Why CGRP Migraine Drugs Don't Work for Everyone: Personality Traits May Hold Clues | Research

The takeaway

Migraine patients who didn't respond to anti-CGRP antibodies showed significantly higher levels of disinhibition, anhedonia, and depressivity on personality assessments compared to responders.

32% non-response rate
Nearly one-third of patients treated with anti-CGRP antibodies for migraine showed less than 30% improvement in headache days, with non-responders having significantly different personality profiles

What the researchers found

Among 97 patients treated with CGRP monoclonal antibodies (33 galcanezumab, 13 fremanezumab, 51 erenumab), response rates for monthly headache day reduction were: 54.6% full responders (>50% reduction), 13.4% partial responders (30-50%), and 32% non-responders (<30%).

PID-5 personality assessment revealed that non-responders had significantly higher scores in disinhibition, particularly in anhedonia and depressivity facets. For painkiller use reduction, non-responders showed increased depressivity and distractibility. For disability (MIDAS) improvement, non-responders scored higher in antagonism and submissiveness. The pattern suggests that traits associated with depressed mood and difficulty experiencing pleasure predict poorer treatment response.

Why it matters

Anti-CGRP therapies are expensive (often $600+/month) and the 32% non-response rate represents a significant clinical and economic burden. If personality traits can help predict who will and won't respond, clinicians could make better prescribing decisions, set realistic patient expectations, and potentially combine CGRP therapy with psychological interventions for patients with higher-risk personality profiles.

How the study worked

Observational study of 97 patients treated with anti-CGRP monoclonal antibodies. Three response parameters were measured: monthly headache days (MHD), monthly painkiller intake (MPI), and MIDAS disability score. Patients were classified as full (>50% reduction), partial (30-50%), or non-responders (<30%). All patients completed the Personality Inventory for DSM-5 (PID-5). Personality trait differences between response groups were compared.

What this study cannot tell us

Small sample size (97 patients) limits statistical power and generalizability. The study is observational with no control group. Personality traits may correlate with other variables (medication overuse, comorbid depression, chronicity) that independently affect treatment response. The short communication format limits methodological detail. The PID-5 assesses personality pathology and may not capture more nuanced trait variations.

How to read the evidence

This is a small observational study (97 patients) published as a short communication. While the findings are intriguing and statistically significant, the sample size, lack of control group, and potential confounders limit the evidence strength. Replication in larger cohorts is needed.

When this study was published

Published in 2022, this study addresses a timely question as anti-CGRP antibodies become widely prescribed and clinicians seek to predict treatment response.

The bigger picture

This study raises the provocative question of whether migraine treatment response is influenced by brain circuits beyond the CGRP pain pathway. The personality traits associated with non-response (anhedonia, depressivity) implicate reward and mood circuits — suggesting that in some patients, migraine involves broader neurological dysfunction that CGRP blockade alone cannot address. This could drive the development of combination treatments targeting both CGRP and mood pathways.

Questions still open

Would treating comorbid depression or anhedonia in non-responders improve their subsequent response to CGRP antibodies?
Are the personality traits identified as predictors stable, or do they change after successful migraine treatment?
Could a brief personality screen be incorporated into clinical practice to predict CGRP antibody response before initiating expensive therapy?

Common questions

Why would personality traits affect whether a migraine drug works?

Personality traits like anhedonia (inability to feel pleasure) and depressivity reflect how certain brain circuits function — particularly those involved in mood, reward, and pain processing. If a patient's migraine involves dysfunction in these broader circuits rather than just the CGRP pain pathway, then blocking CGRP alone may not be enough. The personality assessment may be indirectly measuring the complexity of each patient's underlying neurology.

Does this mean depressed migraine patients shouldn't try CGRP drugs?

No — over half of all patients still responded well, and having depressive traits doesn't guarantee non-response. The study suggests that these personality traits are associated with lower odds of response, not that they rule it out. It may mean that patients with these traits could benefit from addressing mood symptoms alongside migraine treatment, potentially improving outcomes for both conditions.

Read the original research

Personality traits and efficacy of anti-CGRP monoclonal antibodies in migraine prevention.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(9), 5765-5767

View on PubMed ↗Publisher’s paper ↗

Citation

Lovati, Carlo; Bernasconi, Gianna; Capogrosso, Chiara; Molteni, Laura; Giorgetti, Federica; Dell'Osso, Bernardo; Pantoni, Leonardo. (2022). Personality traits and efficacy of anti-CGRP monoclonal antibodies in migraine prevention.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(9), 5765-5767. https://doi.org/10.1007/s10072-022-06251-0