A preliminary naturalistic study of low-doseketamine for depression and suicide ideation in the emergency department.
by Larkin GL and Beautrais AL
International Journal of Neuropsychopharmacology. 2011 14[8]:1127-1131.
We examined the preliminary feasibility, tolerability and efficacy of single-dose, intravenous [i.v.] ketamine in depressed emergency department [ED] patients with suicide ideation [SI]. Fourteen depressed ED patients with SI received a single i.v. bolus of ketamine [0.2 mg/kg] over 1-2 min. Patients were monitored for 4 h, then re-contacted daily for 10 d. Treatment response and time to remission were evaluated using the Montgomery-Asberg Depression Rating Scale [MADRS] and Kaplan-Meier survival analysis, respectively. Mean MADRS scores fell significantly from 40.4 [s.e.m.=1.8] at baseline to 11.5 [s.e.m.=2.2] at 240 min. Median time to MADRS score ≤10 was 80 min [interquartile range 0.67-24 h]. SI scores [MADRS item 10] decreased significantly from 3.9 [s.e.m.=0.4] at baseline to 0.6 [s.e.m. =0.2] after 40 min post-administration; SI improvements were sustained over 10 d. These data provide preliminary, open-label support for the feasibility and efficacy of ketamine as a rapid-onset antidepressant in the ED.
"There are no validated approaches to the pharmacotherapy of depression or suicidality in the emergency department (ED) setting. Available antidepressant drugs have slow onset of action, and inherent short-term liabilities. Indeed, many suicidal patients are admitted to hospital for safety reasons alone, despite the disruptive and costly nature of this disposition. However, recent studies suggest that ketamine, an N-methyl-D-aspartic acid (NMDA) glutamate receptor antagonist, may exert a rapid antidepressant effect in research subjects with treatment-resistant depression (TRD), bipolar disorder and suicide ideation (SI). In these studies a slow sub-anaesthetic infusion of intravenous (i.v.) ketamine rapidly reduced depressive symptoms within several hours of drug infusion, with this response maintained in some patients for up to 7 d. Recent studies also suggest an anti-suicidal effect of ketamine. Thus, there is a possibility that rapidly acting antidepressant medications might play a role in alleviating distress, reducing SI, and mitigating hospitalization in some subsets of ED patients. To explore this hypothesis, this study evaluated the effects of a low-dose i.v. ketamine bolus on depression and suicidality in ED patients."
My first post-residency job was running the psychiatric emergency room at Grady Hospital in Atlanta. This was a popular street drug, dusted on other things like marijuana or taken straight out. It can produce a syndrome that looks for all the world like a schizophrenic break, or a catatonic state, or delirium, or an LSD-like trip, or just about anything else. It can clear quickly or last for days. It’s like Scopolamine in that it’s an amnesiac. The idea that "many suicidal patients are admitted to hospital for safety reasons alone, despite the disruptive and costly nature of this disposition" is a reason to give someone a mind numbing, amnesia producing drug so you can send them home is as offensive a concept as I can imagine – a shameful extrapolation of cost-containment to the theater of the absurd. I guess I don’t think much of IV special·K Rx for SI in the ED [even if it works].
Um… how many SI cases get a daily follow-up contact from the ER for 10 days after their index visit? Um… what would we guess is the placebo value of all that attention? Um… the study was done at Yale, where Special-K was re-invented for mood disorders. Um… is this a case of stealth extension of the brand?
I still read about questionable beneficial uses of LSD and other hallucinogens apart from ketamine, and now we have the legalization of cannabis in two states, so when will we hear about the loosening of standards of controlled 2 substances like opiates and stimulants so people can get them filled by their PAs?
I know it wrong to say, but I am very interested to see the reaction of authorities in Colorado and Washington state WHEN the first traffic fatality by an impaired cannabis user occurs. Oh, they didn’t think that one through before passing the law, eh? Idiots!
More on Beautrais soon
The bean counters are going to love this. It’s cheap, it involves something that looks for all the world like treatment (an IV no less). I’m sure they will be directing ED policies and procedures forthwith to embrace a method with so much promise to save the costly and disruptive bother of admission to a hospital. Good grief.
Full circle! Experimentation with psychedelics and other nerve drugs (see December 17 New Yorker about Vietnam-era Army experiments) leads to new-generation psych drugs, failure of new-generation psych drugs leads to experiments with psychedelics.
Maybe all the psychoactives have the same therapeutic value? No better than placebo, fun for some, hell for others.
Also see here
with 42 comments.
I talked to a psychiatrist who did an investigation of ketamine in clinical practice. He said the effect was inconsistent and, where it could be called beneficial, temporary. Patients did not get positive effects from a second IV.
Exactly the results you would expect from a street drug temporarily rehabilitated as a psychiatric treatment. Some people get high, others don’t, the novelty wears off.
The only group not represented were those prone to chronic recreational use. For that, see bluelight.ru or erowid.
There have certainly been more developments in the use of ketamine and NMDA antagonists for depression since the article you posted was published. While the effect generally only lasts for days to a week, the effect has a lower NNT than conventional antidepressants and does onset within hours. With the doses involved, you don’t need to fuzz out people and studies are currently underway in the use in intranasal ketamine for suicidality which should decrease the need for monitoring. Lets not forget that SSRIs usually take 2-3 weeks to begin action and the only rapid alternative available now is electroconvulsive therapy. At my insitution, the current treatment for the acute suicidal patient is a talk with the psych nurse, then a locked room till morning or whenever the psychiatrist can see them. Should we not look at alternatives?
Hot off the presses:
http://www.nature.com/nm/journal/v19/n1/full/nm0113-8.html?WT.ec_id=NM-201301
Respectfully:
* Dr. Hassman, I’m not sure bringing LSD into the dialogue is terribly useful. The chemical structure of SSRIs (or Ketamine) is very different from LSD. Structural complexity does not equal efficacy, or specificity, but… show the formula for fluoxetine (or most other SSRIs) to a chemist, and their reaction is usually, “You have GOT to be kidding.” One guy I know described the chemical structure of SSRIs as “impoverished,” noting: “The chemical messaging keys that they are allusions to are also very simple. The active-end parts of the keys are formed in just a few atoms…” Also: “The passive psychoactive structures developed this way are similarly simple but with some almost random novelty. Since there are so many receptors in the human system, about 700, the simple novel molecule may find resonances elsewhere in the body, too. Look at the similarity between testosterone, the estrogens, and cortisol for example: the active ends are similar enough to require close scrutiny to discern them.” Hoffman was not trying to create a psych med when he stumbled upon LSD, he was trying to create a respiratory and circulatory stimulant (per Wiki.) I would also argue that LSD might– MIGHT– have some clinical value for some carefully screened populations no more than 2x per year in the 25-50 microgram range, with well-trained facilitators, but this is only a hunch that’s not informed by research or clinical practice, and may be based on obsolete assumptions. Our culture is now so paranoid and dysfunctional that hallucinogens may have become completely irrelevant and impractical. Your points about cannabis and driving are very well taken, of course. There are plenty of otherwise sensible people who think nothing of getting behind the wheel after consuming large quantities of very, very strong marijuana; I’ve never understood this.
* I do not consider Partnership for a Drug Free America to be a reliable source (probably worse than Wiki) and would never refer a client to any research they conducted, or use any of their research in group or in a school setting. But yes, it is pathetic that Ketamine is being considered for depression in the ER (what a weird little chemical… the Yugo of psychoactive substances), but IMHO there is little chance that insurance companies will find it economically viable; there’s too much liability there and they probably know it.
* Carl, I’m not sure that the bean counters actually will like this. What Pharma craves is continued, endless R&D. Any drug that is inexpensive and actually “cured” suicidal ideation in an ER setting just isn’t that helpful to their bottom line.
VERY interesting discussion, I am so glad I discovered this blog! Thanks to the author and everyone who posted.