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Retirada versus continuación del uso de medicamentos antipsicóticos a largo plazo para los síntomas conductuales y psicológicos en las personas mayores con demencia

Appendices

Appendix 1. Initial search: 9 February 2009

Source

Date range searched

Hits retrieved

MEDLINE (PubMed)

Up to 9 Feb 2009

108

Embase (Ovid SP)

Up to 10 Feb 2009

37

PsycINFO (Ovid SP)

Up to 10 Feb 2009

20

CINAHL (Ovid SP)

Up to 11 Feb 2009

16

LILACS (Bireme)

Up to 9 Feb 2009

0

CDCIG SR*

Searched 9 Feb 2009

163

CENTRAL (Cochrane Library)

Issue 1 2009

75

ISTP Conference Proceedings portal.isiknowledge.com/portal.cgi

Up to 11 Feb 2009

105

Australian Digital Theses Program adt.caul.edu.au/

Searched 12 Feb 2009  

0

Canadian Theses and Dissertations www.collectionscanada.ca/thesescanada/index-e.html

Searched 12 Feb 2009  

0

WHO ICTRP

Searched 11 Feb 2009  

4

Current Controlled trials: MetaRegister of Controlled trials (mRCT) www.controlled-trials.com/

Searched 11 Feb 2009

1

ISRCTN Register

Searched 12 Feb 2009

0

Nederlands Trial Register www.trialregister.nl/trialreg/index.asp

Searched 12 Feb 2009  

0

ClinicalTrials.gov www.ClinicalTrials.gov

Included in WHO portal

//

IPFMA Clinical Trials Register www.ifpma.org/clinicaltrials.html

Searched 12 Feb 2009

0

UMIN Japan Trial Register www.umin.ac.jp/ctr/

Searched 12 Feb 2009  

0

OPENsigle

Searched 12 Feb 2009

0

Appendix 2. Updated search: 11 March 2011

Source

 

Search strategy

Hits retrieved

1. ALOIS (www.medicine.ox.ac.uk/alois)

Antipsychotic OR neuroleptic OR APSY

126

2. MEDLINE In‐process and other non‐indexed citations and MEDLINE 1950 to 11 March 2011 (Ovid SP)

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. Antipsychotic Agents/

4. neuroleptic*.ti,ab.

5. phenothiazines.ti,ab.

6. Phenothiazines/

7. butyrophenones.ti,ab.

8. Butyrophenones/

9. risperidone.ti,ab.

10. Risperidone/

11. Risperdal*.ti,ab.

12. olanzapine.ti,ab.

13. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

14. haloperidol.ti,ab.

15. Haloperidol/

16. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

17. prothipendyl.ti,ab.

18. methotrimeprazine.ti,ab.

19. Methotrimeprazine/

20. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

21. clopenthixol.ti,ab.

22. Clopenthixol/

23. (Sordinol* or clopentixol).ti,ab.

24. flupenthixol.ti,ab.

25. Flupenthixol/

26. (flupentixol or depixol* or fluanxol*).ti,ab.

27. clothiapine.ti,ab.

28. metylperon.ti,ab.

29. melperon.ti,ab.

30. droperidol.ti,ab.

31. Droperidol/

32. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

33. pipamperone.ti,ab.

34. Dipiperon*.ti,ab.

35. benperidol.ti,ab.

36. Benperidol/

37. Anquil*.ti,ab.

38. bromperidol.ti,ab.

39. Bromidol*.ti,ab.

40. fluspirilene.ti,ab.

41. Fluspirilene/

42. (Redeptin* or Imap*).ti,ab.

43. pimozide.ti,ab.

44. Pimozide/

45. orap*.ti,ab.

46. penfluridol.ti,ab.

47. Penfluridol/

48. (Semap* or Micefal*).ti,ab.

49. sulpiride.ti,ab.

50. Sulpiride/

51. veralipride.ti,ab.

52. (Agreal* or Agradil*).ti,ab.

53. levosulpiride.ti,ab.

54. sultopride.ti,ab.

55. (Barnetil* or Barnotil* or Topral*).ti,ab.

56. aripiprazole.ti,ab.

57. (Abilify* or Aripiprex*).ti,ab.

58. clozapine.ti,ab.

59. Clozapine/

60. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

61. quetiapine.ti,ab.

62. (Seroquel* or Ketipinor*).ti,ab.

63. thioridazine.ti,ab.

64. Thioridazine/

65. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

66. or/1‐65

67. exp Dementia/

68. Delirium/

69. Wernicke Encephalopathy/

70. Delirium, Dementia, Amnestic, Cognitive Disorders/

71. dement*.mp.

72. alzheimer*.mp.

73. (lewy* adj2 bod*).mp.

74. deliri*.mp.

75. (chronic adj2 cerebrovascular).mp.

76. ("organic brain disease" or "organic brain syndrome").mp.

77. ("normal pressure hydrocephalus" and "shunt*").mp.

78. "benign senescent forgetfulness".mp.

79. (cerebr* adj2 deteriorat*).mp.

80. (cerebral* adj2 insufficient*).mp.

81. (pick* adj2 disease).mp.

82. (creutzfeldt or jcd or cjd).mp.

83. huntington*.mp.

84. binswanger*.mp.

85. korsako*.mp.

86. or/67‐85

87. 66 and 86

88. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

89. 87 and 88

90. randomized controlled trial.pt.

91. controlled clinical trial.pt.

92. randomized.ab.

93. placebo.ab.

94. drug therapy.fs.

95. randomly.ab.

96. trial.ab.

97. groups.ab.

98. or/90‐97

99. (animals not (humans and animals)).sh.

100. 98 not 99

101. 89 and 100

102. (2009* or 2010* or 2011*).ed.

103. 101 and 102

86

3. Embase

1980 to 2011 week 12 (Ovid SP)

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. Antipsychotic Agents/

4. neuroleptic*.ti,ab.

5. phenothiazines.ti,ab.

6. Phenothiazines/

7. butyrophenones.ti,ab.

8. Butyrophenones/

9. risperidone.ti,ab.

10. Risperidone/

11. Risperdal*.ti,ab.

12. olanzapine.ti,ab.

13. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

14. haloperidol.ti,ab.

15. Haloperidol/

16. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

17. prothipendyl.ti,ab.

18. methotrimeprazine.ti,ab.

19. Methotrimeprazine/

20. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

21. clopenthixol.ti,ab.

22. Clopenthixol/

23. (Sordinol* or clopentixol).ti,ab.

24. flupenthixol.ti,ab.

25. Flupenthixol/

26. (flupentixol or depixol* or fluanxol*).ti,ab.

27. clothiapine.ti,ab.

28. metylperon.ti,ab.

29. melperon.ti,ab.

30. droperidol.ti,ab.

31. Droperidol/

32. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

33. pipamperone.ti,ab.

34. Dipiperon*.ti,ab.

35. benperidol.ti,ab.

36. Benperidol/

37. Anquil*.ti,ab.

38. bromperidol.ti,ab.

39. Bromidol*.ti,ab.

40. fluspirilene.ti,ab.

41. Fluspirilene/

42. (Redeptin* or Imap*).ti,ab.

43. pimozide.ti,ab.

44. Pimozide/

45. orap*.ti,ab.

46. penfluridol.ti,ab.

47. Penfluridol/

48. (Semap* or Micefal*).ti,ab.

49. sulpiride.ti,ab.

50. Sulpiride/

51. veralipride.ti,ab.

52. (Agreal* or Agradil*).ti,ab.

53. levosulpiride.ti,ab.

54. sultopride.ti,ab.

55. (Barnetil* or Barnotil* or Topral*).ti,ab.

56. aripiprazole.ti,ab.

57. (Abilify* or Aripiprex*).ti,ab.

58. clozapine.ti,ab.

59. Clozapine/

60. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

61. quetiapine.ti,ab.

62. (Seroquel* or Ketipinor*).ti,ab.

63. thioridazine.ti,ab.

64. Thioridazine/

65. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

66. or/1‐65

67. exp dementia/

68. Lewy body/

69. delirium/

70. Wernicke encephalopathy/

71. cognitive defect/

72. dement*.mp.

73. alzheimer*.mp.

74. (lewy* adj2 bod*).mp.

75. deliri*.mp.

76. (chronic adj2 cerebrovascular).mp.

77. ("organic brain disease" or "organic brain syndrome").mp.

78. "supranuclear palsy".mp.

79. ("normal pressure hydrocephalus" and "shunt*").mp.

80. "benign senescent forgetfulness".mp.

81. (cerebr* adj2 deteriorat*).mp.

82. (cerebral* adj2 insufficient*).mp.

83. (pick* adj2 disease).mp.

84. (creutzfeldt or jcd or cjd).mp.

85. huntington*.mp.

86. binswanger*.mp.

87. korsako*.mp.

88. CADASIL.mp.

89. or/67‐88

90. 66 and 89

91. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

92. 90 and 91

93. randomized controlled trial/

94. randomi?ed.ab.

95. controlled clinical trial/

96. placebo.ab.

97. randomly.ab.

98. trial.ab.

99. groups.ab.

100. or/93‐99

101. 92 and 100

102. (2009* or 2010* or 2011*).em.

103. 101 and 102

178

4. PsycINFO

1806 to March week 3 2011 (Ovid SP)

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. neuroleptic*.ti,ab.

4. phenothiazines.ti,ab.

5. butyrophenones.ti,ab.

6. risperidone.ti,ab.

7. Risperidone/

8. Risperdal*.ti,ab.

9. olanzapine.ti,ab.

10. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

11. haloperidol.ti,ab.

12. Haloperidol/

13. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

14. prothipendyl.ti,ab.

15. methotrimeprazine.ti,ab.

16. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

17. clopenthixol.ti,ab.

18. (Sordinol* or clopentixol).ti,ab.

19. flupenthixol.ti,ab.

20. (flupentixol or depixol* or fluanxol*).ti,ab.

21. clothiapine.ti,ab.

22. droperidol.ti,ab.

23. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

24. pipamperone.ti,ab.

25. Dipiperon*.ti,ab.

26. benperidol.ti,ab.

27. bromperidol.ti,ab.

28. Bromidol*.ti,ab.

29. fluspirilene.ti,ab.

30. (Redeptin* or Imap*).ti,ab.

31. pimozide.ti,ab.

32. Pimozide/

33. orap*.ti,ab.

34. penfluridol.ti,ab.

35. (Semap* or Micefal*).ti,ab.

36. sulpiride.ti,ab.

37. Sulpiride/

38. veralipride.ti,ab.

39. levosulpiride.ti,ab.

40. sultopride.ti,ab.

41. (Barnetil* or Barnotil* or Topral*).ti,ab.

42. aripiprazole.ti,ab.

43. (Abilify* or Aripiprex*).ti,ab.

44. clozapine.ti,ab.

45. Clozapine/

46. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

47. quetiapine.ti,ab.

48. (Seroquel* or Ketipinor*).ti,ab.

49. thioridazine.ti,ab.

50. Thioridazine/

51. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

52. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

53. or/1‐51

54. 52 and 53

55. exp Dementia/

56. exp Delirium/

57. exp Huntingtons Disease/

58. exp Kluver Bucy Syndrome/

59. exp Wernickes Syndrome/

60. exp Cognitive Impairment/

61. dement*.mp.

62. alzheimer*.mp.

63. (lewy* adj2 bod*).mp.

64. deliri*.mp.

65. (chronic adj2 cerebrovascular).mp.

66. ("organic brain disease" or "organic brain syndrome").mp.

67. "supranuclear palsy".mp.

68. ("normal pressure hydrocephalus" and "shunt*").mp.

69. "benign senescent forgetfulness".mp.

70. (cerebr* adj2 deteriorat*).mp.

71. (cerebral* adj2 insufficient*).mp.

72. (pick* adj2 disease).mp.

73. (creutzfeldt or jcd or cjd).mp.

74. huntington*.mp.

75. binswanger*.mp.

76. korsako*.mp.

77. ("parkinson* disease dementia" or PDD or "parkinson* dementia").mp.

78. or/55‐77

79. 54 and 78

80. (2009* or 2010* or 2011*).up.

81. 79 and 80

110

5. CINAHL (EBSCO host)

S1 (MH "Dementia+")  

S2 (MH "Delirium") or (MH "Delirium, Dementia, Amnestic, Cognitive Disorders")

S3 (MH "Wernicke's Encephalopathy")  

S4 TX dement*  

S5 TX alzheimer* 

S6 TX lewy* N2 bod*  

S7 TX deliri* 

S8 TX chronic N2 cerebrovascular  

S9 TX "organic brain disease" or "organic brain syndrome"  

S10 TX "normal pressure hydrocephalus" and "shunt*"  

S11 TX "benign senescent forgetfulness" 

S12 TX cerebr* N2 deteriorat* 

S13 TX cerebral* N2 insufficient*  

S14 TX pick* N2 disease

S15 TX creutzfeldt or jcd or cjd  

S16 TX huntington* 

S17 TX binswanger*  

S18 TX korsako* 

S19 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18

S20 TX "cognit* impair*" 

S21 TX "cognit* defect*" 

S22 (MH "Cognition Disorders+") 

S23 TX MCI 

S24 TX ACMI 

S25 TX ARCD 

S26 TX SMC 

S27 TX CIND 

S28 TX BSF 

S29 TX AAMI 

S30 AB MD 

S31 AB LCD 

S32 AB QD OR "questionable dementia"

S33 TX AACD 

S34 TX MNCD 

S35 TX "N‐MCI" or "A‐MCI" or "M‐MCI"

S36 TX "preclinical AD" 

S37 TX "pre‐clinical AD"

S38 TX "preclinical alzheimer*" or "pre‐clinical alzheimer*" 

S39 TX aMCI OR MCIa 

S40 TX "CDR 0.5" or "clinical dementia rating scale 0.5" 

S41 TX "GDS 3" OR "stage 3 GDS"

S42 TX "global deterioration scale" AND "stage 3" 

S43 TX "Benign senescent forgetfulness" 

S44 TX "mild neurocognit* disorder*" 

S45 TX prodrom* N2 dement*

S46 TX "age‐related symptom*" 

S47 TX cognit* N2 deficit*

S48 TX cognit* N2 deteriorat*

S49 TX cognit* N2 declin*

S50 TX cognit* N2 degenerat*

S51 TX cognit* N2 complain* 

S52 TX cognit* N2 disturb* 

S53 TX cognit* N2 disorder*

S54 TX memory N2 episod* or TX memory N2 los* or TX memory N2 impair* or TX memory N2 complain*

S55 TX memory N2 disturb* or TX memory N2 disorder* or TX cerebr* N2 impair* or TX cerebr* N2 los* 

S56 TX cerebr* N2 complain* or TX cerebr* N2 deteriorat* or TX cerebr* N2 disorder* or TX cerebr* N2 disturb* 

S57 TX mental* N2 declin* or TX mental* N2 los* or TX mental* N2 impair* or TX mental* N2 deteriorat* 

S58 TX "pre‐clinical dementia" or TX "preclinical dementia" 

S59 S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46 or S47 or S48 or S49 or S50 or S51 or S52 or S53 or S54 or S55 or S56 or S57 or S58 

S60 S19 or S59 

99

6. ISI Web of Knowledge – all databases (includes: Web of Science (1945 to present); BIOSIS Previews (1926 to present); MEDLINE (1950 to present); Journal Citation Reports)

#1 Topic=(antipsychotic* OR neuroleptic* OR phenothiazines OR butyrophenones OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR methotrimeprazine OR clopenthixol OR flupenthixol)

#2 Topic=(clothiapine OR melperon OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide OR penfluridol OR sulpiride)

#3 Topic=(veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine)

#4 Topic=(discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*)

#5 #3 OR #2 OR #1

#6 #5 AND #4

#7 Topic=(dementia OR alzheimer* OR "lew* bod*" OR "parkinson disease dementia" OR VAD OR PDD)

#8 #7 AND #6

#9 Topic=(randomly OR randomized OR randomised OR placebo* OR trial OR RCT)

#10 #9 AND #8

#11 Topic=(#10) AND Year Published=(2009‐2011)

90

7. LILACS (Bireme)

antipsychotic OR antipsychotics OR neuroleptic OR neuroleptics [Words] and dementia OR demenc$ OR alzheimer$ [Words] and 2009 OR 2010 OR 2011 [Country, year publication]

17

8. CENTRAL (Cochrane Library) (Issue 1, January 2011)

#1 "anti‐psychotic*"

#2 antipsychotic*:ti,ab

#3 MeSH descriptor Antipsychotic Agents explode all trees

#4 neuroleptic*:ti,ab

#5 phenothiazines OR butyrophenones OR risperidone OR Risperdal* OR olanzapine

#6 Zyprexa* OR Zalasta* OR Zolafren* OR Olzapin* OR Oferta* OR Zypadhera*

#7 haloperidol

#8 Aloperidin* OR Bioperidolo* OR Brotopon* OR Dozic* OR Duraperidol*

#9 prothipendyl OR methotrimeprazine OR Nosinan* OR Nozinan* OR Levoprome*

#10 clopenthixol OR Sordinol* OR clopentixol OR flupenthixol OR flupentixol OR depixol* OR fluanxol*

#11 clothiapine OR metylperon OR melperon OR droperidol OR Droleptan* OR Dridol* OR Inapsine* OR Xomolix*

#12 pipamperone OR Dipiperon* OR benperidol OR Anquil* OR bromperidol OR Bromidol* OR fluspirilene OR Redeptin* OR Imap*

#13 pimozide OR orap* OR penfluridol OR Semap* OR Micefal*

#14 sulpiride OR veralipride OR Agreal* OR Agradil* OR levosulpiride OR sultopride

#15 Barnetil* OR Barnotil* OR Topral*

#16 aripiprazole OR Abilify* OR Aripiprex* OR clozapine OR Clozaril* OR Azaleptin* OR Leponex* OR Fazaclo* OR Froidir* OR Denzapine* OR Zaponex* OR Klozapol*

#17 quetiapine OR Seroquel* OR Ketipinor*

#18 thioridazine OR Mellaril* OR Novoridazine* OR Thioril*

#19 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18)

#20 Dement*

#21 Deliri*

#22 alzheimer*

#23 "organic brain disease" OR "organic brain syndrome"

#24 creutzfeldt OR jcd OR cjd

#25 huntington*

#26 binswanger*

#27 korsako*

#28 "parkinson* disease dementia*" OR PDD

#29 "lew* bod*" OR DLB OR LDB OR LBD

#30 MeSH descriptor Dementia explode all trees

#31 (#20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30)

#32 (#19 AND #31), from 2009 to 2011

46

9. Clinicaltrials.gov (www.clinicaltrials.gov)

Search 1: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | antipsychotic OR neuroleptic OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR clopenthixol | received from 01/01/2009 to 03/31/2011

Search 2: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | clothiapine OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide | received from 01/01/2009 to 03/31/2011

Search 3: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | penfluridol OR sulpiride OR veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine | received from 01/01/2009 to 03/31/2011

9 + 0 + 2 = 11

10. ICTRP Search Portal (apps.who.int/trialsearch) (includes: Australian New Zealand Clinical Trials Registry; ClinicalTrials.gov; ISRCTN; Chinese Clinical Trial Registry; Clinical Trials Registry – India; Clinical Research Information Service – Republic of Korea; German Clinical Trials Register; Iranian Registry of Clinical Trials; Japan Primary Registries Network; Pan African Clinical Trial Registry; Sri Lanka Clinical Trials Registry; Netherlands National Trial Register)

Search 1: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | antipsychotic OR neuroleptic OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR clopenthixol | received from 01/01/2009 to 03/31/2011

Search 2: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | clothiapine OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide | received from 01/01/2009 to 03/31/2011

Search 3: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | penfluridol OR sulpiride OR veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine | received from 01/01/2009 to 03/31/2011

13

TOTAL before de‐duplication

776

TOTAL after de‐duplication and first‐assess

70

Appendix 3. Top‐up searches: June 2012, November 2012, March 2017, January 2018

Source

Search strategy

Hits retrieved

1. ALOIS (www.medicine.ox.ac.uk/alois)

[Date of most recent search: 10 January 2018]

Antipsychotic OR neuroleptic OR APSY

Jun 2012: 58

Nov 2012: 1

Mar 2017: 0

Jan 2018: 0

2. MEDLINE In‐process and other non‐indexed citations and MEDLINE 1950‐present (Ovid SP)

[Date of most recent search: 10 January 2018]

 

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. Antipsychotic Agents/

4. neuroleptic*.ti,ab.

5. phenothiazines.ti,ab.

6. Phenothiazines/

7. butyrophenones.ti,ab.

8. Butyrophenones/

9. risperidone.ti,ab.

10. Risperidone/

11. Risperdal*.ti,ab.

12. olanzapine.ti,ab.

13. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

14. haloperidol.ti,ab.

15. Haloperidol/

16. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

17. prothipendyl.ti,ab.

18. methotrimeprazine.ti,ab.

19. Methotrimeprazine/

20. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

21. clopenthixol.ti,ab.

22. Clopenthixol/

23. (Sordinol* or clopentixol).ti,ab.

24. flupenthixol.ti,ab.

25. Flupenthixol/

26. (flupentixol or depixol* or fluanxol*).ti,ab.

27. clothiapine.ti,ab.

28. metylperon.ti,ab.

29. melperon.ti,ab.

30. droperidol.ti,ab.

31. Droperidol/

32. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

33. pipamperone.ti,ab.

34. Dipiperon*.ti,ab.

35. benperidol.ti,ab.

36. Benperidol/

37. Anquil*.ti,ab.

38. bromperidol.ti,ab.

39. Bromidol*.ti,ab.

40. fluspirilene.ti,ab.

41. Fluspirilene/

42. (Redeptin* or Imap*).ti,ab.

43. pimozide.ti,ab.

44. Pimozide/

45. orap*.ti,ab.

46. penfluridol.ti,ab.

47. Penfluridol/

48. (Semap* or Micefal*).ti,ab.

49. sulpiride.ti,ab.

50. Sulpiride/

51. veralipride.ti,ab.

52. (Agreal* or Agradil*).ti,ab.

53. levosulpiride.ti,ab.

54. sultopride.ti,ab.

55. (Barnetil* or Barnotil* or Topral*).ti,ab.

56. aripiprazole.ti,ab.

57. (Abilify* or Aripiprex*).ti,ab.

58. clozapine.ti,ab.

59. Clozapine/

60. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

61. quetiapine.ti,ab.

62. (Seroquel* or Ketipinor*).ti,ab.

63. thioridazine.ti,ab.

64. Thioridazine/

65. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

66. or/1‐65

67. exp Dementia/

68. Delirium/

69. Wernicke Encephalopathy/

70. Delirium, Dementia, Amnestic, Cognitive Disorders/

71. dement*.mp.

72. alzheimer*.mp.

73. (lewy* adj2 bod*).mp.

74. deliri*.mp.

75. (chronic adj2 cerebrovascular).mp.

76. ("organic brain disease" or "organic brain syndrome").mp.

77. ("normal pressure hydrocephalus" and "shunt*").mp.

78. "benign senescent forgetfulness".mp.

79. (cerebr* adj2 deteriorat*).mp.

80. (cerebral* adj2 insufficient*).mp.

81. (pick* adj2 disease).mp.

82. (creutzfeldt or jcd or cjd).mp.

83. huntington*.mp.

84. binswanger*.mp.

85. korsako*.mp.

86. or/67‐85

87. 66 and 86

88. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

89. 87 and 88

90. randomized controlled trial.pt.

91. controlled clinical trial.pt.

92. randomized.ab.

93. placebo.ab.

94. drug therapy.fs.

95. randomly.ab.

96. trial.ab.

97. groups.ab.

98. or/90‐97

99. (animals not (humans and animals)).sh.

100. 98 not 99

101. 89 and 100

102. (2011* or 2012*).ed.

103. 101 and 102

Jun 2012: 60

Nov 2012: 28 (plus suppl search hits)

Mar 2017: 284

Jan 2018: 63

3. Embase

1980 to 2018 January 09 (Ovid SP)

[Date of most recent search: 10 January 2018]

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. Antipsychotic Agents/

4. neuroleptic*.ti,ab.

5. phenothiazines.ti,ab.

6. Phenothiazines/

7. butyrophenones.ti,ab.

8. Butyrophenones/

9. risperidone.ti,ab.

10. Risperidone/

11. Risperdal*.ti,ab.

12. olanzapine.ti,ab.

13. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

14. haloperidol.ti,ab.

15. Haloperidol/

16. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

17. prothipendyl.ti,ab.

18. methotrimeprazine.ti,ab.

19. Methotrimeprazine/

20. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

21. clopenthixol.ti,ab.

22. Clopenthixol/

23. (Sordinol* or clopentixol).ti,ab.

24. flupenthixol.ti,ab.

25. Flupenthixol/

26. (flupentixol or depixol* or fluanxol*).ti,ab.

27. clothiapine.ti,ab.

28. metylperon.ti,ab.

29. melperon.ti,ab.

30. droperidol.ti,ab.

31. Droperidol/

32. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

33. pipamperone.ti,ab.

34. Dipiperon*.ti,ab.

35. benperidol.ti,ab.

36. Benperidol/

37. Anquil*.ti,ab.

38. bromperidol.ti,ab.

39. Bromidol*.ti,ab.

40. fluspirilene.ti,ab.

41. Fluspirilene/

42. (Redeptin* or Imap*).ti,ab.

43. pimozide.ti,ab.

44. Pimozide/

45. orap*.ti,ab.

46. penfluridol.ti,ab.

47. Penfluridol/

48. (Semap* or Micefal*).ti,ab.

49. sulpiride.ti,ab.

50. Sulpiride/

51. veralipride.ti,ab.

52. (Agreal* or Agradil*).ti,ab.

53. levosulpiride.ti,ab.

54. sultopride.ti,ab.

55. (Barnetil* or Barnotil* or Topral*).ti,ab.

56. aripiprazole.ti,ab.

57. (Abilify* or Aripiprex*).ti,ab.

58. clozapine.ti,ab.

59. Clozapine/

60. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

61. quetiapine.ti,ab.

62. (Seroquel* or Ketipinor*).ti,ab.

63. thioridazine.ti,ab.

64. Thioridazine/

65. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

66. or/1‐65

67. exp dementia/

68. Lewy body/

69. delirium/

70. Wernicke encephalopathy/

71. cognitive defect/

72. dement*.mp.

73. alzheimer*.mp.

74. (lewy* adj2 bod*).mp.

75. deliri*.mp.

76. (chronic adj2 cerebrovascular).mp.

77. ("organic brain disease" or "organic brain syndrome").mp.

78. "supranuclear palsy".mp.

79. ("normal pressure hydrocephalus" and "shunt*").mp.

80. "benign senescent forgetfulness".mp.

81. (cerebr* adj2 deteriorat*).mp.

82. (cerebral* adj2 insufficient*).mp.

83. (pick* adj2 disease).mp.

84. (creutzfeldt or jcd or cjd).mp.

85. huntington*.mp.

86. binswanger*.mp.

87. korsako*.mp.

88. CADASIL.mp.

89. or/67‐88

90. 66 and 89

91. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

92. 90 and 91

93. randomized controlled trial/

94. randomi?ed.ab.

95. controlled clinical trial/

96. placebo.ab.

97. randomly.ab.

98. trial.ab.

99. groups.ab.

100. or/93‐99

101. 92 and 100

102. (2011* or 2012*).em.

103. 101 and 102

Jun 2012: 109

Nov 2012: 35 (plus suppl search hits)

Mar 2017: 533

Jan 2018: 133

4. PsycINFO

1806 to January week 1 2018 (Ovid SP)

[Date of most recent search: 10 January 2018]

1. antipsychotic*.ti,ab.

2. "anti‐psychotic*".ti,ab.

3. neuroleptic*.ti,ab.

4. phenothiazines.ti,ab.

5. butyrophenones.ti,ab.

6. risperidone.ti,ab.

7. Risperidone/

8. Risperdal*.ti,ab.

9. olanzapine.ti,ab.

10. (Zyprexa* or Zalasta* or Zolafren* or Olzapin* or Oferta* or Zypadhera*).ti,ab.

11. haloperidol.ti,ab.

12. Haloperidol/

13. (Aloperidin* or Bioperidolo* or Brotopon* or Dozic* or Duraperidol*).ti,ab.

14. prothipendyl.ti,ab.

15. methotrimeprazine.ti,ab.

16. (Nosinan* or Nozinan* or Levoprome*).ti,ab.

17. clopenthixol.ti,ab.

18. (Sordinol* or clopentixol).ti,ab.

19. flupenthixol.ti,ab.

20. (flupentixol or depixol* or fluanxol*).ti,ab.

21. clothiapine.ti,ab.

22. droperidol.ti,ab.

23. (Droleptan* or Dridol* or Inapsine* or Xomolix*).ti,ab.

24. pipamperone.ti,ab.

25. Dipiperon*.ti,ab.

26. benperidol.ti,ab.

27. bromperidol.ti,ab.

28. Bromidol*.ti,ab.

29. fluspirilene.ti,ab.

30. (Redeptin* or Imap*).ti,ab.

31. pimozide.ti,ab.

32. Pimozide/

33. orap*.ti,ab.

34. penfluridol.ti,ab.

35. (Semap* or Micefal*).ti,ab.

36. sulpiride.ti,ab.

37. Sulpiride/

38. veralipride.ti,ab.

39. levosulpiride.ti,ab.

40. sultopride.ti,ab.

41. (Barnetil* or Barnotil* or Topral*).ti,ab.

42. aripiprazole.ti,ab.

43. (Abilify* or Aripiprex*).ti,ab.

44. clozapine.ti,ab.

45. Clozapine/

46. (Clozaril* or Azaleptin* or Leponex* or Fazaclo* or Froidir* or Denzapine* or Zaponex* or Klozapol* or Clopine*).ti,ab.

47. quetiapine.ti,ab.

48. (Seroquel* or Ketipinor*).ti,ab.

49. thioridazine.ti,ab.

50. Thioridazine/

51. (Mellaril* or Novoridazine* or Thioril*).ti,ab.

52. (discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*).ti,ab.

53. or/1‐51

54. 52 and 53

55. exp Dementia/

56. exp Delirium/

57. exp Huntingtons Disease/

58. exp Kluver Bucy Syndrome/

59. exp Wernickes Syndrome/

60. exp Cognitive Impairment/

61. dement*.mp.

62. alzheimer*.mp.

63. (lewy* adj2 bod*).mp.

64. deliri*.mp.

65. (chronic adj2 cerebrovascular).mp.

66. ("organic brain disease" or "organic brain syndrome").mp.

67. "supranuclear palsy".mp.

68. ("normal pressure hydrocephalus" and "shunt*").mp.

69. "benign senescent forgetfulness".mp.

70. (cerebr* adj2 deteriorat*).mp.

71. (cerebral* adj2 insufficient*).mp.

72. (pick* adj2 disease).mp.

73. (creutzfeldt or jcd or cjd).mp.

74. huntington*.mp.

75. binswanger*.mp.

76. korsako*.mp.

77. ("parkinson* disease dementia" or PDD or "parkinson* dementia").mp.

78. or/55‐77

79. 54 and 78

80. (2011* or 2012*).up.

81. 79 and 80

Jun 2012: 70

Nov 2012: 58 (plus suppl search hits)

Mar 2017: 281

Jan 2018: 73

5. CINAHL (EBSCO host)

[Date of most recent search: 10 January 2018]

S1 (MH "Dementia+")  

S2 (MH "Delirium") or (MH "Delirium, Dementia, Amnestic, Cognitive Disorders")

S3 (MH "Wernicke's Encephalopathy")  

S4 TX dement*  

S5 TX alzheimer* 

S6 TX lewy* N2 bod*  

S7 TX deliri* 

S8 TX chronic N2 cerebrovascular  

S9 TX "organic brain disease" or "organic brain syndrome"  

S10 TX "normal pressure hydrocephalus" and "shunt*"  

S11 TX "benign senescent forgetfulness" 

S12 TX cerebr* N2 deteriorat* 

S13 TX cerebral* N2 insufficient*  

S14 TX pick* N2 disease

S15 TX creutzfeldt or jcd or cjd  

S16 TX huntington* 

S17 TX binswanger*  

S18 TX korsako* 

S19 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18

S20 TX "cognit* impair*" 

S21 TX "cognit* defect*" 

S22 (MH "Cognition Disorders+") 

S23 TX MCI 

S24 TX ACMI 

S25 TX ARCD 

S26 TX SMC 

S27 TX CIND 

S28 TX BSF 

S29 TX AAMI 

S30 AB MD 

S31 AB LCD 

S32 AB QD OR "questionable dementia"

S33 TX AACD 

S34 TX MNCD 

S35 TX "N‐MCI" or "A‐MCI" or "M‐MCI"

S36 TX "preclinical AD" 

S37 TX "pre‐clinical AD"

S38 TX "preclinical alzheimer*" or "pre‐clinical alzheimer*" 

S39 TX aMCI OR MCIa 

S40 TX "CDR 0.5" or "clinical dementia rating scale 0.5" 

S41 TX "GDS 3" OR "stage 3 GDS"

S42 TX "global deterioration scale" AND "stage 3" 

S43 TX "Benign senescent forgetfulness" 

S44 TX "mild neurocognit* disorder*" 

S45 TX prodrom* N2 dement*

S46 TX "age‐related symptom*" 

S47 TX cognit* N2 deficit*

S48 TX cognit* N2 deteriorat*

S49 TX cognit* N2 declin*

S50 TX cognit* N2 degenerat*

S51 TX cognit* N2 complain* 

S52 TX cognit* N2 disturb* 

S53 TX cognit* N2 disorder*

S54 TX memory N2 episod* or TX memory N2 los* or TX memory N2 impair* or TX memory N2 complain*

S55 TX memory N2 disturb* or TX memory N2 disorder* or TX cerebr* N2 impair* or TX cerebr* N2 los* 

S56 TX cerebr* N2 complain* or TX cerebr* N2 deteriorat* or TX cerebr* N2 disorder* or TX cerebr* N2 disturb* 

S57 TX mental* N2 declin* or TX mental* N2 los* or TX mental* N2 impair* or TX mental* N2 deteriorat* 

S58 TX "pre‐clinical dementia" or TX "preclinical dementia" 

S59 S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46 or S47 or S48 or S49 or S50 or S51 or S52 or S53 or S54 or S55 or S56 or S57 or S58 

S60 S19 or S59 

S61 EM 2011

S62 EM 2012

S63 S61 OR S62

S64 S60 AND S63

Jun 2012: 71

Nov 2012: 51 (plus suppl search hits)

Mar 2017: 26

Jan 2018: 8

6. ISI Web of Knowledge – all databases (includes: Web of Science (1945 to present); BIOSIS Previews (1926 to present); MEDLINE (1950 to present); Journal Citation Reports)

[Date of most recent search: 10 January 2018]

#1 Topic=(antipsychotic* OR neuroleptic* OR phenothiazines OR butyrophenones OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR methotrimeprazine OR clopenthixol OR flupenthixol)

#2 Topic=(clothiapine OR melperon OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide OR penfluridol OR sulpiride)

#3 Topic=(veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine)

#4 Topic=(discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*)

#5 #3 OR #2 OR #1

#6 #5 AND #4

#7 Topic=(dementia OR alzheimer* OR "lew* bod*" OR "parkinson disease dementia" OR VAD OR PDD)

#8 #7 AND #6

#9 Topic=(randomly OR randomized OR randomised OR placebo* OR trial OR RCT)

#10 #9 AND #8

Jun 2012: 56

Nov 2012: 260 (plus suppl search hits)

Mar 2017: 290

Jan 2018: 48

7. LILACS (Bireme)

[Date of most recent search: 10 January 2018]

antipsychotic OR antipsychotics OR neuroleptic OR neuroleptics [Words] and dementia OR demenc$ OR alzheimer$ [Words]

Jun 2012: 6

Nov 2012: 1

Mar 2017: 0

Jan 2018: 0

8. CENTRAL (Cochrane Library) (Issue 1, 2018)

[Date of most recent search: 10 January 2018]

#1 "anti‐psychotic*"

#2 antipsychotic*:ti,ab

#3 MeSH descriptor Antipsychotic Agents explode all trees

#4 neuroleptic*:ti,ab

#5 phenothiazines OR butyrophenones OR risperidone OR Risperdal* OR olanzapine

#6 Zyprexa* OR Zalasta* OR Zolafren* OR Olzapin* OR Oferta* OR Zypadhera*

#7 haloperidol

#8 Aloperidin* OR Bioperidolo* OR Brotopon* OR Dozic* OR Duraperidol*

#9 prothipendyl OR methotrimeprazine OR Nosinan* OR Nozinan* OR Levoprome*

#10 clopenthixol OR Sordinol* OR clopentixol OR flupenthixol OR flupentixol OR depixol* OR fluanxol*

#11 clothiapine OR metylperon OR melperon OR droperidol OR Droleptan* OR Dridol* OR Inapsine* OR Xomolix*

#12 pipamperone OR Dipiperon* OR benperidol OR Anquil* OR bromperidol OR Bromidol* OR fluspirilene OR Redeptin* OR Imap*

#13 pimozide OR orap* OR penfluridol OR Semap* OR Micefal*

#14 sulpiride OR veralipride OR Agreal* OR Agradil* OR levosulpiride OR sultopride

#15 Barnetil* OR Barnotil* OR Topral*

#16 aripiprazole OR Abilify* OR Aripiprex* OR clozapine OR Clozaril* OR Azaleptin* OR Leponex* OR Fazaclo* OR Froidir* OR Denzapine* OR Zaponex* OR Klozapol*

#17 quetiapine OR Seroquel* OR Ketipinor*

#18 thioridazine OR Mellaril* OR Novoridazine* OR Thioril*

#19 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18)

#20 Dement*

#21 Deliri*

#22 alzheimer*

#23 "organic brain disease" OR "organic brain syndrome"

#24 creutzfeldt OR jcd OR cjd

#25 huntington*

#26 binswanger*

#27 korsako*

#28 "parkinson* disease dementia*" OR PDD

#29 "lew* bod*" OR DLB OR LDB OR LBD

#30 MeSH descriptor Dementia explode all trees

#31 (#20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30)

#32 (#19 AND #31)

Jun 2012: 13

Nov 2012: 2 (plus suppl search hits)

Mar 2017: 105

Jan 2018: 96

9. Clinicaltrials.gov (www.clinicaltrials.gov)

[Date of most recent search: 10 January 2018]

Search 1: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | antipsychotic OR neuroleptic OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR clopenthixol

Search 2: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | clothiapine OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide

Search 3: Advanced search: discontinue OR withdraw OR cessation OR reduce or reducing OR reduction OR taper OR stop | dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | penfluridol OR sulpiride OR veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine

Jun 2012: 2 + 0 + 2 = 4

Nov 2012: 0 (plus suppl search hits)

Mar 2017: 1

Jan 2018: 0

10. ICTRP Search Portal (apps.who.int/trialsearch) (includes: Australian New Zealand Clinical Trials Registry; ClinicalTrilas.gov; ISRCTN; Chinese Clinical Trial Registry; Clinical Trials Registry – India; Clinical Research Information Service – Republic of Korea; German Clinical Trials Register; Iranian Registry of Clinical Trials; Japan Primary Registries Network; Pan African Clinical Trial Registry; Sri Lanka Clinical Trials Registry; Netherlands National Trial Register)

[Date of most recent search: 10 January 2018]

Search 1: Advanced search: dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | antipsychotic OR neuroleptic OR risperidone OR olanzapine OR haloperidol OR prothipendyl OR clopenthixol

Search 2: Advanced search: dementia OR alzheimer OR alzhimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | clothiapine OR droperidol OR pipamperone OR benperidol OR bromperidol OR fluspirilene OR pimozide

Search 3: Advanced search: dementia OR alzheimer OR alzheimers OR alzheimer's OR lewy OR DLB OR AD OR LBD | penfluridol OR sulpiride OR veralipride OR levosulpiride OR sultopride OR aripiprazole OR clozapine OR quetiapine OR thioridazine

Jun 2012: 7 + 1 + 4 = 13

Nov 2012: 0 (plus suppl search hits)

Mar 2017: 20

Jan 2018: 3

TOTAL before de‐duplication and first‐assessment

Jun 2012: 454

Nov 2012: 436 (plus Nov suppl search hits)

Mar 2017: 1540

Jan 2018: 424

TOTAL after de‐duplication and first‐assessment by CDCIG Information specialists based on tiles and abstarcts

Jun 2012: 11

Nov 2012: 20

Mar 2017: 75

Jan 2018: 26

Supplementary search of additional antipsychotics not covered in previous searches (all dates)

MEDLINE In‐process and other non‐indexed citations and MEDLINE 1950 to present (Ovid SP)

1. exp Dementia/

2. Delirium/

3. Wernicke Encephalopathy/

4. Delirium, Dementia, Amnestic, Cognitive Disorders/

5. dement*.mp.

6. alzheimer*.mp.

7. (lewy* adj2 bod*).mp.

8. deliri*.mp.

9. (chronic adj2 cerebrovascular).mp.

10. ("organic brain disease" or "organic brain syndrome").mp.

11. ("normal pressure hydrocephalus" and "shunt*").mp.

12. "benign senescent forgetfulness".mp.

13. (cerebr* adj2 deteriorat*).mp.

14. (cerebral* adj2 insufficient*).mp.

15. (pick* adj2 disease).mp.

16. (creutzfeldt or jcd or cjd).mp.

17. huntington*.mp.

18. binswanger*.mp.

19. korsako*.mp.

20. or/1‐19

21. amisulpiride.ti,ab.

22. Chlorpromazine/

23. chlorpromazine.ti,ab.

24. Promazine/

25. promazine.ti,ab.

26. Trifluoperazine/

27. trifluoperazine.ti,ab.

28. Prochlorperazine/

29. prochlorperazine.ti,ab.

30. or/21‐29

31. 20 and 30

32. randomized controlled trial.pt.

33. controlled clinical trial.pt.

34. randomized.ab.

35. placebo.ab.

36. drug therapy.fs.

37. randomly.ab.

38. trial.ab.

39. groups.ab.

40. or/32‐39

41. 31 and 40

194

Embase

1980 to 2012 August 03 (Ovid SP)

1. exp dementia/

2. Lewy body/

3. delirium/

4. Wernicke encephalopathy/

5. cognitive defect/

6. dement*.mp.

7. alzheimer*.mp.

8. (lewy* adj2 bod*).mp.

9. deliri*.mp.

10. (chronic adj2 cerebrovascular).mp.

11. ("organic brain disease" or "organic brain syndrome").mp.

12. "supranuclear palsy".mp.

13. ("normal pressure hydrocephalus" and "shunt*").mp.

14. "benign senescent forgetfulness".mp.

15. (cerebr* adj2 deteriorat*).mp.

16. (cerebral* adj2 insufficient*).mp.

17. (pick* adj2 disease).mp.

18. (creutzfeldt or jcd or cjd).mp.

19. huntington*.mp.

20. binswanger*.mp.

21. korsako*.mp.

22. CADASIL.mp.

23. or/1‐22

24. amisulpride/

25. amisulpiride.ti,ab.

26. chlorpromazine/

27. Chlorpromazine.ti,ab.

28. promazine/

29. promazine.ti,ab.

30. trifluoperazine/

31. trifluoperazine.ti,ab.

32. prochlorperazine/

33. prochlorperazine.ti,ab.

34. or/24‐33

35. 23 and 34

36. randomized controlled trial/

37. controlled clinical trial/

38. randomi?ed.ab.

39. placebo.ab.

40. randomly.ab.

41. trial.ab.

42. groups.ab.

43. ("double‐blind*" or "single‐blind*").ti,ab.

44. or/36‐43

45. 35 and 44

425

PsycINFO

1806 to July week 5 2012 (Ovid SP)

1. exp Dementia/

2. exp Delirium/

3. exp Huntingtons Disease/

4. exp Kluver Bucy Syndrome/

5. exp Wernickes Syndrome/

6. exp Cognitive Impairment/

7. dement*.mp.

8. alzheimer*.mp.

9. (lewy* adj2 bod*).mp.

10. deliri*.mp.

11. (chronic adj2 cerebrovascular).mp.

12. ("organic brain disease" or "organic brain syndrome").mp.

13. "supranuclear palsy".mp.

14. ("normal pressure hydrocephalus" and "shunt*").mp.

15. "benign senescent forgetfulness".mp.

16. (cerebr* adj2 deteriorat*).mp.

17. (cerebral* adj2 insufficient*).mp.

18. (pick* adj2 disease).mp.

19. (creutzfeldt or jcd or cjd).mp.

20. huntington*.mp.

21. binswanger*.mp.

22. korsako*.mp.

23. ("parkinson* disease dementia" or PDD or "parkinson* dementia").mp.

24. or/1‐23

25. amisulpiride.ti,ab.

26. Chlorpromazine/

27. chlorpromazine.ti,ab.

28. Promazine/

29. promazine.ti,ab.

30. Trifluoperazine/

31. trifluoperazine.ti,ab.

32. Prochlorperazine/

33. prochlorperazine.ti,ab.

34. or/25‐33

35. 24 and 34

36. randomized.ab.

37. placebo.ab.

38. randomly.ab.

39. trial.ab.

40. groups.ab.

41. "control group".ab.

42. ("double‐blind*" or "single‐blind*").ti,ab.

43. exp Clinical Trials/

44. or/36‐43

45. 35 and 44

27

Total for supplementary searches

646

Total for pre‐publication and supplementary search

1100

Total post first assess and de‐duplication

33

Appendix 4. Abbreviations

ADAS

Alzheimer's Disease Assessment Scale (ADAS)

AIMS

Abnormal Involuntary Movement Scale

BADLS

Bristol Activities of Daily Living Scale

BCRS

Brief Cognitive Rating Scale

BDS

Blessed Dementia Scale

BEHAVE‐AD

Behavioural Pathology in Alzheimer's disease Rating Scale

BFAS

Blessed Functional Activity Scale

BPRS

Brief Psychiatric Rating Scale

CAS

Cognitive Assessment Scale

CDR

Clinical Dementia Rating Scale

CERAD

Consortium to Establish a Registry for Alzheimer's Disease

CGI‐C

Clinical Global Impression‐Change

CMAI

Cohen‐Mansfield Agitation inventory

CUSPAD

Columbia University Scale for Psychopathology in Alzheimer's Disease

DCM

Dementia Care Mapping

DSM‐III

Diagnostic and Statistical Manual of Mental Disorders, 3th Edition

DSM‐IV

Diagnostic and Statistical Manual of Mental Disorders, 4th Edition

ESRS

Extrapyramidal Symptom Rating Scale

FAS

F‐A‐S scale, assessing phonemic verbal fluency

FAST

Functional Assessment Staging

FDA

Food and Drug Administration

ICD‐9

International Statistical Classification of Diseases and Related Health Problems, Ninth Revision

ICD‐10

International Statistical Classification of Diseases and Related Health Problems, Tenth Revision

LPRS

London Psychogeriatric Rating Scale Score

MDRS

Mattis Dementia Rating Scale

mITT

modified intention‐to‐treat

MMSE

Mini‐Mental State Examination

M‐UPDRS

Modified Unified Parkinson's Disease Rating Scale

NINCDS‐ADRDA

National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association

NPI

Neuropsychiatric Inventory Score

NPS

Neuropsychiatric symptoms

PAB

Physical Aggressive Behaviour

PSMS

Physical Self‐Maintenance Scale

QoL

Quality of life

ROAS

Retrospective Overt Aggression scale

RTD

Rockland Tardive Dyskinesia

SCAGS

Sandoz Clinical Assessment Geriatric Scale

SIB

Severe Impairment Battery

SMMSE

Standardised Mini‐Mental State Examination

STALD

Sheffield Test for Acquired Language Disorder = STALD receptive and STALD expressive skill

TESS

Treatment Emergent Symptom Scale

UPDRS

Unified Parkinson's Disease Rating Scale

Forest plot of comparison: 1 Discontinuation versus continuation of long‐term antipsychotic drug use: continuous data, analysis method: mean difference, outcome: 1.1 Behavioural assessment by using Neuropsychiatric Inventory (NPI) measuring neuropsychiatric symptoms (NPS) at 3 months (Ballard 2004 and Ballard DART‐AD) (Analysis 1.1).

Figuras y tablas -
Figure 1

Forest plot of comparison: 1 Discontinuation versus continuation of long‐term antipsychotic drug use: continuous data, analysis method: mean difference, outcome: 1.1 Behavioural assessment by using Neuropsychiatric Inventory (NPI) measuring neuropsychiatric symptoms (NPS) at 3 months (Ballard 2004 and Ballard DART‐AD) (Analysis 1.1).

Inclusions of trials of study flow diagram 2018

Figuras y tablas -
Figure 2

Inclusions of trials of study flow diagram 2018

Risk of bias graph for the 10 included studies in the review.

Figuras y tablas -
Figure 3

Risk of bias graph for the 10 included studies in the review.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study in the review.

Figuras y tablas -
Figure 4

Risk of bias summary: review authors' judgements about each risk of bias item for each included study in the review.

Comparison 1: Discontinuation versus continuation of long‐term antipsychotic drug use (continuous data, analysis method mean difference), Outcome 1: Behavioural assessment

Figuras y tablas -
Analysis 1.1

Comparison 1: Discontinuation versus continuation of long‐term antipsychotic drug use (continuous data, analysis method mean difference), Outcome 1: Behavioural assessment

Summary of findings 1. Discontinuation compared to continuation of antipsychotic medication for behavioural and psychological symptoms in older people with dementia

Discontinuation compared to continuation of antipsychotic medication for behavioural and psychological symptoms in older participants with dementia

Patient or population: older people with dementia who had been taking an antipsychotic drug for at least 3 months
Setting: any setting
Intervention: discontinuation of long‐term antipsychotic drug use
Comparison: continuation of long‐term antipsychotic drug use

Outcomes

Illustrative comparative risks (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Continuation antipsychotics

Corresponding risk

Discontinuation antipsychotics

Success of withdrawal from antipsychotics

Measured with a variety of outcomes related to failure to complete the study

Follow‐up: 1 to 8 months

In 7 studies there was no overall difference in the outcomes reported for success of withdrawal.

In two studies of participants with psychosis, aggression or agitation who had responded to antipsychotic treatment, discontinuation accelerated symptomatic relapse without affecting the number of participants experiencing a relapse in one study and was associated with a higher rate of symptomatic relapse in the other study.

In one small study a high proportion of the participants in the discontinuation group failed to complete the study.

575 (9 RCTs)

⊕⊕⊝⊝

LOWab

Our intended primary outcome, success of withdrawal defined as the ability to complete the study in the allocated study group, i.e. no failure due to worsening of NPS or relapse to antipsychotic drug use, was not reported in any study. We used the difference between groups in the number of non‐completers of the study as a proxy for our primary outcome. However, data could not be pooled due to variability in outcome measures.

Behavioural and psychological symptoms

Assessed with various scales.

Follow up: 1 to 8 months

In 2 pooled studies there was no difference in NPI scores between the continuation and discontinuation groups (see Data and analyses and Figure 1).

In five non‐pooled studies, there was no difference in the outcomes on scales measuring overall behaviour and psychological symptoms between groups.

519 (7 RCTs)

⊕⊕⊝⊝
LOW⊝bc

Data could only be pooled for 2 studies due to variability in outcome measures.

The two pooled studies performed subgroup analyses according to baseline NPI‐score (≤ 14 or > 14). In one study, some participants with milder symptoms at baseline were less agitated at three months in the discontinuation group. In both studies, discontinuation led to worsening of NPS in some participants with more severe baseline NPS.

Adverse events

Assessed with various scales.

Follow‐up: 1 to 8 months

In 5 studies, there was no evidence of a difference between groups in adverse events.

381 (5 RCTs)

⊕⊕⊝⊝

LOWab

Data could not be pooled due to variability in outcome measures. Adverse events of antipsychotics were not systematically reported.

Quality of life (QoL)

Assessed with DCM or QoL‐AD.

Follow‐up: 3 months to 25 weeks

In 2 studies, there was no evidence of an effect on quality of life.

119 (2 RCTs)

⊕⊕⊝⊝
LOWbc

Data could not be pooled due to variability in outcome measures.

There was no difference between discontinuation and continuation group in the overall cohort or in subgroups with baseline NPI score above or below the median (14).

Cognitive function

Assessed with various scales.

Follow‐up: 1 to 8 months

In 5 studies, there was no evidence of an impact on scales measuring overall cognitive function.

In one of these trials, discontinuation improved a measure of verbal fluency.

365 (5 RCTs)

⊕⊕⊝⊝
LOWbc

Data could not be pooled due to variability in outcome measures.

Use of physical restraint

Follow‐up: 1 month

In one study there was no effect on the use of physical restraint.

36 (1 RCT)

⊕⊝⊝⊝
VERY LOWcd

Conclusion made by the authors but not supported by data.

Mortality

Assessed with various scales.

Follow‐up: 4 to 12 months

In two studies there was no evidence of an effect on mortality.

275 (2 RCTs)

⊕⊝⊝⊝
VERY LOWcd

Data could not be pooled due to clinical heterogeneity.

In a long‐term follow‐up of 36 months after the 12 months randomised discontinuation trial (Devanand 2012), we were uncertain whether discontinuation decreased mortality.

*The basis for the assumed risk (e.g. the median control group risk across the studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High‐quality evidence: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐quality evidence: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low‐quality evidence: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low‐quality evidence: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

a Downgraded one level for indirectness.

b Downgraded one level for risk of bias.

c Downgraded one level for imprecision due to a small number of participants.

d Downgraded two level for risk of bias.

Figuras y tablas -
Summary of findings 1. Discontinuation compared to continuation of antipsychotic medication for behavioural and psychological symptoms in older people with dementia
Table 1. Antipsychotic drug classes

Phenothiazines with aliphatic side chain

Phenothiazines with piperazine structure

Fhenothiazines with piperidine structure

Butyrophenone derivatives

Indole derivatives

Thioxanthene derivatives

Diphenylbutylpiperidine derivatives

Diazepines, Oxazepines and Thiazepines

Benzamides

Other antipsychotics

Figuras y tablas -
Table 1. Antipsychotic drug classes
Table 2. Antipsychotic drugs with defined daily doses

Phenothiazines with aliphatic side‐chain

N05AA01 Chlorpromazine 0.3 g per os

N05AA02 Levomepromazine 0.3 g per os

N05AA03 Promazine 0.3 g per os

N05AA04 Acepromazine 0.1 g per os

N05AA05 Triflupromazine 0.1 g per os

N05AA06 Cyamemazine

N05AA07 Chlorproethazine

Phenothiazines with piperazine structure

N05AB01 Dixyrazine 50 mg per os

N05AB02 Fluphenazine 10 mg per os

N05AB03 Perphenazine 30 mg per os

N05AB04 Prochlorperazine 0.1 g per os

N05AB05 Thiopropazate 60 mg per os

N05AB06 Trifluoperazine 20 mg per os

N05AB07 Acetophenazine 50 mg per os

N05AB08 Thioproperazine 20 mg per os

N05AB09 Butaperazine 10 mg per os

N05AB10 Perazine 0.1 g per os

N05AB20 Homophenazine

Phenothiazines with piperidine structure

N05AC01 Periciazine 50 mg per os

N05AC02 Thioridazine 0.3 g per os

N05AC03 Mesoridazine 0.2 g per os

N05AC04 Pipotiazine 10 mg per os

Butyrophenone derivatives

N05AD01 Haloperidol 8 mg per os

N05AD02 Trifluperidol 2 mg per os

N05AD03 Melperone* 0.3 g per os

N05AD04 Moperon 20 mg per os

N05AD05 Pipamperone 0.2 g per os

N05AD06 Bromperidol 10 mg per os

N05AD07 Benperidol 1.5 mg per os

N05AD08 Droperidol

N05AD09 Fluanisone

N05AE Indole derivatives

N05AE01 Oxypertine 0.12 g per os

N05AE02 Molindone 50 mg per os

N05AE03 Sertindole* 16 mg per os

N05AE04 Ziprasidone* 80 mg per os

Thioxanthene derivatives

N05AF01 Flupentixol 6 mg per os

N05AF02 Clopenthixol 0.1 g per os

N05AF03 Chlorprothixene 0.3 g per os

N05AF04 Tiotixene 30 mg per os

N05AF05 Zuclopenthixol 30 mg per os

Diphenylbutylpiperidine derivatives

N05AG01 Fluspirilene

N05AG02 Pimozide 4 mg per os

N05AG03 Penfluridol 6 mg per os

Diazepines, Oxazepines and Thiazepines

N05AH01 Loxapine 0.1 g per os

N05AH02 Clozapine* 0.3 g per os

N05AH03 Olanzapine* 10 mg per os

N05AH04 Quetiapine* 0.4 g per os

Benzamides

N05AL01 Sulpiride 0.8 g per os

N05AL02 Sultopride 1.2 g per os

N05AL03 Tiapride 0.4 g per os

N05AL04 Remoxipride 0.3 g per os

N05AL05 Amisulpride* 0.4 g per os

N05AL06 Veralipride

N05AL07 Levosulpiride 0.4 g per os

Other antipsychotics

N05AX07 Prothipendyl 0.24 g per os

N05AX08 Risperidone* 5 mg per os

N05AX09 Clotiapine 80 mg per os

N05AX10 Mosapramine*

N05AX11 Zotepine* 0.2 g per os

N05AX12 Aripiprazole* 15 mg per os

N05AX13 Paliperidone*

*atypical antipsychotics

* Atypical antipsychotic agents.

Figuras y tablas -
Table 2. Antipsychotic drugs with defined daily doses
Table 3. Characteristics of included studies

Study IDI

Setting

Duration

Randomised number

Discontinuation group

Continuation group

Discontinuation schedule

Control

Behavioural inclusion criteria

Notes

Ballard 2004

Residents in long‐term care facilities

3 months

100

46

54

Abrupt

Typical APa or risperidone

NPIb not higher than 7

Ballard 2008

Residents in long‐term care facilities

6 months

12 months

165

82

83

Abrupt

Typical and risperidone

NRc

Bergh 2011

Residents in nursing homes

25 weeks

19

9

10

Tapering over 2 week

Risperidone

NRc

Unpublished study

Bridges‐Parlet 1997

Residents in long‐term care facilities

1 month

36

22

14

Abrupt + tapering over 2 weeks

Typical APa

Physically aggressive participants identified by nurse supervisors

Cohen‐Mansfield 1999

Residents in nursing homes

7 weeks followed by 7 weeks cross‐over

58

29

29

Tapering over 3 weeks

Typical APa + lorazepam

NRc

Cross‐over study

Devanand 2011

Residents in the community

6 months (primary analysis)

12 months

20

10

10

Abrupt + tapering over 2 weeks

Haloperidol

Current symptoms of psychosis, agitation or aggression

Participants had a response to haloperidol open treatment for 20 weeks

Devanand 2012

Residents in the community and

nursing homes

4 months

8 months

110

70

40

Abrupt + tapering over 2 week

Risperidone

NPIb score higher than 4 on psychosis or agitation/aggression subscale

Participants had a response to risperidone open treatment for 16 weeks

Findlay 1989

Residents in nursing homes

1 month

36

18

18

Tapering over 1 week

Thioridazine

NRc

Ruths 2008

Residents in nursing homes

1 month

55

27

28

Abrupt

Haloperidol risperidone, olanzapine

All participants regardless individual symptoms

van Reekum 2002

Residents in nursing homes

26 weeks

34

17

17

Tapering over 2 weeks

Typical APa

Stable behaviour

a AP: antipsychotic drug.

b NPI: Neuropsychiatric Inventory.

c NR: not reported.

Figuras y tablas -
Table 3. Characteristics of included studies
Comparison 1. Discontinuation versus continuation of long‐term antipsychotic drug use (continuous data, analysis method mean difference)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Behavioural assessment Show forest plot

2

194

Mean Difference (IV, Fixed, 95% CI)

‐1.49 [‐5.39, 2.40]

Figuras y tablas -
Comparison 1. Discontinuation versus continuation of long‐term antipsychotic drug use (continuous data, analysis method mean difference)