The Relationship Between Depression and Migraine

The Relationship Between Depression and Migraine

Written by: Kylie Petrarca RN, BSN

Medically reviewed by: Dr. Lucy Rathier

Edited by: Melissa Calise and Leigh Serth

What is Depression?

Depression is a mood disorder that results in profound feelings of sadness, hopelessness and loss of self worth. It often causes loss of interest and pleasure in activities, fatigue and changes in sleep. For a diagnosis of major depressive disorder these symptoms must persist for a minimum of two weeks and should be diagnosed after exclusion of other medical conditions or behavioral health conditions due to overlapping symptoms. It is important to note, people can have episodes of depressed mood for situational variables such as grief/loss and this does not typically require a diagnosis. 

 How are Migraine and Depression Related?

Although the direct link between migraine and depression has not been discovered, it is likely the relationship is multifactorial. Studies have found changes in brain structures, genetics, neurotransmitters, sex hormones and stress as possible connections between both diseases.1

    • Abnormal brain structures: A study found those with both migraine and depression had reduced brain volume, decreased gray and white matter volume and reduced levels of cerebrospinal fluid.1 
    • Genetics: Diagnosis of migraine and depression in parents lead to an increased susceptibility to these conditions in their offspring. 
    • Neurotransmitters: Serotonin, norepinephrine and/or dopamine may be involved in the neurobiology of these conditions.
    • Sex hormones: Migraine and depression are almost 2 times more likely to occur in women.2 Estrogen may play a role in the underlying pathophysiology of these two conditions.
    • Stress: Stress increases the risk for developing depression and is considered a trigger for a migraine attack.

Migraine and depression share a bidirectional relationship, meaning depression increases the risk of migraine and vice versa. According to Dr. Dawn Buse at the AMD 2021 symposium, those with depression are 3.4 times more likely to develop migraine and conversely those with migraine are 5.8 times more likely to develop depression.

What are the Recommended Treatments for Migraine and Depression?

Commonly used first-line treatments for depression are selective serotonin reuptake inhibitors (SSRIs) such as sertraline, escitalopram and citalopram. SSRI’s did not prove to be effective for migraine. Conversely, beta blockers are considered one of the first line treatments for migraine but can increase the risk of depression. 

Tricyclic antidepressants such as amitriptyline and nortriptyline are another class of first-line treatments for migraine. While these medications are also used for depression, they aren’t typically one of the top choices. Also, serotonin-norepinephrine reuptake inhibitors(SNRIs) such as venlafaxine are used for both depression and migraine. According to a review in the Journal of Neurology, Neurosurgery, and Psychiatry, there is no current evidence that improved control of depression helps to control migraine. However, identifying and treating depression in patients with migraine is important because it is a significant predictor of migraine chronification, which is the transition from episodic to chronic migraine.3 

Cognitive-behavioral therapy is also an evidence-based treatment that may help patients with depression and migraine. Although medications can be helpful with boosting mood, it is also important for a person to learn skills and strategies necessary to deal with stressors, including the stress of migraine disease. Many studies have found that psychotherapy is equally as effective in clinical outcomes as antidepressants. In addition, there are no adverse effects from participating in cognitive behavioral therapy compared to some medications. For more information on cognitive behavioral therapy click here.

Anxiety, Depression and Migraine

Anxiety is a mental health disorder that is associated with excess fear and worry that interferes with most daily life activities for six months or greater. Depression, migraine and anxiety are comorbid disorders and can lead to increased financial burden, disability and poor treatment outcomes. A study found that the average outpatient, prescription drug and total medical costs per year for one migraine patient was $5,590, compared to a migraine patient with anxiety and depression which totaled $13,442.4 In addition to the financial burden, those with anxiety, depression and migraine were more likely to be classified as having a severe disability per the MIDAS scale compared to migraine and depression alone as well as migraine and anxiety alone.4 Lastly, those with migraine, anxiety and depression are less likely to respond to treatments.4 

What Type of Doctor Should I See for Migraine and Depression?

A neurologist with a headache specialty is the preferred doctor to treat migraine and other headache disorders. For depression, a psychiatrist and psychologist are most useful for diagnosing and treating this condition. A primary care provider may also be involved to help manage these conditions as well. The health care providers should utilize an interdisciplinary approach to treating migraine and depression.

A Note to Patients and Providers 

Although migraine and depression are more likely to occur in females, it is important to note that anyone can develop both of these conditions regardless of age or gender. The gold standard for diagnosing depression is through individual clinical interviews with a health care provider. Those living with migraine should be screened for comorbid depression and vice versa. The patient should inform the provider if they are showing signs and symptoms of depression. This will allow the physician to create an individualized treatment plan and decrease the risk of transitioning from episodic to chronic migraine.

The National Suicide Prevention Lifeline

The National Suicide Prevention Lifeline is a national network of local crisis centers that provides free and confidential emotional support to people in suicidal crisis or emotional distress 24 hours a day, 7 days a week in the United States.

Call the National Suicide Prevention Lifeline if you or someone you know is in a crisis. 1-800-273-8255

Recording Available – Migraine and Depression Webinar 

On February 22, 2022, we hosted a webinar to discuss the relationship between Migraine and Depression. We heard perspectives from a neurologist, researcher, and patient on the connection between the two diseases. We also learned about depression resources from the Anxiety and Depression Association of America.

Thank you to our speakers: Dr. Teshamae Monteith, Dr. Elizabeth Seng, Sarah Arndt and Dr. Sanjay Mathew for their time and wonderful presentations.




  1. Depression Information:
  2. Understanding Depression:
  3. Treatment Options:
  4. Support Groups:

Thank you to our sponsor Axsome Therapeutics!

Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are committed to developing products that meaningfully improve the lives of patients.

*The contents of this blog are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The writer does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.

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