Robust Antidepressant Effect Following Alternating Intravenous Racemic Ketamine and Electroconvulsive Therapy in Treatment-Resistant Depression: A Case Report

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To the Editor:
Treatment-resistant depression (TRD) affects approximately 10% to 30% of all depressed patients, is associated with large socioeconomic burden and higher risk of relapse and suicide, and often remains misdiagnosed and undertreated.1,2 Electroconvulsive therapy (ECT) and subanesthetic ketamine, which has increasingly gained attention in psychiatry during the last decades,1 have repeatedly shown efficacy in TRD patients. Clinical outcome following ECT with ketamine, used as an anesthetic component to augment antidepressant efficacy of ECT, has already been investigated, with mixed results.1,3,4 Antidepressant effects of a combination of ECT and ketamine, administered alternately, have not been reported yet.
We present a severely depressed, chronically suicidal, and therapy-refractory female inpatient (age: 45 years, weight: 87 kg) without relevant somatic comorbidities. Numerous antidepressant treatment attempts including selective and nonselective monoamine reuptake inhibitors and receptor antagonists, monoamine oxidase inhibitors, tricyclic antidepressants, augmentation with antipsychotics, lithium, thyroxine, psychostimulants, and intravenous S-ketamine, as well as ECT, sleep deprivation, bright light- and cognitive behavioral therapy, did not result in a sufficient response. Eventually, a combination of tranylcypromine and lithium, which was augmented with regular infusions of intravenous S-ketamine,5 improved her clinical condition. However, tranylcypromine was discontinued because of prominent weight gain (30 kg) and necessity of keeping a diet. Subsequently, severe depressive symptoms requiring frequent psychiatric admissions reappeared. In acute suicidal crises, intravenous S-ketamine (up to 75 mg per infusion) was repeatedly administered, which, however, did not lead to a satisfying clinical improvement. Consequently, we used intravenous racemic ketamine (up to 75 mg per infusion), which resulted in antisuicidal and antidepressant efficacy lasting up to 55 hours.
Because she did not achieve a sustained response, and available conventional and nonconventional antidepressant therapies were nearly exhausted, she finally underwent an alternating treatment with ECT (previously she had shown partial but nonsustained response to bilateral stimulation) and ketamine infusions. She received ECT thrice weekly (bilateral stimulation up to 150%), while on ECT-free days intravenous racemic ketamine (up to 75 mg per infusion) was administered 2 to 3 times per week. Already in the first treatment week, we observed robust antisuicidal and antidepressant effects (>50% reduction from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), without any changes in her routine blood parameters and vital-signs, including blood pressure, heart rate, and oxygen saturation. Temporarily occurring mild cognitive disturbances (subjective forgetfulness) disappeared after the last ECT. In summary, the patient received 9 ECT treatments and 7 ketamine infusions, leading to a stable response (baseline MADRS score, 44; discharge MADRS score, 16).
Following discharge from psychiatric inpatient care, we established a maintenance therapy comprising ECT (bilateral stimulation at 150%) once monthly accompanied by 2 ketamine infusions (up to 100 mg per infusion) administered on the day before and after ECT in order to prevent relapse. After approximately 6 months of this maintenance therapy, our patient is still in a stable psychopathological state without relevant exacerbations of depressive symptoms. Our experience with alternating bilateral ECT and intravenous racemic ketamine on a daily basis, which have been proven safe and long-term effective after numerous failed antidepressant trials including ECT and ketamine alone, may thus encourage clinicians to widen the therapeutic armamentarium in severe TRD.
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