Re-examining the role of benzodiazepines in the treatment of schizophrenia: A systematic review

Journal of Psychopharmacology

Volumn 29, Issue 2, 2015, Pages 212-223

  Sim, Faye ^a   Sweetman, Isabel ^a   Kapur, Shitij ^a   Patel, Maxine X ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

antipsychotics; benzodiazepines; clinical trials; placebo; Schizophrenia; systematic review

Indexed keywords

BENZODIAZEPINE DERIVATIVE; NEUROLEPTIC AGENT;

ANOREXIA; AUTONOMIC DYSFUNCTION; BEHAVIOR DISORDER; CLINICAL PRACTICE; COMBINATION CHEMOTHERAPY; COMPARATIVE EFFECTIVENESS; CONFUSION; DRUG EFFICACY; DRUG SAFETY; DYSARTHRIA; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; INSOMNIA; IRRITABILITY; LACTATION DISORDER; META ANALYSIS; MONOTHERAPY; MOTOR DYSFUNCTION; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; RISK FACTOR; SCHIZOPHRENIA; SUICIDAL IDEATION; SYSTEMATIC REVIEW; TOTAL QUALITY MANAGEMENT; TREATMENT DURATION; TREATMENT INDICATION; VASOMOTOR DISORDER; URINE;

ANTIPSYCHOTIC AGENTS; BENZODIAZEPINES; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SCHIZOPHRENIA;

EID: 84922268401     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881114541013     Document Type: Review

References (78)

1. Agid O, Siu CO, Potkin SG, et al. Meta-regression analysis of placebo response in antipsychotic trials, 1970-2010. Am J Psychiatry. 2013 ; 170: 1335-1344
2. Altamura A, Mauri M, Mantero M, et al. Clonazepam/haloperidol combination therapy in schizophrenia: A double blind study. Acta Psychiatr Scand. 1987 ; 76: 702-706
3. Asberg M, Perris C, Schalling D, et al. CPRS: Development and applications of a psychiatric rating scale. Acta Psychiatr Scand. 1978 ; 271: 69
4. Barbee JG, Mancuso DM, Freed CR, et al. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia. Am J Psychiatry. 1992 ; 149: 506-510
5. Barker M, Greenwood KM, Jackson M, et al. Cognitive effects of long-term benzodiazepine use. CNS Drugs. 2004 ; 18: 37-48
6. Battaglia J. Pharmacological management of acute agitation. Drugs. 2005 ; 65: 1207-1222
7. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996 ; 276: 637-639
8. Bitter L, Chou JC-Y, Ungvari GS, et al. Prescribing for inpatients with schizophrenia: An international multi-center comparative study. Pharmacopsychiatry. 2003 ; 36: 143-149
9. Boden WE. Meta-analysis in clinical trials reporting: Has a tool become a weapon?. Am J Cardiol. 1992 ; 69: 681-686
10. Dell'osso B, Lader M. Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical reappraisal. Eur Psychiatry. 2013 ; 28: 7-20
11. Carpenter WT, Buchanan RW, KirkPatrick B, et al. Diazepam treatment of early signs of exacerbation in schizophrenia. Am J Psychiatry. 1999 ; 156: 299-303
12. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia: Past issues and future opportunities. Neuropsychopharmacology. 2008 ; 33: 2061-2079
13. Chakos MH, Glick ID, Miller AL, et al. Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial. Psychiatr Serv. 2006 ; 57: 1094-1101
14. Cheung HK. Schizophrenics fully remitted on neuroleptics for 3-5 years - to stop or continue drugs?. Br J Psychiatry. 1981 ; 138: 490-494
15. Chouinard G, Ross-Chouinard A, Annable L, et al. Extrapyramidal rating scale. Can J Neurol Sci. 1980 ; 7: 233
16. Chouinard G, Annable L, Turnier L, et al. A double-blind randomized clinical trial of rapid tranquilization with IM clonazepam and IM haloperidol in agitated psychotic patients with manic symptoms. Can J Psychiat. 1993 ; 38: S114-121
17. Csernansky JG, Riney SJ, Lombrozo L, et al. Double-blind comparison of alprazolam, diazepam, and placebo for the treatment of negative schizophrenic symptoms. Arch Gen Psychiat. 1988 ; 45: 655-659
18. Deeks JJ, Higgins JPT, Altman DG Cochrane Handbook for Systematic Reviews of Interventions. Higgins JPT Green S, ed. Chichester: Wiley & Sons ; 2011 :
19. Dold M, Leucht MD. Efficacy and acceptability of benzodiazepine augmentation of antipsychotics in schizophrenia and schizophrenia-like psychoses: A meta-analysis of randomized controlled trials. Schizophr Res ; 2012 ; 2012. S264.
20. Dold M, Tardy M, Khorsand V, et al. Benzodiazepines for schizophrenia. Cochrane DB Syst Rev. 2012 ; 11 :
21. Dorevitch A, Katz N, Zemishiany Z, et al. Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. Am J Psychiatry. 1999 ; 156: 142-144
22. Egger M, Smith GD, Sterne JAC. Uses and abuses of meta-analysis. Clin Med. 2001 ; 1: 478-484
23. Endicott J, Spitzer RL, Fleiss JL, et al. The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiat. 1976 ; 33: 766-771
24. Fang M, Chen H, Li LH, et al. Comparison of risperidone oral solution and intramuscular haloperidol with the latter shifting to oral therapy for the treatment of acute agitation in patients with schizophrenia. Int Clin Psychopharm. 2012 ; 27: 107-113
25. Feighner JP, Robins E, Guze SB, et al. Diagnostic criteria for use in psychiatric research. Arch Gen Psychiat. 1972 ; 26: 57-63
26. Food and Drug Administration (FDA) (2013) Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Available at: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Updated May17, 2013. Last (accessed 6 March 2014).
27. Fountoulakis KN, Samara MT, Siamouli M. Burning issues in the meta-analysis of pharmaceutical trials for depression. J Psychopharmacol. 2013 ; 28: 106-117
28. Gillies D, Beck A, McCloud A, et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane DB Syst Rev. 2010 ;:
29. Gillies D, Sampson S, Beck A, et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane DB Syst Rev. 2013 ;:
30. Gundlach R, Engelhardt DM, Hankoff L, et al. A double-blind outpatient study of diazepam valium and placebo. Psychopharmacologia. 1966 ; 9: 81-92
31. Guy W ECDEU assessment manual for psychopharmacology. Rockville, MD: U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs ; 1976 :
32. Guz I, Moraes R, Sartoretto JN. The therapeutic effects of lorazepam in psychotic patients treated with haloperidol: A double-blind study. Curr Ther Res. 1972 ; 14: 767-774
33. Hankoff L D, Rudorfer L, Paley HM. A reference study of ataraxics. A two-week double blind outpatient evaluation. J New Drugs. 1962 ; 2: 173-178
34. Hanlon TE, Ota KY, Agallianos DD, et al. Combined drug treatment of newly hospitalized, acutely ill psychiatric patients. Dis Nerv Syst. 1969 ; 30: 104-116
35. Hanlon TE, Ota KY, Kurland AA. Comparative effects of fluphenazine, fluphenazine-chlordiazepoxide and fluphenazine-imipramine. Dis Nerv Syst. 1970 ; 31: 171-176
36. Haw C, Stubbs J. Benzodiazepines a necessary evil? A survey of prescribing at a specialist UK psychiatric hospital. J Psychopharmacol. 2007 ; 21: 645-649
37. Holden JM, Itil TM, Keskiner A, et al. Thioridazine and chlordiazepoxide,alone and combined, in the treatment of chronic schizophrenia. Compr Psychiatry. 1968 ; 9: 633-643
38. Honigfeld G, Gillis RD, Klett CJ. Nurses' observation scale for inpatient evaluation: A new scale for measuring improvement in chronic schizophrenia. J Clin Psychol. 1965 ; 21: 65-71
39. Jayaram M, Rattenhallt RD, Adams CE. Where does evidence from new trials for schizophrenia fit with the existing evidence: A case of the emperor's new clothes?. Schizophr Res Treatment. 2012 ;:
40. British National Formulary (BNF) 62. London: Pharmaceutical Press ; 2011 :
41. Karagianis J, Novick D, Pecenak J, et al. Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO): Baseline characteristics of pan-regional observational data from more than 17,000 patients. Int J Clin Pract. 2009 ; 63: 1578-1588
42. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987 ; 13: 261-276
43. Kemp AS, Schooler NR, Kalali AH, et al. What is causing the reduced drug-placebo difference in recent schizophrenia clinical trials and what can be done about it?. Schizophr Bull. 2010 ; 36: 504-509
44. Langle G, Steinert T, Weiser P, et al. Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Acta Psychiatr Scand. 2012 ; 125: 372-381
45. Lerner Y, Lwow E, Levitin A, et al. Acute high-dose parenteral haloperidol treatment of psychosis. Am J Psychiatry. 1979 ; 136: 1061-1064
46. Lingjaerde O, Engstrand E, Ellingsen P, et al. Antipsychotic effect of diazepam when given in addition to neuroleptics in chronic psychotic patients: A double-blind clinical trial. Curr Ther Res. 1979 ; 26: 505-514
47. Lingjaerde O. Effect of the benzodiazepine derivative estazolam in patients with auditory hallucinations. Acta Psychiatr Scand. 1982 ; 65: 339-354
48. Lorr M, McNair DC, Klett CJ, et al Inpatient Multidimensional Psychiatric Scale. Palo Alto: Consulting Psychologists Press ; 1962 :
49. Lund CE, Mortimer AM, Rogers D, et al. Motor, volitional and behavioural disorders in schizophrenia. 1: Assessment using the Modified Rogers scale. Br J Psychiatry. 1991 ; 158: 323-327
50. Maculans GA. Comparison of diazepam, chlorprothixene and chlorpromazine in chronic schizophrenic patients. Dis Nerv Syst. 1964 ; 25: 164-168
51. Mann C. Meta-analysis in the breech. Science. 1990 ; 249: 476-480
52. McGorry P, Alvarez-Jimenez M, Killackey E. Antipsychotic medication during the critical period following remission from first-episode psychosis: Less is more. JAMA Psychiatry. 2013 ; 70: 898-900
53. Merlis S, Turner WJ, Krumholz W. A double blind comparison of diazepam, chlordiazepoxide, and chlorpromazine in psychotic patients. J Neuropsychiatry. 1962 ; 3: 133-138
54. Michaux MH, Kurland AA, Agallianos DD. Chlorpromazine-chlordiazepoxide and chlorpromazine-imipramine treatment of newly hospitalized, acutely ill psychiatric patients. Curr Ther Res. 1966 ; 8: 117-152
55. Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. BMJ. 2010 ; 340: 869
56. Möhler H. GABAA receptor diversity and pharmacology. Cell Tissue Res. 2006 ; 326: 505-516
57. Morphy MA. A double-blind comparison of alprazolam and placebo in the treatment of anxious schizophrenic outpatients. Curr Ther Res. 1986 ; 40: 551-560
58. Nestoros JN, Suranyi-Cadotte BE, Spees RC, et al. Diazepam in high doses is effective in schizophrenia. Progress Neuro-Psychopharmacol Biol Psychiatry. 1982 ; 6: 513-516
59. Nishikawa T, Tsuda A, Tanaka M, et al. Prophylactic effect of neuroleptics in symptom-free schizophrenics. Psychopharmacology. 1982 ; 77: 301-304
60. Novick D, Bousono M, Suarez D, et al. Use of concomitant medication with antipsychotic treatment in outpatients with schizophrenia: Results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. Progress Neurosychopharmacol Biol Psychiatry. 2005 ; 29: 972-982
61. Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep. 1962 ; 10: 790-812
62. Parkes CM. Interhospital and intrahospital variations in the diagnosis and severity of schizophrenia. Br J Prev Soc Med. 1963 ; 17: 85-89
63. Procyshyn RM, Honer WG, Wu TK, et al. Persistent antipsychotic polypharmacy and excessive dosing in the com-munity psychiatric treatment setting: A review of medication profies in 435 Canadian outpatients. J Clin Psychiatry. 2010 ; 71: 566-573
64. Rabinowitz J, Werbeloff N, Kinon B, et al. Effects of benzodiazepine and other hypnotic use on efficacy results in placebo controlled antipsychotic trials: Lessons learned from the NewMeds repository of RCT data from AstraZeneca, Eli Lilly, Lundbeck and Pfizer. Schizophr Res. 2012 ; 136: S1 - S375
65. Shinfuku M, Uchida H, Tsutsumi C, et al. How psychotropic polypharmacy in schizophrenia begins: A longitudinal perspective. Pharmacopsychiatry. 2012 ; 45: 133-137
66. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand. 1970 ; S212: 11-19
67. Suokas JT, Suvisaari JM, Haukka J, et al. Description of long-term polypharmacy among schizophrenia outpatients. Soc Psychiatry Psychiatr Epidemiol. 2013 ; 48: 631-638
68. Stevens A, Stevens I, Mahal A, et al. Haloperidol and lorazepam combined: Clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. Pharmacopsychiatry. 1992 ; 256: 273-277
69. Taylor D, Paton C, Kapur S The Maudsley Prescribing Guidelines 11th Edition. Chichester: Wiley-Blackwell ; 2012 :
70. Tiihonen J, Suokas JT, Suvisaari JM, et al. Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiat. 2012 ; 69: 476-483
71. Ungvari GS, Chiu HFK, Chow LY, et al. Lorazepam for chronic catatonia: A randomized, double-blind, placebo-controlled cross-over study. Psychopharmacology. 1999 ; 142: 393-398
72. Vares M, Saetre P, Strålin P, et al. Concomitant medication of psychoses in a lifetime perspective. Human Psychopharmacol. 2011 ; 26: 322-331
73. Volz A, Khorsand V, Gillies D, et al. Benzodiazepines for schizophrenia. Cochrane DB Syst Rev. 2007 ; 1 :
74. Wolkowitz OM, Pickar D. Benzodiazepines in the treatment of schizophrenia. A review and re-appraisal. Am J Psychiatry. 1991 ; 148: 714-726
75. Wunderink L, Nieboer RM, Wiersma D, et al. 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: 913-920
76. Wyant MB, Diamond I, O'Neal E, et al. The use of midazolam in acutely agitated psychiatric patients. Psychopharmacol Bull. 1990 ; 261: 126-129
77. Yudofsky SC, Silver JM, Jackson W, et al. The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psychiatry. 1986 ; 143: 35-39
78. Zimbroff DL. Pharmacological control of acute agitation. CNS Drugs. 2008 ; 2: 199-212