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• University of Exeter researchers have published a review of research evaluating ketamine’s value in mental health therapy.
• The review of studies found that ketamine may quickly alleviate depression and thoughts of suicide.
• Ketamine’s usefulness for other mental health conditions is less clear.
• As ketamine is an addictive opioid with strong disassociative properties, its use is not without hazards.

Doctors primarily use ketamine as a general anesthetic for medical procedures during which a person must be unconscious, but muscle relaxation is not required. Ketamine is also a dissociative medication, and researchers have been exploring the use of sub-anesthetic dosages of ketamine for treating depression for some time.

Researchers at the University of Exeter in the United Kingdom have reported that an analysis of existing studies confirms that ketamine therapy offers fast-acting, short-term relief from depression and, to some extent, suicidal thoughts and other mental health symptoms.

The meta-analysis of 83 existing studies has assessed the value of ketamine therapy for treating a wide range of mental health conditions. These studies include 29 randomized controlled trials, 21 observational studies, bupropion ejaculatory anhedonia and 33 systematic reviews. According to the review’s authors:

“The current review integrates parallel reviews of the nascent research on ketamine as a treatment for mental health conditions and related research germane to the therapeutic potential of ketamine for mental health more broadly.”

The study features in the British Journal of Psychiatry Open. The team carried it out in collaboration with the University of British Columbia and with support from the Society for the Study of Addiction.

Ketamine’s general mental health promise

The strongest effect that the studies document is the value of intravenous ketamine therapy for relieving depression.

A reduction in unipolar depression severity occurred within anywhere from 1 to 24 hours, and it lasted for 1–2 weeks. In comparison, oral doses took up to 2 weeks to have an effect.

Bipolar depression relief was also rapid, occurring as quickly as 4 hours after administration and consistently by 24 hours. The full effect lasted for up to 3 days, with some relief still apparent after 7 days.

The studies also support the use of ketamine for treating affective disorders and thoughts of suicide.

Of suicidal ideation, co-author and University of Exeter Ph.D. candidate Ozden Merve Mollaahmetoglu told Medical News Today:

“It is really interesting that there is some evidence of an effect on suicidal thoughts independent of depressive symptoms, and it would be great to understand the mechanism of this effect. This finding is important because there is a risk of suicide in several mental health problems, so it would be interesting to see if we could treat suicidal thoughts in other conditions, such as substance use disorders.”

Mollaahmetoglu also noted: “Since the effect of ketamine on suicidal thoughts was short-lived, it would also be important to determine how this can be extended — for instance, in combination with psychotherapy. We also don’t know whether multiple doses of ketamine are more effective than a single dose for reducing suicidal thoughts, as this hasn’t been directly compared.”

Other research found some therapeutic benefit to the use of ketamine for other psychiatric disorders such as “post-traumatic stress disorder, obsessive-compulsive disorder, anxiety, and substance use disorders.” However, write the authors, “the evidence base comprised a small number of mostly nonrandomized trials with often short follow-up periods, therefore requiring corroboration and extension.”

Safe in a clinical setting

The study emphasizes the importance of restricting the administration of ketamine, which is an opioid, to carefully controlled clinical circumstances.

Mollaahmetoglu told MNT:

“Ketamine is a very safe drug in a clinical setting. When people are given ketamine, we see mild increases in blood pressure and heart rate, which can be monitored and managed in clinical settings.” She also noted that people who might be at “increased risk of negative psychological reactions to ketamine, like people with a personal or family history of schizophrenia, can be screened out.”

Additionally, in such a setting, “People are provided with preparation and psychological support during and after the ketamine infusions, which likely reduces [the] risk of adverse psychological reactions.”

Finally, it is possible to protect individuals in a clinical setting from accidental injury and physical vulnerability due to ketamine’s disassociative effect. This effect promotes a “reduced awareness of their environment, lack of coordination, inability to communicate, and considerably diminished sensory input.”

Ketamine requires caution

Dr. Alan F. Schatzberg, a professor of psychiatry and behavioral sciences at Stanford University, told MNT that “whether, in fact, these drugs are effective enough to be worth it is still unanswered.”

Dr. Schatzberg cautioned, “I haven’t seen enough real data to say that we [have] got a huge winner there.”

His concern is that, “ketamine works through an opioid mechanism, and ketamine in certain forms and in certain situations, it’s highly addictive.”

Dr. Schatzberg also noted the difficulty of conducting unbiased, blind studies of ketamine’s effect on mental health due to the disassociation it produces because “a patient, in fact, has a sense of what drug or placebo they got.” He recalled that in some approved esketamine trials, “they didn’t ask the patients, ‘Hey, do you think you got [the] drug or placebo?’”

“The way the study frames it,” said Dr. Schatzberg, “is positive, positive, positive. But you know, you have to wonder when you’re dealing with something like ketamine.”

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