Ketamine infusion combined with accelerated sequential theta burst stimulation in multi-therapy-resistant bipolar...

Treatment resistance in bipolar depression is one of the most challenging clinical conditions to treat in psychiatry. We present a case of an elderly gentleman with chronic Multi-Therapy Resistant Bipolar Depression (MTRBD), where ketamine, a preferential NMDAR blocker on cortical GABAergic interneurons, is used adjunctively with sequential theta burst stimulation (sTBS) to achieve remission.

Intravenous ketamine thrice a week was administered with sequential bilateral intermittent- and continuous-Theta Burst Stimulation (iTBS and cTBS) in 69-year-old man, with 2 years of bipolar depressive episode with multiple comorbidities, resistant to numerous antidepressants, anticonvulsants and antipsychotic mood stabilizers, individualised psychotherapies, trial of electroconvulsive therapy and sTBS. Roving mismatch negativity (rMMN), a robust passive EEG-ERP paradigm measuring neuroplasticity, was evaluated before and after this treatment protocol RESULT: A significant clinical improvement with Hamilton depression rating scale (HDRS 17) score improving from 15 to 8 with progressive improvement to achieve complete remission that persisted even at the latest 2-year follow-up on stable medications. A pronounced correction of dysregulated repetitive positivity, partial correction of deviant negativity was noted in rMMN after the treatment.

The novel combination of ketamine has resulted in sustained clinical remission in a patient with MTRBD. Earlier failure of sTBS and ECT underlines the importance of this combination. The rMMN findings were consistent with changes in short-term adaptive plasticity and may represent a potential neurophysiological correlate of treatment response. Combining Ketamine.