From the Guidelines
Methysergide can cause several significant side effects, with retroperitoneal fibrosis being the most serious long-term concern, as reported in studies such as 1.
Side Effects of Methysergide
The most commonly reported adverse events associated with methysergide include gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain, as well as leg symptoms like restlessness or pain 1.
- Other side effects may include dizziness, drowsiness, insomnia, and muscle cramps.
- Methysergide can also cause fibrotic reactions affecting not only the retroperitoneum but also heart valves, pleura, and lungs after prolonged use.
- Due to these serious fibrotic complications, methysergide requires drug holidays (typically 3-4 weeks off after every 6 months of treatment) and regular monitoring with imaging studies to check for fibrosis, as suggested by the manufacturer and reported in studies like 1.
Monitoring and Management
Patients should be monitored for signs of fibrosis such as lower back pain, leg edema, or decreased peripheral pulses.
- The drug works by antagonizing serotonin receptors, which explains both its therapeutic effect in preventing migraines and many of its side effects related to serotonergic pathways.
- Because of its significant side effect profile, methysergide is now rarely used and generally reserved for severe, refractory migraine cases when other treatments have failed, as indicated in guidelines and studies such as 1 and 1.
From the Research
Methysergide Side Effects
- Methysergide can induce retroperitoneal fibrosis and pleural and heart valve fibrosis with an estimated incidence of 1 in 5,000 treated patients 2
- The drug has been associated with various contraindications, including pregnancy, peripheral vascular disorders, severe arteriosclerosis, coronary artery disease, severe hypertension, thrombophlebitis or cellulitis of the legs, peptic ulcer disease, fibrotic disorders, lung diseases, collagen disease, liver or renal function impairment, valvular heart disease, debilitation, or serious infection 2
- A case study reported a patient who developed retroperitoneal fibrosis while taking methysergide, with laboratory studies showing increased serum procollagen III levels and anticardiolipin antibodies accompanied with anti-beta(2) glycoprotein I 3
- Psychiatric side effects have also been reported, including impaired concentration and thought projection, severe anxiety, and depression 4
- Methysergide should be reserved for severe cases in which other migraine preventive drugs are not effective due to its potential side effects 2, 5