Antidepressant Effect of Ketamine During ECT
To the Editor: There has been recent interest in the use of ketamine as anesthesia for ECT because of its low anticonvulsant effects and possible reduction of cognitive side effects (1). Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, has also been shown to have putative antidepressant effects (2–4). The following case serves to highlight the possible antidepressant effects of ketamine in a patient who unintentionally received an induction dose alone during two failed ECT sessions.
Ms. A was a 47-year-old white woman who was hospitalized for an episode of severe depression in the context of a 20-year history of schizoaffective disorder. Ms. A had been treated for depression with ECT 8 years previously and had experienced profound confusion and short-term memory problems. However, she did respond, with remission of her depression. The current episode of depression had persisted for 16 weeks, during which she did not respond to venlafaxine, bupropion, sertraline, olanzapine, or lamotrigine. She had been simultaneously taking valproic acid. Ms. A’s depression was characterized by profound dysphoria, anergia, anorexia, insomnia, anhedonia, and passive suicidal ideation. There was no observed or reported mood variability, except for mild morning worsening of the dysphoria. She was hospitalized because of a decline in her activities of daily living to the point of not dressing herself without assistance.
Ms. A complained of severe memory problems, although her score on the Mini-Mental Status Examination was 30 of 30. The results of an EEG and magnetic resonance imaging were normal. Ms. A was withdrawn from valproic acid, 1500 mg/day, and lamotrigine, 50 mg/day, 24 hours before her first ECT treatment. For the index ECT treatment, ketamine was used as an induction agent at a dose of 0.5 mg/kg because we have found that it reduces cognitive side effects in some patients. Ms. A had no previous exposure to ketamine. Bifrontal lead placement was used, and a stimulus with the Spectrum 5000 Q ECT apparatus (MECTA Corp., Lake Oswego, Ore.) was administered by using the dose-titration method. The cuff method was used to monitor the motor seizure, and the electrical seizure was monitored with an EEG. No motor or electrical seizure was observed during the first treatment session.
Ms. A reported an immediate improvement of her mood after regaining consciousness. This improvement continued the next day when she awoke in the morning and reported a subjective improvement in well-being and an appetite for the first time in 2 weeks. The following day, ECT was again administered with the dose-titration method because we assumed that the antiepileptic agents interfered with the induction of a seizure during the first treatment session. Again, no electrical or motor seizure was observed. Strikingly, Ms. A reported a further improvement in her mood that persisted the following day. Her core symptoms, interest, energy, motivation, mood, and appetite all improved. On our 0–10-point rating scale of clinical improvement, Ms. A rated herself at 7, having initially rated herself at 2. Session 2 fell on a Friday, so there was an extra day to observe Ms. A’s response.
Forty-eight hours after her second ECT session, Ms. A still noted improvement. She did note some decline in her mood and felt that the improvement was starting to dissipate. Because of the timing of the treatments, we had 5 days to observe her clear improvement over baseline in response to ketamine. At session 3, a full grand mal seizure was observed. Three more treatment sessions were necessary before remission was reached.
Ketamine, as both an adjunctive dose (3) and an inductive dose (4), has been noted to improve mood in patients undergoing surgery. Two studies have demonstrated its potential antidepressant effects in major depression (2, 3). Of interest, acute administration of NMDA antagonists has been demonstrated to induce neurogenesis, a characteristic seen in many antidepressant agents. NMDA-mediated involvement of the glutamatergic system in the pathophysiology of depression is of growing interest (5, 6). Ketamine is also a weak dopamine transporter antagonist and can be psychotomimetic. Its role as a primary anesthetic agent in ECT deserves more study. It may have its greatest use in patients with severe nonpsychotic depression.
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