100 Migraine Drugs, A to Z: ketamine

Ketamine (Ketalar) was officially approved for human use by Food and Drug Administration (FDA) in 1970 and, because of its wide margin of safety, was even administered as a field anaesthetic to soldiers during the Vietnam war. Concerns over the psychedelic effects of ketamine and the arrival of new intravenous hypnotics such as propofol led to a marked decrease in the use of ketamine for anesthesia, but in the recent years its use has been increasing. Its unique properties have led many researchers to do clinical trials for the treatment of pain and depression. Intranasal ketamine was just approved by the FDA for treatment-resistant depression.

True efficacy of ketamine for the treatment of pain and migraine headaches is less clear. There have been no double-blind studies of ketamine for the treatment of migraine headaches. A major obstacle to doing such studies is that it is very difficult to blind patients to the effect of ketamine. We do have anecdotal evidence, that is a description of series of patients who were given intravenous ketamine. A report entitled, Ketamine Infusions for Treatment Refractory Headache describes 77 chronic migraine patients who “failed aggressive outpatient and inpatient treatments”. These patients were hospitalized and were receiving ketamine infusions for an average of 5 days. Over 70% of these patients improved, although only 27% had sustained improvement.

In a report published in The Journal of Headache and Pain authors describe 6 patients admitted to the hospital whose refractory migraines improved with intravenous ketamine, albeit the improvement was only short-term. One patient reported a transient out-of-body hallucination, which resolved after decreasing the rate of infusion.

Intranasal ketamine was shown to relieve severe migraine aura in 5 of 11 patients with familial hemiplegic migraine. In some patients, the aura can be more debilitating than the headache or other symptoms of migraine and we have no effective treatment to stop the aura once it stops.

A Randomized Controlled Trial of Intranasal Ketamine in Migraine With Prolonged Aura, was a study of 18 patients published in Neurology. It showed that intranasal ketamine reduces the severity but not the duration of migraine aura.

I have referred a small number of patients whose migraines fail to respond to a wide variety of treatments for outpatient intravenous ketamine infusions. A few of these patients found ketamine to be very helpful. This is not a fair test of the drug’s efficacy because those who failed to respond to 20 different treatments are not likely to respond to the 21st one. Considering that ketamine is fairly safe (the dose given is much smaller than the dose used for anesthesia), it would be useful to have a controlled randomized trial in less refractory patients.