Journal List > J Korean Neuropsychiatr Assoc > v.57(3) > 1100363

Kim, Piao, Shen, and Chung: Pharmacotherapeutic Strategies to Prevent Relapse in Schizophrenia


Successful treatment is very high in patients with first episode schizophrenia (FES). On the other hand, the problem is a frequent relapse often caused by non-compliance. The non-compliance rate in patients with FES is 40–60% within 1 year. The causes of non-compliance are diverse, such as poor insight, drug side effects, attitude of caregiver, social stigma, etc. Clinicians should be able to provide appropriate psychosocial intervention and long acting injectable antipsychotics (LAI) to overcome non-compliance. Recently, there is solid and accumulating evidence demonstrating superiority of LAI over oral medication in terms of reducing relapse or rehospitalization. In particular, a substantial portion (approximately 30–50%) of patients and caregivers prefer LAI to oral medication. Shared decision-making is the process that clinicians and patients/caregiver should go through in order to obtain the full benefits from LAI.


Conflicts of Interest The authors have no financial conflicts of interest.


1. Kirkbride JB, Errazuriz A, Croudace TJ, Morgan C, Jackson D, Mc-Crone P, et al. Systematic review of the incidence and prevalence of schizophrenia and other psychoses in England, 1950-2009. London: Department of Health Policy Research Programme;2011.
2. Hong JP, Lee DW, Hahm BJ, Lee SH, Seong SJ, Youn T, et al. 2016 The survey of mental disorders in Korea. Ministry of Health & Welfare;2016.
3. Lieberman JA, Tollefson G, Tohen M, Green AI, Gur RE, Kahn R, et al. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry. 2003; 160:1396–1404.
4. Merlo MC, Hofer H, Gekle W, Berger G, Ventura J, Panhuber I, et al. Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning. J Clin Psychiatry. 2002; 63:885–891.
5. Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, et al. Predictors of relapse following responses from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999; 56:241–247.
6. The Scottish Schizophrenia Research Group. The Scottish first episode schizophrenia study. VIII. Five-year follow-up: clinical and psychosocial findings. Br J Psychiatry. 1992; 161:496–500.
7. Robinson DG, Woerner MG, Alvir JM, Geisler S, Koreen A, Sheitman B, et al. Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 1999; 156:544–549.
8. Altamura AC, Bobo WV, Meltzer HY. Factors affecting outcome in schizophrenia and their relevance for psychopharmacological treatment. Int Clin Psychopharmacol. 2007; 22:249–267.
9. Lieberman JA, Alvir JM, Koreen A, Geisler S, Chakos M, Sheitman B, et al. Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology. 1996; 14:3 Suppl. 13S–21S.
10. Cahn W, Hulshoff Pol HE, Lems EB, van Haren NE, Schnack HG, van der Linden JA, et al. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 2002; 59:1002–1010.
11. Ho BC, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry. 2003; 60:585–594.
12. Sun D, Stuart GW, Jenkinson M, Wood SJ, McGorry PD, Velakoulis D, et al. Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Mol Psychiatry. 2009; 14:976–986.
13. Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology. 2005; 30:1649–1661.
14. Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry. 2011; 68:128–137.
15. Konopaske GT, Dorph-Petersen KA, Pierri JN, Wu Q, Sampson AR, Lewis DA. Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology. 2007; 32:1216–1223.
16. Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry. 2005; 62:361–370.
17. Perkins DO. Adherence to antipsychotic medications. J Clin Psychiatry. 1999; 60:Suppl 21. 25–30.
18. Verdoux H, Lengronne J, Liraud F, Gonzales B, Assens F, Abalan F, et al. Medication adherence in psychosis: predictors and impact on outcome. A 2-year follow-up of first-admitted subjects. Acta Psychiatr Scand. 2000; 102:203–210.
19. Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002; 106:286–290.
20. Mojtabai R, Lavelle J, Gibson PJ, Sohler NL, Craig TJ, Carlson GA, et al. Gaps in use of anttpsychotics after discharge by first-admission patients with schizophrenia, 1989 to 1996. Psychiatr Serv. 2002; 53:337–339.
21. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011; 168:603–609.
22. Rabinovitch M, Cassidy C, Schmitz N, Joober R, Malla A. The influence of perceived social support on medication adherence in first-episode psychosis. Can J Psychiatry. 2013; 58:59–65.
23. Spaniel F, Vohlídka P, Kozený J, Novák T, Hrdlicka J, Motlová L, et al. The information technology aided relapse prevention programme in schizophrenia: an extension of a mirror-design follow-up. Int J Clin Pract. 2008; 62:1943–1946.
24. Komatsu H, Sekine Y, Okamura N, Kanahara N, Okita K, Matsubara S, et al. Effectiveness of information technology aided relapse prevention programme in schizophrenia excluding the effect of user adherence: a randomized controlled trial. Schizophr Res. 2013; 150:240–244.
25. Robinson DG, Woerner MG, Alvir JMJ, Bilder RM, Hinrichsen GA, Lieberman JA. Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder. Schizophr Res. 2002; 57:209–219.
26. Lepage M, Bodnar M, Joober R, Malla A. Is there an association between neurocognitive performance and medication adherence in first episode psychosis? Early Interv Psychiatry. 2010; 4:189–195.
27. Baloush-Kleinman V, Levine SZ, Roe D, Shnitt D, Weizman A, Poyurovsky M. Adherence to antipsychotic drug treatment in early-episode schizophrenia: a six-month naturalistic follow-up study. Schizophr Res. 2011; 130:176–181.
28. Quach PL, Mors O, Christensen TØ, Krarup G, Jørgensen P, Bertelsen M, et al. Predictors of poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder. Early Interv Psychiatry. 2009; 3:66–74.
29. Ko NY, Yeh ML, Hsu ST, Chung HH, Yen CF. Investigation of insight formation using narrative analyses of people with schizophrenia in remission. J Nerv Ment Dis. 2006; 194:124–127.
30. Lester H, Marshall M, Jones P, Fowler D, Amos T, Khan N, et al. Views of young people in early intervention services for first-episode psychosis in England. Psychiatr Serv. 2011; 62:882–887.
31. Staring AB, Van der Gaag M, Van den Berge M, Duivenvoorden HJ, Mulder CL. Stigma moderates the associations of insight with depressed mood, low self-esteem, and low quality of life in patients with schizophrenia spectrum disorders. Schizophr Res. 2009; 115:363–369.
32. Chatterjee A, Chakos M, Koreen A, Geisler S, Sheitman B, Woerner M, et al. Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never medicated schizophrenic patients. Am J Psychiatry. 1995; 152:1724–1729.
33. Curtis J, Watkins A, Rosenbaum S, Teasdale S, Kalucy M, Samaras K, et al. Evaluating an individualized lifestyle and life skills intervention to prevent antipsychotic-induced weight gain in first-episode psychosis. Early Interv Psychiatry. 2016; 10:267–276.
34. Verma S, Liew A, Subramaniam M, Poon LY. Effect of treatment on weight gain and metabolic abnormalities in patients with first-episode psychosis. Aust N Z J Psychiatry. 2009; 43:812–817.
35. Kampman O, Laippala P, Väänänen J, Koivisto E, Kiviniemi P, Kilkku N, et al. Indicators of medication compliance in first-episode psychosis. Psychiatry Res. 2002; 110:39–48.
36. Robinson DG, Woerner MG, Alvir JM, Bilder RM, Hinrichsen GA, Lieberman JA. Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder. Schizophr Res. 2002; 57:209–219.
37. Abhijnhan A, Adams CE, David A, Ozbilen M. Depot fluspirilene for schizophrenia. Cochrane Database Syst Rev. 2007; 24:CD001718.
38. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophreni--a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res. 2011; 127:83–92.
39. Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtälä J, Hoti F, Jedenius E, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with Schizophrenia. JAMA Psychiatry. 2017; 74:686–693.
40. Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, et al. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011; 132:35–41.
41. Nasrallah HA. Triple advantages of injectable long acting second generation antipsychotics: relapse prevention, neuroprotection, and lower mortality. Schizophr Res. 2018; 197:69–70.
42. Kirschner M, Theodoridou A, Fusar-Poli P, Kaiser S, Jäger M. Patients' and clinicians' attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis. Ther Adv Psychopharmacol. 2013; 3:89–99.
43. Přikryl R, Přikrylová Kučerová H, Vrzalová M, Cešková E. Role of long-acting injectable second-generation antipsychotics in the treatment of first-episode schizophrenia: a clinical perspective. Schizophr Res Treatment. 2012; 2012:764769.
44. Taylor M, Ng KY. Should long-acting (depot) antipsychotics be used in early schizophrenia? A systematic review. Aust N Z J Psychiatry. 2012; 47:624–630.
45. Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia. JAMA Psychiatry. 2015; 72:822–829.
46. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161:2 Suppl. 1–56.
47. Canadian Psychiatric Association. Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry. 2005; 50:13 Suppl 1. 7S–57S.
48. National Collaborating Centre for Mental Health (UK). Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care. Leicester: British Psychological Society;2009.
49. Moore TA, Buchanan RW, Buckley PF, Chiles JA, Conley RR, Crismon ML, et al. The Texas medication algorithm project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007; 68:1751–1762.
50. Kane JM, Garcia-Ribera C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry Suppl. 2009; 52:S63–S67.
51. Castle DJ, Galletly CA, Dark F, Humberstone V, Morgan VA, Killackey E, et al. The 2016 Royal Australian and New Zealand College of Psychiatrists guidelines for the management of schizophrenia and related disorders. Med J Aust. 2017; 206:501–505.
52. Kang G, Kang SH, Yoon HJ, Lee JI. Attitudes of patients with schizophrenia and their caretakers toward treatment with long-acting injectable antipsychotic medication. J Korean Assoc Soc Psychiatry. 2010; 15:67–73.
53. Barnes TR, Shingleton-Smith A, Paton C. Antipsychotic long-acting injections: prescribing practice in the UK. Br J Psychiatry Suppl. 2009; 52:S37–S42.
54. Jaeger M, Rossler W. Attitudes towards long-acting depot antipsychotics: a survey of patients, relatives and psychiatrists. Psychiatry Res. 2010; 175:58–62.
55. Lee Y, Lee NY, Youn T, Choi YS, Kim YS, Chung IW. The preference survey for long-acting injectable antipsychotics of community-dwelling patients with schizophrenia and their caregivers. Korean J Schizophr Res. 2013; 16:14–24.
56. Yeo SU, Park JI, Jang JM, Kang NI, Cui Y, Kim MG, et al. Acceptance rate of long-acting injection after short information: a survey in patients with first- and multiple-episode psychoses and their caregivers. Early Interv Psychiatry. 2017; 11:509–516.
57. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. 2012; 27:1361–1367.
58. Dolder CR, Lacro JP, Dunn LB, Jeste DV. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am J Psychiatry. 2002; 159:103–108.
59. Gilmer TP, Dolder CR, Lacro JP, Folsom DP, Lindamer L, Garcia P, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004; 161:692–699.
Similar articles