Pharmaco-TMS reveals specific GABAergic action of Quetiapine associated with depression remission in a case of comorbid bipolar and substance use disorders

We report a case of a 32-year-old male patient who suffered from bipolar depression complicated by severe alcohol dependence and chronic cannabis abuse. No medication could help him to control a strong craving leading to frequent relapse until off-label treatment by baclofen at high dosage (300 mg/day). The subject became completely abstinent in alcohol for several months. Thymic evaluation showed a major depressive episode with Beck Depression Inventory (BDI) score at 13/39. Treatment by quetiapine was then introduced at 300 mg/day. Motor cortical excitability was assessed before starting quetiapine and after 4 weeks of stable intake. A complete remission of depressive state was observed according to the BDI score at 2/39. Before quetiapine and under chronic and stable baclofen and cannabis consumption, we observed: – hugely lengthening of CSP in both hemispheres (right more than left), probably due both to baclofen and cannabis use; – absent SICI in left hemisphere and present SICI in right hemisphere in agreement with a major depressive disorder. Baclofen could also have accentuated SICI decrease via presynaptic inhibition action; – present ICF in left hemisphere and absent ICF in right side. These results may be consequence of SICI abnormalities described above. After quetiapine, we observed bilateral CSP shortening, SICI restoration in left hemisphere, and ICF restoration in right hemisphere. In summary, we observed for the first time normalization of cortical excitability associated with bipolar depression (i.e. deficit in motor cortical gabaergic transmission in left hemisphere) due to pharmacological intervention. This case shows the feasibility and the physiological insight of pharmaco-TMS, even in complex “real-life” clinical situations.