Mental health is often marginalized and misrepresented in society. But in the United States, there is a mental health crisis. Around 46.6 million adults in America experience a mental health disorder each year, and around 4.5% of U.S. adults experience a serious mental health disorder. Even more alarming, though, is the fact that only 42.6% of Americans with a mental health disorder and 66.7% of Americans with a serious mental health disorder receive treatment. (CSP)
This rampant prevalence of mental health disorders is not just a problem that can be ignored. It is deadly. Mental health disorders are identified as one of the top risk factors for suicide. Specifically, Major Depressive Disorder, commonly known as depression, is one of the most commonly found factors in people that commit suicide. Those suffering from depression are 25 times more likely to commit suicide than those in the general population, and it is shown that 50-80% of people that commit suicide suffer from depression. (NIMH)
Despite this clear relationship between depression and suicide, the current understanding of depression is limited, and the treatment options often take a long time before taking action. The current treatment for depression most commonly involves prescribing a reuptake inhibitor. These work by blocking the reuptake, or natural absorbance of many key chemicals, such as serotonin, dopamine, and norepinephrine in the brain. Instead of being absorbed, these chemicals stay in the synapses, or the gaps, between the nerves. By having an abundance of these important neurotransmitters in the synapses, different parts of the brain are able to communicate more effectively, which is thought to increase mood. (WebMD) Although this can be effective, it is a lengthy process. These treatments take around four weeks before showing any major effects. Even after this time period, a patient’s symptoms may not be resolved. In this case, patients will switch medications and repeat the lengthy process. This process can be exhausting for the patient and further exacerabate the risk of suicide.
To combat this problem, medical researchers are attempting to find drugs that will act more quickly. One drug that has shown initial promise is ketamine. It is important to note that this is not the same as the street drug ketamine. Like many street drugs, ketamine has actual use in clinical settings. Ketamine is a drug in the class of anesthetics. The most appealing aspect of ketamine in medicinal use is that it does not repress the respiratory system like many other anesthetics. This means that ketamine doesn’t require the same oxygen and electricity supply as others in its class, making it a vital medicine in many developing countries.
While previous studies have shown ketamine’s promise in treating depression, there are still many questions regarding its use. Earlier studies focused on short term results. For example, a 2010 study came to the conclusion that a single dose of ketamine could lower idealization of suicide within 40 minutes. (DiazGranados N et al 2010) Another 2013 study showed similar results, with the conclusion that ketamine improved depression symptoms for 24 hours following the dose. However, this same study concluded that the ketamine dose had no long term effects, as no improvements were seen 7 days after the dose. (Murrough J et. al 2013) These studies both showed ketamine’s efficacy in the short term, but researchers wondered if repeated doses could replicate effects and improve a patient’s symptoms in the longer term.
Dr. Signh and her research team set out to answer these questions. They conducted their study across 14 hospitals located in the United States on patients that have been diagnosed with treatment-resistant depression. These patients were then randomized into 4 groups, at an equal ratio. The first group received two doses of ketamine each week, and the second group received 2 doses of a placebo of sodium chloride each week. The third group received three doses of ketamine each week, and the fourth group received three doses of a placebo of sodium chloride each week. All groups that received ketamine received the same dose of .5mg per kg of body weight. All of these groups then received their doses for at least two weeks. Following the two week period, some patients had the option to complete a two week open label phase, where they received two doses of ketamine each week and were told exactly what they were receiving. The rest of the patients continued forward with their double-blind testing. The research team assessed the patient’s depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS) each day.
The main conclusion of the study was that ketamine significantly improved the patient’s symptoms of depression during a two week period. The mean drop in CADRS score for twice weekly groups was -18.4 for those that received ketamine and -5.7 for the placebo group. In thrice weekly groups, the drop was -17.7 for the group that received ketamine and -3.1 for the placebo group. Interestingly, there was little difference in results between the twice a week ketamine and thrice a week ketamine groups, showing that two doses a week should suffice if used clinically. The open label group also showed similar results, with a mean drop of 12.2 points at the end of the two week period. The group that continued their ketamine treatment for four continuous weeks also showed promising results. The twice a week groups had a mean drop of -21.2 for the ketamine group and -4.0 for the placebo. The thrice a week group had a drop of -21.1 for the ketamine group and -3.6 for the placebo. (Singh J et al. 2016)
Although these results are promising, the authors admit there are some flaws and know that further studies will be needed to completely determine the clinical use of ketamine for depression. Firstly, the researchers did not use an active placebo, or a placebo that can cause similar adverse effects as the main drug. Without this active placebo, patients could likely determine whether or not they were given a placebo, which could jeopardize the results of the study. Lastly, the study has very little concrete evidence supporting research beyond two weeks of ketamine doses. Because the longest duration of ketamine doses was only four weeks and the responses were not measured in the long term, the study gives no introspection into the possible long term effects of ketamine to treat depression. There also needs to be more research done into ketamine’s ability to treat depression for four weeks. Although some of the patients received ketamine for four weeks and still showed improvement, this sample size was likely too small, as many patients dropped out of the study and only a portion of each original group was continually tested for four weeks.
Despite the few flaws in this study, it still provides tremendous hope for those suffering from depression. The diagnosis and treatment of depression is demoralizing. The lack of understanding regarding depression leaves many patients frustrated, and the extensive treatment process can be exasperating. A quick-acting drug like ketamine is exactly what many patients need, as even momentary relief from the weight of depression can be life-altering.
Singh J, Fedgchin M, Daly E, Boer P, Cooper K, Lim P, Pinter C, Murrough J, Sanacora G, Shelton R, Kurian B, Winokur A, Fava M, Manji H, Drevets W, Nueten L. 2016. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. American Journal of Psychiatry. [accessed 2020 Sep 16]; 173(8): 816-826. https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2016.16010037
Ezquerra-Romana I, Lawn W, Krupitsky E, Morgan C. 2018. Ketamine for the treatment of addiction: evidence and potential mechanisms. Neuropharmacology. [accessed 2020 Sep 16]; 142: 72-82. https://doi.org/10.1016/j.neuropharm.2018.01.017
Murrough J, Iosifescu D, Chang L, Jurdi R, Green C, Perez A, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney D, Mathew S. 2013. American Journal of Psychiatry. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. [accessed 2020 Sep 16]; 170(11): 1134-1142. https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2013.13030392
DiazGranados N, Ibrahim L, Brutsche N, Ameli R, Henter I, Luckenbaugh D, Machado-Vieira R, Zarate C. 2010. Rapid resolution of suicidal ideation after a single infusion of an nmda antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. [accessed 2020 Sep 16]; 71(12): 1606-1611. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012738/
[WebMD] How Different Antidepressants Work. WebMD; c2019 [accessed 2020 Sep 16]. https://www.webmd.com/depression/how-different-antidepressants-work#3
[NIMH] Mental Health Information. 2017. United States. National Institute of Mental Health; [accessed 2020 Sep 16]. https://www.nimh.nih.gov/health/statistics/mental-illness.shtml
[CSP] Depression and Suicide Prevention. 2014. Canada. Centre for Suicide Prevention. [accessed 2020 Sep 16].
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