Management of bipolar disorder in South Africa: National Department of Health essential medicine selection and treatment algorithms
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Abstract
Background. Bipolar disorder (BD) is a severe mental illness associated with multimorbidity, psychosocial disability and significant public health issues. However, guideline heterogeneity clouds therapeutic decisions, particularly in relapse prevention. Polypharmacy and poor health outcomes are common. For low- and middle-income countries, deciding which medicines to procure and how to treat BD in an integrated manner remains elusive. Although South Africa (SA) is committed to universal health coverage, the estimated treatment gap for mental disorders in the public health sector is 91%. An Essential Medicines List (EML) enables equitable access to medicines, while Standard Treatment Guidelines (STGs) facilitate rational prescribing and quality care.
Objectives. To describe the medicine selection process for the treatment of BD in the SA public health sector, and the treatment algorithms developed to guide integrated care.
Methods. Evidence-based medicine principles, stakeholder consultation and consensus decision-making were used. The existing (2015) BD guideline and stakeholder comments were reviewed by a ministerially appointed expert review committee, following which a research question with eligibility criteria was formed, and rapid systematic evidence synthesis conducted. PubMed and Cochrane databases were searched for systematic reviews of randomised controlled trials and observational studies of acute and maintenance treatment in BD, with an additional PubMed search for primary research. Quality of the systematic reviews was appraised using the 11-item assessment of multiple systematic reviews. After costing to ensure affordability, final recommendations were made to the National EML Committee (NEMLC) using the strength of recommendation taxonomy classification. Following approval by the NEMLC, proposed medicines were incorporated into the 2019 National Department of Health Adult Hospital STGs. As the STGs are updated every 3 years, stakeholder input was sought in 2021 and 2023, with no changes to the medicine selection.
Results. Seven systematic reviews and one observational study were included in the evidence synthesis. Six medicines were selected as essential for maintenance treatment: lithium, valproate, lamotrigine, olanzapine, quetiapine and clozapine. While risperidone and benzodiazepines were retained for acute mania, carbamazepine and fluoxetine were removed from acute depression. Treatment algorithms for predominantly manic and depressive courses of illness were constructed to encourage person-centred care, aiming for euthymia, individual functioning and relapse prevention.
Conclusion. Evidence-based medicine principles enabled the NEMLC to select a range of essential medicines for the management of BD in a middle-income country. Local monitoring and evaluation are needed to inform future editions of the STGs and EML.
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References
South Africa. About South Africa: Health. https://www.gov.za/about-sa/health (accessed 11 November 2023).
Essential Medicine Guidance. https://info.emguidance.com/ (accessed 11 November 2023).
National Department of Health, South Africa. Standard Treatment Guidelines and Essential Medicines List. Pretoria: NDoH, 2023. https://knowledgehub.health.gov.za/content/
standard-treatment-guidelines-and-essential-medicines-list (accessed 11 November 2023).
Barbui C, Dua T, Kolappa K, Saraceno B, Saxena S. Mapping actions to improve access to medicines for mental disorders in low and middle income countries. Epidemiol Psychiatr
Sci 2017;26(5):481-490. https://doi.org/10.1017/S2045796016001165
Perumal-Pillay VA, Suleman F. Selection of essential medicines for South Africa – an analysis of in-depth interviews with national essential medicines list committee members.
BMC Health Serv Res 2017;17(1):17. https://doi.org/10.1186/s12913-016-1946-9
Wilkinson M, Gray AL, Wiseman R, et al. Health technology assessment in support of national health insurance in South Africa. Int J Technol Assess Health Care 2022;38(1):e44.
https://doi.org/10.1017/s0266462322000265
American Psychiatric Association DSM-5 Task Force. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. Washington, D.C.: APA, 2013.
Fountoulakis KN. Neurocognitive impairment and evidence-based treatment options in bipolar disorder. Ann Gen Psychiatry 2020;19:54. https://doi.org/10.1186/s12991-020-00304-4.
Hibar DP, Westlye LT, Doan NT, et al. Cortical abnormalities in bipolar disorder: An MRI analysis of 6 503 individuals from the ENIGMA Bipolar Disorder Working Group. Mol
Psychiatry 2018;23(4):932-942. https://doi.org/10.1038/mp.2017.73
Institute for Health Metrics and Evaluation. Global Burden of Disease Results Tool. Seattle: University of Washington. 2019. http://ghdx.healthdata.org/gbd-results-tool (accessed 11
November 2023).
World Health Organization. Meeting report on excess mortality in persons with severe
mental disorders. Geneva: WHO 2015. https://www.who.int/publications/i/item/978-92-
-155038-3 (accessed 31 August 2018).
Rusner M, Berg M, Begley C. Bipolar disorder in pregnancy and childbirth: A systematic
review of outcomes. BMC Pregnancy Childbirth 2016;16(1):331. https://doi.org/10.1186/
s12884-016-1127-1
Anke TMS, Slinning K, Moe V, Brunborg C, Siqveland TS, Skjelstad DV. Bipolar offspring and mothers: Interactional challenges at infant age 3 and 12 months – a developmental pathway to enhanced risk? Int J Bipolar Disord 2020;8(1):27. https://doi.org/10.1186/ s40345-020-00192-3
Shalev A, Merranko J, Goldstein T, et al. A longitudinal study of family functioning in offspring of parents diagnosed with bipolar disorder. J Am Acad Child Adolesc Psychiatr 2019;58(10):961-970. https://doi.org/10.1016/j.jaac.2018.10.011
Ranning A, Munk Laursen T, Thorup A, Hjorthoj C, Nordentoft M. Serious mental illness and disrupted caregiving for children: A nationwide, register-based cohort study. J Clin Psychiatr 2015;76(8):e1006-e1014. https://doi.org/10.4088/JCP.13m08931
Jallow A, Ljunggren G, Wandell P, Wahlstrom L, Carlsson AC. HIV-infection and psychiatric illnesses – a double edged sword that threatens the vision of a contained epidemic: The Greater Stockholm HIV Cohort Study. J Infect 2017;74(1):22-28. https://doi.org/10.1016/j. jinf.2016.09.009
De Sousa Gurgel W, da Silva Carneiro AH, Barreto Reboucas D, et al. Prevalence of bipolar disorder in a HIV-infected outpatient population. AIDS Care 2013;25(12):1499-1503. https://doi.org/10.1080/09540121.2013.779625
Chen SF, Wang LY, Chiang JH, Shen YC. Bipolar disorder is associated with an increased risk of sexually transmitted infections: A nationwide population-based cohort study. Sex Transm Dis 2018;45(11):735-740. https://doi.org/10.1097/OLQ.0000000000000863
Belayneh Z, Alemu W, Mekuriaw B, Abebe Z. Bipolar spectrum disorders and associated factors among adults attending an antiretroviral therapy clinic in Gedeo zone health centers, southern Ethiopia. Neuropsychiatric disease and treatment. 2019;15:503-509. https://doi.org/10.2147/NDT.S187669.
Moore DJ, Posada C, Parikh M, et al. HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence. AIDS Behav 2012;16(8):2257-2266. https://doi.org/10.1007/s10461-011-0072-2
Posada C, Moore DJ, Deutsch R, et al. Sustained attention deficits among HIV-positive individuals with comorbid bipolar disorder. J Neuropsychiatr Clin Neurosci 2012;24(1):61-70. https://doi.org/10.1176/appi.neuropsych.11010028
Meade CS, Sikkema KJ. HIV risk behavior among adults with severe mental illness: A systematic review. Clin Psychol Rev 2005;25(4):433-457. https://doi.org/10.1016/j.cpr.2005.02.001
Castilho JL, Rebeiro PF, Shepherd BE, et al. Mood disorders and increased risk of noncommunicable disease in Adults with HIV. J Acquir Immune Defic Syndr 2020;83(4):397- 404. https://doi.org/10.1097/QAI.0000000000002269
McIntyre RS, Berk M, Brietzke E, Goldstein BI, Lopez-Jaramillo C, Kessing LV, et al. Bipolar disorders. Lancet. 2020;396(10265):1841-56.10.1016/S0140-6736(20)31544-0.
Levin JB, Krivenko A, Bukach A, Tatsuoka C, Cassidy KA, Sajatovic M. A reexamination of nonpsychiatric medication adherence in individuals with bipolar disorder and medical comorbidities. J Nervous Mental Dis 2017;205(3):182-187. https://doi.org/10.1097/ NMD.0000000000000544
Hunt GE, Malhi GS, Cleary M, Lai HM, Sitharthan T. Comorbidity of bipolar and substance use disorders in national surveys of general populations, 1990 - 2015: Systematic review and meta-analysis. J Affect Dis 2016;206:321-330. https://doi.org/10.1016/j.jad.2016.06.051
Hunt GE, Malhi GS, Cleary M, Lai HM, Sitharthan T. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990 - 2015: Systematic review and meta- analysis. J Affect Dis 2016;206:331-349. https://doi.org/10.1016/j.jad.2016.07.011
Evins AE, Cather C, Laffer A. Treatment of tobacco use disorders in smokers with serious mental illness: Toward clinical best practices. Harvard Rev Psychiatr 2015;23(2):90-98. https://doi.org/10.1097/HRP.0000000000000063
Amare AT, Schubert KO, Klingler-Hoffmann M, Cohen-Woods S, Baune BT. The genetic overlap between mood disorders and cardiometabolic diseases: A systematic review of genome wide and candidate gene studies. Transl Psychiat 2017;7(1):e1007. https://doi. org/10.1038/tp.2016.261
Sayuri Yamagata A, Brietzke E, Rosenblat JD, Kakar R, McIntyre RS. Medical comorbidity in bipolar disorder: The link with metabolic-inflammatory systems. J Affect Dis 2017;211:99- 106. https://doi.org/10.1016/j.jad.2016.12.059
United Nations Department of Economic and Social Affairs – Disability. Convention on the Rights of Persons with Disabilities (CRPD). Geneva: UN, 2023. https://www.un.org/ development/desa/disabilities/convention-on-the-rights-of-persons-with-disabilities. html (accessed 11 November 2023).
Butler M, Urosevic S, Desai P, et al. Treatment for Bipolar Disorder in Adults: A Systematic Review. Comparative Effectiveness Review No. 208. Rockville, MD: Agency for Healthcare Research and Quality, 2018. https://doi.org/10.23970/AHRQEPCCER208
Fornaro M, De Berardis D, Koshy AS, et al. Prevalence and clinical features associated with bipolar disorder polypharmacy: A systematic review. Neuropsychiatr Dis Treatment 2016;12:719-735. https://doi.org/10.2147/NDT.S100846
Holzhapfel EM, Szabo CP. Pharmacotherapy prescribing patterns in the treatment of bipolar disorder in a South African outpatient population. Glob Psychiatr 2018;1(2):39-51. https://doi.org/10.2478/gp-2018-0006
Robertson LJ, Miot JK, Janse van Rensburg B. A retrospective record review and assessment of cost of quetiapine use in a community psychiatric setting in the Sedibeng district of Gauteng. S Afr J Psychiatr 2017;23(0):1057. https://doi.org/10.4102/sajpsychiatry. v23i0.1057
World Health Organization. Mental health and substance use. Mental Health Gap Action Programme (mhGAP). Geneva: WHO, 2023. https://www.who.int/teams/mental-health- and-substance-use/treatment-care/mental-health-gap-action-programme (accessed 11 November 2023).
Colin F. Bipolar disorder. The South African Society of Psychiatrists (SASOP) Treatment Guidelines for Psychiatric Disorders. S Afr J Psychiatr 2013;19(S3):164-171. https://doi. org/10.4102/sajpsychiatry.v19i3.942
Docrat S, Besada D, Cleary S, Daviaud E, Lund C. Mental health system costs, resources and constraints in South Africa: A national survey. Health Pol Planning 2019;34(9):706-719. https://doi.org/10.1093/heapol/czz085
Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry. 11th ed. Hoboken, NJ: Wiley-Blackwell, 2012.
Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: A measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007;7:10. https://doi.org/10.1186/1471-2288-7-10
Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature. J Am Board Fam Practice 2004;17(1):59-67. https://doi.org/10.3122/jabfm.17.1.59
MiuraT,NomaH,FurukawaTA,etal.Comparativeefficacyandtolerabilityofpharmacological treatments in the maintenance treatment of bipolar disorder: A systematic review and network meta-analysis. Lancet Psychiatr 2014;1(5):351-359. https://doi.org/10.1016/S2215- 0366(14)70314-1
Selle V, Schalkwijk S, Vazquez GH, Baldessarini RJ. Treatments for acute bipolar depression: Meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics. Pharmacopsychiatry 2014;47(2):43-52. https://doi.org/10.1055/s-0033-1363258
McGirr A, Vohringer PA, Ghaemi SN, Lam RW, Yatham LN. Safety and efficacy of adjunctive second-generation antidepressant therapy with a mood stabiliser or an atypical antipsychotic in acute bipolar depression: A systematic review and meta- analysis of randomised placebo-controlled trials. Lancet Psychiatr 2016;3(12):1138-1146. https://doi.org/10.1016/S2215-0366(16)30264-4
Lindstrom L, Lindstrom E, Nilsson M, Hoistad M. Maintenance therapy with second generation antipsychotics for bipolar disorder – a systematic review and meta-analysis. J Affect Dis 2017;213:138-150. https://doi.org/10.1016/j.jad.2017.02.012
Li XB, Tang YL, Wang CY, de Leon J. Clozapine for treatment-resistant bipolar disorder: A systematic review. Bipolar Dis 2015;17(3):235-247. https://doi.org/10.1111/bdi.12272
Kessing LV, Bauer M, Nolen WA, Severus E, Goodwin GM, Geddes J. Effectiveness of maintenance therapy of lithium vs other mood stabilisers in monotherapy and in combinations: A systematic review of evidence from observational studies. Bipolar Dis 2018;20(5):419-431. https://doi.org/10.1111/bdi.12623
Joas E, Karanti A, Song J, Goodwin GM, Lichtenstein P, Landen M. Pharmacological treatment and risk of psychiatric hospital admission in bipolar disorder. Br J Psychiatr 2017;210(3):197-202. https://doi.org/10.1192/bjp.bp.116.187989
Smith KA, Cipriani A. Lithium and suicide in mood disorders: Updated meta-review of the scientific literature. Bipolar Dis 2017;19(7):575-586. https:doi.org/10.1111/bdi.12543
National Department of Health, South Africa. Medicines and Related Substances Act, No. 101 of 1965. Consolidated schedules 25 May 2021 https://www.sahpra.org.za/wp- content/uploads/2021/06/Consolidated-schedules_25-May-2021.docx.pdf (accessed 11 November 2023).
National Department of Health, South Africa. Adult Primary Care (APC) Clinical Tool (2023). Pretoria: NDoH, 2023. https://knowledgehub.health.gov.za/elibrary/adult-primary-care- apc-clinical-tool-2023 (accessed 11 November 2023).
National Department of Health. 2030 Human Resources for Health Strategy: Investing in the health workforce for Universal Health Coverage. Pretoria: NDoH, 2020. https://www. health.gov.za/wp-content/uploads/2023/06/2030-HRH-Strategy-Final.pdf (accessed 11 November 2023).
National Department of Health, South Africa. Referral Policy for South African Health Services and Referral Implementation Guidelines. Pretoria: NDoH, 2020. https://www. knowledgehub.org.za/elibrary/referral-policy-south-african-health-services-and-referral- implementation-guidelines (accessed 11November 2023).
South Africa. Mental Health Care Act No. 17 of 2002. https://www.gov.za/sites/default/ files/gcis_document/201409/a17-02.pdf (accessed 11 November 2023).
National Department of Health, South Africa. National Mental Health Policy Framework and Strategic Plan 2023 – 2030: https://www.health.gov.za/wp-content/ uploads/2023/08/National-Mental-Health-Policy-framework-and-strategic-Plan-for- Web-15%EF%80%A208%EF%80%A223-2.pdf (accessed 11 November 2023).
National Department of Health, South Africa. Current Master Health Product List -1 November 2023. Pretoria: NDoH, 2023. https://www.health.gov.za/tenders/ (accessed 11 November 2023).