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Table 2 Summary of mechanisms and implications for therapy

From: Understanding the nature of psychiatric comorbidity in migraine: a systematic review focused on interactions and treatment implications

Disorder

Possible Mechanisms

Implications for treatment

Potential Benefits

Caveats (and potential antidotes)

Depression

- Heritability

- Genes (e.g. 5-HT transporter gene, D2 receptor gene)

- Neurotransmitter systems (serotonin, dopamine, GABA)

- HPA axis

- “neuro-limbic” pain network

- Effects of serotonin agonists in both disorders

- Specific antidepressants are recommended for migraine and depression (e.g., amitriptyline)

- Specific migraine agents can have positive effects for migraine and depression (e.g., onabotulinum toxin A)

- Combined pharmacotherapy and psychotherapy can have synergistic effects

- Psychotherapy is recommended for migraine and depression (could help to increase adherence to pharmacotherapy or help to use less / no pharmacotherapy)

- Flunarizine and beta-blockers are contraindicated for depression (diagnostic procedures should always include diagnosing for depression)

- Patients may not speak about it because of fearing stigma / shame (therapist should try to create an appreciative atmosphere)

- Antidepressants recommended for migraine and depression differ in optimal dose for each treatment (weighing of benefits and risks)

Bipolar disorder

- Heritability

- Neurotransmitter systems (serotonin, dopamine, glutamate)

- Alterations in sodium/calcium channels, pro-inflammatory cytokines

- Effects of antiepileptic drugs in both disorders

- Valproate and topiramate (lamotrigine?) can have positive effects for migraine and BD

- Psychotherapy is recommended as addition to pharmacotherapy in BD (could help increasing adherence to pharmacotherapy)

- SSRIs and SNRIs have the risk of exacerbating mania or initiating a more rapid cycling course (diagnostic procedures should always include diagnosing for [hypo]manic symptoms, also in family history)

- Manic episodes may result in risky behavior (i.e., not taking medication)

Anxiety Disorders

- Heritability

- Neurotransmitter systems (serotonin, GABA)

- Ovarian hormones

- CBT recommended for migraine and anxiety disorders

- Patients may show avoidant behavior and be skeptical about treatment options

- Patients may not speak about anxiety due to several reasons, e.g., subthreshold levels (Therapist should be aware of subthreshold symptoms)

Stress and PTSD

- Central sensitization

- Neurotransmitter systems (serotonin)

- CBT (especially stress management) recommended for migraine and stress-related disorders

- Patients may not speak about previous traumatic events

Personality disorders

- ?

- ?

- Personality disorders seem to negatively influence treatment outcome (personality should be considered an influencing factor)

Substance use behavior / disorders

- Depression and other comorbid disorders as associated disorder

- Managing substance use might prevent MOH

- Migraine could be associated with more liberal medication intake (diagnostic procedures should always cover questions on substance use)

Somatoform disorders

- ?

- Reduction in headache may be accompanied by a decrease in somatic symptoms

- Somatic symptoms may complicate treatment (e.g., avoidance behavior)

Eating disorders

- Depression as associated disorder

- For specific subgroups, treating the eating disorder (i.e., avoid fasting, skipping meals, etc.) could reduce headache symptoms

- Eating disorders may be characterized by specific behavior (i.e., avoid fasting, skipping meals, etc.) that may trigger migraine (diagnostic procedures should always cover questions on potential triggers)

- Eating disorders are often linked to depression (diagnostic procedures should always include diagnosing for depression)

- Patients may not speak about it because of fearing stigma / shame and may hide it with clothes (therapist should be perceptive for eating disorder symptoms)

  1. 5-HT serotonin, BD bipolar disorder, D2 receptor dopamine D2 receptor, GABA gamma-Aminobutyric acid, HPA axis hypothalamic-pituitary adrenal axis, PTSD post-traumatic stress disorder, SNRIs serotonin–norepinephrine reuptake inhibitors, SSRIs selective serotonin reuptake inhibitors