Antidepressant response within hours? Experts weigh evidence on ketamine as fast-acting treatment for depression

February 22, 2018, Wolters Kluwer Health

Recent studies suggest that ketamine, a widely used anesthetic agent, could offer a wholly new approach to treating severe depression—producing an antidepressant response in hours rather than weeks. Two reviews of recent evidence on ketamine and related drugs for treating depression appear in the Harvard Review of Psychiatry.

Ketamine and related drugs may represent a "paradigm shift" in the treatment of (MDD) and bipolar depression—especially in patients who do not respond to other treatments, according to a review by Carlos A. Zarate, Jr, MD and colleagues at the National Institute of Mental Health. A second article explores evidence on the mechanisms behind 's rapid antidepressant effects.

Growing Evidence, Clinical Caution about Ketamine for Severe Depression

Current treatments for MDD and bipolar depression have major limitations. Many patients with severe depressive symptoms don't respond to available antidepressant drugs. Even for those who do respond, it may take several weeks before symptoms improve.

Ketamine, an anesthetic, is one of several glutamatergic drugs affecting neurotransmitters in the central nervous system. Over the past decade, several studies have reported "rapid, robust, and relatively sustained antidepressant response" to ketamine, injected intravenously at low, subanesthetic doses.

Dr. Zarate and colleagues review the research on ketamine and other glutamatergic drugs for depression. Ketamine, by far the best-studied of these medications, is notable for its very rapid antidepressant effects. In patients with treatment-resistant MDD, ketamine has produced initial reductions in depressive symptoms within two hours, with peak effects at 24 hours.

Ketamine may also rapidly reduce suicidal thoughts. Combined with other medications, ketamine has also produced rapid antidepressant effects in patients with treatment-resistant bipolar depression.

Prompted by these studies, some doctors are already using ketamine in patients with severe or treatment-resistant depression. However, since it is FDA-approved only as an anesthetic, use of ketamine in depressive disorders is "off-label," unregulated, and not standardized. Many questions remain about its short- and long-term side effects and potential for abuse.

"Efforts are underway to bring ketamine to market, standardize its use, and determine its real-world effectiveness," Dr. Zarate and coauthors write. They also present evidence on several other glutamatergic drugs. One , esketamine, has been given "breakthrough therapy" status by the FDA for at imminent risk of suicide.

Cristina Cusin, MD of Massachusetts General Hospital and colleagues review neuroimaging studies evaluating ketamine's effects in the brain. The studies show ketamine-induced changes in several brain areas involved in the development of depression. Ketamine may exert its antidepressant effects by "acutely disabl[ing] the emotional resources required to perpetuate the symptoms of depression," as well as by increasing emotional blunting and increasing activity in reward processing.

Independent of how ketamine works or its ultimate role in clinical treatment, antidepressant response to glutamatergic drugs points to an exciting conclusion: "that rapid antidepressant effects are indeed achievable in humans," Dr. Zarate and coauthors write. "This paradigm shift lends additional urgency to the development of novel treatments for MDD and bipolar , particularly for patient subgroups that do not respond to currently available therapies."

Explore further: Suicidal thoughts rapidly reduced with ketamine, finds study

More information: Dawn F. Ionescu et al. Ketamine-Associated Brain Changes, Harvard Review of Psychiatry (2018). DOI: 10.1097/HRP.0000000000000179

Ioline D. Henter et al. Glutamatergic Modulators in Depression, Harvard Review of Psychiatry (2018). DOI: 10.1097/HRP.0000000000000183

Related Stories

Suicidal thoughts rapidly reduced with ketamine, finds study

December 14, 2017
Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's ...

Antidepressant effects of ketamine

December 8, 2016
New preclinical evidence was put forward by investigators in a series of presentations at the recent meeting of the American College of Neuropsychopharmacology suggest that the a metabolite of ketamine can produce antidepressant-like ...

Ketamine found to reduce bursting in brain area reducing depression quickly

February 15, 2018
A team of researchers at Zhejiang University in China has found that the drug ketamine reduces neuronal bursting in the lateral habenula (LHb) brain region, reducing symptoms of depression in rodent models. In their paper ...

Ketamine produces rapid-onset antidepressant action

January 5, 2015
(HealthDay)—Ketamine has rapid-onset antidepressant action, although the mechanism of its positive effect is currently unclear, according to research published online Dec. 26 in the Journal of Clinical Pharmacy and Therapeutics.

Treating depression—an expert discusses risks, benefits of ketamine

October 20, 2017
Up to a third of patients with depression don't respond to traditional forms of treatment. For those patients, the dark fog that hovers over their lives feels like it will never lift. But a new treatment called ketamine has ...

Ketamine no 'wonder drug' for depression

March 6, 2017
There is no added benefit to using ketamine over a standard anaesthetic during electroconvulsive therapy (ECT) according to new research from the University of Aberdeen.

Recommended for you

College students choose smartphones over food

November 16, 2018
University at Buffalo researchers have found that college students prefer food deprivation over smartphone deprivation, according to results from a paper in Addictive Behaviors.

Study finds mindfulness apps can improve mental health

November 15, 2018
A University of Otago study has found that using mindfulness meditation applications (apps) on phones is associated with improvements in people's mental health.

Social media is affecting the way we view our bodies—and not in a good way

November 15, 2018
Young women who actively engage with social media images of friends who they think are more attractive than themselves report feeling worse about their own appearance afterward, a York University study shows.

New research has revealed we are actually better at remembering names than faces

November 14, 2018
With the Christmas party season fast approaching, there will be plenty of opportunity to re-live the familiar, and excruciatingly-awkward, social situation of not being able to remember an acquaintance's name.

Older adults' abstract reasoning ability predicts depressive symptoms over time

November 14, 2018
Age-related declines in abstract reasoning ability predict increasing depressive symptoms in subsequent years, according to data from a longitudinal study of older adults in Scotland. The research is published in Psychological ...

The illusion of multitasking boosts performance

November 13, 2018
Our ability to do things well suffers when we try to complete several tasks at once, but a series of experiments suggests that merely believing that we're multitasking may boost our performance by making us more engaged in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.