Reply To: Subanesthetic Dose Ketamine Does Not Induce an Affective Switch in Three Independent Samples of Treatment-Resistant Major Depression

To the Editor: We agree with several excellent points raised by Niciu and colleagues: 1) the case report that we presented was a description of possible induction of mania in a patient receiving ketamine therapy. Because it was a case report, several issues could not be controlled for, including toxic or withdrawal effects of medications that the patient was receiving/using; 2) the data presented from controlled studies of effects of ketamine in depression is likely to be much more reliable; 3) an increase in manic symptoms is likely in bipolar (particularly bipolar I) patients, if antidepressants are not given under the cover of mood stabilizer medication. However, despite there being insufficient evidence from 98 patients studied with ketamine by the National Institutes of Health group, there are several indications that ketamine, like other antidepressants, could potentially induce mania. At least one bipolar II patient in the ketamine study developed mania despite being on lithium, and two patients in the ketamineriluzole study developed transitory mania-like symptoms. If ketamine is classified as an antidepressant, then there is no reason to think that it would be less likely than a traditional