Research Paper on Ketamine
The stigma of illicit drugs is hard to surpass but what if there is some medical benefit behind felonious drugs for example hallucinogenic drugs. It is evident that although the world's society attributes the use of ketamine or rather called “club drugs” what if remarkable effects come from evaluating psychological uses. Ketamine was originally discovered in 1956 and was utilized as an anesthetic due to its numbing properties (Maisto et al., 2019). Maisto et al. (2016) points out that ketamine can be legally prescribed by physicians for anesthetic use but is not FDA approved for treatment of depression (p.322). Modern day ketamine use is still applied in a medical setting and can be prescribed as an “off label” treatment (Maisto et al., 2019). Previous research has been done on the psychotherapeutic uses of Ketamine and some data indicates that ketamine can subside the effects of depression (Kishimoto et al., 2016, as cited in Maisto et al., 2019). The interesting effects that Ketamine has on the symptoms of depression are deserving of more complex clinical trials. Most prescribed antidepressant act on the monoamine system in the brain and have a slow acting therapeutic effect (Siegal et al., 2021). Due to traditional antidepressant lagging therapeutic effects, has motivated researchers to research novel medicinal uses for unconventional drugs.
Modern research has inquired the relationship of ketamine and neurocognitive effects and evaluation of two different dose quantities (Shiroma et al., 2020). Shiroma and associates (2020) conducted a randomized, double-blind, placebo controlled clinical trial in treatment resistant patients comparing single intravenous iv infusions of ketamine and six infusions of ketamine. To also point of this study also aimed at understanding and measuring neurocognitive differences from baseline to the end of treatment, to get a better understanding of not only antidepressant effects but also short-term cognitive effects (Shiroma et al., 2020). Participants obtained in this study were outpatients Veterans who met the standard for major depression disorder and failed to respond to a minimum of 2 antidepressant trials (Shiroma et al., 2020). Shiroma and colleagues (2020) obtained 43 participants and were randomized to either six infusions of ketamine or five infusions of midazolam succeeded by a single iv infusion of ketamine, the final dose of ketamine was kept disclosed to the participants. Each ketamine infusion was administered at a dose of 0.5 mg or midazolam at 0.0045 mg over a course of 12 days (Shiroma et al., 2020). Additional measures were used to identify depressions symptoms prior to treatment and following each iv-infusion using the Montgomery-Asberg Depression Rating Scale (Shiroma et al., 2020). Coupled with MADRS scale a battery of cognitive tests were implemented at baseline and at 24 hours after las infusion, this included 12 tasks to evaluate 6 neurocognitive functions (Collie et al., 2003, sited in Shiroma et al., 2020). Shiroma and associates (2020), utilized the neurocognitive battery to evaluate set shifting, speed of processing, and attention before and after ketamine treatment. Shiroma and researchers (2020) results indicated strong cognitive improvements from evaluation baseline to completion of treatment. Additional findings indicated greater performance on complex working memory anticipated a decrease in extremity of depression regarding participants with five ketamine infusions when compared to midazolam (Shiroma et al., 2020). Shiroma and associates (2020) established limitations within their research including lack of generalizability due to the small sample size and limited demographic, and the need for follow up study to understand cognitive effects of ketamine independent of depressions effects
Subsequent research has taken an interest in the effect ketamine has on treatment resistant depression with a prolonged intravenous infusion (Siegal et al., 2021). Siegal et al (2021) another area of interest was not only cognitive symptoms but also the effect Ketamine has on the brain. To examine the effects of Ketamine on subjects with treatment resistant depression, Siegal and associates (2021) recruited 23 individuals to take part within the open label clinic trial. The 23 participants were admitted to Washington University Clinical Research Unit for 4 nights, where they were given 96-h infusion of Ketamine for 5 days (Siegal et al., 2021). Siegal and collogues (2021) set the target dose of ketamine as tolerated at 0.6 mg, additionally oral dose of clonidine was given 7 days prior to treatment to combat ketamine side effects. Also, to look at the neurological effects participants also consented to an MRI scan at pretreatment and post treatment to also investigate neurocognitive effects (Siegal et al., 2021). Siegal and associated (2021) additionally, gathered antidepressant feedback at 2,4,6, and 8 weeks after infusion by phone call, utilizing the Montgomery-Asberg Depression Rating Scale. Results indicated a reduction of depression symptoms utilizing the MADRS scale, and the effects were sustained at 8 weeks post infusion (Siegal et al., 2021). Siegal and associated (2021) also identified increased connectivity between the frontal areas and the limbic system, also emphasized finding of pre scan MRI smaller right hippocampal volume was associated with larger MADRS changes. Some limitations identified, was a lack of an active control group to quantify the differentiation between ketamine infusion (Siegal et al., 2021). Additionally, Clonidine was given orally in congruence with infusion to offset psychotomimetic side effects, which could’ve potentially skewed results of the clinical study (Siegal et al., 2021). Siegal et al. (2021) ultimately found key information for exploratory analysis of the use of Ketamine in treatment resistant patients. Further research needs to be acquired to enhance the validity of the results found within the trial. It is evident Ketamine does offer some relief to persisting depression, it is a means to discover the quantity of administration that will be most sustainable (Seigal et al., 2021).
Similarly, both ketamine studies both had limited sample sizes 43 participants, and latent 23 subjects within both studies of intravenous ketamine (Siegal et al., 2021, Shiroma et al., 2020). Additionally, both clinical research articles coupled together identified that there is a cognitive component that ketamine influences. For example, Siegal and associates (2021) revolved their research on the effects of ketamine on the context of physiological neurocognitive determiners within the brain. Alternatively, Shiroma and colleagues (2020) researched outward cognitive processes are affected by ketamine, for example memory, and task completion combined with ketamine infusion. Shiroma et al. also conveyed that ketamine offers precognitive effects might provide a better solution for treatment resistant patients versus current use of eltroconvulsive therapy which comes with adverse cognitive aftereffects (Shrioma et al., 2020). Although both research articles bear limitations, both research experimentations have a limited sample size which lacks generalizability to the whole population. Similarly, both evaluation between differing dosing of ketamine found the higher dose group to have the most substantial effects (Shiroma et al., 2020, Siegal., 2021). Further in-depth research should be done to explore dosing rate is most economical and optimal for patients with depression, and inquiry the cognitive effects that coincide with the rapid treatment of depression. This novel study of use of ketamine for depression can potentially change commonly prescribed psychotherapeutic antidepressant drugs. If ketamine can combat severe depression and have a positive impact on cognition, this allows for a modern intervention for treatment resistant depression patients.
To emphasize, depression is the most diagnosed psychiatric illness in the United States (Maisto et al., 2019). The amount of time it takes for commonly prescribed medication to take effect, ketamine could potentially act as an emergency use for severe depression. It is important to understand that although both analyses offer key information regarding psychological use for ketamine, it gives us some hope for modern alternative for antidepressant usage. It is encouraging to perceive that ketamine potentially aids in not only acute depression but also individuals with severe depression or persistent depression. To also identify ketamine’s quick action of relief of depression it might offer clinical emergency use for hospitalized patients for depression. Additionally, if ketamine can provide safe and significant reduction of depression, can ultimately allow for other interventions to occur in the future.
Conclusion
It is evident that Ketamine does offer some relief to severe depression, but what is not understood is how sustained the effect is. Additionally, what also needs to investigated is a relevant dose for treatment. Although considering both evaluations of ketamine, similar results came about revolving around antidepressant effect. It is evident that ketamine offers quick relief of severe depression but what fails to be understood is how long does ketamine suppress depression, and at what would be relative dose that offers the best results to achieve chronic depression.
