Paper Summary
Source: The British Journal of Psychiatry
Authors: Colleen Loo et al.
Published Date: 2023-01-01
Podcast Transcript
Hello, and welcome to paper-to-podcast, where I, your helpful assistant, have read 100 percent of the research papers so you don't have to. Today's paper comes with a twist, a dance, and a jab - a jab of ketamine, that is.
Our paper of the day, straight from the British Journal of Psychiatry, is titled "Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial." The authors, Colleen Loo and colleagues, have been busy bees, turning the party drug ketamine into a potential superweapon against depression.
In the study, they ran a trial where they jabbed folks suffering from stubborn depression with either ketamine or midazolam, a sedative. The results were as surprising as a llama at a birthday party. The first group of 68 people didn’t see much difference between the two. But the second group of 106 people had a remission rate of 19.6% with ketamine compared to a mere 2% with midazolam. That’s right folks, ketamine was twelve times more likely to give depression the boot!
Now, before you start seeing psychedelic butterflies, any strange side effects like feeling a bit trippy or a spike in blood pressure, usually disappeared within 2 hours.
The research was carried out at seven mood disorder centres in Australia and New Zealand, where the participants were given twice-weekly subcutaneous injections of either ketamine or midazolam for four weeks. The success of the treatment was measured using the Montgomery-Åsberg Rating Scale for Depression, with the main goal to see if participants' scores were 10 or less at the end of the four weeks.
This study had its strengths. It was comprehensive, well-structured, and randomized. It had a large sample size, stringent ethical standards, and even used a generic form of ketamine, which is globally available and cost-effective.
But every rose has its thorns. The characteristic subjective effects of ketamine made it difficult to fully blind participants and assessors to the treatment conditions, which could have influenced the results.
The potential applications of using ketamine injections for treatment-resistant depression could be significant for mental health care. Not only does it provide an effective treatment for those unresponsive to traditional antidepressant medications, but it's also easier and less costly than other methods like intravenous infusion.
In conclusion, it seems that ketamine, the party drug, turned out to be a bit of a superhero, helping people battle depression. But like all superheroes, it had its side effects or should we say, secret identities?
That's all for today's paper. Remember, this is just a summary. You can find this paper and more on the paper2podcast.com website.
Supporting Analysis
Well, this research paper gave the classic party drug, ketamine, a shot at treating depression (literally!). The scientists ran a trial where they jabbed people suffering from tough-to-treat depression with ketamine or midazolam (a sedative) twice a week for 4 weeks. Lo and behold, ketamine turned out to be a pretty good ally in the fight against depression. The study had two groups of participants. The first group (68 people) didn’t see much difference between the ketamine and the midazolam. But the second group (106 people) had a remission rate of 19.6% with ketamine compared to a mere 2% with midazolam. The numbers suggest that ketamine was 12 times more likely to kick depression to the curb than midazolam. The scientists also found that any strange side-effects, like feeling a bit psychedelic or a spike in blood pressure, usually disappeared within 2 hours. So, the party drug turned out to be a bit of a superhero, helping people battle depression. But like all superheroes, it had its side-effects (or should I say, secret identities?).
The researchers decided to conduct a phase 3, double-blind, randomised, and active-controlled trial at seven mood disorders centres in Australia and New Zealand. The study participants, who were all suffering from treatment-resistant depression, were given twice-weekly subcutaneous injections of either ketamine or midazolam for four weeks. At first, the researchers used fixed doses of the drugs, but then they switched to flexible doses after a recommendation from a Data Safety Monitoring Board. The success of the treatment was measured using the Montgomery-Åsberg Rating Scale for Depression (MADRS). The main goal was to see if participants' MADRS scores were 10 or less (indicating remission) at the end of the four weeks. The researchers also monitored adverse effects and evaluated the overall safety of the treatment. They even asked participants and raters to guess their treatment allocation to test the effectiveness of the study's blinding. After all that, they crunched the numbers to see what worked best.
The researchers conducted a comprehensive, well-structured and randomized controlled trial, which is considered the gold standard in clinical research. They utilized a large sample size, enhancing the reliability of their results. They also employed rigorous ethical standards, ensuring all participants provided informed consent and aligning their procedures with the Helsinki Declaration. The use of an active control group (midazolam) to maintain the double-blind aspect of the trial is a noteworthy practice. Another compelling aspect is their choice to use a generic form of ketamine, which is globally available and cost-effective, making the research highly applicable in real-world settings. The researchers also did an excellent job of assessing both acute and cumulative safety, using a tool specifically designed to evaluate adverse effects of ketamine. This comprehensive approach to evaluating safety is rarely seen in such trials. Lastly, their decision to adapt the dosing protocol mid-trial based on interim results demonstrates their flexible and responsive approach to research.
One potential limitation of this research is that the masking of treatment was not entirely successful. The characteristic subjective effects of ketamine made it difficult to fully blind participants and assessors to the treatment conditions, which could have influenced the results. This is a common issue with studies involving sub-anaesthetic doses of ketamine and could lead to bias in the results due to expectancy and disappointment effects. The degree to which unmasking influenced the outcome remains uncertain. It's also important to note that while the study showed promising results for the use of ketamine in treating treatment-resistant depression, further research is needed to confirm these findings and to explore longer-term effects and potential side effects of the treatment.
The research on the efficacy and safety of subcutaneous ketamine injections for treatment-resistant depression could have significant implications for mental health care. The findings may help to establish more effective treatment protocols for individuals who are unresponsive to traditional antidepressant medications. Since the study involves a relatively simple subcutaneous injection method, it could potentially increase access to effective treatments, being easier and less costly than other methods like intravenous infusion. This could be particularly beneficial in areas with limited mental health resources. Moreover, if future research supports these findings, it might lead to broader global acceptance and use of ketamine in treating depression considering it's already on the World Health Organization Essential Medicines List as an anaesthetic. The study could also stimulate further research into optimal routes of administration and strategies to extend the benefits and reduce relapse rates.