Ketamine Studied as Antidepressant

[Arcticpheonix]

BETHESDA, Md. - Aug. 7

Symptoms of depression can be made to disappear in less than two hours with a common anesthetic, not the weeks or months required for onset of relief with traditional antidepressants, according to results of a pilot study.
Action Points

"We have broken the sound barrier in depression treatment," said Carlos A. Zarate, Jr., M.D., chief of the mood disorders section the National Institute of Mental Health, who reported on the effects of ketamine, a common anesthetic, in the August 8 issue of the Archives of General Psychiatry.

Dr. Zarate and colleagues said a single injection of ketamine, which targets the N-methlyl-D-aspartate (NMDA) receptor, can eliminate depression symptoms within 110 minutes.

After a two-week drug-free run-in, patients were given IV ketamine hydrocholoride (0.5 mg/kg) or placebo on two test days a week apart. Twelve of the participants were women and the mean age of participants was 46.7 (range 16 to 60).

The endpoint of the trial was changes in score on the 21-item Hamilton Depression Rating Scale. The effect size for the drug difference was large (d=1.46 [95% CI 0.91-2.01]) after 24 hours and moderate to large (d=0.68 [95% CI 0.13-1.23]) after one week, they wrote.

At 110 minutes, patients given ketamine had an average Hamilton Depression Rating Scale score of 15, down from more than 25 at baseline which was significant (P<0.05) and at day one the average score was less than 15 which was highly significant (P<0.001). There were no significant changes from baseline among patients who received placebo injections.

"We are not replacing depression with a manic phase," Dr. Zarate said. "The effect is simply the elimination of depression. The patients, essentially, return to normal."

Of 17 patients who received ketamine injections 71% met response criteria and 29% met remission criteria the day following ketamine infusion, Dr. Zarate and colleagues wrote. Thirty-five percent of subject maintained that response for a week.

Interestingly, ketamine is a popular street drug, which is sold under a number of names including kit kat, jet and super C. Dr. Zarat acknowledged that common side effects included perceptual disturbances, confusion, increased blood pressure, euphoria, dizziness, and increased libido.

But the effects never lasted longer than 110 minutes, while the beneficial effect of a single dose was generally durable for seven days.

Ketamine is approved for human use, but is most commonly used as a veterinary anesthetic.

Despite his obvious enthusiasm for treatment, Dr. Zarate cautioned that the results are preliminary and are not yet ready for "the general clinician." Nonetheless, he said that the results of the 18-patient trial provide a proof-of-principle that rapid-almost instantaneous-treatment of clinical depression is possible.

And while the speed of the drug's effect was impressive, "how to maintain that effect and how to achieve it consistently is not so clear," he said.

Moreover, since the trial was limited to patients with treatment resistant major depression, it is not clear whether an N-methlyl-D-aspartate will work as well or as quickly in patients with less severe depression.

Additionally, the authors note that "limitations in preserving study blindness may have biased patient reporting by diminishing placebo effects, thereby potentially confounding results."

Dr. Zarate said his team plans additional studies with the aim of "developing strategies for maintaining the rapid response," which may mean adding one or more drugs that can "piggyback" the ketamine effect to maintain a durable response.

Primary source: Archives of General Psychiatry
Source reference:
Zarate CA "A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression" Arch Gen Psychiatry 2006; 63:856-864

Posted from http://www.medpagetoday.com/Psychiatry/Depression/3877

 

[Caduceus Mercurius]

Fascinating. But if the effects last only 7 days, it's not that impressive yet. Of course very interesting for the pharmaceutical companies, because patients will have to keep using the ketamine.

It would be nice to hear under what circumstances the ketamine was given to these patients. If the administration of ketamine would be combined with proper understanding of set & setting and the potential of holotropic states, they might achieve more permanent results.

which may mean adding one or more drugs that can "piggyback" the ketamine effect to maintain a durable response.

It comes in another small bottle. 8)

 

[Forkbender]

exactly my thoughts. If you combine ketamine with good therapy and a psychedelic session after a few days, it might work.

The research itself is already 3 years old, btw.

 

[Arcticpheonix]

Oh is it three years old? I never thought to check. My friend read this in a magazine, and I looked up an article online to post. I didn't realize it was out of date. Does anyone have a move recent article on this program?

 

[Caduceus Mercurius]

Does anyone have a move recent article on this program?

Not really, but I found this (see the lines in bold):

http://www.ejbjs.org/cgi/content/full/91/9/2296

September 1, 2009
What's New in Orthopaedic Rehabilitation

....
....

Although the orthopaedic community has spent the majority of its time on the technical aspects of amputation, two recent studies examined the development and treatment of pain that the amputee experiences postoperatively, one of the major clinical complaints that the orthopaedic surgeon has to address postoperatively. Schley et al.9 examined the potential mechanisms for the development and origin of phantom-limb pain in a study of ninety-six upper limb amputees (all but one of whom had undergone an amputation because of a traumatic injury). Using a questionnaire, they assessed pre-amputation pain and the presence or absence of phantom pain, phantom sensation, stump pain, and stump sensation. The median duration of follow-up in the study was 3.2 years. The authors reported stump sensation to be the most prevalent finding in their cohort (78.5%), followed by stump pain (61.5%), phantom sensation (53.8%), and phantom pain (44.6%). Phantom pain decreased in only 48.2% of the patients and either remained stable or worsened in the remainder. A similar finding was found for stump pain, with only 47.5% of the patients noting reduction in the pain at the time of the questionnaire. Interestingly, phantom pain occurred immediately after amputation in only 28% of the amputees, within one year in 10%, and after one year in 41%. The authors concluded that stump pain/sensation is the initial predominating source of patient discomfort and that phantom pain/sensation is a long-term consequence (with some patients noting an onset almost a year after surgery).

That study indicates that clinicians must be fluid in their use of pain-relieving measures after amputation, dealing with stump pain/sensation initially and then focusing their efforts on phantom pain/sensation at a later time with different modalities and pharmacologic measures. Furthermore, that study demonstrates that a more nuanced approach to postoperative pain after amputation must be taken (by not simply grouping all pain as "phantom" pain) and shows that phantom pain may appear much later than originally thought and may be a challenge to treat or alleviate.

In the same light, Wilson et al. examined modalities that potentially could be used to deal with persistent pain after lower extremity amputation; specifically, they performed a double-blind, randomized trial evaluating the effect of ketamine on pain and sensory processing after amputation. Fifty-three patients who were undergoing lower limb amputation participated in the study. After receiving a combined intrathecal-epidural anesthetic for surgery, patients either received an epidural infusion of racemic ketamine and bupivacaine (group K) or saline solution and bupivacaine (group S). No other analgesics were allowed in the postoperative period (ranging from forty-eight to seventy-two hours) except the epidural infusions. Pain characteristics were assessed for twelve months after surgery, with a specific focus on the prevalence and severity of postoperative pain. In the immediate postoperative period while the epidural anesthetic was being infused, the patients receiving ketamine and bupivacaine (group K) had significantly lower pain scores than those receiving saline solution and bupivacaine (group S). After discontinuation of the epidural anesthetic until the time of the one-year follow-up, the rates of stump and phantom pain did not differ between the two groups (21% and 50%, respectively, for group K, compared with 33% and 40%, respectively, for group S). Interestingly, the levels of depression and anxiety were found to decrease significantly in group K during the course of the study, whereas a similar decrease was not seen in group S.

The results of that study suggest that epidural infusions of ketamine combined with bupivacaine may be of value for the control of post-amputation pain in the immediate postoperative period. Furthermore, ketamine may have a potential effect on decreasing postoperative levels of depression and anxiety; this observation requires additional study.

That study highlights another major battle that amputees face in the postoperative period: depression and anxiety over the loss of the limb. Singh et al.11 examined the course of symptoms of depression and anxiety after amputation during inpatient rehabilitation. One hundred and five patients who were admitted to inpatient rehabilitation following a lower limb amputation were examined. The Hospital Anxiety and Depression Scale was utilized to assess symptoms of anxiety and depression at the times of admission and discharge, and these symptoms were correlated with demographic and patient features, including the level of amputation, the success of limb-fitting, age, and sex. At the time of admission, 26.7% of the patients had symptoms of depression and 24.8% had anxiety; these values decreased significantly to 3.8% and 4.8%, respectively, at the time of discharge (at a mean of 54.3 days later). Patients who had higher levels of depression and anxiety required longer inpatient rehabilitation stays, and patients with depression were more likely to have other medical comorbidities or to live in isolation. The level of amputation, the success of limb-fitting, age, and sex were not associated with the failure of these symptoms to resolve.

The results of that study indicate that postoperative depression and anxiety can resolve more rapidly (in a period of nearly two months) than what was previously thought (in a period of several years). This finding indicates that, during the immediate postoperative course, inpatient rehabilitation should be focused on teaching the patient skills that can improve his or her function at the time of discharge as the symptoms of depression and anxiety will rapidly resolve even in patients who are in severe distress. Furthermore, patients at greater risk for post-amputation depression (those who have medical comorbidities or who are living alone) can be identified, and additional support can be given to them both preoperatively and postoperatively.

 

[Caduceus Mercurius]

But let's not forget that "ketamine is reported by the US Drug Enforcement Agency to have potential consequences of delirium, amnesia, depression,..."

:roll:

 

[Brugmansia]

^ That goes for abuse. K = very spiritual if used rarely. And it should be done IM in order to get the full potential out of it.

I have a bit less than a gram left of my last seal which I had bought in 2007... but not exactly remembering where I have stored it... :lol:

 

[silv]

Interesting though how this'd work on someone sucicidically depressed. If you can stop them from wanting to slit their wrists/jump from a building (even if only for a week) in two hours, I think a lot people can be saved by that, and it surely will be less traumatising than being sedated or chained to a bed :)