Oral ketamine augmentation for chronic suicidality in treatment-resistant depression

To the Editor

In a recent article in this journal, the effectiveness of intravenous ketamine in treatment-resistant depression was highlighted (Katalinic et al., 2013). The following case reports describe the use of oral ketamine as augmentation treatment in patients presenting with chronic suicide ideation and at least two significant past suicide attempts.

Mr B was a 44-year-old male with a history of bipolar depression and chronic suicide ideation since adolescence. His condition was further complicated by severe chronic pain and a family history of suicide. Despite multiple pharmacotherapy combinations and the current regime of amitriptyline (200 mg nocte) and quetiapine (100 mg bid) he remained depressed, with scores of 36 on the Montgomery–Åsberg Depression Rating Scale (MADRS) and 4/6 on the suicide item. Following written informed consent, oral ketamine was added. The treatment involved fortnightly doses of a ketamine solution (100 mg/ml) ingested orally with a flavoured drink. Starting with an initial dose of 0.5 mg/kg and gradually increasing by 0.5 mg/kg with each treatment, we achieved a sustained clinical response at around 3 mg/kg without any adverse or side effects. Within 24 hours of his first treatment his scores on the MADRS and suicide item decreased to 17 and 1, respectively. Repeated treatments every 2–3 weeks produced sustained remission of his suicidal ideation.

Mrs A was a 37-year-old female with bipolar depression and suicide ideation since adolescence. Her medication history included adequate trials of venlafaxine, mirtazapine, fluoxetine, quetiapine, olanzapine and several courses of electroconvulsive therapy (ECT). Her current regime included venlafaxine (150 mg qd) and quetiapine (700 mg qd). She remained depressed with scores on the MADRS and suicide item of 31 and 4, respectively. After obtaining written informed consent, oral ketamine was added. The initial dose of 0.5 mg/kg was gradually increased to 1.5 mg/kg. Within 24 hours of her first treatment the scores decreased to 10 on the MADRS and 2 on the suicide item. She continued to receive monthly doses of oral ketamine and her mental state continued to improve with no suicide ideation between treatments.

Pretreatment blood tests included liver function tests and complete blood count with differential. Blood pressure and pulse rate were monitored before and 30 minutes after each dose. Neither patient experienced adverse events or significant changes in vital signs during the treatment.

Although case reports require cautious consideration, these results are consistent with recent findings supporting the use of ketamine in treating severe depression. The possibility of using oral ketamine as a viable alternative to intravenous ketamine infusion is of special interest.