It can be helpful for some people with treatment resistant depression or major depressive disorder.
Ketamine is a medication commonly used during surgery and was first developed to be an anesthesia medication with fewer side effects. It is an N-methyl-D-aspartate receptor (NMDAR) antagonist and has been studied for nearly 20 years in mental health because of its potential to act on glutamate.
Ketamine works on glutamate, a neurotransmitter that influences many brain signals, but can change the brain to be less adaptable and less able to communicate when there is too much of it. Ketamine is a glutamate receptor blocking drug and may affect psychiatric symptoms by stopping transmission of signals from glutamate. This can result in better communication between neurons, increased stress tolerance, and the creation of new neural pathways. The creation of new neural pathways is what may help people to think differently and change their perspective when they are stuck. Ketamine likely also works on other receptors, like the dopamine and opioid receptors, which can influence mood and pain perception.
Ketamine itself is commonly available, but the FDA has only approved one formulation, the nasal spray Spravato (Esketamine) in 2020, for use in combination with oral antidepressants.* It is indicated for Major Depressive Disorder (MDD) with suicidal ideation and Treatment Resistant Depression (TRD). In the studies on Spravato, up to 70% of participants showed remission of depression symptoms compared to the group that received standard treatment. Spravato is approved under a Risk Evaluation and Mitigation Strategy (REMS), where the person must receive the medication in a REMS-certified location and be observed for several hours during and after administration. It is given with a daily antidepressant twice a week for the first four weeks, then once a week for weeks 4-8 and then once every one to two weeks from week 9 onward.
Studies have also examined single doses of intravenous (IV) ketamine in lower doses than would be given for anesthesia (less than half the dose). Two randomized, double-blind, placebo-controlled studies demonstrated that a single dose of IV ketamine improved self-reported depressive symptoms, but that these effects were short lived (approximately 24-72 hours). A recent systematic review and meta-analysis (big study of studies and effects with 687 articles) on IV ketamine suggest that repeated doses (more than 2) and higher doses may have a more robust and sustained effect on improving depression symptoms than single dose IV ketamine administration and treatment with esketamine. Evidence also suggests that the route of administration may not affect improvement of symptoms (they all help!), although most of the studies just looked at the IV route. This is promising because future research may look at improving access to ketamine and efficacy with other routes of administration.
Although this is all positive, caution is advised.
Ketamine is an option for treatment for you if you have depression. While there are promising studies looking at treatment of anxiety, OCD, PTSD, and other conditions with ketamine, more data is needed. The FDA has not approved esketamine for treatment of conditions other than treatment resistant depression (TRD) or major depressive disorder (MDD) with suicidal ideation or behavior. This means that IV ketamine and other formulations are being used off-label. While off-label use is common in mental health, it is important that anyone receiving ketamine be aware of safety concerns and ensure that the clinician offering treatment is following treatment guidelines.
In all formulations, there are some safety risks including sedation, dizziness, dissociation, increased heart rate, increased blood pressure, bladder problems, and heart palpitations. Ketamine is generally well tolerated, but up to 10% of people may experience side effects. Ketamine is not appropriate for people who are pregnant or who have uncontrolled hypertension, psychosis symptoms, substance use concerns, or intracranial hypertension among other pre-existing medical conditions. For this reason, it is critical to speak with a primary care and mental health clinician prior to starting to talk about risks and benefits and to be monitored before, during, and after treatment. It is also important to note that the FDA cautions patients and clinicians against using compounded oral, sublingual, or nasal spray formulations of ketamine for at home use as they are neither FDA approved nor monitored for safety.
For people suffering with depression and crippling mental health symptoms, it is understandable that many are seeking relief, but it is important to ensure that treatment is received safely. The American Association of Ketamine Psychiatrists, Psychotherapists, and Practitioners (ASKP3) offers patient information to help people understand what to look for in a clinic. Academic medical centers and affiliated clinics may also offer patients the opportunity to participate in clinical trials and provide support and monitoring after treatment.
Finally, supportive treatment, including regular therapy, coordination with a primary care clinician, and follow up support are critical parts of treatment. Newer modalities of treatment with ketamine such as Ketamine Assisted Psychotherapy (KAP), which pairs ketamine with structured psychotherapy, offer great promise for relieving symptoms of depression and other conditions. Ketamine treatment is promising for people suffering with unrelenting mental health symptoms. Instilling hope that this treatment and others are on the horizon is critical for people who are struggling.
Stay safe. Stay well.
Those Nerdy Girls
*For the super nerdies, Esketamine is one of the mirror image molecules (enantiomer) of ketamine, the S-enantiomer. Ketamine is a racemic mixture of S and R ketamine.
Please note: If you or a loved one need additional resources, Mental Health America (MHA) offers a great way to search for resources. And if you are in need of immediate assistance, please contact the National Suicide Prevention Lifeline at 988 OR 1-800-273-8255 (Español: 1-888-628-9454; Hearing Support: 1-800-799-4889) or the Crisis Text Line by texting HOME to 741741.
Sources:
FDA Caution on compounding ketamine
