Antidepressants for migraines

Frequent attacks of migraine are best treated with preventive measures. Several categories of medications have been shown to be effective for the prevention of migraine headaches. These include Botox injections (for chronic migraine), epilepsy drugs (gabapentin, topiramate, divalproex), blood pressure medications (propranolol, atenolol, lisinopril, losartan, and other), as well antidepressants.

Antidepressants, like most other preventive drugs, were discovered to be effective for pain and headaches by accident. We have good scientific proof that you do not need to be depressed to obtain pain and headache relief from these drugs. The effect on pain and on anxiety or depression are independent of each other. However, many patients who have pain and headaches have higher rates of depression and anxiety and these drugs can relieve both conditions.

The oldest category of antidepressants are tricyclic antidepressants. Elavil or amitriptyline was introduced in the US in 1961. Amitriptyline has been extensively tested for a variety of painful conditions, including low back pain, neuropathy pain, migraines, and other. The main side effects of amitriptyline are dry mouth, drowsiness, constipation, and sometimes, weight gain. Other drugs in the family of tricyclic antidepressants often have fewer side effects. Many doctors always begin with nortriptyline or Pamelor, which is a derivative of amitriptyline and may have fewer side effects. Amitriptyline is broken down in the body into nortriptyline, which is less sedating. We also prescribe other tricyclics, desipramine (Norpramine), doxepin (Sinequan), and protriptyline (Vivactil), which also tend to have fewer side effects. When a patient has insomnia and is not prone to gaining wait, amitriptyline may be the better choice since it will also improve sleep.

The starting dose of amitriptyline, nortriptyline, doxepin, and desipramine is 10 or 25 mg taken at night. Then, if this starting dose is ineffective, the dose is gradually increased to 50 mg, then 75, and sometimes higher. Besides being very effective, tricyclics have another advantage – there is a blood test to measure how much of the medicine is absorbed and is circulating in the body. When a patient takes more than 75 – 100 mg without obtaining relief, we do a blood test to see if the blood level is low and we need to increase the dose or if the level is high and the drug is just ineffective. With protriptyline, the least sedating drug, the starting dose is 10 mg and the highest dose is around 30 mg. Treatment of pain and migraines usually requires a much lower dose of a tricyclic than for depression. All of the tricyclics are available in a generic form and are inexpensive.

Another category of antidepressants that relieve pain and headaches is serotonin and norepinephrine reuptake inhibitors, or SNRIs. Some of the SNRIs are FDA-approved for various painful conditions, such as neuropathy, shingles, fibromyalgia, and back pains. Most popular SNRIs are Effexor (venlafaxine), which is available in a generic form, Cymbalta (duloxetine), Pristiq (desvenlafaxine), Savella (milnacipran), and Fetzima (levomilnacipran). These drugs have fewer side effects than tricyclics, although they are sometimes difficult to stop because they can cause heightened anxiety and other withdrawal symptoms.

Nardil (phenelzine) is an antidepressant in the family of MAO inhibitors and it has also been used for the preventive treatment of migraine headaches. However, this drug has many potential serious drug-drug and drug–food interactions and most doctors avoid this medicine. Other MAOI drugs are Parnate (tranylcypromine), Emsam patch (selegiline) and other.

SSRIs are the most popular drugs for the treatment of anxiety and depression, but they are ineffective for the treatment of pain, migraines, and other headaches. These drugs include Prozac (fluoxetine), Paxil (paroxetine), Lexapro (escitalopram), Zoloft (sertraline) and other. They are very popular because they have fewer side effects than other antidepressants, although they probably cause higher rates of sexual dysfunction.

  1. Dr. Mauskop says: 05/10/20159:48 pm

    Serotonin syndrome is extremely rare, but it does happen. The best antidepressants for the prevention of migraine headaches and for the treatment of pain in general, are tricyclic antidepressants, which also relieve depression and anxiety. They are also not known to cause serotonin syndrome when taken along with a triptan, such as Maxalt. Amitriptyline can have more side effects than SSRI (selective serotonin reuptake inhibitors) such Lexapro and citalopram. The main side effect is drowsiness, but you can take it once a day, before going to sleep so it will help insomnia as well. Or, you can try other tricyclics, such as nortriptyline, desipramine, or protriptyline, which can be less sedating. Constipation is another common side effect. The starting dose of amitriptyline or nortriptyline is 10 or 25 mg and then the dose is slowly increased. The average dose for the prevention of migraines is between 25 and 75 mg, but occasionally people need 100 mg or even more. Among my patients, weight gain is the most feared side effect, but it is not common at lower doses. Another drug to ask your doctor about is trazodone, which is a tetracyclic antidepressant that is often used for insomnia, but can also help anxiety and depression.

    An even better treatment for anxiety and depression is meditation, which can be started while taking medications. Mindfulness in Plain English by Gunaratana is an excellent book to learn meditation. offers an app and a desktop guided meditation. Here is a list of 10 best free guided meditation sites

  2. Morgan says: 05/10/201512:49 am

    I know this post is a little older but I thought I’d try and ask. I follow your blog posts and have learned so much; I’ve benefited greatly from the addition of magnesium supplementation daily. In the past year I have had a lot of career and family stress and my migraines became more chronic, along with more migraines with aura. I’ve had difficulty sleeping for the first time in my life, which also has made my migraines worse. I have had anxiety and depression as well. Anyway, my doctor put me on citalopram 20mg and after being on it for 2 weeks, I took my normal maxalt 10mg for a migraine. That night I became severely ill – shaking, sweating, vomiting, diarrhea and agitation. I went to the ER and was told I had serotonin syndrome from the 2 drugs together and was told never to take the two again together. Since I rely so heavily on maxalt, I went off the SSRI. Now, several months later I’m still suffering from insomnia and anxiety/depression but can’t take both drugs (I tried therapy and that helped but only to an extent). My doctor now wants me to take Lexapro and try Fioricet for migraines, or 800mg Advil. I need to treat my insomnia and anxiety/depression (which I think are all making my migraines more frequent) but I am scared to not be able to rely on maxalt. Can you offer advice please- I feel so stuck! I read one study that lexapro can help prevent migraines almost as well as Effexor and should be tried first due to less side effects. Thank you in advance!

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