Skip to main content Accessibility help

Physical health trajectories of young people commenced on clozapine

  • B. O’Donoghue (a1) (a2) (a3), A. Mujanovic (a4), S. Young (a5), T. Bridson (a6), L. Mora (a3), M. Bismark (a7), J. Cocks (a3), D. Siskind (a8) (a9) and P. McGorry (a1) (a2)...



Clozapine is the most effective antipsychotic medication, but it has the highest propensity for metabolic side effects. A clozapine clinic was established within an early intervention for psychosis service to facilitate the timely commencement of clozapine and to manage the associated adverse effects. This study describes the changes in the weight, body mass index (BMI), waist circumference and blood pressure after 6 months in young people commenced on clozapine.


This was a prospective cohort study of all young people, aged 15–24 years, commenced on clozapine within an early intervention service in Melbourne, Australia, between 01.04.2016 and 30.06.2018. Continuous data were analyzed with paired t-test and categorical with Wilcoxon signed-rank test.


Twenty-six young people received 6 months of treatment with clozapine, of whom the mean age was 19.8 years (s.d. ±3.1) and 66.7% were male. After 6 months, the mean weight gain was 5.1 kg (s.d. ±10.1 kg) and over half (53.8%) gained clinically significant weight. The proportion of young people classified as either overweight or obese rose from 69.2% to 88.5% (p = 0.006). The proportion of young people with a waist circumference above the recommended parameters increased from 57.9% to 78.9% (p = 0.008). Hypertension was present in 30%, and after 6 months, 45% had hypertension (p = 0.64). Metformin was prescribed to 34.6%, typically to those with the greatest and most rapid weight gain.


Among young people with treatment resistant psychosis, clozapine is associated with significant metabolic side effects in the early stages of commencement. More interventions aimed at attenuating this weight gain are needed.


Corresponding author

*Address for correspondence: B. O’Donoghue, Orygen, National Centre of Excellence in Youth Mental Health, 35 Poplar rd, Parkville, Melbourne, Victoria, Australia. (Email:


Hide All
Cho, J, Hayes, RD, Jewell, A, Kadra, G, Shetty, H, MacCabe, JH, Downs, J (2019). Clozapine and all-cause mortality in treatment-resistant schizophrenia: a historical cohort study. Acta Psychiatrica Scandinavica 139, 237247.
Connolly, A, Taylor, D (2014). Factors associated with non evidence-based prescribing of antipsychotics. Therapeutic Advances in Psychopharmacology 4, 247256.
Curtis, J, Watkins, A, Rosenbaum, S, Teasdale, S, Kalucy, M, Samaras, K, Ward, PB (2015). Evaluating an individualized lifestyle and life skills intervention to prevent antipsychotic-induced weight gain in first-episode psychosis. Early Intervention in Psychiatry 10, 267276.
Demjaha, A, Lappin, JM, Stahl, D, Patel, MX, MacCabe, JH, Howes, OD, Heslin, M, Reininghaus, UA, Donoghue, K, Lomas, B, Charalambides, M, Onyejiaka, A, Fearon, P, Jones, P, Doody, G, Morgan, C, Dazzan, P, Murray, RM (2017). Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors. Psychological Medicine 47, 19811989.
Eaton, S, Harrap, B, Downey, L, Thien, K, Bowtell, M, Bardell-Williams, M, Ratheesh, A, McGorry, P, O’Donoghue, B (2019). Incidence of treated first episode psychosis from an Australian early intervention service and its association with neighbourhood characteristics. Schizophrenia Research 209, 206211.
Hayes, RD, Downs, J, Chang, CK, Jackson, RG, Shetty, H., Broadbent, M., Hotopf, M, Stewart, R. (2015). The effect of clozapine on premature mortality: an assessment of clinical monitoring and other potential confounders. Schizophrenia Bulletin 41, 644655.
Health Service Executive (2019). Early intervention for psychosis model of care ( Accessed June 2019.
International Diabetes Federation (2006). The IDF consenus worldwide definition of the metabolic syndrome ( Accessed June 2019.
Kahn, RS, Winter Van Rossum, I, Leucht, S, McGuire, P, Lewis, SW, Leboyer, M, Arango, C, Dazzan, P, Drake, R, Heres, S, Diaz-Caneja, CM, Rujescu, D, Weiser, M, Galderisi, S, Glenthoj, B, Eijkemans, MJC, Fleischhacker, WW, Kapur, S, Sommer, IE (2018). Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study. Lancet Psychiatry 5, 797807.
Lappin, JM, Wijaya, M, Watkins, A, Morell, R, Teasdale, S, Lederman, O, Rosenbaum, S, Dick, S, Ward, P, Curtis, J (2018). Cardio-metabolic risk and its management in a cohort of clozapine-treated outpatients. Schizophrenia Research 199, 367373.
Larsen, JR, Svensson, CK, Vedtofte, L., Jakobsen, ML, Jespersen, HS, Jakobsen, MI, Koyuncu, K, Schjerning, O, Nielsen, J, Ekstrom, CT, Holst, JJ, Correll, CU, Vilsboll, T, Fink-Jensen, A (2018). High prevalence of prediabetes and metabolic abnormalities in overweight or obese schizophrenia patients treated with clozapine or olanzapine. CNS Spectrums, 112. Published online ahead of print. doi:10.1017/S1092852918001311.
Leucht, S, Cipriani, A, Spineli, L, Mavridis, D, Orey, D, Richter, F, Samara, M, Barbui, C, Engel, RR, Geddes, JR, Kissling, W, Stapf, MP, Lassig, B, Salanti, G, Davis, JM (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382, 951962.
Nielsen, J, Dahm, M, Lublin, H, Taylor, D (2010). Psychiatrists’ attitude towards and knowledge of clozapine treatment. Journal of Psychopharmacology 24, 965971.
Paranthaman, R, Baldwin, RC (2006). Survey of clozapine use by consultant old age psychiatrists. Psychiatric Bulletin 30, 410412.
Siskind, D, Friend, N, Russell, A, McGrath, JJ, Lim, C, Patterson, S, Flaws, D, Stedman, T, Moudgil, V, Sardinha, S, Suetani, S, Kisely, S, Winckel, K, Baker, A (2018). CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine. BMJ Open 8, e021000. doi: 10.1136/bmjopen-2017-021000.
Siskind, D, McCartney, L, Goldschlager, R, Kisely, S (2016a). Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. British Journal of Psychiatry 209, 385392.
Siskind, D, Reddel, T, MacCabe, JH, Kisely, S (2019). The impact of clozapine initiation and cessation on psychiatric hospital admissions and bed days: a mirror image cohort study. Psychopharmacology (Berl) 236, 19311935.
Siskind, DJ, Leung, J, Russell, AW, Wysoczanski, D, Kisely, S (2016b). Metformin for clozapine associated obesity: a systematic review and meta-analysis. PLoS One, 11, e0156208.
Thien, K, Bowtell, M, Eaton, S, Bardell-Williams, M, Downey, L, Ratheesh, A, McGorry, P, O’Donoghue, B (2018). Clozapine use in early psychosis. Schizophrenia Research 199, 374379.
Thien, K, O’Donoghue, B (2018). Delays and barriers to the commencement of clozapine in eligible people with a psychotic disorder: a literature review. Early Intervention in Psychiatry, 13, 1823.
Tiihonen, J, Lonnqvist, J, Wahlbeck, K, Klaukka, T, Niskanen, L, Tanskanen, A, Haukka, J (2009). 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 374, 620627.
Wimberley, T, MacCabe, JH, Laursen, TM, Sorensen, HJ, Astrup, A, Horsdal, HT, Gasse, C, Stovring, H (2017). Mortality and self-harm in association with clozapine in treatment-resistant schizophrenia. American Journal of Psychiatry 174, 990998.


Physical health trajectories of young people commenced on clozapine

  • B. O’Donoghue (a1) (a2) (a3), A. Mujanovic (a4), S. Young (a5), T. Bridson (a6), L. Mora (a3), M. Bismark (a7), J. Cocks (a3), D. Siskind (a8) (a9) and P. McGorry (a1) (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.