In Li et al. they have presented the issues that we have seen frequently thus far regarding the efficacy of antidepressants, with only one third of patients showing significant mood improvement and, if they do have effect, the time in which they take to work. Li et al. presented convincing evidence that a single dose of one of the most common NMDA receptor antagonists, ketamine, could rapidly reverse (a) the behavioral deficits caused by CUS, (with a requirement for mTOR signalling), (b) the deficit in synaptic proteins resulting from CUS, (c) the deficit in spine density resulting from CUS, and (d) the deficit in synaptic functions resulting from CUS. Similar effects were also observed with a selective NR2B antagonist , Ro 25-691.
What I found interesting with this article, is that if one of the main problems with antidepressants is with the duration of how long they take to work, then couldn't there be a study done in which an NMDA receptor antagonist such as ketamine could be used at a safe dosage so that it could be combined with an antidepressant to use for the first three weeks? As we know if antidepressants do show to work, the minimal amount of time they take to have an effect is three weeks. I am not a scientist so I do not know obviously if this could be a reasonable idea to present and I researched this online and did not find anything that combined the two, but the article says that the effects of ketamine lasts for 7 days from a single dose, therefore perhaps the study could look at one dose of ketamine per week for three weeks, combined with an antidepressant and if this could help overcome the problem of the time lag of efficacy antidepressants currently take. I understand that ketamine has highly addictive qualities, so it may not be reasonable to expect to see it used so frequently in the future for depression, but perhaps the NR2B antagonist, RO 25-691 could be a more promising substitute as the results in this experiment show it has similar results.
I thought the article presented really high quality arguments for the rapid effects of ketamine and Ro 25-6981 except that we only really see results presented for a further explanation of the mechanisms and roles that antidepressants can take and the duration rapidity of ketamine that provides a base for research into the problem of that lag time antidepressant treatments have. However, I would have liked to see more specific results focussing on the percentages of rats that the ketamine and RO 25-691 worked in (the efficacy rates) as that wasn't entirely clear to me (maybe it was just me!). As I have mentioned above and we have seen so far, the efficacy of antidepressant treatments themselves has been a major issue thus far and is something that further needs to be looked at, especially with depression being such a prevalent disorder today.
I am very much on the same page as Tamara. When reading this, my first thought was when looking at the presented timeline of events, “why did they only administer the ketamine at one point without comparisons”? Since ketamine seems to be so fast acting, I would have liked to see what would happen if the ketamine were administered before the CUS, during the CUS, a week after the CUS and see when the most effective time would be. In a future clinical application; what would this mean for time dependency for taking this antidepressant? Would it mean that the person would have to take this medicine directly after a depression-inducing event for it to have any effect? If the ketamine were administered 2 weeks after the CUS would there be any effect, and if so, what would be the difference between that and ketamine administered without CUS even happening?
ReplyDeleteSince antidepressants are used for extended periods usually I would also have liked to see a longitudinal study, maybe just 2 or 3 weeks for the rodent model to see the long term effects. If previous studies showed that the effects of ketamine are not long lasting then perhaps giving a second dose around 2 weeks and seeing if there is any change/ negative effects. What concerns me is that since ketamine is used as a tranquilizer, how will the long-term effects affect the animal? I am wondering about the long-term effects with mice treated with CUS as well as the long-term effects of without. I think the reason why I am so interested in the other sides of what is going on is because of how clear- and quick of a response the ketamine and Ro 25-6981 had. It seems like a “solve-all” treatment, which automatically makes me think that it can’t be perfect. The results are clear though, there is an obvious positive short-term effect.
My last concern is with the down-the-line marketing of this potential anti-depressants. What has been working with typical SSRI’s and similar medications is that they do not seem to have a distinctly “positive” effect when taking, for example, without depression or recreationally. With any drug that has a quick effect there is a concern with dependence, especially with a drug such as ketamine that has already been known as a drug that is taken recreationally. Although it seems like it has great effects, the downside is the dependence some may form with an already controversial drug. I am aware that this is looking far down the line, but there would need to be investigation done to see how the recreational “fun” and serious danger of the drug could be taken out without taking away the healing effects.