These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways.
Electro-Convulsive Therapy (ECT) is an effective intervention for treatment resistant depression (TRD) (Pagnin et al., 2004). However, therapeutic alternatives are limited if ECT is deemed medically unsafe. Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence (Slotema et al., 2010) in the management of depression. We describe a complex scenario in which we used rTMS to manage TRD.Mr T is a 56-year-old man who presented with depression, nihilistic delusions, and progressive deterioration in functioning over two years. Over three prolonged admissions in a 13-month period his symptoms were refractory to pharmacological trials of citalopram, sertraline, venlafaxine, aripiprazole, and risperidone. Comprehensive screening revealed no organic aetiology and neuropsychological assessment revealed mild impairment in attention related tasks. MRI-Brain revealed an incidental right cortical telangiectasia.Mr T's presentation was formulated as TRD and five sessions of brief pulse-width (1ms) bifrontal ECT were performed. Mr T showed a marked improvement following ECT but developed lower limb deep vein thrombosis necessitating anticoagulation. Anticoagulation and cerebral telangiectasia in combination potentially increased the risk of intracerebral haemorrhage with ECT, and therefore ECT was ceased. Given inadequate response to medication trials we administered adjunctive low frequency rTMS (1Hz) to the right dorsolateral prefrontal cortex thrice weekly for six weeks. Mr T's mental state improved partially with emerging reactivity of affect and improvements in self-care. His Hamilton depression scale score improved from 13 to 5 points, Hamilton anxiety scale score improved from 17 to 7 points and MADRS improved from 24 to 16 points. However, Mr T's symptoms recurred objectively and subjectively within a fortnight of ceasing rTMS. He required further ECT following the 6-month course of anticoagulation and this resulted in complete remission of his depression.Mr T had partial remission on combination rTMS (with antidepressants) when compared to antidepressants alone. While literature suggests that ECT is superior to rTMS in severe depression, the effect size for rTMS (0.55) in depression is higher when compared to antidepressants (0.17 to 0.46) (Slotema et al., 2010). Moreover combining rTMS with antidepressants has been shown to accelerate the antidepressant response (Huang et al., 2012). Our case while confirming the effectiveness of ECT, also demonstrates that combination rTMS is superior to antidepressant monotherapy, particularly when ECT is medically contraindicated. Hence rTMS is a potentially valuable intervention to be considered earlier in TRD, rather than sequential extended medication trials. Declaration of interestThe authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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