Table 1. PRISMA checklist
Section/topic # Checklist item
Reported on page
# TITLE
Title 1 Identify the report as a systematic review, meta-analysis, or both. 1 ABSTRACT
Structured summary
2 Provide a structured summary including, as applicable: background;
objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results;
limitations; conclusions and implications of key findings; systematic review registration number.
2
INTRODUCTION
Rationale 3 Describe the rationale for the review in the context of what is already known.
3 Objectives 4 Provide an explicit statement of questions being addressed with
reference to participants, interventions, comparisons, outcomes, and study design (PICOS).
3
METHODS Protocol and registration
5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information
including registration number.
N/A
Eligibility criteria
6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.
5
Information sources
7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.
5
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.
5 Study
selection
9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta- analysis).
5
Data collection process
10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.
5,6
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.
5.6 Risk of bias in
individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.
16-17
Summary measures
13 State the principal summary measures (e.g., risk ratio, difference in means).
6 Synthesis of 14 Describe the methods of handling data and combining results of 7-9
results studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.
Risk of bias across studies
15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).
13 Additional
analyses
16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.
N/A
RESULTS Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
5, 29
Study
characteristics
18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.
21-28 Risk of bias
within studies
19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).
N/A Results of
individual studies
20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.
21-28
Synthesis of results
21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.
N/A Risk of bias
across studies
22 Present results of any assessment of risk of bias across studies (see Item 15).
N/A Additional
analysis
23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).
N/A
DISCUSSION Summary of evidence
24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).
15-16
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).
16-17
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.
17-18
FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.
1
Table 2. Migraine and suicidal behaviour (Chronological order)
Author(s) Sample Study design Measures Main findings Quality Score*
Migraine Suicidal behaviour Breslau et
al. (21)
1,007 Young adults (aged 21 to 30 years old) from a large Health Maintenance Organisation in the USA, interviewed in 1989
Cross-sectional (population- based)
Lifetime prevalence of migraine (with and without aura) assessed in the NIMH- Diagnostic Interview Schedule (DIS), revised – DSM-III-R
Lifetime prevalence of suicide attempts assessed in the NIMH-Diagnostic Interview Schedule (DIS), revised – DSM-III-R
Males and females with migraine of either subtype (aura or without aura) had higher risk of attempted suicide males and females without migraine; the highest risk was for migraine with aura. (Males: RR=6.9, 95% CI 1.6-29.3; Females: RR=5.2, 95% CI 2.7-9.9).
When major depression was controlled for, persons with migraine had higher rates of suicide attempt than persons with no migraine. Suicide attempts had significantly stronger associations with migraine with aura than with migraine without aura. The adjusted odds ratio for suicide attempts in migraine with aura was 3.0 (95% CI 1.4- 6.6), independent of major depression, other psychiatric comorbidity, and sex.
I = 0 II = 1 III = 1 IV = 0 V = 1
Total Score = 3
Breslau (22)
1,007 Young adults (aged 21 to 30 years old) from a large Health Maintenance Organisation in the USA, interviewed in 1989
Cross-sectional (population- based)
DSM-III-R Lifetime prevalence of migraine (with and without aura) assessed in the NIMH- Diagnostic Interview Schedule (DIS), revised – DSM-III-R
Lifetime prevalence of suicidal ideation and attempts assessed in the NIMH-Diagnostic Interview Schedule (DIS), revised – DSM-III-R
After adjusting for coexisting affective mood disorders and substance use disorder, persons with migraine with aura alone had greater odds of thinking about suicide (AOR=2.4, 95% CI 1.1-5.3) and having attempted suicide (AOR=4.3, 95% CI 1.2-15.7) than those without both migraine and Major Depressive Disorder (MDD).
Odds of suicide attempt were greatest among persons with migraine with aura and MDD (AOR=23.2, 95% CI 8.4-63.8).
Migraine without aura alone was not
I = 0 II = 1 III = 1 IV = 0 V =1
Total Score = 3
associated with increased rates of suicidal ideation and suicide attempt.
Breslau &
Davis (23)
1,007 Young adults (aged 21 to 30 years old) from a large Health Maintenance Organisation in the USA, interviewed in 1989 with a 14-month telephone interview follow-up
Cross-sectional (population- based)
Lifetime prevalence of migraine (with and without aura) assessed in the NIMH- Diagnostic Interview Schedule (DIS), revised – DSM-III-R
Lifetime prevalence of suicide attempts assessed in the NIMH-Diagnostic Interview Schedule (DIS), revised – DSM-III-R
Persons with migraine alone had a higher lifetime prevalence of suicide attempts than those with no history of migraine;
7.1% versus 2.2%. After adjusting for sex and other psychiatric conditions, risk of suicide attempt in people with migraine (AOR=3.0, 95% CI 1.2-8.0) than in people without migraine (does not include people with MDD).
Persons with migraine and MDD had a higher prevalence of suicide attempts than those with MDD alone; 31.8% versus 16.5%. After adjusting for sex and other psychiatric conditions, risk of suicide attempt in subjects with migraine and MDD (AOR=16.2, 95% CI 6.7-39.4) were far greater than in those with MDD alone (AOR=7.6, 95% CI 3.4-16.8) (people without migraine and MDD are used as a reference group).
I = 0 II = 1 III = 1 IV = 0 V = 1
Total Score = 3
Oedegaard et al. (13)
201 psychiatric patients with major affective syndrome in Norway
Cross-sectional (clinical)
ICHD-I criteria was used for diagnosis of migraine
Lifetime prevalence of suicide attempt and suicidal thoughts using semi-structured interview based on DSM-IV criteria
Significantly lower prevalence of suicide attempts in patients having migraine aura without headache (17%) compared to the patients with migraine with aura (53%) was reported (p=.013).
Frequency of suicidal thoughts was not significantly different between migraine with aura and migraine aura without headache.
I = 0 II = 1 III = 1 IV = 0 V = 1
Total Score = 3
Wang et al.
(16)
121 students from 7th - 9th grades in 5 selected middle
Cross-sectional (school-based)
ICHD-II appendix
The MINI-kid suicidality module
Of the CDH sample, subjects with migraine were more likely to have high suicidal risk
I = 0 II = 1
schools in Taiwan with diagnosed Chronic Daily Headache (CDH) in 2000
criteria for chronic migraine (Chinese version of the PedMIDAS)
was used to rate current (past month) suicidal risk. Subjects divided into two groups (cut-off score 10)
than those without migraine (OR=4.3 95%
CI 1.2-15.5). The association remained only for migraine with aura after controlling for age, sex, major depression, and anxiety disorders (AOR=7.8; p=.021), but not for migraine without aura.
III = 0 IV = 0 V = 1
Total Score = 2
Ratcliffe et al. (26)
36,984 respondents from the 2002 Canadian Community Health Survey Cycle 1.2 (CCHS 1.2) (aged 15 years and above)
Cross-sectional (population- based)
Long-term migraine assessed through self- reported health professional diagnosis
Suicidal ideation (thoughts of taking one’s own life) and suicide attempt (attempt to take one’s own life) in the preceding 12 months
Adjusting for demographics, migraine was associated with suicidal ideation
(AOR=2.27, 95% CI 1.88-2.74; p<.001) and suicide attempt (AOR=3.65, 95% CI 2.40- 5.56; p<.001).
After adjusting for socio-demographic factors, mental disorders, and comorbidity (three or more mental disorders), and other chronic pain conditions, a strong positive association remained between migraine and suicidal ideation (AOR=1.45, 95% CI 1.14-1.84; p<.01) and suicide attempt (AOR=1.85, 95% CI 1.10-3.11;
p<.05).
I = 1 II = 1 III = 2 IV = 0 V = 1
Total Score = 5
Wang et al.
(17)
3,963 students, aged 13 to 15, from three middle schools in Taiwan
(respondents in the 2005 Taitung County Adolescent Headache Survey)
Cross-sectional (school-based)
Headache diagnosis (including migraine) based on ICHD-II diagnostic criteria
Item 17 of the adolescent depression inventory (ADI) - reported current (past month) prevalence of suicidal ideation
Suicidal ideation was associated with higher headache frequencies and
headache-related disability in migraine and non-migraine participants.
Compared with subjects without migraine, suicidal ideation was associated with subjects presenting migraine with aura (OR=4.6, 95% CI 3.0-7.0).
Subjects with migraine with aura are more likely to report suicidal ideation compared to those with migraine without aura or probable migraine (23.9% vs.
I = 1 II = 1 III = 2 IV = 0 V = 1
Total Score = 5
14.2%; OR=1.83, 95% CI 1.2-2.56).
After controlling for age, gender, depression score, and the factor of living arrangements, the association with suicidal ideation remained only for migraine with aura (AOR=1.79, 95% CI 1.07-2.99; p=.025) and high headache frequency (>7
days/month: AOR=1.69, 95% CI 1.12-2.56;
p=.013).
Ortiz et al.
(14)
Study 1: 323 bipolar patients (109 from the McGill University Health Centre; 214 from the Maritime Bipolar Register in Canada)
Study 2: 79 bipolar patients with comorbid migraine
Cross-sectional (clinical)
Diagnosis based on ICHD-I
(assessed with the Standard questionnaire - ID migraine)
Lifetime suicidal behaviour based on diagnostic
interviews following the Schedule for Affective Disorders and Schizophrenia
Among BD patients, migraine was
associated with lifetime history of suicidal behaviour (OR=1.7, 95% CI 1.0-3.0).
I = 0 II = 1 III = 0 IV = 0 V = 1
Total Score = 2
Breslau et al. (15)
Of the 4,765 persons screened (aged 25-55 years), 1,696 were selected for psychiatric assessment in face-to-face interviews.
(1) all persons who met ICHD criteria for migraine in the last year (n = 683);
(2) all persons who met criteria for non-migraine severe headache in the last year, as defined above (n = 253); and (3) a subset of the remaining sample who did not meet criteria
Longitudinal case-control study (population- based)
Diagnosis based on ICHD-I (using a computer- assisted telephone interview - CATI)
Item on lifetime suicide attempt and re-occurrence during a 2-year follow-up from the World Health Organization Composite International Diagnostic Interview (CIDI) was used at baseline and follow-up
The two-year cumulative occurrence of suicide attempt for migraine (OR=7.21, 95%
CI 3.21-16.2) were significantly higher than for those with no history of severe
headache. This comparison was not as pronounced as those with severe headaches (OR=8.38, 95%CI 3.35-21.0).
Both migraine (AOR=4.43, 95%CI 1.93- 10.2) and severe headache remained significant in the model adjusted for gender, depression, anxiety and baseline lifetime suicide attempts. Although not significantly different, severe non-migraine headache showed higher odds or suicide attempt compared to migraine.
I = 0 II = 1 III = 1 IV = 1 V = 1
Total Score = 4
for either migraine or severe headache in a lifetime frequency matched by sex and age to the migraine group (n = 760).
Suicide attempt for migraine with aura vs.
no aura was significantly greater (OR=2.14, 95% CI 1.14-4.02). However, adjusted OR for suicide attempt for migraine with aura vs. migraine without aura was 1.74 (95% CI 0.91-3.33), indicating that co-occurring psychiatric disorders accounted in part for the higher risk of suicide attempt among persons with migraine with aura compared to persons with migraine without aura.
Serafini et al. (18)
56 women (hospital outpatients) with chronic migraine at Sant’ Andrea Hospital of Rome, Italy, followed between 2010- 2011
Cross-sectional (clinical)
Chronic migraine outpatients based on ICHD-II
Current (within the last year) suicidality measured using the Suicidal History Self-Rating Screening Scale (SHSS)
Patients (chronic migraine) with high total scores on affective dysregulated
temperaments, compared to those with lower scores on the measure, are more likely to have higher SHSS total scores (4.79±3.31 vs. 1.05±2.31; t[17,74] = -3.90;
p<.001).
I = 0 II = 0 III = 0 IV = 0 V = 1
Total Score = 1 Fuller-
Thomson et al. (27)
81,468 respondents from four provinces where suicide question was asked and valid data on migraine and suicidal ideation existed from the 2005 Canadian Community Health Survey (aged 15 years and above)
Cross-sectional (population- based)
Self-report of a health professional diagnosis of migraine
Lifetime suicidal ideation measured using a single question
(consideration of suicide or taking own life) obtained in the CCHS (only asked to
respondents 15 years and older)
Suicidal ideation was more common for those with migraine (men: 15.6% vs 7.9%, p<.001; women: 17.6% vs. 9.1%, p<.001).
After adjusting for age, race, marital status, income, education, activity
limitations, and activities of daily living, the adjusted odds of suicidal ideation among those with migraine were higher than those without migraine (men AOR=1.70, 95% CI 1.55-1.96; women AOR=1.72, 95%
CI 1.59-1.86).
For both genders, the younger age group (under 30 years of age) had greater odds of lifetime suicidal ideation (men: AOR=4.43, 95% CI 1.25-15.66; women: AOR=4.25, 95%
CI 2.17-8.31) when compared to those
I = 1 II = 1 III = 2 IV = 0 V = 1
Total Score = 5
aged 65+.
Ilgen et al.
(24)
4,823 individuals who had used the Veterans Health Administration in 2005 fiscal year and were followed up for three years in USA
Cohort (registry based)
Migraine based on International Classification of Diseases-9- Clinical Modification (ICD-9-CM)
Suicide mortality (ICD-10)
After controlling for age, sex, and Charlson Comorbidity Index, migraine was
associated with greater risk of death by suicide (HR=1.68, 99% CI 1.28-2.20; p<.001) compared to headache or tension-type headache (HR=1.38, 99% CI 1.17-1.64;
p<.001).
After controlling for age, sex, Charlson index, and psychiatric diagnosis, migraine remained to be associated with an increased risk of suicide (HR=1.34, 99% CI 1.02-1.77; p=.005) whereas headache or tension-type headache did not (HR=1.07, 99% CI 0.91-1.27; p=.28).
I = 0 II = 1 III = 2 IV = 1 V = 1
Total Score = 5
Nguyen &
Low (28)
36,984 respondents from the 2002 Canadian Community Health Survey Cycle 1.2 (aged 15 years and above)
Cross-sectional (population- based)
Self-reported migraine which had been previously diagnosed by a health professional
Lifetime suicidal ideation and suicide attempt from the World Health
Organization Composite International Diagnostic Interview (CIDI)
Migraine, compared with the absence of migraine, was associated with significantly increased prevalence of lifetime suicidal ideations in subjects without mood disorders (14.6% vs. 8.2%), subjects with manic episodes (47.0% vs. 33.1%), and increased lifetime suicide attempts in subjects with unipolar depression (13.0%
vs. 5.2%).
I = 1 II = 1 III = 2 IV = 0 V = 1
Total Score = 5
Fuller- Thomson et al. (29)
5,788 Canadian
respondents aged between 15 and 19 years in the 2000/2001 Canadian Community Health Survey 1.1
Cross-sectional (population- based)
Self-report of a health professional diagnosis with migraine lasting 6 or more months
Suicidal ideation (considered suicide) in the past 12 months
Suicidal ideation was more common among adolescents who reported a
diagnosis of migraine compared with those who did not (7.2% vs. 3.6%; p<.001).
Logistic regression including 5
demographic characteristics (e.g., age and school attendance), 2 health behaviours (smoking status and alcohol dependency)
I = 1 II = 1 III = 1 IV = 0 V = 1
Total Score = 4
and 6 physical health characteristics (e.g., self-perceived health status and presence of migraine) indicated that the presence of migraine did not predict suicidal ideation when depression was excluded from the model (OR=1.35, 95% CI 0.71-2.56) or included in the model (OR=1.25, 95% CI 0.64-2.45).
Kim & Park (19)
185 patients with migraine invited to a headache clinic in Korea and 53 age and education matched healthy controls between Nov 2009 and Feb 2012
Case-control (clinical)
ICHD-II diagnostic criteria;
chronic migraine ≥ 15 headache days/month, with 8 days per month meeting criteria for migraine without aura
Current suicidal ideation severity (SSI-Beck)
measuring specific attitudes,
behaviours, and plans to die by suicide; score > 8 for adults, > 13 for college students, >
15 for high school students
Adjusted for age and sex, people with migraine were more likely to report suicidal ideation than healthy controls, (OR=5.09, 95% CI 1.17-22.10; p=.03); not sustained after controlling for depression and anxiety (OR=1.51, 95% CI 0.31-7.50; p=.61).
Among patients with migraine, factors associated with suicidal ideation were increased frequency of headache attacks per 3 months (OR=1.02, 95% CI 1.00-1.04;
p=.045), higher headache intensity (OR=1.45, 95% CI 1.14-1.86; p=.003), headache intensity on day questionnaire administered (OR=1.31, 95% CI 1.12-1.54;
p=.001), depression (OR=16.34, 95% CI 5.88-45.42; p<.001), and anxiety (OR=6.28, 95% CI 2.78-14.20; p<.001). Protective associations included education > 9 years (OR=0.39, 95% CI 0.17-0.91; p=.029) and phonophobia (OR=0.32, 95% CI 0.13-0.82;
p=.018).
Significant predictors of suicidal ideation among migraine people in the final model were depression (OR=15.36, 95% CI 5.39- 43.78; p<.001) and headache intensity on
I = 0 II = 1 III = 1 IV = 0 V = 1
Total Score = 3
day questionnaire was administered (OR=1.29, 95% CI 1.08-1.55; p=.006).
Singhal et al. (25)
Linked dataset of English Hospital Episode Statistics (HES) and mortality data from 1999-2011 (147,330 people admitted with migraine)
Cohort study (national)
Hospital admissions and day cases coded with G43
(migraine) in the
International Classification of Diseases (ICD)
Self-harm (ICD-9 codes E950-E959;
ICD-10 codes X60- X64, X66-X84) and death from suicide (on death record:
ICD-9 codes E950- E959; ICD-10 codes X60-X84)
When compared with a reference cohort, migraine was associated with an increased risk of self-harm occurring within one year of hospital admission (RR=1.8, 95% CI 1.7- 1.8) and occurring after the first year of hospital admission (RR=1.7, 95% CI 1.6- 1.7).
With comparison to the reference cohort, results showed that migraine had a
significant increase in risk of suicide (RR=1.3, 95% CI 1.0-1.8) with a ratio of self- harm events to suicide of 65.3.
I = 1 II = 1 III = 2 IV = 1 V = 1
Total Score = 6
Desai &
Pandya (20)
101 adults (> 18 years) attending a neurology clinic in India with a diagnosis of a headache disorder
Cross-sectional (clinical)
Diagnosis of migraine made according to the ICHD-II
Current (past month) suicidality as measured in MINI English version 5.0.0
Migraine plus tension-type headache has a higher prevalence of suicidality compared to migraine alone (25% vs. 18%).
I = 0 II = 0 III = 0 IV = 0 V = 1
Total Score = 1
* Quality ratings reported have a maximum score of 6.The criteria used to assess quality are listed below ([adapted from Pompili et al (10)]:
I) Representativeness of the sample to the general population: 0 points = not representative; 1 point = representative II) Presence of a control/comparison group: 0 points = no control group; 1 point = control group
III) Number of participants with the condition (migraine): 0 points = <100; 1 point = <500; 2 points = >500 IV) Longitudinal (follow-up): 0 points = no follow up; 1 point = with a follow-up
V) Data presentation: 0 points = unclear data presentation; 1 point = clear data presentation