A 35-year-old woman with refractory chronic migraine has been referred to the pain clinic for pain management. She reports missing work quite often because of migraines. You consider prescribing intranasal ketamine. Based on a recent study, which of the following was the MOST likely patient-reported outcome of administering intranasal ketamine to treat refractory chronic migraine?
- □ (A) High rate of the therapy being described as “very effective” or “somewhat effective”
- □ (B) Low rate of adverse effects
- □ (C) No improvement in quality of life
Refractory chronic migraine is diagnosed when a patient fails to respond to multiple acute and preventive migraine medications and reports significant impairment in quality of life. Intravenous ketamine is effective in treating refractory chronic migraine but requires dose titration and a hospital setting for administration. However, intranasal ketamine is known to have rapid absorption, provide antinociceptive effects, and offer convenient self-administration. A recent retrospective study of intranasal ketamine, conducted at a single tertiary center, sought to assess its effectiveness and tolerability in the treatment of refractory chronic migraine. Although intranasal ketamine has been evaluated in small studies in other types of migraine headaches (e.g., status migrainosus) with some benefit, this is the first study that evaluates its role in refractory chronic migraine.
It was the clinical practice of this center to offer intranasal ketamine to patients after they had failed standard antimigraine medications. The intranasal ketamine was compounded by a local pharmacy as 10 mg/0.1 mL, and patients were instructed to use one to two sprays in each nostril per dose every 15 minutes as needed, with up to 20 sprays per day and 40 sprays per week at the discretion of their providers. Use of controlled substances, drinking alcohol, and driving were all restricted when using intranasal ketamine, or else treatment would be terminated.
Patients with refractory chronic migraine who were prescribed intranasal ketamine were identified by querying the hospital electronic data records between 2019 and 2020. Those who consented underwent a structured telephone interview. In addition to demographic data, information was collected on the frequency of ketamine use, time to pain relief, consistency of pain relief, changes in pain level on an 11-point numerical rating scale, effectiveness of ketamine compared to other rescue medications, global impression of effectiveness, overall impact on quality of life, and any accompanying adverse effects. Data from 169 patients were available for analysis.
All patients carried the diagnosis of migraine; other coexisting headache diagnoses present were daily persistent headache (13.0%; n=22), posttraumatic headache (17.8%; n=8), and intracranial hypertension (3.0%; n=5). Most patients (67.5%) reported daily headaches. Most had failed three preventive medications and were on at least two acute medications for migraine management. Neck pain (61.5%, n=104) was the most prevalent coexisting non-headache diagnosis. Nearly a quarter (24.7%; n=41) of the patients were prescribed intranasal ketamine before intravenous ketamine infusion while 47.6% did not receive prior ketamine infusion treatment.
In terms of effectively treating headaches, 49.1% (n=83) and 39.6% (n=67) of the patients rated ketamine as very effective or somewhat effective, respectively. Among these patients, 78.1% (n=132) stated intranasal ketamine made their quality of life much better or somewhat better. When asked to compare intranasal ketamine with other acute headache medications, it was rated much better (43.2%; n=73), somewhat better (29.6%; n=50), no difference (10.7%; n=18), somewhat inferior (8.9%; n=15), and much inferior (3.0%; n=5). Surprisingly, nearly 35% (n=59) of the patients had stopped using intranasal ketamine at the time of the study. Daily use was reported by 13.6% (n=23) of patients while 21.9% (n=37) were using it more than 15 days per month. Pain intensity decreased with more than 70% treatment response consistency. In addition, nearly three-quarters of patients reported less use of other acute medications when using intranasal ketamine. However, 74.0% (n=125) of patients reported at least one adverse effect. The most common adverse effects were fatigue, diplopia, blurred vision, hallucination, confusion, and vivid dreams. Of 142 participants for whom laboratory data were available, transient elevation of transaminases was seen in 10 patients (7%) but without any rise in bilirubin. Most patients found use of intranasal ketamine tolerable, and they were able to continue use.
It should be noted that intranasal administration of ketamine for headache is an off-label use. Pharmacology and the optimal dose-delivery system have not been fully determined. The optimal dose for this route is still unknown; time to onset and bioavailability are variable and affected by the nasal spray apparatus, individual nasal passage, site of deposition, and spray viscosity. It is preferred that the medication be deposited higher in the nasal cavity for greater effectiveness. In the study, the average daily intranasal ketamine dose (60-80 mg) was still lower than the average infusion dose (960-1,920 mg). Excessive spray leads to the drug ending up in the stomach. The risk of drug dependence or misuse is possible and requires extensive counseling, education, and monitoring.
This study has several possible limitations, including selection bias in enrollment and data analysis. The participants were mostly White women, and concomitant use of abortive and preventative medications was not specifically addressed. The reasons for discontinuation, which occurred in 35% of the patients prescribed intranasal ketamine, were not evaluated.
In conclusion, this study showed that intranasal ketamine can improve headache and quality of life in patients with refractory chronic migraine who have failed standard medications, with a tolerable adverse effect profile.
Answer: A