Appendix
Appendix Table 1. Search Strings
Database(s): PubMed January 2011
Strings / NSearch "Migraine Disorders"[Mesh] AND "Migraine Disorders"[Mesh] Limits: Humans, Meta-Analysis, English / 97
Search "Migraine Disorders"[Mesh] AND "Migraine Disorders"[Mesh] Limits: Humans, Randomized Controlled Trial, English / 907
Database(s): PubMed January 2011
Strings / NSearch migraine NOT acute Limits: Humans, Randomized Controlled Trial, English / 655
Search migraine Limits: Humans, Randomized Controlled Trial, English / 1040
Search melatonin AND migraine / 55
Search melatonin AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 7
Search "Brain-Derived Neurotrophic Factor"[Mesh] AND migraine / 6
Search "Brain-Derived Neurotrophic Factor"[Mesh] AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 1
Search "Brain-Derived Neurotrophic Factor"[Mesh] Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 94
Search Risperidone AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Paliperidone AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Methiothepin AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Metergoline AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Lisuride AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 5
Search Bromocriptine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 4
Search Zotepine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Ziprasidone AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Trifluoperazine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Tenilapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Sulpiride AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 1
Search Spiperone AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Sertindole AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Olanzapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Loxapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Ketanserin AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Imipramine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Fluperlapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Fluphenazine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Cyproheptadine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 9
Search Clozapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Clomipramine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 2
Search Aripiprazole AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Amoxapine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Amitriptyline AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 34
Search Amitriptyline AND migraine Limits: Humans, English / 150
Search 5-HT7 AND migraine Limits: Humans, English / 12
Search 5-HT7 Limits: Humans, English / 150
Search Quetiapine AND migraine Limits: Humans, English / 5
Search "Antipsychotic Agents "[Pharmacological Action] AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 41
Search "Antipsychotic Agents "[Pharmacological Action] AND migraine Limits: Humans, English / 206
Search "Antipsychotic Agents "[Pharmacological Action] Limits: Humans, English / 51308
Search 5-HT2A AND migraine Limits: Humans, English / 14
Search 5-HT2A antagonists AND migraine Limits: Humans, English / 3
Search 5-HT2A antagonists Limits: Humans, English / 394
Search Alpha-2 agonists AND migraine Limits: Humans, English / 6
Search Alpha-2 agonists AND migraine / 17
Database(s): PubMed January 2011
Search telcagepant AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 4Search olcegepant AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search Arachidonic cascade modulators Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search tonabersat) AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 6
Search dextromethorphan AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search dextromethorphan AND migraine NOT acute Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search loxapine AND migraine NOT acute Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 0
Search prochlorperazine AND migraine NOT acute Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 8
Search prochlorperazine AND migraine Limits: Humans, Clinical Trial, Randomized Controlled Trial, English / 20
Database(s): PubMed August 2011
Strings / NSearch Phenelzine AND migraine Limits: Humans, Journal Article, English / 11
Search Bupropion AND migraine Limits: Humans, Journal Article, English / 1
Search Imipramine AND migraine Limits: Humans, Journal Article, English / 15
Search Imipramine AND headache Limits: Humans, Journal Article, English / 60
Search Doxepin AND headache Limits: Humans, Journal Article, English / 15
Search Desipramine AND headache Limits: Humans, Journal Article, English / 13
Search Desipramine AND migraine Limits: Humans, Journal Article, English / 1
Search Protriptyline AND headache Limits: Humans, Journal Article, English / 4
Search Protriptyline AND migraine Limits: Humans, Journal Article, English / 0
Database(s): Ovid MEDLINE(R) 1948 to November, Week 3, 2011
# / Searches / N1 / exp migraine disorders/dt / 5944
2 / exp migraine disorders/pc / 1669
3 / ad.fs. / 998247
4 / 2 and 3 / 286
5 / 1 or 4 / 6112
6 / 1 or 2 / 7065
7 / exp "off-label use"/ / 519
8 / off label.mp. / 2412
9 / 7 or 8 / 2412
10 / 6 and 9 / 14
11 / exp calcium channel blockers/ / 68976
12 / exp antihypertensive agents/ / 216956
13 / exp antidepressive agents/ / 113058
14 / exp anticonvulsants/ / 111349
15 / exp botulinum toxin type a/ / 4832
16 / exp alzheimer disease/dt / 8107
17 / 11 or 12 or 13 or 14 or 15 or 16 / 476372
18 / 6 and 17 / 1675
19 / 5 or 10 or 18 / 6489
20 / limit 19 to (humans and yr="2000 -Current") / 3195
21 / limit 20 to updaterange="mesz(20111121020154-20111121091315]" / 0
Database(s): Ovid MEDLINE(R) 1946 to December, Week 4, 2011
# / Searches / N1 / exp migraine disorders/dt / 5882
2 / exp migraine disorders/pc / 1659
3 / ad.fs. / 975844
4 / 2 and 3 / 284
5 / 1 or 4 / 6048
6 / 1 or 2 / 6996
7 / exp "off-label use"/ / 510
8 / off label.mp. / 2358
9 / 7 or 8 / 2358
10 / 6 and 9 / 13
11 / exp calcium channel blockers/ / 67571
12 / exp antihypertensive agents/ / 1420023
13 / exp antidepressive agents/ / 110836
14 / exp anticonvulsants/ / 1012405
15 / exp botulinum toxin type a/ / 4648
16 / exp alzheimer disease/dt / 7829
17 / 11 or 12 or 13 or 14 or 15 or 16 / 2510533
18 / 6 and 17 / 1831
19 / 5 or 10 or 18 / 6431
Database(s): Ovid MEDLINE(R) 1946 to May, Week 2, 2012
# / Searches / N1 / drug management.mp. / 467
2 / exp patient care team/ / 49789
3 / exp delivery of health care, integrated/ / 7185
4 / integrated care.mp. / 1087
5 / exp managed care programs/ / 38113
6 / (managed care or coordinated care).mp. / 28360
7 / exp Patient Education as Topic/ / 64554
8 / exp Health Education/ / 125606
9 / drug surveillance.mp. / 432
10 / exp drug monitoring/ / 12104
11 / 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 / 231287
12 / exp patient compliance/ / 46268
13 / exp patient satisfaction/ / 52327
14 / exp patient care management/ / 475066
15 / 12 or 13 or 14 / 555310
16 / exp migraine disorders/dt / 5965
17 / 11 and 16 / 111
18 / 15 and 16 / 360
Database(s): Ovid MEDLINE(R) 1946 to May, Week 2, 2012
# / Searches / N1 / exp migraine disorders/dt / 5965
2 / exp migraine disorders/pc / 1692
3 / ad.fs. / 1002489
4 / 2 and 3 / 291
5 / 1 or 4 / 6136
6 / 1 or 2 / 7101
7 / exp "off-label use"/ / 628
8 / off label.mp. / 2572
9 / 7 or 8 ( / 2572
10 / 6 and 9 ( / 14
11 / exp calcium channel blockers/ ( / 68722
12 / exp antihypertensive agents/ / 217035
13 / exp antidepressive agents/ / 113333
14 / exp anticonvulsants/ ( / 112028
15 / exp botulinum toxin type a/ / 4853
16 / exp alzheimer disease/dt / 8211
17 / 11 or 12 or 13 or 14 or 15 or / 477138
18 / 6 and 17 / 1689
19 / 5 or 10 or 18 / 6514
20 / limit 19 to (humans and yr="2000 -Current") ( / 3226
Table 2. Definition of migraine
Repeated attacks of headache lasting four to 72 hours in patients with a normal physical examination, no other reasonable cause for the headache, and: / At least two of the following features:
– Unilateral pain
– Throbbing pain
– Aggravation by movement
– Moderate or severe intensity
Plus at least one of the following features:
– Nausea/vomiting
– Photophobia and phonophobia
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Table 3. Bayesian models summary under the noninformative prior probability of the outcome
Fixed effect model / Random effect model (homogeneous) / Random effect model (heterogeneous) / Random effect model (inconsistency)Data
rik ~ Bin(nik, pik)
i = 1, …, NS; k = 1, …, NT
(NS = number of study; NT = number of trt)
Model
logit(pik) = µiB + ΔBk
where B is for the baseline treatment, µiB is the log odds of the baseline treatment and ΔBk is the fixed effect of the kth drug versus the baseline treatment defined by dk – dB with the fixed effect of the kth drug versus placebo, dk (dB = 0)
Prior
dk ~ N(0, 10000)
µiB ~ N(0, 10000) / Data
rik ~ Bin(nik, pik)
Model
logit(pik) = µiB + δiBk
where δiBk is the random effect of the kth drug versus the baseline treatment in the ith study
Prior
δiBk ~ N(dk – dB, σ2)
dk ~ N(0, 10000)
µiB ~ N(0, 10000)
σ ~Unif(0.01,2) / Data
rik ~ Bin(nik, pik)
Model
logit(pik) = µiB + δiBk
where δiBk is the random effect of the kth drug versus the baseline treatment in the ith study
Prior
δiBk ~ N(dk – dB, σBk2)
dk ~ N(0, 10000)
µiB ~ N(0, 10000)
logσxy = logσ0 + νxy
σ0 ~Unif(0.01,2)
νxy ~ N(0, ψ2) / Data
rik ~ Bin(nik, pik)
Model
logit(pik) = µiB + δiBk
where δik is the random effect of of the kth drug versus the placebo in the ith study
1. dBC = dAC – dAB + wABC
wABC is the amount of inconsistency between direct and indirect comparisons
Prior
δiBk ~ N(dk – dB, σ2)
dk ~ N(0, 10000)
µiB ~ N(0, 10000)
wABC ~ N(0, σw2)
σ, σw ~Unif(0.01,2)
[Example] Study 1: Drugs 1 vs. 2 vs. 3 trial (drug 1 is the baseline treatment)
Fixed effect model / Random effect model (homogeneous) / Random effect model (heterogeneous) / Random effect model (inconsistency)
Data
r11 ~ Bin(n11, p11)
r12 ~ Bin(n12, p12)
r13 ~ Bin(n13, p13)
Model
2. logit(p11) = µ11
3. logit(p12) = µ11+ d2
4. logit(p13) = µ11+ d3
Prior
d2, d3 ~ N(0, 10000)
µ11 ~ N(0, 10000) / Model
5. logit(p11) = µ11
6. logit(p12) = µ11 + δ12
7. logit(p13) = µ11 + δ13
Prior (assume ρ=0.5)
è
è
d2, d3 ~ N(0, 10000)
µ11 ~ N(0, 10000)
σ ~Unif(0.01,2) / Model
8. logit(p11) = µ11
9. logit(p12) = µ11 + δ12
10. logit(p13) = µ11 + δ13
Prior (assume ρ=0.5)
è
è
d2, d3 ~ N(0, 10000)
µ11 ~ N(0, 10000)
logσ11 = logσ0 + ν11
logσ12 = logσ0 + ν12
logσ22 = logσ0 + ν22
σ0 ~ Unif(0.01,2)
ν11, ν12, ν22 ~ Unif(0.01, ψ2) / Study 1: 1 vs. 2 vs. 3 trial
11. Study 2: 1 vs. 2
12. Study 3: 1 vs. 3
è We can estimate w123 because the data permit estimation via the equation
d23 = d13 – d13 + w123
Model and priors are similarly defined as in Model2. Additional prior is
w123 ~ N(0, σw2)
σw ~ Unif(0.01,2)
13
Table 4. Pharmacological groups and agents examined in randomized controlled trials for migraine prevention in adults
Pharmacological group of the drug in active group / Active drug / The Anatomical Therapeutic Chemical (ATC) classification system /ACE inhibitors / Captopril / C09AA01
ACE iInhibitors / Lisinopril / C09AA03
Angiotensin II receptor blockers / Candesartan / C09CA06
Angiotensin II receptor blockers / Telmisartan / C09CA07
Antiadrenergic / Clonidine / C02AC01
Antiadrenergic / Guanfacine / C02AC02
Antidepressant / Amitriptyline / N06AA09
Antidepressant / Clomipramine / N06AA04
Antidepressant / Escitalopram / N06AB10
Antidepressant / Femoxetine / N06AB05
Antidepressant / Fluoxetine / N06AB03
Antidepressant / Fluvoxamine / N06AB08
Antidepressant / Mianserin / N06AX03
Antidepressant / Nortriptyline / N06AA10
Antidepressant / Venlafaxine / N06AX16
Antiepileptic / Acetazolamide / S01EC01
Antiepileptic / Carbamazepine / N03AF01
Antiepileptic / Divalproex / N03AG01
Antiepileptic / Gabapentin / N03AX12
Antiepileptic / Lamotrigine / N03AX09
Antiepileptic / Levetiracetam / N03AX14
Antiepileptic / Oxcarbazepine / N03AF02
Antiepileptic / Topiramate / N03AX11
Antiepileptic / Valproate / N03AG01
Antiepileptic / Vigabatrin / N03AG04
Antiepileptic / Zonisamide / N03AX15
Beta-blocker / Acebutolol / C07AB04
Beta-blocker / Alprenolol / C07AA01
Beta-blocker / Atenolol / C07AB03
Beta-blocker / Bisoprolol / C07AB07
Beta-blocker / Metoprolol / C07AB02
Beta-blocker / Nadolol / C07AA12
Beta-blocker / Nebivolol / C07AB12
Beta-blocker / Pindolol / C07AA03
Beta-blocker / Practolol / C07AB01
Beta-blocker / Propranolol / C07AA05
Beta-blocker / Timolol / C07AA06
Cortical spreading depression inhibitor / Tonabersat / Not available
Dopaminergic agent / Dihydroergocryptine / N04BC03
Ergot alkaloid / Dihydroergotamine / N02CA01
Ergot alkaloid / Lisuride / N02CA07
Ergot alkaloid / Methysergide / N02CA04
Leukotriene receptor antagonists / Montelukast / R03DC03
Magnesium / Magnesium / A12CC
Muscle relaxant / Tizanidine / M03BX02
Nonsteroidal antiinflammatory and antirheumatic products / Aspirin / N02BA01
Nonsteroidal antiinflammatory and antirheumatic products / Fenoprofen / M01AE04
Nonsteroidal antiinflammatory and antirheumatic products / Flurbiprofen / M01AE09
Nonsteroidal antiinflammatory and antirheumatic products / Indobufen / B01AC10
Nonsteroidal antiinflammatory and antirheumatic products / Indomethacin / M01AB01
Nonsteroidal antiinflammatory and antirheumatic products / Induprofen / Not available
Nonsteroidal antiinflammatory and antirheumatic products / Ketoprofen / M01AE03
Nonsteroidal antiinflammatory and antirheumatic products / Naproxen / M01AE02
Nonsteroidal antiinflammatory and antirheumatic products / Rofecoxib / M01AH02
Nonsteroidal antiinflammatory and antirheumatic products / Tolfenamic Acid / M01AG02
Selective calcium channel blockers / Nicardipine / C08CA04
Selective calcium channel blockers / Nifedipine / C08CA05
Selective calcium channel blockers / Nimodipine / C08CA06
Selective calcium channel blockers / Verapamil / C08DA01
13