The sedating party drug that immediately lifts suicidal depression: Ketamine, a veteran drug originally developed as an anesthetic, has been returning to the center of the medical stage in recent years, this time as a therapeutic option for severe and treatment–resistant depression. A new review of clinical studies found that a single infusion of ketamine may bring rapid relief from depression symptoms and even reduce suicidal thoughts within hours to a day. However, alongside the impressive results, researchers warn that the effect of the treatment is limited in time, that knowledge regarding long–term safety is still insufficient, and that unsupervised use could be dangerous.
The new study, published this month in the journal JAMA Psychiatry, is not a single trial but rather a systematic review and meta–analysis, meaning a collection and analysis of previous clinical studies. The researchers examined 26 clinical trials that together included more than 1,100 patients suffering from significant depression. About 626 of the participants received ketamine, while about 540 served as a control group. Most of the studies included patients with major depression, and a smaller portion included patients with bipolar depression or combined diagnoses.
The central finding was exceptionally rapid: Compared to a placebo, a single infusion of ketamine reduced depression symptoms within about four hours, and led to a marked decrease in suicidal thoughts within 24 hours. According to the researchers, the relief from depression symptoms persisted in some patients even after a week, and the decrease in suicidal thoughts was reported up to a month after the single infusion. In patients who received multiple infusions, a similar decrease in depression symptoms and suicidal thoughts was recorded at the end of the treatment series.
This figure is particularly significant because regular antidepressant treatments, mainly drugs that affect serotonin and norepinephrine, usually require weeks before a full effect appears. In situations where the patient suffers from severe depression, intense emotional distress, or suicidal thoughts, this period of time can be critical. Here exactly lies the medical interest in ketamine: It acts through a different mechanism, related among other things to the glutamate system in the brain, and therefore may affect neural circuits related to mood more quickly.
However, the findings do not turn ketamine into a "wonder drug." The researchers emphasize that the benefit after a single infusion is usually relatively short, and that many patients experience a return of symptoms after some time. In other words, even if ketamine may provide a swift window of relief, it does not replace comprehensive psychiatric treatment, continuous follow–up, psychotherapy, medication balancing, and treatment of underlying diseases. In cases of resistant depression, a series of treatments rather than a single infusion may be required.
Ketamine has been known to medicine for decades as an anesthetic and painkiller, but outside the medical system it is also known as a drug that is subject to abuse. This is the reason why enthusiasm for it is accompanied by great caution. The common side effects described in the studies included headaches, numbness, nausea, dizziness, visual disturbances, and a sense of dissociation, meaning an experience of detachment from the body or environment. In most cases, these effects were temporary and passed within hours of the infusion.
Nevertheless, authorities in the United States emphasize that ketamine itself is not approved by the US Food and Drug Administration for the treatment of psychiatric disorders. Another preparation, esketamine in a nasal spray, which is a derivative of ketamine, has been approved for the treatment of resistant depression and depression symptoms in patients with major depression and acute suicidal thoughts or behavior, but it too is given under strict regulatory limitations and within an organized medical framework.
The US Food and Drug Administration has even warned in the past against using compounded or home–use ketamine products without medical monitoring, due to the risk of sedation, dissociation, increased blood pressure, respiratory depression, abuse, and dependence.
The practical implication is that the research direction is promising, but not suited for simplistic interpretation. Ketamine is not a treatment that a patient is supposed to take alone, order over the internet, or receive at a clinic that is not equipped for medical monitoring. Such treatment, if considered, must be carried out by a skilled medical team, with a psychiatric evaluation, monitoring of blood pressure, pulse, state of consciousness, and side effects, and especially a suicidal risk assessment before and after the treatment.
The study also includes important limitations. Since ketamine sometimes causes distinct physical and mental sensations, it is possible that some patients realized they were receiving the active substance and not a placebo. Such a situation could affect the patients' self–reporting and the evaluation of efficacy. Some of the studies included in the review were relatively small, and in an analysis of different studies it is always difficult to draw precise conclusions regarding each and every patient. The researchers themselves noted that short–term efficacy appears clearer than the information on long–term safety and efficacy.
In Israel, as in other countries, severe depression and treatment–resistant depression are a significant challenge for the healthcare system. Many patients respond well to regular drug treatment, psychotherapy, lifestyle changes, and family and community support. However, in a small portion of them, even after repeated treatment attempts, the symptoms remain severe. In such cases, more advanced options are sometimes considered, including electroconvulsive therapy,
transcranial magnetic stimulation, complex drug treatments, or esketamine treatment within an appropriate framework.
The innovation in the current study is not the very idea that ketamine may affect depression, but rather the intensity of the concentration of findings from a relatively large number of clinical trials. The picture that emerges from it points to real potential for rapid relief in severe situations, especially when dealing with patients at suicidal risk or those who have not responded to conventional treatments. But precisely because these are vulnerable patients, double caution is required: Not to turn ketamine into a trend, not to sell it as a shortcut, and not to blur the difference between supervised medical treatment and dangerous use of an active substance.
In the case of severe depression, suicidal thoughts, or sharp mental deterioration, the most important recommendation remains an immediate appeal for medical help. Ketamine may in the future occupy a clearer place in the psychiatric toolbox, but even according to the new study, its place is within an organized therapeutic system, not outside of it.