Antidepressant response within hours? Experts weigh evidence on ketamine as fast-acting treatment for depression in Harvard Review of Psychiatry

February 22, 2018

Feb.22, 2018 - 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, published by Wolters Kluwer.

Ketamine and related drugs may represent a "paradigm shift" in the treatment of major depressive disorder (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 ketamine'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 drug, esketamine, has been given "breakthrough therapy" status by the FDA for patients 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 depression, particularly for patient subgroups that do not respond to currently available therapies."
-end-
Click here to read "Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature."

DOI: 10.1097/HRP.0000000000000179

Click here to read "Glutamatergic Modulators in Depression."

DOI: 10.1097/HRP.0000000000000183

About the Harvard Review of Psychiatry

The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on a diverse range of important topics in psychiatry. Founded by the Harvard Medical School Department of Psychiatry, the journal is peer reviewed and not industry sponsored. It is the property of Harvard University and is affiliated with all of the Departments of Psychiatry at the Harvard teaching hospitals. Articles encompass major issues in contemporary psychiatry, including neuroscience, epidemiology, psychopharmacology, psychotherapy, history of psychiatry, and ethics.

About Wolters Kluwer

Wolters Kluwer N.V. (AEX: WKL) is a global leader in information services and solutions for professionals in the health, tax and accounting, risk and compliance, finance and legal sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services.

Wolters Kluwer reported 2016 annual revenues of €4.3 billion. The company, headquartered in Alphen aan den Rijn, the Netherlands, serves customers in over 180 countries, maintains operations in over 40 countries and employs 19,000 people worldwide.

Wolters Kluwer Health is a leading global provider of information and point of care solutions for the healthcare industry. For more information about our products and the organization, visit http://www.wolterskluwer.com/, follow @WKHealth or @Wolters_Kluwer on Twitter, like us on Facebook, follow us on LinkedIn, or follow WoltersKluwerComms on YouTube.

For more information about Wolters Kluwer's solutions and organization, visit http://www.wolterskluwer.com, follow us on Twitter, Facebook, LinkedIn, and YouTube.

Wolters Kluwer Health

Related Depression Articles from Brightsurf:

Children with social anxiety, maternal history of depression more likely to develop depression
Although researchers have known for decades that depression runs in families, new research from Binghamton University, State University of New York, suggests that children suffering from social anxiety may be at particular risk for depression in the future.

Depression and use of marijuana among US adults
This study examined the association of depression with cannabis use among US adults and the trends for this association from 2005 to 2016.

Maternal depression increases odds of depression in offspring, study shows
Depression in mothers during and after pregnancy increased the odds of depression in offspring during adolescence and adulthood by 70%.

Targeting depression: Researchers ID symptom-specific targets for treatment of depression
For the first time, physician-scientists at Beth Israel Deaconess Medical Center have identified two clusters of depressive symptoms that responded to two distinct neuroanatomical treatment targets in patients who underwent transcranial magnetic brain stimulation (TMS) for treatment of depression.

A biological mechanism for depression
Researchers report that in depressed individuals there are increased amounts of an unmodified structural protein, called tubulin, in lipid rafts compared with non-depressed individuals.

Depression in adults who are overweight or obese
In an analysis of primary care records of 519,513 UK adults who were overweight or obese between 2000-2016 and followed up until 2019, the incidence of new cases of depression was 92 per 10,000 people per year.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.

Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.

CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.

Read More: Depression News and Depression Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.