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Niciu MJ, Luckenbaugh DA, Ionescu DF, Mathews DC, Richards EM, Zarate CA. 
“Subanesthetic dose ketamine does not induce an affective switch in three independent samples of treatment-resistant major depression”. 
Biol Psychiatry. 2013 Nov 22;74(10):e23-4.
In the August 15, 2011, issue of Biological Psychiatry, Ricke and colleagues (1) presented a 42-year-old female patient with a history of reflex sympathetic dystrophy, depression, and insomnia admitted for the treatment of intractable pain. Her outpatient medications (duloxetine, mirtazapine, quetiapine, and high-dose opioids) were held at admission, and she received intravenous ketamine (.1–.2 mg/kg for 5 days) for analgesia. During this time, she developed symptoms consistent with mania (euphoric mood, decreased need for sleep, grandiose ideas, and loose associations) that the authors attributed to ketamine. However, there are at least four other diagnostic possibilities that have not been conclusively ruled out. First, the authors stated that the patient “appeared oversedated and admitted to self-administering opioids from a supply she kept in her purse, but when asked to, she was reluctant to turn these over to her physicians.” In the context of potential opioid intoxication, delirium must be ruled out (her level of attention and cognition during the hospitalization were not reported). Second, if the patient was self-administering opioids and reluctant to relinquish them to her inpatient providers, she may also have been using other illicit substances with analgesic properties that explain her manic-like syndrome (e.g., cocaine use). Unfortunately, there was no report of urine toxicology. Third, excessive opioid administration can cause a substance-induced mood disorder analogous to a mania in some patients. Finally, Ms. M.’s manic-like presentation occurred in the context of multiple medication adjustments (including increasing duloxetine on Day 8 in the midst of purported mania). Thus, antidepressant-induced mania is another important diagnostic consideration.
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