Selection Process
A total of 640 articles were identified from all searches. Based on the title and abstract screening, 48 full-text articles were retrieved. Of these, 24 studies met the inclusion criteria and included in the final review (Figure 1).
General Characteristics of Included Studies
The description of the included studies is displayed in Table 1, 2 & 3. Although there were no limitations on the year of publication, studies only started to emerge since 2000. Nineteen studies examined the humanistic burden, twelve examined HRQoL [1, 7, 14-24] and seven examined disability [7, 17, 24-28] and two studies assessed the economic burden, three studies examine the healthcare cost[9, 29, 30] and medical services utilization [4, 29]. All studies employed validated measures of migraine, HRQoL, depression, and anxiety. The total number of included participants was 26,967 with sample sizes ranging from 70 to 11,332. In general, the participants' age ranged from 18 to 75 years, with women percentages ranging from 51.0% to 100%. Many studies included mixed-sex but two studies [20, 24] exclusively investigated women.
Quality Assessment
Overall, the included studies scored well for clearly stating the study aims, design, target population, risk factors and outcomes measurement, result explanation, and discussion and conclusion justified by the results. The main issues were mainly related to failure to address the sample calculation or addressing the non-response rate.
Main Findings
For this review, the results have been categorized into humanistic (Table 1&2) and economic burden (Table 3).
Depression and or Anxiety Comorbidity
Depression and anxiety were mainly evaluated using the Beck Depression Inventory (BDI) in four studies. Other scales were also used such as Hospital Anxiety and Depression Score (HADS), Patient Health Questionnaire-4 (PHQ-4), and the Center for Epidemiologic Studies-Depression Scale.
Humanistic Burden of Comorbid Depression and Anxiety among Adults with Migraine
The humanistic burden was measured using the HRQoL and disability. HRQoL instruments evaluate the burden of a disease on a person’s overall well-being [31]. Twelve studies gave data for the HRQoL outcome for adults with migraine and comorbid depression and/or anxiety. The results from these studies showed that depression and/or anxiety had a negative impact on the HRQoL. HRQoL instruments used were either generic or disease-specific. Most studies mentioned in this review that assessed the HRQoL among individuals with migraine used generic instruments (Table 1). The generic HRQoL instruments included: 36-item Short Form Health Survey (SF-36), the 12-item Short Form Health Survey (SF-12). The Short-Forms measures HRQoL in two domains: a mental health component score (MCS-12) and a physical health component score (PCS-12). The disease-specific HRQoL measure, Migraine-Specific Quality-of-Life Questionnaire (MSQ), was used in five studies.
A national population-based study in Canada using a national data from the Canadian Community Health Survey evaluated the impact of depression or anxiety on HRQoL [22]. This study found that among adults with migraine; those with depression or anxiety had lower HRQoL compared to those without these conditions. Studies in China, France, Germany, Italy, India, and South Korea have also demonstrated poor HRQoL among individuals with migraine and depression and/or anxiety [15, 18, 19]. A nation-wide population-based survey in France among subjects with migraine (n=1,957), in which 28.0% had anxiety, 3.5% depression, and 19.1% had both conditions [7]. The investigators reported that subjects with anxiety only, depression only or combined with depression had significantly lower scores across all domains of the SF-12 scale than in subjects with neither anxiety nor depression. To summarize, poor HRQoL among adults with migraine was explained by depression and /or anxiety comorbidity in most of the studies compared to groups without these comorbidities.
Disability is a measure of disease burden. Seven studies gave data for the disability outcome for adults with migraine and comorbid depression and/or anxiety (Table 3). The results from the studies included in this review showed that depression and anxiety had a negative impact on the disability using either generic (e.g., World Health Organization Disability Assessment Schedule II) or disease-specific (e.g., Migraine Disability Assessment) measures. Seng et al. in their study among adults with migraine have used migraine-specific measure, Migraine Disability Assessment (MIDAS), to measure disability associated with mental health conditions [25]. The researchers found that a higher depressive symptoms (Odds Ratio (OR) =3.5, 95%CI: 1.4-8.4), or anxiety symptoms (OR =3.6, 95% CI: 1.6-8.0) were associated with severe migraine-related disability. In summary, depression and anxiety have been associated with higher disability among adults with migraines when compared to those without these comorbidities.
Economic Burden of Comorbid Depression and Anxiety among Adults with Migraine
Economic burden was measured using the healthcare cost and healthcare utilization. Three studies gave data for the healthcare cost and the healthcare utilization outcomes for adults with migraine and comorbid depression and/or anxiety. With regard to healthcare costs, depression and/or anxiety comorbidity can exacerbate the economic burden of the payers. The economic burden was measured with the direct medical costs related to medical resource utilization of inpatient, outpatient and pharmaceutical services for treating adults with migraine. The current evidence among adults with migraine reported that individuals with comorbid depression and/or anxiety have higher healthcare costs [9, 29, 30] and medical services utilization[29] than those without these comorbid mental health conditions.
Pesa et al. examined the direct healthcare cost of comorbid depression and/or anxiety among individuals with migraine using retrospective employer database [9]. The investigators found that the mean annual total healthcare costs for coexisting depression and/or anxiety along with migraine were higher when compared to migraine alone (P < .0001) ($12,642 vs $5,179 anxiety; $11,290 vs $3,135 depression). Wu et al. examined the direct healthcare costs of comorbid depression and/or anxiety among individuals with migraine using retrospective Medical Expenditures Panel survey of US adults [29]. They reported that migraine subjects with depression have a higher mean annual total health expenses ($10,012 vs. $4,740, P <.001) and mean migraine‐related health expenses ($723 vs $499, P = .014) compared to those without depression.
Further, comorbid depression and or anxiety significantly affected healthcare utilization patterns. Wu et al. reported a higher odds of emergency department visit in adults with migraine and comorbid depression compared to those without depression (OR=1.36, 95% CI: 1.08, 1.71) [29]. This study suggests that depression increases healthcare utilization among adults with migraine, however, the impact of anxiety alone or comorbid depression and anxiety on healthcare utilization not been evaluated yet.