Withdrawal from acute medication normalises short-term cortical synaptic potentiation in medication overuse headache

Neurol Sci. 2019 May;40(5):963-969. doi: 10.1007/s10072-019-03735-4. Epub 2019 Feb 1.


Objectives: To study the effects of a standard acute medication withdrawal program on short-term cortical plasticity mechanisms in patients with medication overuse headache (MOH).

Methods: Thirteen patients with MOH and 16 healthy volunteers underwent repetitive transcranial magnetic stimulation (rTMS) over the left motor cortex; in patients with MOH, recordings were performed before and after a 3-week medication withdrawal program. Ten trains of 10 stimuli each (120% resting motor threshold) were delivered at 1 Hz or 5 Hz in two separate sessions in a randomised order. Motor evoked potential (MEP) amplitudes were measured from the right first dorsal interosseous muscle and the slope of the linear regression line from the first to the tenth stimuli was calculated for each participant.

Results: All subjects exhibited MEP amplitude inhibition in response to 1 Hz rTMS. Alternatively, the 5-Hz trains of rTMS inhibited rather than potentiated MEP amplitudes in patients with MOH. The physiological potentiating effect of 5 Hz rTMS on MEP amplitudes was restored after drug withdrawal and in proportion with the percentage reduction in monthly headache days in patients with MOH.

Conclusions: The results suggest that acute medication withdrawal normalises brain responses in patients with MOH. Clinical improvements after medication withdrawal may reflect the reversal of neurophysiological dysfunction. Accordingly, medication withdrawal should be offered to patients with MOH as early as possible in order to prevent the development of more pronounced alterations in brain plasticity.

Keywords: Chronic migraine; Repetitive transcranial magnetic stimulation; Short-term depression; Short-term potentiation; Synaptic plasticity.

MeSH terms

  • Adult
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Female
  • Headache Disorders, Secondary / physiopathology*
  • Humans
  • Male
  • Motor Cortex / drug effects
  • Motor Cortex / physiopathology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiopathology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Substance Withdrawal Syndrome / physiopathology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Transcranial Magnetic Stimulation