Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression.
BACKGROUND
Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive.


OBJECTIVE
To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS).


METHODS
Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS.


RESULTS
At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine.


CONCLUSIONS
Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.
Münchau
A
A
Sobell Department of Motor Neuroscience and Movement Disorders, Dept. of Clinical and Experimental Epilepsy, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. Muenchau@uke.uni-hamburg.de
Langosch
J M
JM
Gerschlager
W
W
Rothwell
J C
JC
Orth
M
M
Trimble
M R
MR
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001143:Arousal / Q000187:drug effects*; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy*; D004558:Electric Stimulation; D055590:Electromagnetic Phenomena; D004827:Epilepsy / Q000150:complications* / Q000503:physiopathology; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D008875:Middle Aged; D000078785:Mirtazapine; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine