Appendix 1. Search strategy used in 2003

The search strategy combined the subject search with phases 1 and 2 of the Cochrane Sensitive Search Strategy for RCTs (as published in Appendix 5c in the Cochrane Handbook for
Systematic Reviews of Interventions).

The subject search used a combination of controlled vocabulary and free‐text terms in addition to the basic Cochrane Sensitive Search Strategy. These terms included the following:

Disease: anxiety, agitation, adjustment disorders, obsessive‐compulsive disorders, phobias, panic disorders, post‐traumatic stress disorder, generalised anxiety disorders and terminal restlessness.

Individual treatments: alprazolam, bromazepam, chlordiazepoxide, clobazam, clonazepam, chlorazepate, diazepam, estazolam, flunitrazepam, flurazepam, halazepam, ketazolam, lorazepam, midazolam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, triazolam, buspirone, hydroxyzine, amitriptyline, nortriptyline, desipramine, doxepin, fluoxetine, paroxetine, sertraline, citalopram, venlafaxine, droperidol, haloperidol, chlorpromazine, olanzapine, risperidone, thioridazine, methotrimeprazine and propofol.

Drug class names: anxiolytics, antidepressants, antipsychotics, benzodiazepines, butyrophenones, phenothiazines and thienobenzodiazepine.

Appendix 2. MEDLINE search 2012

MEDLINE Ovid

1 exp Anxiety/

2 exp Anxiety Disorders/

3 Adjustment Disorders/

4 Psychomotor Agitation/

5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp.

6 1 or 2 or 3 or 4 or 5

7 drug therapy.fs.

8 exp Anti‐Anxiety Agents/

9 exp Antidepressive Agents/

10 exp Antipsychotic Agents/

11 exp Benzodiazepines/

12 exp Butyrophenones/

13 exp Phenothiazines/

14 exp Monoamine Oxidase Inhibitors/

15 exp Serotonin Agents/

16 exp Histamine Agents/

17 exp Barbiturates/

18 exp "Hypnotics and Sedatives"/

19 exp Adrenergic Agents/

20 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or droperidol or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propofol or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp.

21 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20

22 Palliative Care/

23 exp Terminal Care/

24 Terminally Ill/

25 palliat*.mp.

26 (terminal* adj6 (care or ill* or diseas*)).mp.

27 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp.

28 (end adj3 life).mp.

29 hospice*.mp.

30 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp.

31 (incurable adj6 (disease* or illness*)).mp.

32 (advanced adj6 disease*).mp.

33 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32

34 6 and 21 and 33

35 randomized controlled trial.pt.

36 controlled clinical trial.pt.

37 randomized.ab.

38 placebo.ab.

39 drug therapy.fs.

40 randomly.ab.

41 trial.ab.

42 groups.ab.

43 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42

44 34 and 43

key:

mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier

pt=publication type

ab=abstract

fs=floating subheading

Appendix 3. CENTRAL search 2012

#1 MeSH descriptor Anxiety explode all trees

#2 MeSH descriptor Anxiety Disorders explode all trees

#3 MeSH descriptor Adjustment Disorders, this term only

#4 MeSH descriptor Psychomotor Agitation, this term only

#5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*)

#6 (#1 OR #2 OR #3 OR #4 OR #5)

#7 Any MeSH descriptor with qualifier: DT

#8 MeSH descriptor Anti‐Anxiety Agents explode all trees

#9 MeSH descriptor Antidepressive Agents explode all trees

#10 MeSH descriptor Antipsychotic Agents explode all trees

#11 MeSH descriptor Benzodiazepines explode all trees

#12 MeSH descriptor Butyrophenones explode all trees

#13 MeSH descriptor Phenothiazines explode all trees

#14 MeSH descriptor Monoamine Oxidase Inhibitors explode all trees

#15 MeSH descriptor Serotonin Agents explode all trees

#16 MeSH descriptor Histamine Agents explode all trees

#17 MeSH descriptor Barbiturates explode all trees

#18 MeSH descriptor Hypnotics and Sedatives explode all trees

#19 MeSH descriptor Adrenergic Agents explode all trees

#20 acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisprolol or bromazepam or buproprion or buspirone or carbamezepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlopromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cypropheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or droperidol or doloxetin

#21 escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propofol or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem

#22 (#7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21)

#23 MeSH descriptor Palliative Care, this term only

#24 MeSH descriptor Terminal Care explode all trees

#25 MeSH descriptor Terminally Ill, this term only

#26 palliat*

#27 terminal* near/6 (care or ill* or diseas*)

#28 end near/6 life

#29 hospice*

#30 (end ‐stage* or end stage*) near/6 (disease* or illness* or care)

#31 incurable near/6 (disease* or illness*)

#32 advanced near/6 disease*

#33 terminal‐stage* or terminal stage* or dying or (close near/6 death)

#34 (#23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33)

#35 (#6 AND #22 AND #34)

Appendix 4. Embase search 2012

Embase Ovid

1 anxiety/

2 exp anxiety disorder/

3 adjustment disorder/

4 agitation/

5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp.

6 1 or 2 or 3 or 4 or 5

7 dt.fs.

8 exp anxiolytic agent/

9 exp antidepressant agent/

10 exp neuroleptic agent/

11 exp benzodiazepine derivative/

12 exp butyrophenone derivative/

13 exp phenothiazine derivative/

14 exp serotonin receptor affecting agent/

15 exp histaminergic receptor affecting agent/

16 exp barbituric acid derivative/

17 exp hypnotic sedative agent/

18 beta adrenergic receptor blocking agent/ or exp adrenergic receptor blocking agent/

19 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or droperidol or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propofol or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp.

20 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19

21 exp palliative therapy/

22 exp terminally ill patient/

23 exp terminal care/

24 palliat*.mp.

25 (terminal* adj6 (care or ill* or diseas*)).mp.

26 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp.

27 (end adj3 life).mp.

28 hospice*.mp.

29 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp.

30 (incurable adj6 (disease* or illness*)).mp.

31 (advanced adj6 disease*).mp.

32 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31

33 6 and 20 and 32

34 crossover procedure/

35 randomized controlled trial/

36 single blind procedure/

37 random*.mp.

38 factorial*.mp.

39 (crossover* or cross over* or cross‐over).mp.

40 placebo*.mp.

41 (doubl* adj blind*).mp.

42 (singl* adj blind*).mp.

43 assign*.mp.

44 allocat*.mp.

45 volunteer*.mp.

46 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45

47 33 and 46

key:

[mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

Appendix 5. PsycINFO search 2012

PsycINFO Ovid

1 exp anxiety/

2 exp anxiety disorders/

3 adjustment disorders/

4 Agitation/

5 restlessness/

6 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp.

7 1 or 2 or 3 or 4 or 5 or 6

8 exp drug therapy/

9 exp tranquilizing drugs/

10 exp antidepressant drugs/

11 benzodiazepines/

12 exp monoamine oxidase inhibitors/

13 exp neurotransmitter uptake inhibitors/

14 exp antihistaminic drugs/

15 exp barbiturates/

16 exp hypnotic drugs/

17 exp sedatives/

18 exp adrenergic blocking drugs/

19 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or droperidol or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propofol or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp.

20 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19

21 palliative care/

22 hospice/

23 palliat*.mp.

24 (terminal* adj6 (care or ill* or diseas*)).mp.

25 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp.

26 (end adj3 life).mp.

27 hospice*.mp.

28 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp.

29 (incurable adj6 (disease* or illness*)).mp.

30 (advanced adj6 disease*).mp.

31 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30

32 7 and 20 and 31

key:

mp=title, abstract, heading word, table of contents, key concepts, original title, tests & measures

Appendix 6. CINAHL plus 2012

1. MW anxiety

2. MH exp adjustment disorders

3. MH agitation

4. (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*)

5. 1 or 2 or 3 or 4

6. MH exp drug therapy

7. MH exp tranquilizing agents

8. MH exp antidepressant agents

9. MH exp antianxiety agents

10. MH exp monoamine oxidase inhibitors

11. MH exp neurotransmitter uptake inhibitors

12. MH exp histamine agents

13. MH exp barbiturates

14. MH exp hypnotic and sedatives

15. MH exp adrenergic agents

16. MH exp antipsychotic agents

17. (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or droperidol or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propofol or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp.

18. 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17

19. MH palliative care

20. MH hospice

21. MH exp terminally ill patient

22. terminal care or ill* or diseas*

23. terminal disease

24. terminal stage* or terminal‐stage*

25. dying

26. hospice

27. end‐stage or end stage

28. incurable disease

29. advanced disease

30. incurable illness

31. 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30

32. 5 and 18 and 31

Appendix 7. Antiepileptic drugs

To enhance the completeness of this review an additional search was run in January 2012 for antiepileptic drugs. The searches were run on MEDLINE, Embase, CINAHL, PsycINFO and CENTRAL. In these searches we used the following terms for the intervention:

exp Antiepileptic Agents/

carbamazepine or eslicarbazepine or ethosuximide or gabapentin or lacosamide or lamotrigine or levetiracetam or oxcarbazepine or phenobarbital or pregabalin or primidone or phenytoin or retigabine or rufinamide or tiagabine or topiramate or valproate or vigabatrin or zonisamide.

Appendix 8. Searches run in May 2016

CENTRAL (CRSO)

#1 MESH DESCRIPTOR Anxiety EXPLODE ALL TREES 5582

#2 MESH DESCRIPTOR Anxiety Disorders EXPLODE ALL TREES 4375

#3 MESH DESCRIPTOR Adjustment Disorders EXPLODE ALL TREES 192

#4 MESH DESCRIPTOR Psychomotor Agitation EXPLODE ALL TREES 602

#5 ((anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*)):TI,AB,KY 65130

#6 #1 OR #2 OR #3 OR #4 OR #5 65442

#7 MESH DESCRIPTOR drug therapy EXPLODE ALL TREES 117835

#8 MESH DESCRIPTOR Anti‐Anxiety Agents EXPLODE ALL TREES 8799

#9 MESH DESCRIPTOR Antidepressive Agents EXPLODE ALL TREES 10354

#10 MESH DESCRIPTOR Antipsychotic Agents EXPLODE ALL TREES 7126

#11 MESH DESCRIPTOR Benzodiazepines EXPLODE ALL TREES 7745

#12 MESH DESCRIPTOR Butyrophenones EXPLODE ALL TREES 1787

#13 MESH DESCRIPTOR Phenothiazines EXPLODE ALL TREES 2181

#14 MESH DESCRIPTOR Monoamine Oxidase Inhibitors EXPLODE ALL TREES 854

#15 MESH DESCRIPTOR Serotonin Agents EXPLODE ALL TREES 11113

#16 MESH DESCRIPTOR Histamine Agents EXPLODE ALL TREES 7708

#17 MESH DESCRIPTOR Barbiturates EXPLODE ALL TREES 1837

#18 MESH DESCRIPTOR Hypnotics and Sedatives EXPLODE ALL TREES 11260

#19 MESH DESCRIPTOR Adrenergic Agents EXPLODE ALL TREES 27721

#20 ((acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem)):TI,AB,KY 59251

#21 ((Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine)):TI,AB,KY 5824

#22 #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 190456

#23 MESH DESCRIPTOR Palliative Care 1215

#24 MESH DESCRIPTOR Terminal Care EXPLODE ALL TREES 315

#25 MESH DESCRIPTOR Terminally Ill 60

#26 palliat*:TI,AB,KY 3307

#27 ((terminal* near6 (care or ill* or diseas*))):TI,AB,KY 563

#28 ((terminal‐stage* or terminal stage* or dying or (close adj6 death))):TI,AB,KY 510

#29 ((end adj3 life)):TI,AB,KY 352

#30 hospice*:TI,AB,KY 280

#31 (((end‐stage* or end stage*) adj6 (disease* or illness* or care))):TI,AB,KY 1869

#32 ((incurable adj6 (disease* or illness*))):TI,AB,KY 51

#33 ((advanced adj6 disease*)):TI,AB,KY 2462

#34 #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 8421

#35 #6 AND #22 AND #34 90

#36 14/03/2012 TO 31/05/2016:DL 272867

#37 #35 AND #36 27

MEDLINE (Ovid)

1 exp Anxiety/ (64420)

2 exp Anxiety Disorders/ (69302)

3 Adjustment Disorders/ (4031)

4 Psychomotor Agitation/ (4308)

5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp. (1246199)

6 or/1‐5 (1260505)

7 drug therapy.fs. (1854584)

8 exp Anti‐Anxiety Agents/ (60302)

9 exp Antidepressive Agents/ (128780)

10 exp Antipsychotic Agents/ (110788)

11 exp Benzodiazepines/ (60534)

12 exp Butyrophenones/ (21427)

13 exp Phenothiazines/ (48388)

14 exp Monoamine Oxidase Inhibitors/ (20566)

15 exp Serotonin Agents/ (144506)

16 exp Histamine Agents/ (88729)

17 exp Barbiturates/ (52978)

18 exp "Hypnotics and Sedatives"/ (111515)

19 exp Adrenergic Agents/ (355644)

20 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp. (304943)

21 (Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] (66773)

22 or/7‐21 (2507015)

23 Palliative Care/ (44411)

24 exp Terminal Care/ (43801)

25 Terminally Ill/ (5769)

26 palliat*.mp. (69308)

27 (terminal* adj6 (care or ill* or diseas*)).mp. (33751)

28 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp. (29543)

29 (end adj3 life).mp. (14084)

30 hospice*.mp. (12120)

31 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp. (33473)

32 (incurable adj6 (disease* or illness*)).mp. (2694)

33 (advanced adj6 disease*).mp. (35405)

34 or/23‐33 (202878)

35 randomized controlled trial.pt. (415460)

36 controlled clinical trial.pt. (90651)

37 randomized.ab. (312371)

38 placebo.ab. (158310)

39 drug therapy.fs. (1854584)

40 randomly.ab. (220598)

41 trial.ab. (323081)

42 groups.ab. (1391694)

43 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 (3523448)

44 exp animals/ not humans.sh. (4239199)

45 43 not 44 (3001538)

46 6 and 22 and 34 and 45 (1510)

47 (2012* or 2013* or 2014* or 2015* or 2016*).ed. (3534743)

48 46 and 47 (382)

Embase (Ovid)

1 exp Anxiety/ (146866)

2 exp Anxiety Disorders/ (174195)

3 Adjustment Disorders/ (2312)

4 Psychomotor Agitation/ (5927)

5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp. (2126678)

6 or/1‐5 (2147293)

7 drug therapy.fs. (3275744)

8 exp Anti‐Anxiety Agents/ (172725)

9 exp Antidepressive Agents/ (349098)

10 exp Antipsychotic Agents/ (244079)

11 exp Benzodiazepines/ (162297)

12 exp Butyrophenones/ (69061)

13 exp Phenothiazines/ (98054)

14 exp Monoamine Oxidase Inhibitors/ (44772)

15 exp Serotonin Agents/ (339905)

16 exp Histamine Agents/ (229873)

17 exp Barbiturates/ (139016)

18 exp "Hypnotics and Sedatives"/ (328978)

19 exp Adrenergic Agents/ (507749)

20 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp. (712225)

21 (Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine).mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword] (124603)

22 or/7‐21 (4380654)

23 Palliative Care/ (48518)

24 exp Terminal Care/ (52379)

25 Terminally Ill/ (6594)

26 palliat*.mp. (113733)

27 (terminal* adj6 (care or ill* or diseas*)).mp. (45785)

28 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp. (42652)

29 (end adj3 life).mp. (22725)

30 hospice*.mp. (19005)

31 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp. (58599)

32 (incurable adj6 (disease* or illness*)).mp. (4815)

33 (advanced adj6 disease*).mp. (57862)

34 or/23‐33 (315911)

35 random$.tw. (1080929)

36 factorial$.tw. (27596)

37 crossover$.tw. (57278)

38 cross over$.tw. (25537)

39 cross‐over$.tw. (25537)

40 placebo$.tw. (237354)

41 (doubl$ adj blind$).tw. (167979)

42 (singl$ adj blind$).tw. (17556)

43 assign$.tw. (285956)

44 allocat$.tw. (103682)

45 volunteer$.tw. (206547)

46 Crossover Procedure/ (46987)

47 double‐blind procedure.tw. (235)

48 Randomized Controlled Trial/ (403142)

49 Single Blind Procedure/ (22048)

50 or/35‐49 (1693538)

51 (animal/ or nonhuman/) not human/ (5029808)

52 50 not 51 (1503726)

53 6 and 22 and 34 and 52 (591)

54 (2012* or 2013* or 2014* or 2015* or 2016*).dd. (6852351)

55 53 and 54 (227)

PsycINFO (Ovid)

1 exp Anxiety/ (58004)

2 exp Anxiety Disorders/ (68090)

3 Adjustment Disorders/ (570)

4 Agitation/ (1198)

5 restlessness/ (321)

6 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp. (486813)

7 or/1‐6 (487305)

8 exp drug therapy/ (125834)

9 exp tranquilizing drugs/ (41641)

10 exp antidepressant drugs/ (34233)

11 benzodiazepines/ (4635)

12 exp monoamine oxidase inhibitors/ (2163)

13 exp neurotransmitter uptake inhibitors/ (12703)

14 exp antihistaminic drugs/ (984)

15 exp barbiturates/ (2092)

16 exp hypnotic drugs/ (5517)

17 exp sedatives/ (18535)

18 exp adrenergic blocking drugs/ (3619)

19 (acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem).mp. (66204)

20 (Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine).mp. (8915)

21 or/8‐20 (180411)

22 palliative care/ (8996)

23 hospice/ (2649)

24 palliat*.mp. (11674)

25 (terminal* adj6 (care or ill* or diseas*)).mp. (6641)

26 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp. (31725)

27 (end adj3 life).mp. (7716)

28 hospice*.mp. (4266)

29 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp. (1314)

30 (incurable adj6 (disease* or illness*)).mp. (402)

31 (advanced adj6 disease*).mp. (2076)

32 or/22‐31 (48760)

33 7 and 21 and 32 (404)

34 clinical trials/ (9558)

35 (randomis* or randomiz*).tw. (60920)

36 (random$ adj3 (allocat$ or assign$)).tw. (34606)

37 ((clinic$ or control$) adj trial$).tw. (51502)

38 ((singl$ or doubl$ or trebl$ or tripl$) adj3 (blind$ or mask$)).tw. (22211)

39 (crossover$ or "cross over$").tw. (8245)

40 random sampling/ (688)

41 Experiment Controls/ (855)

42 Placebo/ (4532)

43 placebo$.tw. (34693)

44 exp program evaluation/ (17993)

45 treatment effectiveness evaluation/ (19892)

46 ((effectiveness or evaluat$) adj3 (stud$ or research$)).tw. (69778)

47 or/34‐46 (218371)

48 33 and 47 (67)

49 limit 48 to yr="2012 ‐Current" (25)

CINAHL (EBSCO)

S47 S45 AND S46

S46 EM 20120101‐20160531

S45 S35 AND S44

S44 S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43

S43(allocat* random*)

S42(MH "Quantitative Studies")

S41 (MH "Placebos")

S40 placebo*

S39(random* allocat*)

S38 (MH "Random Assignment")

S37 (Randomi?ed control* trial*)

Search modes ‐ Boolean/Phrase

S36 (singl* blind* ) or (doubl* blind* ) or (tripl* blind* ) or (trebl* blind* ) or (trebl* mask* ) or (tripl* mask* ) or (doubl* mask* ) or (singl* mask* )

S35 S6 AND S22 AND S34

S24 S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33

S33 (advanced N6 disease*)

S32 (incurable N6 (disease* or illness*))

S31 ((end‐stage* or end stage*) N6 (disease* or illness* or care))

S30 hospice*

S29 (end N3 life)

S28 (terminal‐stage* or terminal stage* or dying or (close N6 death))

S27 (terminal* N6 (care or ill* or diseas*))

S26 palliat*

S25 (MH "Terminally Ill Patients")

S24 (MH "Terminal Care+")

S23 (MH "Palliative Care")

S22 S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21

S21 (Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine)

S20(acebutolol or alimemazine or alprazolam or amitriptyline or atenolol or bisoprolol or bromazepam or buproprion or buspirone or carbamazepine or carisoprodol or carvedilol or celiprolol or clomipramine or chlorazepate or chlordiazepoxide or chlorphenamine or chlorpromazine or citalopram or clemastine or clobazam or clonazepam or co‐tenidone or cyproheptadine or diazepam or desipramine or desvenlafaxine or dexmedetomidine or dosulepin or doxepin or duloxetin or escitalopram or esmolol or estazolam or eszopiclone or etizolam or flunitrazepam or fluoxetine or flurazepam or fluvoxamine or gabapentin or halazepam or haloperidol or hydroxyzine or imipramine or isocarboxazid or ketamine or ketazolam or ketotifen or labetalol or lamotrigine or levetiracetam or levomepromaziene or lofepramine or lorazepam or meprobamate or methotrimeprazine or metoprolol or midazolam or milnacipran or mirtazapine or moclobemide or nadolol or nebivolol or nefazodone or nitrazepam or nortriptyline or olanzapine or ondansetron or oxazepam or oxprenolol or paroxetine or perphenazine or phenelzine or phenobarbital or phenytoin or pindolol or prazepam or pregabalin or primidone or promethazine or propranolol or quazepam or ramelteon or risperidone or sertraline or sotalol or temazepam or thioridazine or tiagabine or timolol or topiramate or tranylcypromine or trazodone or triazolam or trifluoperazine or trimipramine or tropisetron or valproate or venlafaxine or vigabatrin or zaleplon or zolpidem)

S19 (MH "Adrenergic Agents+")

S18 (MH "Hypnotics and Sedatives+")

S17 (MH "Barbiturates+")

S16 (MH "Histamine Agents+")

S15 (MH "Serotonin Agents+")

S14 (MH "Monoamine Oxidase Inhibitors+")

S13 (MH "Antipsychotic Agents, Phenothiazine+")

S12 (MH "Antipsychotic Agents, Butyrophenone+")

S11 (MH "Antianxiety Agents, Benzodiazepine+")

S10 (MH "Antipsychotic Agents+")

S9 (MH "Antidepressive Agents+")

S8 (MH "Antianxiety Agents+")

S7 (MH "Drug Therapy+")

S6 S1 OR S2 OR S3 OR S4 OR S5

S5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*)

S4 (MH "Psychomotor Agitation")

S3 (MH "Adjustment Disorders")

S2 (MH "Anxiety Disorders+")

S1 (MH "Anxiety+")

Appendix 9. Searches run in May 2016 for additional drugs

MEDLINE (Ovid)

1 exp Anxiety/ (64499)
2 exp Anxiety Disorders/ (69373)
3 Adjustment Disorders/ (4031)
4 Psychomotor Agitation/ (4313)
5 (anxious* or anxiet* or agitat* or restless* or panic* or stress* or PTSD or phobia* or phobic or nervous* or obsessive compulsive disorder* or OCD or adjustment disorder*).mp. (1247558)
6 or/1‐5 (1261866)
7 (Lormetazepam or Loprazolam or Zopiclone or Chloral hydrate or Chlormethiazole or Clomethiazole or Pericyazine or Perphenazine or Prochloperazine or Promazine or Paliperidone or Quetiapine or agomelatine or Reboxetine or Tryptophan or Acrivastine or Bilastine or Cetirizine or Desoloratadine or Fexofenadine or Levocetirizine or loratadine or Mizolastine or Rupatadine or Trimeprazine).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] (66822)
8 Palliative Care/ (44450)
9 exp Terminal Care/ (43827)
10 Terminally Ill/ (5772)
11 palliat*.mp. (69375)
12 (terminal* adj6 (care or ill* or diseas*)).mp. (33771)
13 (terminal‐stage* or terminal stage* or dying or (close adj6 death)).mp. (29569)
14 (end adj3 life).mp. (14104)
15 hospice*.mp. (12129)
16 ((end‐stage* or end stage*) adj6 (disease* or illness* or care)).mp. (33508)
17 (incurable adj6 (disease* or illness*)).mp. (2698)
18 (advanced adj6 disease*).mp. (35450)
19 or/8‐18 (203067)
20 randomized controlled trial.pt. (415956)
21 controlled clinical trial.pt. (90682)
22 randomized.ab. (312879)
23 placebo.ab. (158504)
24 drug therapy.fs. (1856488)
25 randomly.ab. (220900)
26 trial.ab. (323631)
27 groups.ab. (1393402)
28 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 (3527435)
29 exp animals/ not humans.sh. (4241825)
30 28 not 29 (3005030)
31 6 and 7 and 19 and 30 (11)