Investigating predictors of response to Transcranial Magnetic Stimulation for the treatment of depression

INTERVENTION: Transcranial Magentic Stimulation (TMS). Magnetic stimulation is a non invasive technique for stimulating neural tissue. A rapid change in magnetic field induces a current in the neural tissue. If the current is of sufficient amplitude and duration it will excite nerve tissues. Patients will receive left sided high frequncy TMS intially, if they do not respond after three weeks they will be randomised to either; continue left sided high frequnecy treatment, crossover over to right sided low frequency TMS or sequential bilateral TMS (i.e. right sided low frequency followed by left sided high frequency). Daily treatment (Mon‐Fri) at 110% of motor threshold, for between 5 and 8 weeks. CONDITION: Treatment resistant depression PRIMARY OUTCOME: Antidepressant effects. ; ; Montgomery Asberg Depression Rating Scale (MADRS) ; ; A reduction of at least 50% on this rating scale indicates response. SECONDARY OUTCOME: Predictors of Response to TMS. ; ; Specifically, we will test the potential predictive capacity of several electrophysiological techniques: ; ; 1. Resting and task related frontal alpha electroencephalography (EEG) activity: Extensive research has demonstrated a relationship between resting frontal alpha activity in depression. More recent research has indicated a substantive functional role of alpha in tasks such as cognitive inhibition. This active alpha activity may provide a more functionally useful measure of alpha as it could potentially relate to response to treatment. ; ; 2. TMS‐EEG measures of cortical inhibition: We have recently pioneered a technique combining single and paired pulse TMS stimulation with EEG to measure the activity of inhibitory GABAergic activity in cortical regions such as the dorsolateral prefrontal cortex (DLPFC). GABA activity has previously been shown to be reduced in patients with depression and to increase with successful treatment although no methods have been available to evaluate functional GABA activity and its relationship to treatment response before now. ; 3. Near infrared spectroscopy (NIRS) is a technique for non invasively measuring cortical blood flow by assaying changes in absorption and diffraction of near infrared light produced by changes in oxygenated and deoxygenated haemoglobin. We have successfully recorded blood flow changes with NIRS during prefrontal TMS and will explore whether the immediate reduction in oxygenated haemoglobin seen in local cortical regions during TMS treatment is associated with treatment response. INCLUSION CRITERIA: Have a DSM‐IV diagnosis of a Major Depressive Episode (SCID II). Are aged 18‐75. Have treatment resistant depression at Stage III of the Thase and Rush classification (27). Have a Hamilton Depression Rating Scale (HAMD) score of > 20 (moderate to severe depression). Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to screening