The role of stress and psychiatric comorbidities as targets of
non-pharmacological therapeutic approaches for migraine


Ruolo dello stress e delle comorbidità psichiatriche come target degli approcci
terapeutici non farmacologici per l’emicrania


CORINNA PANCHERI1, ANNALISA MARAONE1, VALENTINA ROSELLI1, MARTA ALTIERI1,
VITTORIO DI PIERO1, MASSIMO BIONDI1, MASSIMO PASQUINI1, LORENZO TARSITANI1*

*E-mail: lorenzo.tarsitani@uniroma1.it


1Department of Human Neurosciences, Policlinico Umberto I, Sapienza University of Rome, Italy


SUMMARY. This narrative review addresses the interconnections among stress, mental disorders and migraine with a specific focus on non-pharmacological interventions that may be effective in improving both migraine and the psychiatric comorbidity. Migraine is often comorbid with depression, anxiety, personality disorders, and sleep disorders. Subjective stress and stressors are common triggers for migraine attacks and are risk factors for chronification, whilst mental disorders and stress responses are closely linked in a bidirectional relation. Recent studies show that psychiatric comorbidity is associated with migraine severity, worse outcomes, increased disability and reduce quality of life. Numerous studies on non-pharmacological interventions for migraine were published and behavioural treatments included biofeedback, cognitive-behavioural therapy, relaxation training, stress management and brief psychodynamic psychotherapy. Taken together, psychological interventions proved to be effective in migraine treatment and a combination of pharmacological and psychological treatment appear to be more effective than either medication or psychotherapy alone. Non-pharmacological interventions effectiveness should be due to the improvement of migraine, stress-related vulnerability and mental disorders together and the combined treatment could prevent the chronification circuit of migraine. Well-designed long-term studies are needed to clarify comparative effectiveness of non-pharmacological techniques in the treatment and the prevention of migraine.

KEY WORDS: migraine, comorbidity, mental disorders, psychiatric disorders, psychotherapy.


RIASSUNTO. Lo scopo di questa revisione è quello di analizzare la correlazione tra stress, disturbi mentali ed emicrania, con un focus specifico sugli interventi non farmacologici, che possono essere efficaci nel migliorare sia l’emicrania sia la comorbilità psichiatrica. L’emicrania è stata spesso associata a depressione, ansia, disturbi della personalità e disturbi del sonno. Lo stress soggettivo e gli stressor sono elementi scatenanti comuni per gli attacchi di emicrania e, inoltre, sono fattori di rischio per la sua cronicizzazione, mentre i disturbi mentali e le risposte allo stress sono strettamente collegati all’emicrania in una relazione bidirezionale. Studi recenti mostrano che la comorbilità psichiatrica è associata a una maggiore gravità dell’emicrania, a un peggiore outcome, all’aumento della disabilità e alla riduzione della qualità della vita. Gli interventi non farmacologici e i trattamenti comportamentali come il biofeedback, la terapia cognitivo-comportamentale, le tecniche di rilassamento, la gestione dello stress e la psicoterapia psicodinamica breve si sono dimostrati efficaci nel trattamento dell’emicrania. Inoltre, la terapia combinata, farmacologica e non, sembra essere più efficace della sola farmacoterapia o psicoterapia. Gli interventi non farmacologici nei pazienti con emicrania sembrano favorire il miglioramento dei sintomi e la riduzione della vulnerabilità allo stress e ai disturbi mentali e, il trattamento combinato, potrebbe prevenire i meccanismo di cronicizzazione dell’emicrania. Sono necessari studi a lungo termine per chiarire l’efficacia comparativa delle tecniche non farmacologiche nel trattamento e nella prevenzione dell’emicrania.

PAROLE CHIAVE: emicrania, comorbilità, disordini mentali, disturbi psichiatrici, psicoterapia.

IINTRODUCTION

People suffering from psychiatric disorders and emotional difficulties may turn to various providers to ask for help, especially mental health specialists1. In mental health settings, psychotherapy is one of the main therapeutic options available for patients suffering from a variety of common and mild or moderate mental disorders. Psychological interventions are the only indicated options for personality disorders. Also, psychotherapy is often offered to persons seeking help for emotional distress correlated with stressful somatic conditions such as migraine. The scientific literature shows an association between migraine and several psychiatric conditions that may lead people to seek psychotherapeutic help, such as stress-related emotional difficulties, personality disorders, depressive and anxiety disorders, bipolar spectrum disorders and sleep disorders2,3. Furthermore, many studies developed hypotheses on the contribution of depression and anxiety to the chronification of migraine, increasing the interest in psychological integrative solutions4-7. This paper aims at presenting the interconnections between psychiatric disorders and migraine with a specific focus on non-pharmacological interventions that may be effective in improving both migraine and the psychiatric comorbidity and to prevent the so called chronification circuit.

A non-systematic search was performed using MEDLINE/PubMed database with the following key words: (migraine OR headache) AND (depression OR anxiety OR personality disorder); (migraine OR headache) AND (sleep problems OR sleep disorder); (migraine OR headache) AND psych* AND stress; (migraine OR headache) AND (psychological intervention OR psychological treatment OR non-pharmacological intervention OR psychotherapy). In the Table 1, inclusion criteria for papers selection are reported.

MIGRAINE AND PSYCHIATRIC COMORBIDITY

Approximately 12% of the general population suffers from migraine8 and about 9% of people suffering from episodic migraine have chronic migraine9. Several studies suggest that migraine is more than two times more frequent in women than in men10,11. Moreover, women have a greater risk to develop disability12 as well as a greater risk of evolution from episodic to chronic migraine13.

The association between migraine and psychiatric disorders has been described in both clinical and community based populations. Many studies confirmed the presence of a high co-occurrence between depression, anxiety, personality disorders, sleep problems and migraine. Table 1 summarizes main studies on this comorbidity. Patients with migraine presented with a significantly greater number of comorbid psychiatric disorders than patients without migraine14. Epidemiologic studies also report a female tendency to development both depression and anxiety disorders in migraineurs with a prevalence twice in women than men15,16. Moreover some studies demonstrated that psychiatric comorbidities are more prevalent in chronic migraine than in episodic migraine9,17-19.

The presence of a psychiatric comorbidity seems to enhance migraine triggers susceptibility and the number of headaches/month20, as well as to increase disability and to reduce quality of life (QoL). Moreover, patients with comorbid mental disorders and migraine show a worse response to migraine treatment (due especially to low adherence), which can negatively modify long-term outcomes of migraineurs patients21,22.

Patients with migraine and a comorbid mental disorder have worse general health outcomes compared with individuals with one condition23,24.

Concerning depression, the nature of the relation with migraine is not clearly demonstrated, but longitudinal studies suggest a bi-directional relationship. Breslau and colleagues, in three longitudinal studies15,25,26, found similar figures for new onset migraine in subjects with depression and for new onset depression in migraineurs. However, Swartz did not confirm the higher risk of new onset migraine in depressed patients27. A recent review and meta-analysis found that the effects of migraine on depression was equal to OR=1.81 (95% CI=1.20-2.72) in cohort studies, and OR=2.00; 95% CI=1.64-2.43 in cross sectional studies, concluding that migraine can play an important role in increasing the incidence of depression in affected patients28.

Depression was also a significant predictor of onset of chronic migraine in patients with episodic migraine (OR=1.65, 95% CI=1.12-2.45) and the risk of chronic migraine onset increased with depression severity6,19.

Anxiety Disorders too seems to be strongly related to migraine (Table 1) and a factor potentially associated with reduced perception of efficacy with acute treatment, long-term migraine persistence, headache-related disability and with chronic outcomes13,29,30.

Concerning Personality Disorders, recent studies suggest that migraineurs and chronic migraineurs have higher rates of certain personality disorders as compared to individuals without migraine31,32 (Table 1). The coexistence of a borderline personality disorder seems associated with more pervasive headache, more migraine-related disability, and an increase difficulty to treat due to a higher prevalence of medication overuse and more unscheduled visits for acute migraine treatment33,34. Although less investigated than borderline personality disorder, avoidant personality disorder and obsessive-compulsive personality disorder, which are classified in a different cluster of personality disorders, have also been associated with migraine and seem to negatively impact migraine treatment, contributing to medication overuse and poorer prognosis35,36. However, literature is scarce and a cause-effect relationship between personality disorders and migraine remains unproven.

Sleep problems are more prevalent in patients with migraine than in the general population37. The association between severe sleep disturbances and migraine seems to be more pronounced for chronic migraine38. Patients with chronic migraine reported shorter nightly sleep times than those with episodic migraine, and were more likely to exhibit trouble falling asleep, staying asleep and sleep triggering headache39. As with depression and anxiety, also for sleep disturbances the relationship with migraines appear bidirectional with pain negatively impacting sleep and vice versa40.

ROLE OF THE STRESS AND THE CHRONIFICATION CIRCUIT

Stress is the factor listed most often by migraine sufferers as a trigger for their attacks. Some studies show that 50% to 80% of patients report stress as a trigger factor for their migraine attacks. It has been suggested that acute stress can provoke biological modifications lowering the threshold of susceptibility to a migraine attack41. Moreover, when behavioural or physiological stressors are frequent and/or severe, allostatic responses can become dysregulated and maladaptive (“allostatic load”), altering the normal response of physiological systems and leading to alterations in brain networks, both functionally and structurally. These effects can lead to abnormal responses to environmental conditions and to the chronification of the disease42,43. The overuse of analgesic medications, might affect allostasis, too44. Moreover, it has been well established from the 1970s that stress and psychiatric disorders are extremely related with a bidirectional relationship45. Therefore, migraine, stress and psychiatric disorders seem to be tied together, leading patients into a chronification circuit where every condition may provoke or incentivize the other with a final reduction in quality of life and worse outcomes.







NON-PHARMACOLOGICAL INTERVENTIONS

Due to the high prevalence of psychiatric comorbidity and stress in migraine and the impact of comorbidity on outcomes, in the last decades attention was directed to psychological interventions aimed at addressing both migraine and mental conditions. Following the history of psychosomatic medicine started a century ago46, from the ’80s studies on psychological treatment of headache and migraine were published and included biofeedback, cognitive-behavioural therapy (CBT), relaxation training, stress management and other techniques47. These behavioural therapies have very well-established efficacy for treatment of migraine, as confirmed in numerous studies and meta-analyses48. Furthermore, the combination of pharmacological treatment and behavioural therapy has been found to be more effective than either medication or behavioural therapy alone49-51.

CBT is an important treatment component especially for patients with a comorbid psychiatric conditions52. The rationale for the use of CBT in migraine management derives from the observation that the way people cope with everyday stressors can precipitate, exacerbate, or maintain headaches and increase headache-related disability and distress.

Advice to identify and avoid triggers, particularly those related to pathological mental conditions (stress and negative emotions, anger, lack of sleep or excess of sleep, alcohol abuse etc.)53 as a good means of preventing headaches, has been standard practice for decades. Martin and colleagues recently developed an alternative approach to trigger management called “learning to cope with triggers” (LCT)54 consisting in a graduated exposure to selected triggers to promote desensitization. They propose an integrative CBT/LCT approach which aims to enhance the effectiveness of CBT in migraineurs55. The same Authors in a randomized controlled trial in patients with comorbid headaches and depression, found that the CBT group improved significantly more than the control group mostly in men than women56. Indeed, the latest outcome is in contrast with literature57 and it could be associated with a greater tendence to ruminate in females than males58. This ruminative response style may increase the risk to develop a persistence depression59 and this could explaine the gender difference in treatment response56. Improvements achieved with treatment were maintained at four month follow-up. Furthermore, advice to avoid triggers altogether may lead to reduced internal locus of control for headaches, with attendant adverse effects on self-efficacy, particularly concerning perceived capacity to cope effectively with triggers60.

The self-management model, typically employed in cognitive-behavioural interventions, is very useful in patients with migraine and comorbid psychiatric disorders. This model optimizes medication adherence, effects lifestyle changes, improves functioning, limits disability, teaches way to manage stress and affective distress as well as educates about the role of cognitions and behaviours in health and illness61.

In recent studies, different forms of CBT in migraineur patients, have shown to be effective not only to manage patients’ headache pain, but also on reducing the depressed mood and/or the anxiety symptoms62-64. Also the biofeedback treatment proved to be effective both on migraine and anxiety and depressive comorbidity65,66. A recent pilot randomized controlled trial showed that biofeedback added to traditional pharmacological therapy in the treatment of medication overuse headache improved outcome in headache frequency, amount of drug intake and active coping with pain, also after 4 months of follow-up67. Though more research is needed on the effects of treating comorbid psychiatric disorders on headache outcomes and vice versa, these findings help to demonstrate the bidirectional relationship between depression, anxiety and migraine.

Other “emerging therapies” include: acceptance and commitment therapy (ACT)68,69, mindfulness-based intervention70-72, and behavioural interventions that target comorbid conditions as sleep disturbances73,74. Though existing studies are small, these approaches have produced positive outcomes, particularly in the domains of improving headache-related functioning and affective distress75. There is evidence that relaxation techniques, particularly progressive muscle relaxation, and different biofeedback techniques are effective in reducing frequency and severity of migraine76.

In a study on patients with medication overuse headaches, short-term psychodynamic psychotherapy added to pharmacological therapy, at 12-month follow-up, was associated with decreased headache frequency and medication intake, a lower relapse rate, and a lower risk of developing chronic migraine, as compare to pharmacotherapy alone77. Less studied, brief psychodynamic treatments appear promising in terms of feasibility compared to standard psychodynamic therapy. Insight oriented approaches could be helpful in decreasing stress-related vulnerability as well as somatization tendencies, potentially leading to long term results. Future studies are needed to demonstrate this hypothesis.

Importantly, all psychological interventions used in migraine proved to be effective in anxiety, depressive and stress-related disorders alone. Hence, the effect in patients with migraine and psychiatric comorbidity should be due to the improvement of migraine, stress-reactions and mental disorders together. In theory, the psychological effect of treatments could also prevent the chronification circuit addressing all conditions involved.

Finally, it is useful to note that the use of psychological techniques in migraineurs with comorbid mental disorders may provide a nonthreatening way to introduce the patient to the process of psychological treatment and thus, to encourage the patient to acknowledge psychological difficulties and accept treatment for psychiatric disorders61.

From a mental health perspective, non-pharmacological interventions for mental disorders in children and adolescents are highly indicated to improve long-term outcomes and avoid chronicity. However, most studies on migraine with psychiatric comorbidity are on adults. Only 11 trials from 2010 assessed behavioural approaches, mostly CBT, in adolescents or young adults with headache78. Two studies involved only patients with chronic migraine and depression or anxiety were considered as a secondary outcome in 4 studies. Non-pharmacological treatments were shown to produce sizeable effects on headache frequency and marked improvements were noted in depressive and anxiety symptoms. Future well-designed studies are necessary to explore the short- and long-term effectiveness of behavioural intervention in adolescents or young adults with migraine and psychiatric comorbidity.

CONCLUSIONS

Comorbid mental disorders, specially anxiety, depressive, and personality disorders are the rule rather than the exception in migraine. Stress-related vulnerability is associated with both migraine and psychiatric conditions. The co-occurrence of these conditions has a great impact on health. Psychological interventions are clearly indicated and effective for mild/moderate mental disorders and stress vulnerability. Several studies showed their effectiveness in patients with migraine, usually added to pharmacological treatment, suggesting a combined action on psychological and somatic symptoms. Future research is needed to better understand long-term effectiveness and to compare different psychological techniques.


Conflict of interests: the authors have no conflict of interests to declare.

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