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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