What is the link between migraine and psychiatric disorders? From epidemiology to therapeutics.

The association between migraine and psychiatric disorders is well documented through numerous population-based studies. The results of these studies are coherent and show an increased risk of suffering from depression, bipolar disorders, numerous anxiety disorders, especially post-traumatic stress disorder. This raises the question of stress as a precipitating factor for migraine illness. Psychiatric comorbidity is even more frequent in chronic migraine than in episodic migraine patients. Many prospective studies have shown that psychiatric comorbidity could be considered as a risk factor for migraine chronicization. Psychiatric comorbidity is also responsible for an increase of the frequency of anti-migraine drug intake, a worsening of quality of life and a worsening of functional impairment. It is also responsible for an increase in the direct and indirect costs of migraine. The reason why psychiatric comorbidity is so high in migraineurs is not unambiguous. Multiple causal relationships and common etiological factors are linked. Recently, genome-wide association studies gave leads to a genetic common heritability between major depressive disorder and migraine. For clinicians, an important topic remains how to treat migraineurs with psychiatric comorbidity. These patients suffer frequently from severe migraine or refractory migraine. Antidepressant and anti-convulsive drugs can be useful, as well as psychological therapies. But moreover, it is of utmost importance to propose an integrated multidisciplinary approach to these difficult patients.

Medication overuse headache: Updating of the French recommendations regarding the treatment strategies.

Regular and frequent use of analgesics and acute antimigraine drugs can increase the frequency of headache, and induce the transition from episodic to chronic migraine or medication-overuse headache (MOH). The one-year prevalence of this condition is between 1% and 2% in Europe, provoking substantial burden. MOH is more prevalent in people with comorbid depression, anxiety, and other chronic pain conditions. This paper aims at presenting an updating of French recommendations regarding treatments strategies. Prior French recommendations, published in 2014, were written in French. A literature search in the major medical databases including the terms "medication overuse headache", "symptomatic medication overuse", published between 2010 and 2020 was carried out. Three main strategies can be recommended and conducted in parallel: education and explanations about the negative consequences of overusing acute antimigraine drugs, discontinuation of the overused medication, and finally, preventive drug therapy and non-pharmacological prevention. Medication overuse headache remains a debated problem and evidence for the most effective treatment strategy is needed.

Brain structural investigation and hippocampal tractography in medication overuse headache: a native space analysis.

BACKGROUND: Spatial normalization of brain images, a prerequisite for voxel based morphometry analysis, may account for the large variability of the volumetric data in medication overuse headache (MOH); possibly because this disease concerns patients differing on both sex and age, and hence with different brain size and shape. METHODS: The present study aimed at providing a subject-based analysis of macrostructure using a native space volumes segmentation (Freesurfer), and microstructure using a region of interest (ROI: i.e. hippocampus) tractography approach in MOH patients. RESULTS: The results show that MOH patients had decreased volumes of left hemisphere temporal gyri (temporal superior, fusiform) and occipital middle gyrus, together with an increased volume of the left inferior (temporal) lateral ventricle. The left temporal volume was negatively correlated with depression score and medication dependence parameters. Seed-based tractography of the hippocampus revealed a decreased number of reconstructed fibers passing through the left hippocampus. CONCLUSION: To our knowledge, these alterations have not been described with methods involving brain normalization, and they indicate that left hemisphere temporal areas, including the hippocampus, may play a role in MOH pathophysiology. Trial registration number NCT00833209. Registered 29 January 2009.

Brain functional connectivity and morphology changes in medication-overuse headache: Clue for dependence-related processes?

BACKGROUND: Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH). OBJECTIVE: The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs). METHODS: Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain. RESULTS: Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the default-mode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores. CONCLUSIONS: Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance.

[Stress and migraine]. / Stress et migraine.

The link between stress and migraine is complex. In its recent conception, stress is viewed as a transactional process between an individual and his-her environment in which the individual makes a response to an internal or external constraint. This paper reviews the evidence in favor of a relationship between stress and migraine. Many studies show that 50 to 80% of patients report stress as a precipitating factor for their migraine headaches. Many authors have suggested that acute stress can provoke biological modifications lowering the threshold of the individual's susceptibility to a migraine attack. It has also been shown that the incidence of migraine is higher when stress scores are higher in the previous year. This suggests that as well as being a precipitating factor of crisis, stress could also be a precipitating factor of illness in susceptible individuals. Moreover, stress can trigger migraine chronification. This has been shown in many retrospective studies and in one prospective study. Hyperalgesia and central sensitivity to pain induced by chronic stress can partly explain this phenomenon. Many retrospective studies also show that adverse events during childhood, like sexual and physical abuse, are more frequent in migraineurs than non-migraineurs. Nevertheless, there is no prospective study allowing considering a causal link between childhood abuse and migraine in adulthood. Another point that will be tackled is the comorbidity between stress related psychiatric disorders, such as post-traumatic stress disorder, and migraine. Here again, many studies conducted in huge samples from the general population are convincing. All that leads to propose stress management therapies to migraineurs. Randomized control trials and meta-analyses have shown that relaxation therapies, biofeedback and stress management cognitive behavioral therapies are effective in migraine prophylaxis, above all in children. The use of these therapies is of particular interest in association with pharmacological treatments in patients with frequent crises. However, the majority of the studies have poor methodological standards. Nevertheless, stress management therapies are proposed as prophylactic treatment in the French recommendations for migraine management.

[Addictive behaviour in medication overuse headache: A review of recent data]. / Comportement addictif chez les patients souffrant de céphalée par abus médicamenteux : une revue des données de la littérature.

INTRODUCTION: Some data in the current medical literature suggests a link between medication overuse headache (MOH) and addictive behaviors. We present here a review of the clinical and biological data highlighting the role of addictive behaviors in MOH. RESULTS: One third to one half of MOH patients will relapse in their overuse within five years following withdrawal of the offending medication. Some studies have shown that two thirds of MOH patients fulfil DSM-IV criteria for dependence concerning their use of acute headache medication. Moreover, there is a co-morbidity between substance related disorders and MOH and some data suggest a familial co-transmission between MOH and substancerelated disorders. In a prospective study, the use of acute headache medication containing psychoactive substances like opiate derivates increase the risk of transformation from an episodic headache to MOH suggesting the role of conditioning factors among other psychological variables as catastrophizing and a low self-efficacy. Finally, data from the neuroimagery, biology and genetic fields suggest the presence of common pathophysiological features between MOH and addiction. In particular, a study found a hypometabolism in the prefrontal cortex of MOH patients, not recovering after withdrawal, such abnormality being described in addicted patients and suggesting an inability of the prefrontal cortex to inhibit craving. PERSPECTIVES: All these data suggest that with MOH we face two sets of patients. The first one, in which medication overuse is mainly due to the worsening of the headache course, with minimal psychiatric contribution ; the second one, in which addictive behavior can play a major role. In the first case, education can simply lead to a significant reduction of medication intake, whereas in the second case a pluridisciplinary follow-up must be proposed before, during and after acute headache detoxification. CONCLUSION: A pluridisciplinary approach is the only way to reduce the relapse rate which remains too high in MOH.

[Pain and depression: cognitive and behavioural mediators of a frequent association]. / Douleur et dépression : les médiateurs cognitifs et comportementaux d'une association très fréquente.

LITERATURE FINDINGS: The comorbidity between chronic pain and depression is high: in the general population setting, the odds ratio for suffering from one of these disorders when suffering from the other is estimated around 2.5. For chronic pain patients consulting in pain clinics, the comorbidity rate reaches one third to half of the patients. For the International Association for the Study of Pain (IASP), pain consists in an emotional as well as a sensory dimension, both of them have to be assessed systematically. Likewise, affective disorders must be systematically depicted in chronic pain patients. The reasons for such comorbidity are complex and result from the conjunction of common risk factors (environmental and genetic vulnerability factors) and of a bidirectional causality. THE TRANSACTIONAL MODEL OF STRESS AND COPING OF LAZARUS ET FOLKMAN: The appraisal stress model (Lazarus and Folkman, 1984) offers an opportunity to understand how chronic pain can cause depression. Pain is conceptualized as a chronic stress. Its appraisal in terms of loss, injustice, incomprehensibility or changes (primary appraisal), and in terms of control (secondary evaluation) determine how the subject will cope with pain. Several personality traits as optimism, hardiness or internal locus of control play a protective role on these evaluations, whereas others (neuroticism, negative affectivity or external locus of control) are risk factors for depression. Low perceived social support is also related to depression. On the contrary, self-efficiency is linked with low levels of depression. Self-management therapies focus on increase of perceived control of pain by the patient in order to improve his/her motivation to change, and to let the patient become active in the management of his/her pain. CONCLUSION: According to Lazarus and Folkman (1984), coping strategies are the constantly changing cognitive and behavioural efforts to manage specific external and/or internal demands that are appraised as taxing on or exceeding the resources of the person. Pain patients can use a wide variety of pain coping strategies: problem versus emotion focused strategies or cognitive versus behavioural strategies. Some of them are highly dysfunctional, such as catastrophizing (cognitive strategy) or avoidance (behavioural strategy). Their preferential use can lead to the development of a depressive episode. The "fear-avoidance model" (Vlayen, 2000) explains pain chronicization by a vicious circle that begins with the pain catastrophizing; this leads to fear of pain, which in turn leads to avoidance and finally to pain and depression. This is why some behavioural cognitive interventions focus on the reduction of catastrophizing and avoidance. Some functional pain coping strategies were identified: they are active strategies centred on problem resolution such as distraction, reinterpretation or ignorance of pain sensations, acceptance, and exercise and task persistence. New therapeutic interventions focus on the development of better coping strategies such as distraction, relaxation and acceptance.

Clinical determinants of migraine preventive treatment: contribution of SMILE, an observational survey of primary care migraine management in France.

METHODS: SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary care medicine. A total of 1467 GPs and 83 neurologists were included, treating 5417 and 248 migraine sufferers, respectively. RESULTS: The main factors leading physicians to deem a patient eligible for preventive treatment were perceived medication overuse and frequency of headaches, and secondarily, severity of headaches and functional impact. On the other hand, patient satisfaction with the acute treatment of attacks and triptan use, and secondarily, a long migraine history were found to influence patient eligibility negatively. DISCUSSION/CONCLUSION: Noticeably, psychiatric disorders (anxiety, stress) did not appear, aside from somatic factors, among the determinants that significantly influence physicians' judgment about the option of establishing a preventive treatment. However, they are important features of migraine condition and should be listed among the factors guiding choices about migraine preventive therapy.

The GRIM2005 study of migraine consultation in France. III: Psychological features of subjects with migraine.

The objective of this analysis was to describe psychological and cognitive variables in subjects with migraine and to identify those associated with chronicity. Data were collected from 10 000 subjects during face-to-face interview. Subjects with episodic migraine (n = 1127) or chronic daily headache (n = 407) with migrainous features were identified using an algorithm based on the International Classification of Headache Disorders, 2nd edn classification. Data on headache impact was obtained with the Headache Impact Test-6, on psychological distress with the Hospital Anxiety and Depression Scale, on coping with the Coping Strategy Questionnaire catastrophizing score and the Brief COPE inventory, on illness perception with the Brief Illness Perception Questionnaire and on locus of control. Psychological variables associated with chronicity include perceived headache impact, psychological distress, the use of catastrophizing and avoidance coping strategies and an externalized locus of control. In conclusion, maladaptive coping strategies should be taken into account in the management of patients with migraine. Longitudinal studies will be necessary to address the causality of the relationship observed.

Anxiety, stress and coping behaviours in primary care migraine patients: results of the SMILE study.

The objectives of the SMILE study were to assess anxiety, stress, depression, functional impact and coping behaviours in migraine patients consulting in primary care in France. General practitioners (n = 1467) and 83 neurologists included 5417 consulting migraine patients. Of these patients, 67% were found anxious, of whom 59% were also depressive. Patients with both anxiety and depressive dimensions showed a profile similar to that of chronic migraine patients (severe attacks, poor treatment effectiveness and pronounced stress, functional impact and maladaptive behaviours). A quantitative progression in the levels of stress, maladaptive coping behaviours and functional impact was noted from patients with neither dimension to those with both anxious and depressive dimensions. Stress and maladaptive coping strategies were found to be major determinants of anxiety. Anxious and depressive dimensions were associated with elevated consumption of acute treatments for migraine and low treatment effectiveness. Stress and anxiety should be looked for carefully in migraine patients.

SMILE: first observational prospective cohort study of migraine in primary care in France. Description of methods and study population.

The SMILE study was conducted among migraine patients consulting in primary care in France. The first phase aimed to describe the study sample of patients at entry to the study, especially emotional dimension (Hospital Anxiety and Depression scale), functional impact (abridged Migraine Specific Questionnaire), stress (Perceived Stress Scale) and coping behaviours (brief COPE inventory avoidance subscale, Coping Strategies Questionnaire catastrophizing subscale), as well as treatments used and their effectiveness and treatments prescribed at end of consultation. Results indicate that consulting migraine patients suffer frequent migraine attacks, exhibit substantial levels of anxiety, functional impact and stress, and often use maladaptive coping strategies. Abortive treatments appear ineffective in most patients (74%). Patients with more affected psychometric variables and treatment ineffectiveness are more likely to be deemed eligible for prophylactic treatment. These data highlight the seriousness of migraine and maladjustment of patients consulting in primary care.

The GRIM2005 study of migraine consultation in France II. Psychological factors associated with treatment response to acute headache therapy and satisfaction in migraine.

The objective of this analysis was to identify variables associated with treatment response in subjects with migraine. Data were collected from a sample of 10,000 subjects. A battery of questionnaires assessing clinical and psychological variables was completed. Migraine diagnosis was attributed using an algorithm based on the IHS criteria and treatment response using the ANAES criteria. We identified 1534 subjects, of whom 1443 were treated. For 54.2%, at least one ANAES criterion for treatment response was unfulfilled. Non-response was associated with female gender, high HIT-6 impact scores and high HAD psychological distress scores. The strongest associations with non-response were identified for four psychological variables: elevated scores on the CSQ catastrophization subscale and the 'Consequences' and 'Acceptance' dimensions of the Brief COPE, and low scores on the 'Positive Reinterpretation' Brief COPE dimension. In conclusion, many individuals with migraine respond inadequately to treatment. Behavioural interventions aimed at modifying coping strategies may improve outcome.

The GRIM2005 study of migraine consultation in France I. Determinants of consultation for migraine headache in France.

The aim of this study was to evaluate determinants of consultation for migraine in a representative sample of the French general adult population. We interviewed 10,032 subjects, of whom 1534 fulfilled the International Headache Society diagnostic criteria for migraine. These were categorized into migraine, probable migraine and chronic migraine. Information was collected on consultation experience; 436 subjects (28.4%) had never consulted for headache, 473 (30.8%) were in active consultation and 625 (40.7%) had previously consulted but lapsed. Subjects with chronic migraine showed the highest active consultation rates (51.8%). All subjects completed rating instruments for headache [Headache Impact Test (HIT)-6], psychiatric (Hospital Anxiety and Depression Scale scale) and psychological [Brief Illness Perception Questionnaire (BIPQ), Brief COPE Inventory and Coping Strategy Questionnaire] variables. The strongest determinants of active consultation were BIPQ scores, HIT-6 scores and migraine type. Consultation was associated with maladaptive coping strategies (social support, emotional expression and acceptance). Determinants of remaining in consultation were catastrophizing coping scores and previous consultation experience.

[Validation of EHD self questionnaire in multiple sclerosis]. / Validation de l'Echelle d'Humeur Dépressive (EHD), version autoquestionnaire, dans la sclérose en plaques.

Depressive Mood Scale (EHD) aims at assessing the various depressive mood dimensions as "blunted affect" and "lack of emotional control". It is an 18 items hetero-evaluation scale. The aim of this study was the validation of an EHD self questionnaire version. Self questionnaire items were generated from genuine scale items. As in the former version, response format was a Lickert 5 point scale. This validation study was carried out on 77 Multiple Sclerosis (MS) patients. Mood disorders are frequent during the course of MS and might be triggered or worsened by immuno-modulation therapies. Principal Component Analysis (ACP) with Varimax rotation revealed a two factors structure. The first one, corresponding to a "blunted affect" dimension, explained 33.5% of the scale variance and was composed of 7 items. The second one, corresponding to a "lack of emotional control" dimension, explained 20% of total scale variance and was composed of 4 items. The questionnaire internal coherence coefficient (Cronbach alpha) was excellent (=0.87) and the two sub-scales ones were satisfactory [0.89 for "blunted affect" dimension and 0.71 for "lack of emotional control" dimension. The questionnaire's external validity was confirmed by a positive correlation between "lack of control" sub-score and state sub-score of the Stait-Trait Anger eXpression Inventory (STAXI)] (r=0.55, p<0.01). Moreover we found a positive correlation between the total EHD autoquestionnaire score and both sub-scores on the one hand, and the Beck Depression Inventory score on the second hand (EHD/BDI: r=0.76, p<0.01; "lack of emotional control"/BDI: r=0.68, p<0.01; "blunted affect"/BDI: r=0.63, p<0.01). Test-retest reliability was good with a positive correlation between all the initial scores and their retests, a week later. Secondarily, a structural equation modeling analysis confirmed the two-factors structure model suggested by ACP. Various indicators showed a good fit between theoretical variance-covariance matrix and the observed one (chi(2)=41.55, p=0.49, ddl=42, Goodness Fit Index GFI=0.91, Root Mean Square Residual RMSEA=0.00). Thus, we proposed a well validated self questionnaire that allows the assessment of "blunted affect" and "lack of emotional control". It should be challenging to correlate those dimensions with neuro-psycho-logical testing and neuro-imagery, in patients affected by CNS diseases. Moreover, the assessment of those dimensions during interferon treatment in MS could allow a more precise evaluation of the emotional changes potentially induced by immuno-modulatory treatments.

[Headache and transformed migraine with medication overuse: what differences between disability, emotional distress and coping?]. / Migraine et migraine transformée avec abus médicamenteux: quelles différences en termes de handicap, de détresse emotionnelle et de stratégies de coping?

LITERATURE FINDINGS: Twelve percent of general population is estimated to suffer from migraine (Henryet al., 2002), which represent in France 6 to 7 millions of individuals. Transformed migraine (TM) with medication overuse is a complication of migraine characterized by an increase of crisis frequency and by a parallel increase of medication intake. French prevalence of TM with analgesic overuse seems to reach up to 3% of general population (Lanteri-Minet, 2003). TM is associated with an increased disability (concerning housework, leisure, job and social activities). Moreover TM is associated with a bad emotional adjustment, which can lead to anxiety and depressive disorders. Those disorders have been founded to be more frequent in TM than in simple migraine (Radatet al., 1999). As a consequence, TM patients's quality of life is severely impaired. The use of dysfunctional coping strategies against pain should explain bad emotional adjustment in those patients. One study have found a statistical relationship between dysfunctional coping strategies such as nd depressive disorders in migraineurs (Materazzo et al., 2000). METHOD: The aim of this study was to compare 30 simple migraineurs (SM) to 32 transformed migraineurs with medication overuse (TM) for impairment, emotional adjustment and coping strategies. Patients have been assessed with Pain Disability Inventory (PDI) (Pollard et al., 1984), Hospital Anxiety Depression scale (HAD) (Zigmond and Snaith, 1983) and Coping Strategies Questionnaire (CSQ) (Rosentiel and Keefe, 1983). RESULTS: Principal Component Analysis (SPSS Software) confirms the good psychometric properties of PDI and HAD in headache patients. Statistical analysis shows higher emotional distress scores (HAD mean score = 32,2 +/- 10,9) in TM than in SM (24, 1 +/- 7,3) (p < 0,001). Both groups didn't use the same coping strategies against pain. TM were characterized by the use of "dramatisation", "distraction" and "pray", which are considered as dysfunctional coping strategies, although SM used "reinterpretation" which is associated with a better adjustment in term of disability and emotional distress (Riley et al., 1999). CONCLUSION: These results suggest that dysfunctional coping strategies in TM should explained the increased prevalence of emotional distress in this population. It should be of an utmost interest to assess temporal evolution of coping strategies after medication withdrawal. Withdrawal is the main therapeutical measure proposed to TM patients. It should also be supposed that behavioural changes related to medication with drawal evolve in parallel with changes in the use of coping strategies against pain.

[Migraine with psychiatric co-morbidity]. / Migraine et comorbidité psychiatrique.

Investigation of migraine co-morbidity has confirmed a strong association between depression, anxiety disorders (particularly panic and phobia) and migraine. However, research into the possible mechanisms underlying these associations remains limited. The literature also indicates that migrainers are at reduced risk of suffering from anxiety, mood disorders and substance-related disorders compared with medication overuse headache sufferers. Patients suffering from medication overuse headache sometimes exhibit addictive behavior for acute migraine drugs. Finally, migrainers show increased non-specific neurotic suffering.

[Headaches associated with psychiatric disorders]. / Céphalées et affections psychiatriques.

Attributing the cause of headache to psychiatric disorders implies a direct causal relationship between the former and the later. According to the 2nd version of the IHS classification, headache can be secondary to psychotic disorders, somatisation disorders, undifferentiated somatoform disorders, depressive disorders, anxiety disorders (separation anxiety disorders, generalized anxiety disorders, panic disorders, social phobia, and post traumatic stress disorders, especially in case of head injury). Psychosocial functioning of these patients is severely impaired and their medical costs are high.

Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study.

It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose, on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.

[Psychopathology and headache]. / Psychopathologie et céphalées.

Headache patients seen in headache clinics, apart from pain and physical symptoms, commonly present psychological problems of anxio-depressive nature, and in some cases traits of a pathological personnality. It is thus worthwhile to review the present state of knowledge about the comorbidity of psychiatric disorders and migraine, tension type headache, chronic daily headache and transformed migraines. Migraine sufferers in particular have been investigated more thoroughly than patients with other types of headache. Several studies have been conducted on migraine sufferers in the general population diagnosed using well-defined criteria ("International Headache Society" and "American Psychiatric Association"). There is a consensus that migraine sufferers have a higher risk of anxio-depressive disorders than the general population. Some authors also found a higher risk of substance (alcohol, drugs) abuse in migraine sufferers, which is consistent with the abuse of pain-killers commonly noted in patients seen in headache clinics. The patients seen in such clinics are, therefore, not representative of the general population. The coexistence of anxiety and/or depression and analgesic abuse in headache patients has been little explored from an epidemiological point of view. The nature of the link between the two types of disorder remains unknown: cause and effect, common etiological factor. However, it is apparent that the anxio-depressive disorder and analgesic abuse worsens the prognosis of the headache condition and that the treatment of headache in the general sense needs to take account of the underlying psychiatric morbidity rather than be restricted to treatment of the headache per se.