gopa S. Comparative study of risperidone and haloperidol on clinical and psychosocial parameters in treatment of schizophrenia: A randomised open trial Indian J Psychiatry. 2000;42:52–6
62. Srivastava AK, Gupta S, Srinivasan N. Risperidone: Dosing pattern and efficacy in clinical practice- a post-marketing survey Indian J Psychiatry. 2001;43:147–51
63. Suresh Kumar PN, Andrade C, Krishnakutty N, Muralidharan Nair S. An open clinical trial with risperidone in chronic schizophrenia Indian J Psychiatry. 2001;43:152–6
64. Agarwal V, Chadda RK. Once daily dose in treatment of schizophrenia Indian J Psychiatry. 2001;43:32–5
65. Avasthi A, Kulhara P, Kakkar N. Olanzapine in treatment of schizophrenia: An open label comparative clinical trial from India Indian J Psychiatry. 2001;43:257–63
66. Srivastava S, Agarwal AK, Sharma M. A three-year naturalistic follow-up of patients receiving clozapine: Report from India Int J Psychiatry Clin Pract. 2002;6:167–71
67. Chavda RK, Laxmi L, Nair BS, Gandewar K. Efficacy and Tolerability of Aripiprazole in Patients with Schizophrenia and Schizoaffective Disorders Indian J Psychiatry. 2004;46:150–5
68. Sarin A, Nagpal J, Bohra NK, Jiloha RC, Rao GP, Sharma SK, et al Open labeled, randomized, switch-over study of two fixed doses (10/15 mg) of aripiprazole: To evaluate its safety and efficacy in the treatment of Indian patients of schizophrenia Indian J Psychiatry. 2004;46:64–71
69. Raguraman J, Vijay Sagar KJ, Chandrasekaran R. Effectiveness of clozapine in treatment-resistant schizophrenia Indian J Psychiatry. 2005;47:102–5
70. Vijay Sagar KJ, Chandrashekar CR. A double-blind randomized trial between risperidone and haloperidol in drug-naive patients with paranoid schizophrenia Indian J Psychiatry. 2005;47:30–2
71. Potkin SG, Gharabawi GM, Greenspan AJ, Mahmoud R, Kosik-Gonzalez C, Rupnow MF, et al A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization Schizophr Res. 2006;85:254–65
72. Thomas P, Srivastava V, Singh A, Mathur P, Nimgaonkar VL, Lerer B, et al Correlates of response to olanzapine in a north indian schizophrenia sample Psychiatry Res. 2008;161:275–83
73. Dutt A, Grover S, Chakrabarti S, Kulhara P, Avasthi A, Basu D, et al Effectiveness of Clozapine: A study from North India Asian J Psychiatry. (in press)
74. Fernandes J, Pradhan PV, Choudhury P, Chatterji S, Pereira J, Shah H, et al An open trial of zuclopenthixol in management of acute psychoses: A multicentered study Indian J Psychiatry. 1999;41:242–8
75. Khanna S, Vieta E, Lyons B, Grossman F, Eerdekens M, Kramer M. Risperidone in the treatment of acute mania: Double-blind, placebo-controlled study Br J Psychiatry. 2005;187:229–34
76. Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F. Acute and continuation risperidone monotherapy in bipolar mania: A 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol Eur Neuropsychopharmacol. 2005;15:75–84
77. Agarwal V, Sitholey P. A preliminary open trial of olanzapine in pediatric acute and transient psychotic disorders Indian J Psychiatry. 2006;48:43–6
78. Mokashi JM, Chandorkar BL. Thioproperazine (Majeptil) in acute psychotic excitement Indian J Psychiatry. 1967;9:181–5
79. Jayaram SS, Ram PK. Methods of assesment in a trial of haloperidol in anxiety neurosis Indian J Psychiatry. 1971;13:131–5
80. Bagadia VN, Kotwani PN, Dave KP, Saraf KR, Shah LP. Fluphenthixol in certain psychiatric illness (a clinical trial) Indian J Psychiatry. 1972;14:19–23
81. Bagadia VN, Dave KP, Shah LP. Further experience with trifluperidol- A study of 206 patients Indian J Psychiatry. 1972;14:45–54
82. Ramachandran V, Sarada Menon M. A clinical trial of pimozide (R6238) in anxiety state Indian J Psychiatry. 1977;19:79–82
83. Nigam P, Rastogi CK, Kapoor KK, Gupta AK. Prochlorperazine in anxiety Indian J Psychiatry. 1985;27:227–32
84. Alexander J, Tharyan P, Adams CE, John T, Mol C, Philip J. Rapid tranquilisation of violent or agitated patients in a psychiatric emergency setting: A pragmatic randomised trial of intramuscular lorazepam versus haloperidol plus promethazine Br J Psychiatry. 2004;185:63–9
85. Raveendran NS, Tharyan P, Alexander J. TREC-India II Collaborative Group. Rapid tranquillization in psychiatric emergency settings in India: Pragmatic randomized controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine BMJ. 2007;335:865
86. Gupta N, Sharma P, Mattoo SK. Effectiveness of Risperidone in Delirium Can J Psychiatry. 2005;50:75
87. Srinivasan TN, Suresh TR, Jayaram V, Fernandez MP. Nature and treatment of delusional parasitosis: A different experience in India Int J Dermatol. 1994;33:851–5
88. Grover S, Biswas P, Avasthi A. Delusional disorder: Study from north India Psychiatry Clin Neurosci. 2007;61:462–70
89. Bassa OM. Some preliminary observation on the use of trifluperazine (Eskazine) on children Indian J Psychiatry. 1961;3:243–50
90. Somasundaram O. Fluphenazine-a controlled trial in the management of chronic epileptics Indian J Psychiatry. 1967;9:213–25
91. Malhotra S, Gupta N, Singh G. Clozapine in childhood-onset schizophrenia: A report of five cases Clinical Child Psychology and Psychiatry. 2000;5:403–10
92. Nagaraj R, Singhi P, Malhi P. Risperidone in children with autism: Randomized, placebo-controlled, double-blind study J Child Neurol. 2006;21:450–5
93. Tiwari AK, Deshpande SN, Rao AR, Bhatia T, Mukit SR, Shriharsh V, et al Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism Pharmaco genomics J. 2005;5:60–9
94. Vijayan NN, Bhaskaran S, Koshy LV, Natarajan C, Srinivas L, Nair CM, et al Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population Behav Brain Funct. 2007;3:34–45
95. Thomas P, Srivastava V, Singh A, Mathur P, Nimgaonkar VL, Lerer B, et al Correlates of response to olanzapine in a north indian schizophrenia sample Psychiatry Res. 2008;161:275–83
96. Gupta M, Bhatnagar P, Grover S, Kaur H, Baghel R, Bhasin Y, et al Association studies of catechol-O-methyltransferase (COMT) gene with schizophrenia and response to antipsychotic treatment Pharmaco genomics. 2009;10:385–97
97. Borde M, Davis EJB, Sharma LN. Prediction of outcome in schizophrenia using the subjective response to a test dose of a neuroleptic Indian J Psychiatry. 1991;33:58–61
98. Khanna R, Bhandari SN, Das A. Survey of psychotropic drug prescribing patterns for long stay patients Indian J Psychiatry. 1990;32:162–5
99. Padmini Devi D, Amarjeeth R, Sushma M, Guido S. Prescription patterns of psychotropic drugs in hospitalized schizophrenic patients in a tertiary care hospital Calicut Med J. 2007;5:43
100. Shanwey V, Chopra V, Kapoor B, Thappa JR, Tandon VR. Prescription trends in schizophrenia and manic depressive psychosis J K Science. 2005;7:156–8
101. Dutta SB, Dhasmana DC, Bhardwaj R. Psychotropic drug utilization pattern among patients with schizophrenia Indian J Psychiatry. 2005;47:243–4
102. Grover S, Avasthi A. Antipsychotic prescription pattern: A preliminary survey of psychiatrists in india Indian J Psychiatry. (in press)
103. Shrivastava A, Shah N. Prescribing practices of clozapine in India: Results of a opinion survey of psychiatrists Indian J Psychiatry. 2009;51:225–6
104. Khanna BC. Treatment acceptance from walk-in clinic Pilot study. (unpublished data)
105. Kulhara PN. Long term follow-up study of schizophrenia MD thesis. 1974 PGIMER, Chandigarh
106. Murthy SR, Ghosh A, Wig NN. Treatment Acceptance Patterns In A Psychiatric Out-Patient Clinic: Study Of Demographic And Clinical Variables Indian J Psychiatry. 1974;16:323–9
107. Ponnudurai R, Vijayasekaran V, Kameswaran L, Somasundaram O, Rajendran AJ. Therapeutic compliance of patients on phenothiazines Indian J Psychiatry. 1983;25:239–42
108. Srinivasan TN, Thara R. At issue: Management of medication noncompliance in schizophrenia by families in india Schizophr Bull. 2002;28:531–5
109. Baby RS, Gupta S, Sagar R. Attitudes and subjective reasons of medication compliance and noncompliance among outpatients with schizophrenia in India Internet J Epidemiol. 2009;7
110. Thirthalli J, Venkatesh BK, Kishorekumar KV, Arunachala U, Venkatasubramanian G, Subbakrishna DK, et al Prospective comparison of course of disability in antipsychotic-treated and untreated schizophrenia patients Acta Psychiatr Scand. 2009;119:209–17
111. Girish K, Pratima M, Issac MK. Drug treatment in schizophrenia: Issues of comparability and costs Indian J Psychiatry. 1991;41:100–3
112. Sarma PG. General hospital psychiatry: Cost of one visit Indian J Psychiatry. 2000;42:258–61
113. Grover S, Avasthi A, Chakrabarti S, Bhansali A, Kulhara P. Cost of care of schizophrenia: A study of Indian out-patient attenders Acta Psychiatr Scand. 2005;112:54–63
114. Thara R. Cost of illness of schizophrenia-perspective from an NGO Indian J Psychiatry. 2005;47:205–17
115. Desphande SN. Perspective from a general hospital psychiatric unit Indian J Psychiatry. 2005;47:210–2
116. Sarada Menon M, Rarnachandra V. Trifluperidol therapeutic response and extra pyramidal symptoms Indian J Psychiatry. 1972;14:289–92
117. Ananth JV, Ban TA, Lehmann HE, Rizvi FA. A survey of phenothiazine induced skin pigmentation Indian J Psychiatry. 1972;14:76–80
118. Pandurangi AK, Ananth 1, Channabavasanna SM. Dyskinesia in an Indian mental hospital Indian J Psychiatry. 1978;20:339–42
119. Kuruvilla K, Kuruvulla A, Kanagasbapthy AS. Serum prolactin levels in schizophrenia: Effects of neuroleptics medication: A preliminary study Indian J Psychiatry. 1986;28:237–47
120. Bhatia MS, Balkrishna, Dhar NK, Khurana SK, Bohra N. Schizophrenia electrolyte profile and the effect of treatment Indian J Psychiatry. 1987;29:275–7
121. Ray D, Samajdar J, Khanna R. Drug induced akathisia: Preliminary report Indian J Psychiatry. 1992;34:159–61
122. Datta S, Subhalakshmi TP, Jeyaseelan L, Kuruvilla K. Risk factors for tardive dyskinesia Indian J Psychiatry. 1994;36:22–4
123. Suresh Kumar PN, Manoj Kumar T. A comparative study of neuroleptic induced neurological side effects in schizophrenia and mood disorder Indian J Psychiatry. 1997;39:110–4
124. Chopra MP, Prakash SS, Raguram R. The neuroleptic malignant syndrome: An indian experience Comprehensive Psychiatry. 1999;40:19–23
125. Basu D, Mattoo SK, Khurana H, Malhotra S, Kulhara P. Risperidone- truly non-cataleptogenic? Hong Kong J Psychiatry. 2000;10:2–5
126. Chopra MP, Raguram R. Recovery and rechallenge after the neuroleptic malignant syndrome Indian J Psychiatry. 2001;43:41–5
127. Gupta V, Magon R, Mishra BP, Sidhu GB, Mahajan R. Risk factors in neuroleptic malignant syndrome Indian J Psychiatry. 2003;45:30–5
128. Nagaraj AKM, Haque Nizamie S, Akhtar S, Sinha BNP, Goyal S. A comparative study of sexual dysfunction due to typical and atypical antipsychotics in remitted bipolar-I disorder Indian J Psychiatry. 2004;46:261–7
129. Guha P, Roy K, Sanyal D, Dasgupta T, Bhattacharya K. Olanzapine-induced obesity and diabetes in Indian patients: A prospective trial comparing olanzapine with typical antipsychotics J Indian Med Assoc. 2005;103:660–4
130. Jain S, Bhargava M, Gautam S. Weight gain with olanzapine: Drug, gender or age? Indian J Psychiatry. 2006;48:39–42
131. Sahoo S, Manjunatha N, Ameen S, Akhtar S. Effect of olanzapine, risperidone, and haloperidol treatment on weight and body mass index in first-episode schizophrenia patients in India: A randomized, double-blind, controlled, prospective study J Clin Psychiatry. 2007;68:1793–8
132. Sahoo S, Ameen S, Akhtar S. Incidence of new onset metabolic syndrome with atypical antipsychotics in first episode schizophrenia: A six-week prospective study in Indian female patients Schizophr Res. 2007;95:247
133. Sahoo S, Ameen S, Akhtar S. Predictors of antipsychotic-induced weight gain in first-episode psychosis conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol J Clin Psychopharmacol. 2008;28:27–31
134. Sarkar P, Natarajan C, Gode N. Prevalence of neuroleptic malignant syndrome in 672 consecutive male in-patients Indian J Psychiatry. 2009;51:208–11
135. Nagaraj AKM, Pai NB, Rao S. A comparative study of sexual dysfunction involving risperidone, quetiapine, and olanzapine Indian J Psychiatry. 2009;51:265–71
136. Pandey RS, Sreenivas KN, Subbakrishna DK. Neuroleptic - induced acute dystonia in schizophrenia and mania Indian J Psychiatry. 1992;34:331–3

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Conflict of Interest: None declared.

Keywords:

Antipsychotic; research; India

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