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Aim: The impact of migraine on health-related quality of life (HRQoL) among patients with major depressive disorder (MDD) after acute antidepressant treatment has not been addressed. The aim of the present study was to investigate whether or not the negative impact of migraine on HRQoL among outpatients with MDD continued to have an effect after 4 weeks of venlafaxine treatment.
Methods: A total of 135 outpatients with MDD were enrolled, who were then treated with venlafaxine 75 mg per day for 4 weeks in the present open-label study. Migraine was diagnosed based on the International Classification of Headache Disorders (2nd edn). Changes in Short-Form 36 (SF-36) and Hamilton Depression Rating Scale (HAMD) scores were the outcome measures. Multiple linear regression was used to assess whether migraine was an independent factor predicting SF-36 score after treatment.
Results: Seventy-two participants (18M/54F) completed the 4-week treatment. Subjects with migraine had a poorer HRQoL in terms of bodily pain and mental health at baseline. Subjects with and without migraine showed significant improvement in all SF-36 subscales and depression after treatment, but subjects with migraine still had a poorer HRQoL regarding bodily pain and physical functioning after treatment as compared with those without migraine. Migraine could predict a negative outcome after treatment in the subscales of physical functioning, role limitations–physical, and role limitations–emotional.
Conclusions: Migraine may have a negative impact on the improvement of partial SF-36 subscales, especially on functional recovery, after acute treatment among outpatients with MDD. Whether additional intervention besides antidepressant treatment for migraine is indicated may need further study.
MOOD DISORDERS AND migraine are correlated and interact.1–3 The association between migraine and major depressive disorder (MDD) is bidirectional, each disorder increasing the risk of first onset of the other at follow up.4 Depressive symptoms are also related to precipitating or aggravating factors of migraine among patients with MDD,5 and patients with migraine who also suffer from depression or anxiety have more somatic symptoms.6 Depression further decreases the quality of life of patients with chronic migraine,7,8 and also has a negative impact on the long-term prognosis of headache disorders among patients with migraine.9,10
Migraine has a negative impact on patients with MDD. Compared with MDD patients without migraine, those with migraine have: (i) more depressive episodes and clinical features of bipolar spectrum traits;11 (ii) more severe depression, anxiety, and somatic symptoms;12–15 and (iii) a poorer health-related quality of life (HRQoL), especially in the physical dimensions.16 Moreover, migraine also has a negative impact on bipolar disorder.17 These studies, however, were all cross-sectional. The impact of migraine on HRQoL or on the outcome of depression after antidepressant treatment has not previously been addressed. In our previous study, it was reported that migraine is one of the most important comorbidities predicting worse bodily pain in HRQoL assessment, even after controlling anxiety comorbidities;18 it is not known whether MDD patients with migraine still have poorer bodily pain after antidepressant treatment as compared with those without migraine. There are many studies related to HRQoL among patients with MDD.19,20 Previous studies have found that migraine has a negative impact on quality of life,21,22 but the impact of migraine on HRQoL after acute antidepressant treatment among patients with MDD has been neglected to date. Therefore, the purpose of the present study was to investigate whether or not the negative impact of migraine on the HRQoL of patients with MDD continued after a 4-week course of venlafaxine treatment. We hypothesized that the negative impact of migraine on the HRQoL of MDD patients may continue to have an effect after a 4-week course of treatment. Venlafaxine was used in the present study because previous studies have reported this drug to be effective in preventing migraine attacks,23 and the use of venlafaxine only and no other antidepressants avoided potential differential treatment efficacy among different antidepressants.
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The MDD subjects with migraine had poorer SF-36 BP and PF subscale scores after the 4-week treatment as compared with those without migraine; moreover, headache intensity in the migraine group was still higher than that in the non-migraine group. Previous studies have found some antidepressants, such as venlafaxine and duloxetine, to be effective in treating depression, somatic symptoms, and headaches;23,30,34 a 4-week venlafaxine treatment course, however, did not erase the differences in some subscale scores or headache intensity between the two groups. The present study has demonstrated that the negative impact of migraine on some SF-36 subscales and headache intensity among patients with MDD persisted after 4 weeks of venlafaxine treatment.
After controlling for baseline subscale scores and demographic variables, migraine independently predicted lower scores in the PF, RP, and RE subscales after the 4-week treatment. PF, RP and RE are related to functional impairment as a result of physical and emotional problems, which raises the possibility that migraine may hinder recovery after functional impairment. A previous study also found that patients with migraine have a poorer HRQoL, especially in terms of RP and RE.35 In fact, functional impairment resulting from migraine encompasses multiple dimensions, such as worrying about further attacks and limitation in social and family interaction, as well as capacity to work.36 These results also were compatible with the Lipton et al. study, which indicated that migraine and depression independently predict impaired HRQoL in the general population.22
There are four clinical implications of the present study. First, previous studies have reported that depression has a negative impact on the prognosis of migraine.9,10 The present results have demonstrated the interaction of depression and migraine from the other direction; that is, the negative impact of migraine on depression outcome after acute treatment. Second, pain symptoms, especially headache and muscle soreness, are associated with a poor response to treatment for depression.37 MDD patients with migraine had more severe headaches and more pain symptoms at baseline, which remained the case after treatment. This raises some interesting questions: whether more active treatment of migraine may improve treatment response, and whether or not additional intervention besides antidepressant treatment is indicated. And third, the two headache indices were significantly correlated with most SF-36 subscales and the HAMD in the migraine group after the 4-week treatment but not in the non-migraine group, which implied that the impact of headache intensity and frequency on HRQoL was more significant in patients with migraine as compared to those without migraine. And fourth, subjects in both the migraine and non-migraine subgroups exhibited significant improvement in all subscales of the SF-36, the HAMD, and headache intensity after the 1-month treatment. This finding was compatible with previous studies showing that venlafaxine was effective in the treatment of depression and somatic symptoms, including headache.23,30 There was a trend, however, towards the improvement in the physical subscales being smaller than the improvement in the mental subscales. Greco et al. reported that physical or pain symptoms were more difficult to treat than emotional symptoms among patients with depression.38 This might explain in part the fact that patients with migraine had a persistently poorer HRQoL in the PF and BP subscales as well as a higher headache intensity as compared with patients without migraine.
The present study had several methodological issues or limitations: (i) this open-label study with the exclusion criteria described was performed in a medical center, which might introduce bias, and the small sample size precluded statistical significance; (ii) although the present study was an open-label study, all subjects accepted the same treatment, and the raters of the HAMD were blind to headache diagnosis; (iii) although early treatment response is one predictive factor of prognosis,39 it is unknown whether the present results would be consistent if the treatment period was extended to 2–3 months; (iv) the dosage of venlafaxine used in the present study was 75 mg; whether or not a higher dosage of venlafaxine could compensate for the pre-treatment discrepancy between the two groups needs further study; (v) regarding the evaluation of headache intensity and frequency, a more reliable method would be the use of a prospective headache diary; (vi) the duration of headache disorders was not recorded because the headaches of most of the present subjects were episodic and fluctuating, and therefore a reliable headache duration could not be provided; and (vii) although zolpidem is not an analgesic or a medication for migraine prevention, improvement of insomnia may indirectly improve headache; the migraine group appeared more likely to use zolpidem, and this may cause bias. In future studies, a larger sample size, a longer treatment period, and a double-blind placebo-controlled trial design are indicated in order to investigate the impact of migraine on the treatment prognosis of MDD.
In conclusion, MDD patients with migraine still exhibited a poorer HRQoL in terms of the BP and PF subscales than those without migraine after 4 weeks of treatment. Migraine independently predicted a poor HRQoL as measured by the PF, RP and RE after 4 weeks of treatment after controlling for demographic variables and scores at baseline. Whether comorbid migraine is a negative factor of treatment outcome and of functional recovery in patients with MDD and whether additional intervention for MDD patients with migraine is indicated require further study.