The Role of Ketamine Followed by Electroconvulsive Therapy in the Treatment of Depression with Suicidality

We read with interest the article by Arora et al. on a 23-year-old man with major depression manifesting as consistently low mood, anhedonia, cognitive impairment, auditory hallucinations and repeated high-level suicide attempts [1] .The patient benefited from a combination of intravenous ketamine for suicidality and electroconvulsive therapy (ECT) for depression and psychotic features [1] .The study is noteworthy, but some points should be discussed.The first point relates to the study design.A single case is not suitable to assess the efficacy of a therapy.Randomized, placebo-controlled, cross-over studies are necessary to assess whether a therapy is really useful or not and can be recommended as a golden standard.The second point is that the cause of the depression was not specified [1] .Since the patient had recently developed pulmonary tuberculosis and tuberculosis carries a high risk of developing depression [2] , we should know whether or not there is a causal relationship between the two.In addition, the medication he was receiving for tuberculosis was not specified.As some of the tuberculostatics can cause depression and anxiety, it would have been imperative to indicate the specific medication he was receiving.Fluoroquinolones in particular are known to cause depression.Has the patient received antiretroviral therapy, which can also cause depression?The third point is that the general side effects of ketamine have not been adequately discussed [1] .In addition to dizziness, these include hallucinations, confusion, disorientation, paranoia, dysphoria, anxiety, slurred speech, ataxia, dysarthria, trismus, muscular rigidity, psychomotor, psychomimetic, acute dystonic reactions, nausea, high blood pressure, tachycardia, myocardial infarction, elevated body temperature, vomiting, seizures, laryngospasm, and respiratory depression [3,4] .We have also recently encountered a patient with post-traumatic stress disorder (PTSD), severe depression and a history of MELAS who died suddenly after a single ketamine infusion [personal communication].The fourth point is that cerebral imaging was not described in detail [1] .To rule out brain involvement in the tuberculosis or other structural lesions that may have contributed to the depression, it would have been imperative to perform cerebral imaging, specifically MRI with contrast, and to examine the cerebrospinal fluid (CSF) for mycobacteria.Central nervous system (CNS) tuberculosis is known to cause vasculitis, meningitis, encephalitis and abscess formation.To rule out CNS involvement in TB, CSF tests are a must.India not only has one of the highest rates of TB in the world, but also one of the highest rates of drug-resistant TB.The fifth point is that it is incomprehensible why a patient with hallucinations and psychotic phenomena was administered ketamine.Ketamine has hallucinogenic potential and is often used as a recreational and party drug [5] .In addition to hallucinations, ketamine can be complicated by confusion, disorientation, paranoia, dysphoria, anxiety, and impaired consciousness [4] .To summarize, this interesting study has limitations that affect the results and their interpretation.Addressing these limitations could strengthen the conclusions and support the message of the study.Before ketamine in combination with ECT is recommended as a general treatment option for depression with suicidality, the general efficacy of the treatment must be investigated in appropriate studies with an appropriate randomised controlled design.