Current inpatient prescription practices for the treatment of schizophrenia in public hospitals of Minas Gerais, Brazil

Fernando M. Volpe André S. Santos Laíse S. Rodrigues Raíza R. Rocha Patrícia G. de Magalhães Cristina M. Ruas About the authors

Schizophrenia is a chronic disorder with high potential to incapacitate patients for social life and participation in the workforce. The continuous use of antipsychotics has enabled a reduction in length of hospital stay and in number of relapses, allowing patients to remain in the community for longer. As a consequence, economic costs and burden are reduced. The choice of antipsychotic agent potentially affects clinical outcomes.11. Rodrigues LSM. Hospitalization of schizophrenic patients in the public health system of Minas Gerais, Brazil: socio-demographic variables and costs of inpatient care [dissertation]. Belo Horizonte: Universidade Federal de Minas Gerais; 2016.

In the context of the public health system of the state of Minas Gerais, Brazil, hospital treatment of schizophrenia is currently directed to the management of relapses, usually consisting of short-term hospitalizations followed by referral to outpatient care.22. Coelho VAA, Volpe FM, Diniz SSL, Silva EM, Cunha CF. Alteração do perfil de atendimento dos hospitais psiquiátricos públicos de Belo Horizonte, Brasil, no contexto da reforma da assistência à saúde mental. Cienc Saude Coletiva. 2014;19:3605-16. Since research on current pharmacotherapy of schizophrenia in Brazil is scarce, our study aims to describe prescription patterns for schizophrenia in the setting of public hospital care.

The study sample comprised 1,928 patients admitted for schizophrenia to three public psychiatric hospitals in Minas Gerais (Instituto Raul Soares, Hospital Galba Velloso, and Centro Hospitalar Psiquiátrico de Barbacena) between 2010-2014. In these hospitals, both typical and atypical antipsychotic agents were routinely available for inpatients. However, the prescription of atypicals required additional paperwork and their continuation after discharge was possible, but not advocated.33. Brasil, Ministério da Saúde (MS). Protocolo clínico e diretrizes terapêuticas: esquizofrenia [Internet]. Portaria SAS/MS n° 364. Diário Oficial da União, 9 abril 2013. [cited 2017 Mar 10]. bvsms.saude.gov.br/bvs/saudelegis/sas/2013/prt0364_09_04_2013.html
bvsms.saude.gov.br/bvs/saudelegis/sas/20...
To analyze psychopharmaceutical prescribing practices in this sample, we conducted a detailed analysis of patients’ prescriptions on the day before their discharge from hospital.

Typical antipsychotics (haloperidol, chlorpromazine, thioridazine, levomepromazine, trifluoperazine) were the most frequently prescribed drugs; among the atypicals, risperidone was preferred. Similar results were found by Machado et al.44. Machado FB, Mella EAC, Poças CA. Determinação dos antipsicóticos prescritos no Hospital Municipal de Maringá. Semina Cienc Biol Saude. 2009;30:77-82. in their study, conducted in the emergency department of a Brazilian public general hospital in the state of Paraná. (We were unable to find other reports of a similar nature in the literature.) Atypical antipsychotics are considered first-line choices by some,55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.,66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. but not all,77. Canadian Psychiatric Association. Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry. 2005;50:7S-57S. clinical guidelines, and there is a sustained debate on their economic advantages in developing countries.88. Gaebel W, Weinmann S, Sartorius N, Rutz W, McIntyre JS. Schizophrenia practice guidelines: international survey and comparison. Br J Psychiatry. 2005;187:248-55. Although clozapine has proven useful in reducing readmission risks in schizophrenia,99. Werneck AP, Hallak JC, Nakano E, Elkis H. Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine. Psychiatry Res. 2011;188:315-9. it was used in only 4.2% of admissions in our sample, a prevalence lower than that reported internationally (8-25%).1010. Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jørgensen HA. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry. 2009;9:24.,1111. Siskind DJ, Harris M, Phillipou A, Morgan VA, Waterreus A, Galletly C, et al. Clozapine users in Australia: their characteristics and experiences of care based on data from the 2010 National Survey of High Impact Psychosis. Epidemiol Psychiatr Sci. 2016 Jul 18:1-13. [Epub ahead of print]

The only available long-acting antipsychotic was haloperidol decanoate. It was used in 6.7% of cases, mostly (71.6%) in its oral formulation. Long-acting injectable antipsychotic agents provide an important tool for management of nonadherence, and can reduce relapse and rehospitalization rates. However, dose adjustment to optimal levels may not be as flexible as with oral antipsychotics, and prolonged side effects may occur, persisting even after discontinuation.66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. In international samples, long-acting injectable antipsychotics are used in one-quarter to one-third of patients with schizophrenia.1212. Barnes TR, Shingleton-Smith A, Paton C. Antipsychotic long-acting injections: prescribing practice in the UK. Br J Psychiatry Suppl. 2009;52:S37-42.

The mean daily doses of antipsychotics prescribed in our sample were within internationally recommended dose ranges.33. Brasil, Ministério da Saúde (MS). Protocolo clínico e diretrizes terapêuticas: esquizofrenia [Internet]. Portaria SAS/MS n° 364. Diário Oficial da União, 9 abril 2013. [cited 2017 Mar 10]. bvsms.saude.gov.br/bvs/saudelegis/sas/2013/prt0364_09_04_2013.html
bvsms.saude.gov.br/bvs/saudelegis/sas/20...
,1313. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Arlington: American Psychiatric Publishing; 2009.,1414. National Institute for Health and Care Excellence (NICE). Psychosis and schizophrenia in adults: prevention and management [Internet]. Clinical guideline [CG178]. 2014 Mar [cited 2017 Mar 10]. nice.org.uk/guidance/cg178
nice.org.uk/guidance/cg178...
The only exceptions were chlorpromazine and levomepromazine, which were used largely (87.8% and 92.6% of the time, respectively) used at doses < 300 mg/day, a practice not supported by pharmacotherapeutic guidelines,55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.,66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. but common in other countries as well.1010. Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jørgensen HA. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry. 2009;9:24.

Combining antipsychotics was a common practice (46.5% of all admissions), although much of this was due to the combined use of low-dose chlorpromazine and levomepromazine as sedative agents (34.0% of all admissions). Thus, the actual intention to combine two effective antipsychotic agents was present in only 12.5% of admissions. Disadvantages of polytherapy include increased adverse-effect rates, risks, and costs.55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.,1313. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Arlington: American Psychiatric Publishing; 2009.,1414. National Institute for Health and Care Excellence (NICE). Psychosis and schizophrenia in adults: prevention and management [Internet]. Clinical guideline [CG178]. 2014 Mar [cited 2017 Mar 10]. nice.org.uk/guidance/cg178
nice.org.uk/guidance/cg178...
However, the absence of robust evidence in favor of antipsychotic combinations does not mean that patients would not respond to this strategy, which might justify the observed practice in selected patients, particularly in treatment-resistant cases.66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. Worldwide reports estimate the rate of combination antipsychotic therapy at 12-48%.1010. Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jørgensen HA. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry. 2009;9:24.,1515. Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res. 2012;138:18-28.

The most frequently prescribed adjuvant drugs were benzodiazepines (diazepam, clonazepam, lorazepam, nitrazepam, and midazolam), followed by anticholinergics (biperiden and promethazine), anticonvulsants (carbamazepine and valproate), and antidepressants (fluoxetine and tricyclics) (Table 1). Current treatment guidelines provide for the use of these advujants.55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.,66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. Benzodiazepines can be useful in managing anxiety, agitation, and psychosis. However, there is no good evidence to support their use in the longer term.55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.,66. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72. Anticholinergic agents are used to reduce extrapyramidal adverse events, especially in combination with typical antipsychotics, although these agents may increase cognitive problems.55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.

6. Galletly C, Castle D, Dark F, Humberstone V, Jablensky A, Killackey E, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50:410-72.
-77. Canadian Psychiatric Association. Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry. 2005;50:7S-57S. Antidepressants, in turn, can be used with antipsychotics to manage major depressive episodes and negative symptoms.55. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318-78.

Table 1
Pharmacotherapy for schizophrenia admissions in three public psychiatric hospitals, Minas Gerais, Brazil, 2010-2014 (n=1,928)

One particularity of Brazilian prescription patterns is the frequent use of promethazine, a phenothiazine that combines sedative and anticholinergic properties; in this sample, it was prescribed in 11.5% of all admissions. In most cases (67.9%), promethazine was combined with haloperidol. As expected, the use of anticholinergics (biperiden or promethazine) was much more frequent in combination with typical antipsychotics (87.0% of all anticholinergic prescriptions) than with atypicals (13.0%).

In conclusion, prescription practices in the treatment of schizophrenia in the public Brazilian hospitals assessed in this study were mostly aligned with national and international pharmacotherapeutic guidelines, except for the frequent and combined use of low-dose, sedating antipsychotics. Furthermore, clozapine and long-acting antipsychotics were used less frequently than reported in international studies.

Acknowledgements

RRR and PGM are recipients of scholarships from Programa Bolsa a Iniciação Científica e Tecnológica Institucional – Fundação de Amparo à Pesquisa do Estado de Minas Gerais (PIBIC-FAPEMIG).

References

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  • 2
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    Brasil, Ministério da Saúde (MS). Protocolo clínico e diretrizes terapêuticas: esquizofrenia [Internet]. Portaria SAS/MS n° 364. Diário Oficial da União, 9 abril 2013. [cited 2017 Mar 10]. bvsms.saude.gov.br/bvs/saudelegis/sas/2013/prt0364_09_04_2013.html
    » bvsms.saude.gov.br/bvs/saudelegis/sas/2013/prt0364_09_04_2013.html
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  • 6
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    Gaebel W, Weinmann S, Sartorius N, Rutz W, McIntyre JS. Schizophrenia practice guidelines: international survey and comparison. Br J Psychiatry. 2005;187:248-55.
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    Werneck AP, Hallak JC, Nakano E, Elkis H. Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine. Psychiatry Res. 2011;188:315-9.
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    Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jørgensen HA. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry. 2009;9:24.
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    Siskind DJ, Harris M, Phillipou A, Morgan VA, Waterreus A, Galletly C, et al. Clozapine users in Australia: their characteristics and experiences of care based on data from the 2010 National Survey of High Impact Psychosis. Epidemiol Psychiatr Sci. 2016 Jul 18:1-13. [Epub ahead of print]
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    Barnes TR, Shingleton-Smith A, Paton C. Antipsychotic long-acting injections: prescribing practice in the UK. Br J Psychiatry Suppl. 2009;52:S37-42.
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    American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Arlington: American Psychiatric Publishing; 2009.
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    National Institute for Health and Care Excellence (NICE). Psychosis and schizophrenia in adults: prevention and management [Internet]. Clinical guideline [CG178]. 2014 Mar [cited 2017 Mar 10]. nice.org.uk/guidance/cg178
    » nice.org.uk/guidance/cg178
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    Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res. 2012;138:18-28.

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