A 56-year-old woman with major depressive disorder showed considerable resistance to conventional antidepressive therapy. Over the course of a 9-month period of high-dosage standard antidepressant and augmentation treatments, including a combination of antidepressant drugs (citalopram, escitalopram, amitriptyline, clomipramine, venlafaxine, and moclobemide), atypical antipsychotics, and benzodiazepines, we observed no improvement of symptoms. Based on these negative results, we decided to give 0.25 mg/kg of (S)-ketamine intravenously with a 40-minute injection duration (3). Written informed consent was obtained from the patient after the procedure had been fully explained. Blood was collected at baseline and 10 minutes, 40 minutes, and 100 minutes after initiating the (S)-ketamine infusion. Before, during, and after the infusion, the patient was evaluated for depression using the Beck Depression Inventory (BDI), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Brief Psychiatric Rating Scale. The depressive and anxiety parameter scores rapidly improved after (S)-ketamine infusion, and the best results were observed at the end of the treatment (baseline scores: MADRS=29/BDI=18; posttreatment scores: MADRS=4/BDI=3). Acute dissociative symptoms monitored using the Clinician-Administered Dissociative States Scale were slightly elevated during the treatment (baseline=0, posttreatment=12) and returned to basal levels immediately after the end of treatment. No psychotic or delusional symptoms were recorded during or after the (S)-ketamine treatment.
In a Western blot analysis of peripheral blood cells, we observed a continued increase of mTOR phosphorylation on serine 2448 starting from baseline up to 100 minutes after the start of the (S)-ketamine infusion (Figure 1).