FDA Approves Ketamine Nasal Spray for Depression
The landmark approval of ketamine nasal spray by the FDA advisory panel could potentially save millions of lives and help prevent suicide. The advisory panel voted 14-2-1 for the use of a ketamine nasal spray to treat resistant depression. An approval decision is expected by March 4, 2019.
The committee announces that they agreed that the benefits of ketamine outweighs the risk based on research findings.
What is ketamine nasal spray?
The ketamine nasal spray comprises of the molecular mirror of ketamine, esketamine.
Esketamine is a structural mirror of ketamine, a general anesthetic, and dissociative hallucinogen.
An advantage of Esketamine nasal spray is its rapid effects to reduce clinically meaningful and statistically significant improvement of depressive symptoms.
“I voted yes because esketamine has the potential to be a game changer in the treatment of depression; I use the term ‘game changer’ because they’ve demonstrated the rates of response in this treatment-resistant population is better than what we’ve seen for any of our current modalities. Number two, the rapid timeline of response is unprecedented; there’s nothing currently approved that gets patients better this fast,”
Dr. Walter S. Dunn, DSaRM committee member
What is ketamine?
Ketamine is a sister compound of phencyclidine, PCP. Ketamine is a N-methyl-d-aspartate (NMDA) blocker in the brain which interacts with the neurotransmitter glutamate. Ketamine has been used for decades by the medical community for conscious sedation and is mainly used as anesthesia for medical procedures since 1970. When administered, it relieves pain by interfering with pain transmission to the spinal cord.
Ketamine treats depression
Ketamine is observed to be quickly powerful in treatment-resistant depression. Significant research has been done on ketamine and there is potential in ketamine’s use as short-term therapy for depression.
The use of ketamine for treatment-resistant depression was off-label for years which means that physicians are able to prescribe ketamine but it wasn’t considered first-line therapy.
A possible mechanism of action is the ability of ketamine to remodel neurons.
Current theories suggest that severe, treatment-resistant or chronic depression is not simply the result of disturbances of serotonin and norepinephrine systems but involves alterations in the resiliency and neuroplasticity of synapses and circuits.
Carlos Zarate, M.D.
Ketamine’s effect on depression is theorized to stem from its ability to reverse neuron circuit brain changes or damage throughout a person’s lifetime. Researchers used neuroimaging and found that ketamine may change the pattern of your nerve pathways in the brain by modulating activity and connectivity in the reward circuits.
Studies show that after just one dose of ketamine, depressive symptoms decreased significantly within just 3 days. For example, Dr. Carlos Zarate Kr., M.D. has investigated ketamine and its effect on depression and suicidal thoughts and have found that his patients in the trial had marked improvement within a few days and even as little as a couple hours. The biggest downside is that it remains unclear whether ketamine can improve depression in the long run.
If ketamine worked so well on depression, why did it take so long for the FDA to endorse it?
A key ethical dilemma is when to prescribe ketamine to patients since there are concerns about off-label use monitoring says Dominic Sisti, an assistant professor in the Department of Medical Ethics and Health Policy at the Perelman School of Medicine, University of Pennsylvania, PA, USA.
I don’t think patients who have exhausted all options should have to wait, but I worry that off-label use is not being properly monitored…If patients are fully competent and informed, they should have the right to access ketamine—but we have to be sure they understand it is basically an experimental treatment. This is a vulnerable patient population.
Additionally, there were concerns that ketamine may lead to drug abuse and addiction.
Ketamine has positive reinforcement effects such as dissociative anesthetic and euphoria effects basically “getting high”. After stopping ketamine, withdrawal symptoms arise which includes craving, a feeling of unease, anxiety and sleep problems.
Adverse effects of Ketamine
Ketamine is not without adverse effects. Thee include sedation, dissociation and increased blood pressure.
Ketamine side effects include bad hallucinations, disorientation, increased heart rate, elevated blood pressure. In addition, large doses of ketamine can include intense hallucinations with detachment from reality. As with psychotropic drugs, the quality of the hallucinations depends on the user’s state of mind – an unhappy state of mind can lead to unpleasant hallucinations.
The endorsement of ketamine nasal spray to treat resistant depression gives hope to millions of people suffering from depression.
Depression is a debilitating and serious condition affecting more than 16 million individuals in the United States.
Depression is a significant burden to a large percentage of the population and a majority of people with depression are unrecognized and undertreated.
It is predominant in the United States and an estimated 4.5%-9% of women and 3% men have major depressive disorder. Treatment includes subjective psychotherapy and pharmacological medicines, for example, antidepressants including specific serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs).
Reactions to antidepressants can take weeks (~4-6weeks) to work and chances of antidepressants working decrease if patients do not continue to improve.
Typical antidepressants are useful in ~60-70% of cases. Even more shockingly, suicide is the 10th leading cause of death in the United States.
The approval of a ketamine nasal spray paves a brighter road for those suffering from severe depression and for those who typical antidepressants don’t work for. This new class of antidepressants promises an alternative treatment to the usual treatment of depression and has the potential to save lives.
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- Liu, Yu et al. Ketamine abuse potential and use disorder. Brain Research Bulletin. 2016; 126: 68-73
- Medscape. (2019). FDA Panels Endorse Ketamine Spray for Resistant Depression. [online] Available at: https://www.medscape.com/viewarticle/909038?nlid=127991_3901&src=wnl_newsalrt_190213_MSCPEDIT&uac=287026SK&impID=1883933&faf=1#vp_1 [Acessed 15 Feb, 2019].
- Prommer, Eric et al. Ketamine and Depression: Is It Ready for Primetime? Journal of Pain and Symptom Management. 2018; 55(2): 645-645