Skip to main content
×
×
Home

Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials

  • Ying Jiao Zhao (a1), Liang Lin (a2), Monica Teng (a3) (a4), Ai Leng Khoo (a5) (a6), Lay Beng Soh (a1), Toshiaki A. Furukawa (a7), Ross J. Baldessarini (a7), Boon Peng Lim (a7) and Kang Sim (a7) (a8)...
Abstract
Background

For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review.

Aims

To evaluate the comparative long-term effectiveness of antipsychotic drugs.

Method

We systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo.

Results

Studies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4–156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents.

Conclusions

Except for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials
      Available formats
      ×
Copyright
This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Corresponding author
Ying Jiao Zhao, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore 138543. Email: ying_jiao_zhao@nhg.com.sg
Footnotes
Hide All

Declaration of interest

R.J.B. received grants from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund.

Footnotes
References
Hide All
1 Eaton, WW, Martins, SS, Nestadt, G, Bienvenu, OJ, Clarke, D, Alexandre, P. The burden of mental disorders. Epidemiol Rev 2008; 30: 114.
2 Vos, T, Flaxman, AD, Naghavi, M, Lozano, R, Michaud, C, Ezzati, M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–96.
3 Andreasen, NC. Symptoms, signs, and diagnosis of schizophrenia. Lancet 1995; 346: 477–81.
4 Wyatt, RJ. Neuroleptics and the natural course of schizophrenia. Schizophr Bull 1991; 17: 325–51.
5 Rettenbacher, MA, Hofer, A, Eder, U, Hummer, M, Kemmler, G, Weiss, EM, et al. Compliance in schizophrenia: psychopathology, side effects, and patients' attitudes toward the illness and medication. J Clin Psychiatry 2004; 65: 1211–18.
6 Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Davis, JM. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2012; 5: CD008016.
7 Kishimoto, T, Agarwal, V, Kishi, T, Leucht, S, Kane, JM, Correll, CU. Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics. Mol Psychiatry 2013; 18: 5366.
8 Lacro, JP, Dunn, LB, Dolder, CR, Leckband, SG, Jeste, DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry 2002; 63: 892909.
9 Velligan, DI, Wang, M, Diamond, P, Glahn, DC, Castillo, D, Bendle, S, et al. Relationships among subjective and objective measures of adherence to oral antipsychotic medications. Psychiatr Serv 2007; 58: 1187–92.
10 Kane, JM, Garcia-Ribera, C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry Suppl 2009; 52: S637.
11 Kishimoto, T, Robenzadeh, A, Leucht, C, Leucht, S, Watanabe, K, Mimura, M, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull 2014; 40: 192213.
12 Hartling, L, Abou-Setta, AM, Dursun, S, Mousavi, SS, Pasichnyk, D, Newton, AS. Antipsychotics in adults with schizophrenia: comparative effectiveness of firstgeneration versus second-generation medications: a systematic review and metaanalysis. Ann Intern Med 2012; 157: 498511.
13 Essali, A, Al-Haj Haasan, N, Li, C, Rathbone, J. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev 2009; 1: CD000059.
14 Asenjo Lobos, C, Komossa, K, Rummel-Kluge, C, Hunger, H, Schmid, F, Schwarz, S, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010; 11: CD006633.
15 Caldwell, DM, Ades, AE, Higgins, JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 2005; 331: 897900.
16 Yildiz, A, Vieta, E, Correll, CU, Nikodem, M, Baldessarini, RJ. Critical issues on the use of network meta-analysis in psychiatry. Harv Rev Psychiatry 2014; 22: 367–72.
17 Ziakas, PD, Kourbeti, IS, Mylonakis, E. Systemic antifungal prophylaxis after hematopoietic stem cell transplantation: a meta-analysis. Clin Ther 2014; 36: 292–306.e1.
18 Simmonds, MC, Higgins, JP, Stewart, LA, Tierney, JF, Clarke, MJ, Thompson, SG. Meta-analysis of individual patient data from randomized trials: a review of methods used in practice. Clin Trials 2005; 2: 209–17.
19 Mavridis, D, Salanti, G. A practical introduction to multivariate meta-analysis. Stat Methods Med Res 2013; 22: 133–58.
20 Jackson, D, White, IR, Riley, RD. A matrix-based method of moments for fitting the multivariate random effects model for meta-analysis and meta-regression. Biom J 2013; 55: 231–45.
21 Chaimani, A, Higgins, JP, Mavridis, D, Spyridonos, P, Salanti, G. Graphical tools for network meta-analysis in STATA. PLoS One 2013; 8: e76654.
22 Singh, S, Cuzick, J, Mesher, D, Richmond, B, Howell, A. Effect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II, chemoprevention study using anastrozole. Breast Cancer Res Treat 2012; 132: 625–9.
23 Gardner, DM, Murphy, AL, O'Donnell, H, Centorrino, F, Baldessarini, RJ. International consensus study of antipsychotic dosing. Am J Psychiatry 2010; 167: 686–93.
24 Dencker, SJ, Lepp, M, Malm, U. Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate. Acta Psychiatr Scand Suppl 1980; 279: 1028.
25 Wistedt, B, Koskinen, T, Thelander, S, Nerdrum, T, Pedersen, V, Molbjerg, C. Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study. Acta Psychiatr Scand 1991; 84: 1421.
26 Komossa, K, Rummel-Kluge, C, Hunger, H, Schmid, F, Schwarz, S, Duggan, L, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Reviews 2010; 3: CD006654.
27 Komossa, K, Rummel-Kluge, C, Hunger, H, Schwarz, S, Bhoopathi, PS, Kissling, W, et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009; 4: CD006627.
28 Rummel-Kluge, C, Komossa, K, Schwarz, S, Hunger, H, Schmid, F, Lobos, CA, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 2010; 123: 225–33.
29 Komossa, K, Rummel-Kluge, C, Schwarz, S, Schmid, F, Hunger, H, Kissling, W, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2011; 1: CD006626.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

BJPsych Open
  • ISSN: -
  • EISSN: 2056-4724
  • URL: /core/journals/bjpsych-open
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
PDF
Supplementary materials

Zhao et al. supplementary material
Supplementary Material

 PDF (1.0 MB)
1.0 MB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 99 *
Loading metrics...

Abstract views

Total abstract views: 547 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 21st June 2018. This data will be updated every 24 hours.

Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials

  • Ying Jiao Zhao (a1), Liang Lin (a2), Monica Teng (a3) (a4), Ai Leng Khoo (a5) (a6), Lay Beng Soh (a1), Toshiaki A. Furukawa (a7), Ross J. Baldessarini (a7), Boon Peng Lim (a7) and Kang Sim (a7) (a8)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *