BARCELONA — Patients with migraine are less likely to respond to CGRP monoclonal antibody (mAb) preventive treatments if they have certain psychiatric disorders, a new study shows.
Italian researchers report that patients with an anxiety disorder or those with avoidant, dependent, or obsessive-compulsive behaviors are more likely to be nonresponders to these new therapies.
"As well as biological factors, we also have to consider psychological characteristics when considering the most appropriate intervention for patients with migraine," said study investigator Sara Bottiroli, PhD, associate professor of psychology at the University of Pavia, Italy.
The findings were presented at the 17th European Headache Congress (EHC) on December 7, 2023 (session ScS 5).
Highly Variable Treatment Response
CGRP mAbs are the first disease-specific treatment for complicated migraine and have been shown to be effective for migraine prevention in patients with difficult-to-treat migraine, Bottiroli noted. But there is high variability in treatment response, and the patient's psychological profile is one potential factor that may affect response rates.
To look at this further, Bottiroli's group conducted the current study to evaluate the psychological predictors of super-response vs nonresponse to anti-CGRP mAbs.
The study involved 116 patients with chronic or episodic migraine in whom at least three preventive therapies had failed and who underwent 6 months of treatment with an anti-CGRP mAb: erenumab, fremanezumab, or galcanezumab.
Patients were evaluated for psychopathologies at baseline using the Structured Clinical Interview for DSM-5 Clinical Version (SCID-5-CV), and they were asked about early life traumatic experiences, current stressors, and alexithymia, a neuropsychological phenomenon characterized by significant challenges in recognizing, expressing, and describing one's own emotions.
After 6 months of treatment with a CGRP mAb, patients were classified as a nonresponder if they experienced less than a 25% reduction in monthly migraine days or as a super-responder if they had more than a 75% reduction in monthly migraine days.
Of the study population, 19% were classed as nonresponders and 39% as super-responders.
Major Psychological Differences
Results showed major differences in psychological profiling between the two study groups.
Nonresponders had a higher prevalence of patients with psychopathologies, in particular anxiety disorders and personality disorders, and a higher prevalence of stressful life events and childhood trauma.
After other factors were controlled for, nonresponders were seven times more likely than super-responders to have a psychopathology (odds ratio [OR], 7.3; P =.017); almost five times more likely to have a cluster C personality disorder (anxious and fearful behaviors) (OR, 4.9; P =.025); and almost six times more likely to have had stressful life events (OR, 5.9; P =.02).
"The important finding of this study is the identification of a cluster C personality disorder as being representative of a nonresponder," Bottiroli said.
Cluster C personality involves avoidant, dependent, or obsessive-compulsive behaviors. Bottiroli explained that these patients have difficulty managing stress and unpredictable events in daily life, and they often develop anxiety disorders.
"We believe that these factors acting together predispose to a very aggressive form of migraine so that patients are not able to respond to these prophylactic treatments," Bottiroli added.
"My hypothesis is that unmanaged stress and anxiety lead to the development of hyperexcitability of the trigeminal system and central sensitization, together with very disabling migraine and an increase in CGRP expression," she noted.
"It looks apparently that CGRP mAbs can counteract peripheral sensitization in blocking the activation of the CGRP receptor, but the effect seems to be attenuated by the simultaneous role of psychological vulnerability."
These findings, said Bottiroli, "suggest it is important to have a full evaluation of the migraine brain and the factors involved in the pathophysiology of migraine, especially in these complicated patients. In this way, psychological and psychosocial factors should be taken into consideration and patients presenting with this particular type of profile with difficulty managing stress should be treated with special care."
"We believe this type of screening is important to identify which type of patients will respond to this type of treatment and those who do not respond so we can offer personalized therapy," she added.
Other Predictors of Response
In a separate presentation, Fabrizio Vernieri, MD, associate professor of neurology at Campus Bio-Medico University Hospital Foundation in Rome, Italy, reviewed other factors that were associated with a higher or lower likelihood of response to a CGRP mAb.
Factors associated with higher response rate included a lower body mass index, unilateral pain with or without unilateral autonomic symptoms, and a good response to triptans. Whereas factors associated with a poor response included overweight/obesity, daily headaches, interictal allodynia ( pain due to a stimulus that does not normally provoke pain), use of a high number of previous prophylactic medications, and a history of depression, he said.
Lars Edvinsson, MD, chair of the EHC session at which these studies were presented and professor of internal medicine at Lund University Hospital, Sweden, said the results were " Interesting and exciting for clinical practice."
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