Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression

• Published in: Journal of neurology, neurosurgery and psychiatry neurosurgery and psychiatry, 2005-04, Vol.76 (4), p.527-533
• Main Authors: Münchau, A, Langosch, J M, Gerschlager, W, Rothwell, J C, Orth, M, Trimble, M R
• Format: Article
• Language: English
• Subjects: 4th edition; active motor threshold; Adult; AMT; Anticonvulsants; Antidepressants; Antidepressive Agents, Tricyclic - administration & dosage; Antidepressive Agents, Tricyclic - pharmacology; Antidepressive Agents, Tricyclic - therapeutic use; Arousal - drug effects; BDI; Beck depression inventory; Biological and medical sciences; Convulsions & seizures; Depressive Disorder, Major - complications; Depressive Disorder, Major - drug therapy; Diagnostic and Statistical Manual of Mental Disorders; Drug dosages; DSM-IV; Electric Stimulation; Electromagnetic Phenomena; Epilepsy; Epilepsy - complications; Epilepsy - physiopathology; Evoked Potentials, Motor - drug effects; FDI; Female; first dorsal interosseous muscle; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; ICF; ICI; interstimulus interval; intracortical facilitation; intracortical inhibition; ISI; Male; Medical sciences; Mental depression; MEP; Mianserin - administration & dosage; Mianserin - analogs & derivatives; Mianserin - pharmacology; Mianserin - therapeutic use; Middle Aged; mirtazapine; Motor Cortex - drug effects; Motor Cortex - physiopathology; motor evoked potential; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nervous system (semeiology, syndromes); Neural Inhibition - physiology; Neurology; noradrenaline; Patients; resting motor threshold; RMT; selective serotonin reuptake inhibitor; silent period; SSRI; TMS; Transcranial magnetic stimulation
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2004.037010

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.