RESIDENT: Factors influencing potential early discontinuation of antipsychotic medication in first-episode, cannabis- induced psychosis (UofC)
Presenting Author(s): Trenna NorrisCo-Author(s): David Crockford
Date and time: 22 Mar 2025 from 15:50 to 16:05
Location: Hawthorn C
Abstract
Introduction:
Identifying predictors of relapse and remission following first-episode psychosis (FEP) is a key factor in distinguishing patients who may safely discontinue antipsychotics from those who require maintenance treatment. There is currently no data regarding the optimal duration of antipsychotic use for individuals with cannabis-associated FEP who discontinue cannabis use. This is clinically relevant as antipsychotic medications have well-known side effects, and some are irreversible.
Methods:
The online databases MEDLINE, PSYCinfo, and PubMed were searched. Search criteria included antipsychotic treatment and discontinuation, first-episode psychosis, cannabis-induced psychosis, schizophrenia treatment guidelines, remission and relapse predictors, and conversion to primary psychotic disorders/schizophrenia.
Results:
Current guidance on the duration of antipsychotic treatment in FEP generally does not factor in whether cannabis use contributed to the FEP or whether the person has stopped using. Current evidence demonstrates that those who stop using cannabis following FEP have higher rates of remission, greater functional recovery, lower relapse rates, and less negative symptoms compared to those who continue using or have never used cannabis.
Conclusion:
While there is abundant evidence demonstrating the negative prognostic impact of ongoing cannabis use in psychotic disorders, current data shows that those who discontinue cannabis use following FEP have a more favorable prognosis than those who continue or have never used cannabis. It is hypothesized that individuals who discontinue cannabis use following FEP with a full resolution of psychotic symptoms, in the absence of other risk factors, are a group that could be cautiously tapered off antipsychotics earlier than current guidelines recommend.
Learning Objectives
1.Identify common predictors of relapse and remission in the general first-episode psychosis population;
2.Recognize the difference in first-episode psychosis outcomes between cannabis non-users, continued-users, and discontinued-users; and
3.Understand the current limitations regarding the duration of antipsychotic treatment for cannabis-induced, first-episode psychosis.
Literature References
1. Suvisaari J, Mantere O, Keinanen J, Mantyla T, Rikandi E, Lindgren M, Raij TT. Is it possible to predict the future in first-episode psychosis? Front Psychiatry. 2018;9:580. doi:10.3389/fpsyt.2018.00580.
2. Murray RM, Quattrone D, Natesan S, et al. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? Br J Psychiatry. 2016;209(5):361-365. doi:10.1192/bjp.bp.116.182683.
3. Thompson A, Winsper C, Marwaha S, et al. Maintenance antipsychotic treatment versus discontinuation strategies following remission from first episode psychosis: systematic review. BJPsych Open. 2018;4(4):215-225. doi:10.1192/bjo.2018.17.
4. Hegarty JD, Baldessarini RJ, Tohen M, Waternaux C, Oepen G. One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. 1994;151(10):1409-1416. doi:10.1176/ajp.151.10.1409.
5. Revier CJ, Reininghaus U, Dutta R, et al. Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study. JAMA Psychiatry. 2015;72(8):703-711. doi:10.1001/jamapsychiatry.2015.0346.
6. Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial. JAMA Psychiatry. 2013;70(9):913-920. doi:10.1001/jamapsychiatry.2013.19.
7. Conus P, Cotton SM, Francey SM, et al. Predictors of favourable outcome in young people with a first episode psychosis without antipsychotic medication. Schizophr Res. 2017;185:130-136. doi:10.1016/j.schres.2016.12.029.
8. Bowtell M, Ratheesh A, McGorry P, Killackey E, O'Donoghue B. Clinical and demographic predictors of continuing remission or relapse following discontinuation of antipsychotic medication after a first episode of psychosis: a systematic review. Schizophr Res. 2018;197:9-18. doi:10.1016/j.schres.2017.10.030.
9. Landolt K, Aeschlimann A, Kappenstein J, et al. Predictors of discontinuation of antipsychotic medication and subsequent outcomes in the European First Episode Schizophrenia Trial (EUFEST). Schizophr Res. 2016;174(1-3):217-223. doi:10.1016/j.schres.2016.03.036.
10. Alvarez-Jimenez M, Gleeson JF, Henry LP, et al. Prediction of a single psychotic episode: A 7.5-year prospective study in first-episode psychosis. Psychol Med. 2011;41(2):251-262. doi:10.1017/S0033291710001052.
11. Bowtell M, Eaton S, Thien K, Bardell-Williams M, Downey L, Ratheesh A, et al. Rates and predictors of relapse following discontinuation of antipsychotic medication after a first episode of psychosis. Schizophr Res. 2018;195:231-236. doi:10.1016/j.schres.2017.10.030.
12. Wilson M, Harris M, Pereira M, Buckle J, Forshall E, Murphy T, et al. Predictors of hospitalisation and recovery following full antipsychotic discontinuation in first episode psychosis: a naturalistic retrospective cohort study. Schizophr Res. 2023;261:269-274. doi:10.1016/j.schres.2023.10.004.
13. Andreasen NC, Carpenter WT, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441-449. doi:10.1176/appi.ajp.162.3.441.
14. Di Capite S, Upthegrove R, Barnes TR, et al. The relapse rate and predictors of relapse in patients with first-episode psychosis following discontinuation of antipsychotic medications. Schizophr Res. 2018;202:271-278. doi:10.1016/j.schres.2018.06.011.
15. Marshall M, Barrowclough C, Drake R, et al. The HELPER programme: Healthy Living and Prevention of Early Relapse - three exploratory randomised controlled trials of phase-specific interventions in first-episode psychosis. Health Technol Assess. 2015;19(37):1-120. doi:10.3310/hta19370.
16. Schoeler T, Petros N, Di Forti M, et al. Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first-episode psychosis: a prospective analysis. Lancet Psychiatry. 2017;4(8):627-633. doi:10.1016/S2215-0366(17)30233-X.
17. Lally J, Ajnakina O, Stubbs B, et al. Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies. Br J Psychiatry. 2017;211(6):350-358. doi:10.1192/bjp.bp.117.201475.
18. Nuevo R, Chatterji S, Verdes E, et al. The continuum of psychotic symptoms in the general population: a cross-national study. Schizophr Bull. 2012;38(3):475-485. doi:10.1093/schbul/sbq099.
19. Turkington A, Mulholland CC, Rushe TM, et al. Impact of persistent substance misuse on 1-year outcome in first-episode psychosis. Br J Psychiatry. 2009;195(3):242-248. doi:10.1192/bjp.bp.108.056739.
20. Gonzalez-Pinto A, Vega P, Ibanez B, et al. Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use. Schizophr Bull. 2009;35(3):631-639. doi:10.1093/schbul/sbn135.
21. Levi L, Bar-Haim M, Winter-van Rossum I, et al. Cannabis use and symptomatic relapse in first episode schizophrenia: trigger or consequence? Data from the OPTIMISE study. Schizophr Bull. 2023;49(4):903-913. doi:10.1093/schbul/sbad018.
22. Miller BJ. A review of second-generation antipsychotic discontinuation in first-episode psychosis. J Psychiatr Pract. 2008;14(5):289-300. doi:10.1097/01.pra.0000336757.02446.c0.
23. Clausen L, Hjorthoj CR, Thorup A, et al. Change in cannabis use, clinical symptoms and social functioning among patients with first-episode psychosis: a 5-year follow-up study of patients in the OPUS trial. Psychol Med. 2014;44(1):117-126. doi:10.1017/S0033291713000503.
24. Starzer MSK, Nordentoft M, Hjorthøj C. Rates and predictors of conversion to schizophrenia or bipolar disorder following substance-induced psychosis. Psychol Med. 2018;48(10):1630-1639. doi:10.1017/S0033291717003188.
25. Kendler KS, Ohlsson H, Sundquist J, Sundquist K. Prediction of onset of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. Am J Psychiatry. 2019;176(9):711-719. doi:10.1176/appi.ajp.2019.18101217.
26. Niemi-Pynttäri JA, Sund R, Putkonen H, et al. Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases. J Clin Psychiatry. 2013;74(1):e94-e99. doi:10.4088/JCP.12m07746.
27. Alderson HL, Semple DM, Blayney C, et al. Risk of transition to schizophrenia following first admission with substance-induced psychotic disorder: a population-based longitudinal cohort study. Psychol Med. 2017;47(14):2548-2555. doi:10.1017/S0033291717001087.
28. Weibell MA, Hegelstad WTV, Auestad B, et al. The effect of substance use on 10-year outcome in first-episode psychosis. Schizophr Bull. 2017;43(4):843-851. doi:10.1093/schbul/sbw179.
29. Schoeler T, Monk A, Sami MB, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(3):215-225. doi:10.1016/S2215-0366(15)00363-6.
30. Baeza I, Graell M, Moreno D, et al. Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study). Schizophr Res. 2009;113(2-3):129-137. doi:10.1016/j.schres.2009.06.008.
31. Schoeler T, Monk A, Sami MB, Klamerus E, Foglia E, Brown R, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(3):215-25. doi: 10.1016/S2215-0366(15)00363-6. Epub 2016 Jan 15. PMID: 26777297.
32. Hui C, Chen E, et al. Guidelines for discontinuation of antipsychotics in patients who recover from first-episode schizophrenia spectrum disorders: derived from the aggregated opinions of Asian Network of Early Psychosis Experts and literature review. Int J Neuropsychopharmacol. 2022;25(9):737-58. doi: 10.1093/ijnp/pyac002
33. Crockford D, Addington D. Canadian schizophrenia guidelines: schizophrenia and other psychotic disorders with coexisting substance use disorders. Can J Psychiatry. 2017;62(9):624-34. doi: 10.1177/0706743717720196.
34. Baldacara L, Ramos A, Castaldelli-Maia JM. Managing drug-induced psychosis. Int Rev Psychiatry. 2023;35(5-6):496-502. doi: 10.1080/09540261.2023.2261544.
35. Alvarez-Jimenez M, O'Donoghue B, Thompson A, Gleeson JF, Bendall S, Gonzalez-Blanch C, et al. Beyond clinical remission in first episode psychosis: thoughts on antipsychotic maintenance vs. guided discontinuation in the functional recovery era. CNS Drugs. 2016;30(5):357-68.
36. Hjorthøj C, Stürup AE, McGrath JJ, Nordentoft M. Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry. 2017;4(4):295-301.
37. Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, et al. Estimating the consequences of antipsychotic induced weight gain on health and mortality rate. Psychiatry Res. 2001;101(3):277-88. doi: 10.1016/S0165-1781(01)00234-7.
38. Artaloytia JF, Arango C, Lahti A, et al. Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers. Am J Psychiatry. 2006;163(3):488-93.
39. Awad G, Voruganti L. Neuroleptic dysphoria, comorbid drug abuse in schizophrenia and the emerging science of subjective tolerability—towards a new synthesis. J Clin Psychopharmacol. 2005;25(2):83-93. doi: 10.1300/J374v01n02_06.
40. McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007;164:1050-60.
41. Kahn RS, Fleischhacker WW, Boter H, et al. EUFEST study group. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008;371:1085-97.
42. Mullin K, Gupta P, Compton MT, et al. Does giving up substance use work for patients with psychosis? A systematic meta-analysis. Aust N Z J Psychiatry. 2012;46:826-39.
43. Myles H, Myles N, Large N. Cannabis use in first episode psychosis: meta-analysis of prevalence, and the time course of initiation and continued use. Aust N Z J Psychiatry. 2016;50(3):208-19. doi: 10.1177/0004867415599846.
44. Hinton L, et al. Reductions in cannabis and other illicit substance use between treatment entry and early recovery in patients with first-episode psychosis. Early Interv Psychiatry. 2007;1(3):259-66. doi: 10.1111/j.1751-7893.2007.00035.x.
45. Colizzi M, Burnett N, Costa R, De Agostini M, Griffin J, Bhattacharyya S. Longitudinal assessment of the effect of cannabis use on hospital readmission rates in early psychosis: a 6-year follow-up in an inpatient cohort. Psychiatry Res. 2018;268:381-7.
46. Ouellet-Plamondon C, Abdel-Baki A, Salvat E, Potvin S. Specific impact of stimulant, alcohol and cannabis use disorders on first-episode psychosis: 2-year functional and symptomatic outcomes. Psychol Med. 2017;47(14):2461-71.
47. Foti DJ, Kotov R, Guey LT, Bromet EJ. Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalization. Am J Psychiatry. 2010;167(8):987-93.
48. Petrilli K, Ofori S, Hines L, Taylor G, Adams S, Freeman TP. Association of cannabis potency with mental ill health and addiction: a systematic review. Lancet Psychiatry. 2022;9(9):736-50.
49. Crocker CE, Carter AJE, Emsley JG, Magee K, Atkinson P, Tibbo PG. When cannabis use goes wrong: mental health side effects of cannabis use that present to emergency services. Front Psychiatry. 2021;12:640222. doi: 10.3389/fpsyt.2021.640222.
50. Abdel-Baki A, Ouellet-Plamondon C, Salvat E, Grar K, Potvin S. Symptomatic and functional outcomes of substance use disorder persistence 2 years after admission to a first-episode psychosis program. Psychiatry Res. 2017;247:113-9. doi: 10.1016/j.psychres.2016.11.007.
51. Hui C, Honer W, Lee E, Chang W, Chan S, Chen E, et al. Predicting first-episode psychosis patients who will never relapse over 10 years. Psychol Med. 2019;49(13):2206-14. doi: 10.1017/S0033291718003070