Treatment resistant schizophrenia: a comprehensive survey of randomised controlled trials

BMC Psychiatry

Clive E Adams¹  Diarmid Sinclair² 

[1] Cochrane Schizophrenia Group, Institute of Mental Health, University of Nottingham, Nottingham, UK;Sheffield Health and Social Care NHS Foundation Trust, Fullwood House, 5 Old Fulwood Rd, Sheffield S10 3TG, South Yorkshire, UK

关键词: Randomised trials;    Treatment resistant;    Schizophrenia;    Systematic reviews;   

Others  :  1123345
DOI  :  10.1186/s12888-014-0253-4

 received in 2014-01-07, accepted in 2014-08-28,  发布年份 2014

【 摘 要 】

Background

Schizophrenia is a common serious mental health condition which has significant morbidity and financial consequences. The mainstay of treatment has been antipsychotic medication but one third of people will have a ‘treatment resistant’ and most disabling and costly illness. The aim of this survey was to produce a broad overview of available randomised evidence for interventions for people whose schizophrenic illness has been designated ‘treatment resistant’.

Method

We searched the Cochrane Schizophrenia Group’s comprehensive Trials Register, selected all relevant randomised trials and, taking care not to double count, extracted the number of people randomised within each study. Finally we sought relevant reviews on the Cochrane Library and investigated how data on this subgroup of people had been presented.

Results

We identified 542 relevant papers based on 268 trials (Average size 64.8 SD 61.6, range 7–526, median 56 IQR 47.3, mode 60). The most studied intervention is clozapine with 82 studies (total n = 6299) comparing it against other anti-psychotic medications. Cognitive behavioural therapy (CBT), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) supplementing a standard care and risperidone supplementation of clozapine has also been extensively evaluated within trials. Many approaches, however, were clearly under researched. There were only four studies investigating combinations of non-clozapine antipsychotics. Only two psychological approaches (CBT and Family Rehabilitation Training) had more than two studies. Cochrane reviews rarely presented data specific to this important clinical sub-group.

Conclusions

This survey provides a broad taxonomy of how much evaluative research has been carried out investigating interventions for people with treatment resistant schizophrenia. Over 280 trials have been undertaken but, with a few exceptions, most treatment approaches - and some in common use - have only one or two relevant but small trials. Too infrequently the leading reviews fail to highlight the paucity of evidence in this area – as these reviews are maintained this shortcoming should be addressed.

【 授权许可】

   
2014 Sinclair and Adams; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Sartorius N, Shapiro R, Kimura M, Barrett K: WHO international pilot study of schizophrenia. Psychol Med 1972, 2(4):422-425.
• [2]Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J, Dube KC, Ganev K, Giel R, an der Heiden W: Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry 2001, 178:506-517.
• [3]Meltzer HY: Treatment-resistant schizophrenia–the role of clozapine. Curr Med Res Opin 1997, 14(1):1-20.
• [4]Mangalore R, Knapp M: Cost of schizophrenia in England. J Ment Health Policy Econ 2007, 10(1):23-41.
• [5]Suzuki T, Remington G, Mulsant BH, Rajji TK, Uchida H, Graff-Guerrero A, Mamo DC: Treatment resistant schizophrenia and response to antipsychotics: a review. Schizophr Res 2011, 133(1–3):54-62.
• [6]Kane J, Honigfeld G, Singer J, Meltzer H: Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988, 45(9):789-796.
• [7]Conley RR, Buchanan RW: Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997, 23(4):663-674.
• [8]McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK: Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006, 163:600-610.
• [9]Lewis SW, Barnes TR, Davies L, Murray RM, Dunn G, Hayhurst KP, Markwick A, Lloyd H, Jones PB: Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull 2006, 32(4):715-723.
• [10]Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU: Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res 2012, 138(1):18-28.
• [11]Howes OD, Vergunst F, Gee S, McGuire P, Kapur S, Taylor D: Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry 2012, 201(6):481-485.
• [12]Meltzer HY: Treatment of the neuroleptic-nonresponsive schizophrenic patient. Schizophr Bull 1992, 18(3):515-542.
• [13]Trikalinos TA, Churchill R, Ferri M, Leucht S, Tuunainen A, Wahlbeck K, Ioannidis JP: Effect sizes in cumulative meta-analyses of mental health randomized trials evolved over time. J Clin Epidemiol 2004, 57(11):1124-1130.
• [14]Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, Devereaux PJ, Montori VM, Freyschuss B, Vist G, Jaeschke R, Williams JW, Murad MH, Sinclair D, Falck-Ytter Y, Meerpohl J, Whittington C, Thorlund K, Andrews J, Schünemann HJ: GRADE guidelines 6. Rating the quality of evidence—imprecision. J Clin Epidemiol 2011, 64(12):1283-1293.
• [15]Adams CE, Davis J, Duggan L, Essali A, Fenton M, Leucht S, Jayaram M, Li C, Tharyan P, Välimäki M: About the Cochrane collaboration (Cochrane Review Groups (CRGs). ᅟ 2013, ᅟ:ᅟ. Issue 8. Art. No.: SCHI
• [16]Jones C, Hacker D, Cormac I, Meaden A, Irving CB: Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia. Cochrane Database Syst Rev 2012, 4:CD008712.
• [17]Pharoah F, Mari Jair J, Rathbone J, Wong W: Family intervention for schizophrenia. Cochrane Database Syst Rev 2010, ᅟ(12):Art. No.: CD000088. doi:10.1002/14651858.CD000088.pub3
• [18]Rathbone J, Xia J: Acupuncture for schizophrenia. Cochrane Database Syst Rev 2005, ᅟ(4):Art. No.: CD005475. doi:10.1002/14651858.CD005475
• [19]Tharyan P, Adams Clive E: Electroconvulsive therapy for schizophrenia. Cochrane Database Syst Rev 2005, ᅟ(2):Art. No.: CD000076. doi:10.1002/14651858.CD000076.pub2
• [20]Dougall N, McIntosh A, Ebmeier Klaus P: Transcranial magnetic stimulation for schizophrenia. Cochrane Database Syst Rev 2006, ᅟ(3):Art. No.: CD006081. doi:10.1002/14651858.CD006081
• [21]Cipriani A, Boso M, Barbui C: Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia. Cochrane Database Syst Rev 2009, ᅟ(3):Art. No.: CD006324. doi:10.1002/14651858.CD006324.pub2
• [22]Wang J, Omori Ichiro M, Fenton M, Soares Bernardo GO: Sulpiride augmentation for schizophrenia. Cochrane Database Syst Rev 2010, ᅟ(1):Art. No.: CD008125. doi:10.1002/14651858.CD008125.pub2
• [23]Schwarz C, Volz A, Li C, Leucht S: Valproate for schizophrenia. Cochrane Database Syst Rev 2008, ᅟ(3):Art. No.: CD004028. doi:10.1002/14651858.CD004028.pub3
• [24]Premkumar TS, Pick J: Lamotrigine for schizophrenia. Cochrane Database Syst Rev 2006, ᅟ(4):CD005962. doi:10.1002/14651858.CD005962.pub2
• [25]Leucht S, Kissling W, McGrath J: Lithium for schizophrenia. Cochrane Database Syst Rev 2007, ᅟ(3):CD003834. doi:10.1002/14651858.CD003834.pub2
• [26]Kour K, Kaur R, Singh J: Memantine for schizophrenia. Cochrane Database Syst Rev 2013, ᅟ(6):Art. No.: CD010552. doi:10.1002/14651858.CD010552
• [27]Tiihonen J, Wahlbeck K: Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 2006, ᅟ(2):Art. No.: CD003730. doi:10.1002/14651858.CD003730.pub2
• [28]Leucht S, Helfer B, Dold M, Kissling W, McGrath J: Carbamazepine for schizophrenia. Cochrane Database Syst Rev 2014, ᅟ(5):Art. No.: CD001258. doi:10.1002/14651858.CD001258.pub3
• [29]Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Silveira da Mota Neto Joaquim I, Kissling W, Leucht S: Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010, ᅟ(1):Art. No.: CD006624. doi:10.1002/14651858.CD00624.pub2
• [30]Khanna P, Suo T, Komossa K, Ma H, Rummel-Kluge C, El-Sayeh Hany G, Leucht S, Xia J: Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2014, ᅟ(1):Art. No.: CD006569. doi:10.1002/14651858.CD006569.pub5
• [31]Essali A, Al-Haj Haasan N, Li C, Rathbone J: Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev 2009, ᅟ(1):Art. No.: CD000059. doi:10.1002/14651858.CD000059.pub2
• [32]Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Leucht S: Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010, ᅟ(11):Art. No.: CD006633. doi:10.1002/14651858.CD006633.pub2
• [33]Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, Kissling W, Leucht S: Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010, ᅟ(3):Art. No.: CD006654. doi: 10.1002/14651858.CD006654.pub2
• [34]Li C, Xia J, Wang J: Risperidone dose for schizophrenia. Cochrane Database Syst Rev 2009, ᅟ(4):Art. No.: CD007474. doi:10.1002/14651858.CD007474.pub2
• [35]Komossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, Leucht S: Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2011, ᅟ(1):Art. No.: CD006626. doi:10.1002/14651858.CD006626.pub2
• [36]Hunter R, Kennedy E, Song F, Gadon L, Irving Claire B: Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Database Syst Rev 2003, ᅟ(2):Art. No.: CD000440. doi:10.1002/14651858.CD000440.
• [37]Asmal L, Flegar Srnka J, Wang J, Rummel-Kluge C, Komossa K, Leucht S: Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2013, ᅟ(11):Art. No.: CD006625. doi:10.1002/14651858.CD006625.pub3
• [38]Komossa K, Rummel-Kluge C, Hunger H, Schwarz S, Schmid F, Lewis R, Kissling W, Leucht S: Sertindole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009, ᅟ(42):Art. No.: CD006752. doi:10.1002/14651858.CD006752.pub2
• [39]Komossa K, Rummel-Kluge C, Hunger H, Schwarz S, Bhoopathi Paranthaman S, Kissling W, Leucht S: Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009, ᅟ(4):Art. No.: CD006627. doi:10.1002/14651858.CD006627.pub2
• [40]Saha Kumar B, Sampson S, Zaman Rashid U: Chlorpromazine versus atypical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2013, ᅟ(2):Art. No.: CD010631. doi:10.1002/14651858.CD010631
• [41]Sampford J, Sampson S: Fluphenazine (oral) versus atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2013, ᅟ(11):Art. No.: CD010832. doi:10.1002/14651858.CD010832
• [42]Tardy M, Leucht S, Potapov A, Engel R, Huhn M, Kissling W: Fluphenazine versus low-potency first generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2011, ᅟ(8):Art. No.: CD009230. doi:10.1002/14651858.CD009230.pub2
• [43]Dold M, Li C, Tardy M, Leucht S: Haloperidol versus first generation antipsychotics for schizophrenia. Cochrane Database Syst Rev 2012, ᅟ(5):Art. No.: CD009831. doi:10.1002/14651858.CD009831
• [44]Tardy M, Leucht S, Potapov A, Engel R, Huhn M, Kissling W: Perphenazine versus low-potency first generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2011, ᅟ(10):Art. No.: CD009369. doi:10.1002/14651858.CD009369
• [45]Lloyd K, White J: Democratizing clinical research. Nature 2011, 474(7351):277-278.
• [46]Taylor DM, Smith L, Gee SH, Nielsen J: Augmentation of clozapine with a second antipsychotic - a meta-analysis. Acta Psychiatr Scand 2012, 125(1):15-24.
• [47]Faries DA-SH, Zhu B, Correll C, Kane J: Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics. BMC Psychiatry 2005, 5:26. BioMed Central Full Text
• [48]Stahl SM: Emerging guidelines for the use of antipsychotic polypharmacy. Revista de psiquiatria y salud mental 2013, 6(3):97-100.
• [49]Psychosis and schizophrenia in adults: treatment and management [www.nice.org.uk/CG178] webciteNICE clinical guideline 178 ᅟ, ᅟ; 2014, ᅟ. Available at www.nice.org.uk/CG178 [NICE guideline]
• [50]Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J: Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004, 161(2):1-56.
• [51]Kjaergard LL, Villumsen J, Gluud C: Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001, 135(11):982-989.
• [52]Moher D, Dulberg CS, Wells GA: Statistical power, sample size, and their reporting in randomized controlled trials. JAMA 1994, 272(2):122-124.
• [53]Overall JE, Gorham DR: The brief psychiatric rating scale. Psychol Rep 1962, 10:790-812.
• [54]Leucht S, Kane JM, Kissling W, Hamann J, Etschel EVA, Engel R: Clinical implications of brief psychiatric rating scale scores. Br J Psychiatry 2005, 187(4):366-371.