In 6 months (around June 2024) the FDA (US medicine regulator) will likely approve MDMA (ecstasy) as a licensed medicine in the US. This will present a pivotal moment for mental health care around the world as the efficacy rates of MDMA relative to traditional treatments for PTSD, depression and addictions are impressive.

As you can see from above, the most recent data indicates high rates of remission from PTSD (red) with MDMA in comparison to placebo (blue). Further comparing these rates (see picture below) to traditional antidepressant effectiveness rates i.e. from 19 to 70% within SSRIs (Prozac et al.), from 31 to 70% within the SNRI (Duloxetine et al.) treatment arms, and from 23 to 54% within TCAs (Amitriptyline et al.).

This may not seem very impressive, however, there is one major distinction, MDMA is curative. The importance of this cannot be stressed enough. Aside from the cost of having to take traditional antidepressants every day which comes with a wide range of side effects, such as with, TCAs treatment: dry mouth (58%), sweating (28%) and constipation (26%)² there’s the additional burden of anhedonia (not being able to feel anything good, or bad!).

MDMA is different. The medicine treats the root cause of the disease instead of just tranquilising the symptoms such as poor mood or lack of motivation. MDMA does this through a process known as fear memory extinction, which modulates fear memory consolidation. At its simplest, this means MDMA can dissolve bad feelings associated with a memory which in extreme cases is termed trauma. This makes it more comparable to traditionally stronger, last-line treatments like ECT which has its major side effects of memory loss.

When will MDMA be available in Australia?

Well in theory, due to the changes put forth by the TGA on 1 July 2023, it should already be available. However, due to the huge amount of red tape and high demand, the vast majority of 1 in 7 depressed patients in Australia cannot get access. This is why the licensing by MAPS is so important, it puts the medicine in a licensed category meaning, that doctors will have better coverage by indemnity insurance if something were to go wrong, therefore, they will have a higher propensity to prescribe. i.e. the risk to them is a lot lower and therefore, given the demand this should cause an upsurge in supply.

So where to go from here? Stay updated with the latest developments. Whilst it’s likely the FDA will license the medicine in the US in June, it will take a bit of time to come to Australia (usually another 6 months). At this point, it is more than likely it will be considered a Controlled Drug and hopefully be prescribable by regular doctors (however this may be limited to psychiatrists only). By whichever route, it should be available this time next year, for a high price due to the overwhelming demand, this is why we have created the Psychedelic Buyers Club to ensure a lower cost via a bulk buy.

References

¹ MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Published in the Nature Medicine Journal: 10 May 2021: Jennifer M. Mitchell. Accessed on 2 January 2024 via: https://www.nature.com/articles/s41591-021-01336-3

² Tricyclic Antidepressants. Moraczewski J, Awosika AO, Aedma KK. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557791/

³ Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Review published: 2006. Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. M Machado, M Iskedjian, I Ruiz, and TR Einarson. https://www.ncbi.nlm.nih.gov/books/NBK73259/

Introduction

Ketamine, once primarily known as an anaesthetic agent, is gaining traction in Australia as a potential breakthrough treatment for mental health conditions. With the rise of ketamine clinics across the country, Australians now have more options to explore novel therapies. But what should you know about these clinics? Let’s delve into the world of ketamine treatments Down Under.

1. The Therapeutic Potential of Ketamine

Recent studies have indicated that low doses of ketamine can have rapid antidepressant effects, especially for individuals resistant to traditional treatments. These findings have led to a surge in interest and the establishment of specialized clinics offering ketamine-infused therapies for conditions like depression, PTSD, and anxiety.

2. The Legal Landscape in Australia

Ketamine is a Schedule 8 controlled drug in Australia, which means its use is restricted and closely monitored. However, certain approved clinics and practitioners can administer it under strict guidelines for therapeutic purposes.

3. What to Expect at a Ketamine Clinic

Typically, patients undergo a thorough assessment to determine their suitability for ketamine therapy. Once deemed appropriate, they receive the treatment in a controlled environment, often starting with a series of infusions. It’s essential to understand that while many individuals report significant improvements, results can vary.

4. The Rise of Clinics Across Australia

Major cities like Sydney, Melbourne, and Brisbane have seen a steady increase in ketamine clinics, reflecting the growing demand and recognition of its potential benefits. These clinics often have multidisciplinary teams, including psychiatrists, anaesthetists, and nurses, ensuring comprehensive care.

5. Staying Informed and Safe

While the promise of ketamine treatment is exciting, it’s crucial to approach it with an informed perspective. Ensure the clinic is licensed, the practitioners are experienced, and they follow the stringent guidelines set by Australian health authorities.

Conclusion

Ketamine clinics in Australia represent a new frontier in mental health treatments, offering hope to many who haven’t found relief through conventional means. As with any medical treatment, it’s essential to do thorough research, consult with professionals, and stay updated on the latest regulations and findings. If you would like us to help you find the right type of treatment get in contact with one of our healthcare professionals using this form.

As of the last update of this article in October 2022, psilocybin remains a Class A drug in the UK, making it illegal to produce, supply, or possess. The following article is meant for informational purposes only and does not endorse or encourage illegal activities. Always consult with local laws and regulations.

Introduction

Psilocybin, the active compound found in certain mushrooms, has been the subject of much medical and scientific interest in recent years. While it remains a controlled substance in many countries, the potential therapeutic applications of psilocybin are being explored extensively. If you’re interested in understanding the process of obtaining a psilocybin prescription in the UK, here’s what you need to know.

1. Understanding Psilocybin’s Legal Status

Before diving into the intricacies of obtaining a prescription, it’s essential to be clear about psilocybin’s legal status. In the UK, psilocybin mushrooms are classified as a Class A drug. This means it’s illegal to possess, produce, or supply them. Any attempt to procure psilocybin without appropriate authorisation can lead to severe legal consequences.

2. The Potential Therapeutic Uses

Research studies have shown that psilocybin may have potential therapeutic effects, particularly for conditions like depression, anxiety, and PTSD. Clinical trials are underway in various parts of the world to better understand its safety and efficacy.

3. Special Licences for Research

While general possession and supply are prohibited, specific licences can be granted for research purposes. Institutions or researchers looking to study psilocybin’s therapeutic effects can apply for such a licence from the UK Home Office.

4. Consulting with a Healthcare Professional

If you believe that psilocybin might be beneficial for your health, it’s crucial to consult with a healthcare professional. They can provide guidance on potential treatment options, risks, and the legal aspects surrounding psilocybin in the UK.

5. Staying Updated with Changing Regulations

Laws and regulations around controlled substances can evolve. It’s vital to stay informed about any changes in the legal status of psilocybin or its potential therapeutic applications in the UK.

Conclusion

While the therapeutic potential of psilocybin is promising, it remains a controlled substance in the UK. Those interested in its benefits should approach the topic with caution, always prioritising legal considerations and consulting with healthcare professionals. By staying informed and adhering to regulations, individuals can navigate this complex landscape safely and responsibly.

One retrospective study conducted in 2010, looked at how SSRIs might affect people’s personality in the long run as the medicine has been shown to alter the concentration of a key neurotransmitter serotonin. The reason for this is that it has been found that neurotransmitters instead of working like a golden bullet on one aspect of the mind such as regulating depression work in synergy to maintain a whole host of characteristics. By just changing one instruments volume in the neurotransmitter symphony of self can put people on a very different path in your life. Serotonin has been shown to selectively influence moral judgment and behavior through effects on harm aversion¹. Furthermore, another very popular set of medicines the statins has shown to potentially do the opposite, i.e. instead of increasing the the concentration of serotonin like what the SSRIs do they decrease their concentration. This has led to a significant association between low or lowered cholesterol levels and violence is found across many types of studies².

This example is one of many retrospective studies showing the long term unintended personality changes caused by medicines, others include:

• Heartburn pills Among the most commonly used drugs in the world, proton pump inhibitors used to treat heartburn and acid reflux have been linked with a greater risk of developing depression, particularly among the elderly. They interfere with the absorption of vitamin B12, a nutrient that produces chemicals that affect our thinking.
• Asthma and arthritis drugs Corticosteroids such as prednisone can save lives – their powerful anti-inflammatory effect treats asthma, allergies and rheumatoid arthritis. But they can also cause depression, mania and ADHD, because they act on areas of the brain that regulate serotonin and dopamine – our ‘happy’ hormones.
• Parkinson’s drugs A 2010 study showed 17 per cent of people on dopamine agonists – used to treat shaking and other physical symptoms of Parkinson’s – experience ‘impulse control disorder’, from excessive shopping to uncontrollable sexual urges. In 2011 a married father of two sued the manufacturer of one of these drugs, saying it turned him into a gambling and gay sex addict, which led to him being raped and attempting suicide eight times. He won a six-figure payout.
• Antibiotics Overuse can make antibiotics less effective at treating infection – and a 2015 review of UK medical records linked repeat courses of antibiotics to increased anxiety and depression. It’s thought this may be down to their effect on bacteria in our guts, which interact with our brain chemistry.

References

¹Crockett MJ, Clark L, Hauser MD, Robbins TW. Serotonin selectively influences moral judgment and behavior through effects on harm aversion. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17433-8. doi: 10.1073/pnas.1009396107. Epub 2010 Sep 27. PMID: 20876101; PMCID: PMC2951447, accessed on 21st January 2022 via: https://pubmed.ncbi.nlm.nih.gov/20876101/

² Golomb BA. Cholesterol and violence: is there a connection? Ann Intern Med. 1998 Mar 15;128(6):478-87. doi: 10.7326/0003-4819-128-6-199803150-00009. PMID: 9499332., accessed 21st January 2022 via https://pubmed.ncbi.nlm.nih.gov/9499332/

So what can we do to avoid slipping into melancholy during this crisis? Techniques with the most robust evidence to reduce potential depressive symptoms have been shown to primarily be non-pharmacological:

• Exercise – 3+ times a week get heart rate above resting and maintain.
• Adequate sleep – by exposing yourself to sunlight you can reset your Circadian Rhythm whilst exercise will help you sleep.
• Reduce Overstimulation – anti rumination, reduce caffeine intake do more mindfulness and meditation.
• Social interaction – self-therapy, counselling, increase social contact.
• Sunlight – running outside as below can bolster Vitamin D3 as above.
• Healthy diet – supplementation of Vitamin D3 / Omega, ↓ intake of alcohol.

After the above have been exhausted, it is usual that the next step is an antidepressant medicine. Antidepressant usage is skyrocketing year-on-year in every single country³, a handful of people criticize the use of psychotropic drugs which produce mild-to-severe side-effects, cause overdependence or resistance, and are self-limiting. For some, meditation retreats are no more than expensive trips for which vacating time out of a busy life and responsibilities gets difficult while for others, traditional forms of psychotherapy take longer to show results, produce negative patient outcomes, aren’t available throughout and are expensive. Although, depression and other mental diseases can be treated by various strategies, between 76% and 85% of people in low- and middle-income countries do not seek or receive treatment⁴.

But could iPhone / Android (mHealth) apps have enough evidence behind them to be added to this list? We all now create shoppings list apps to aid our poor memory and play the latest version of Candy Crush to cure our boredom so why not an app for curing depression?

Smartphone-based mental health apps represent a unique opportunity to expand the availability and quality of mental health treatment. The number of mobile health (mHealth) apps focused on mental health has rapidly increased; a 2015 World Health Organization (WHO) survey of 15,000 mHealth apps revealed that 29% focus on mental health diagnosis, treatment, or support. Unfortunately, a meta-analysis review published in late 2019 has shown that “mHealth apps cannot be recommended based on the current level of evidence.” However, can some new apps buck this trend? In this article, we will look at three new mHealth apps, Tetr, Misu and Wuju and see if any of their therapeutic claims stand up to scrutiny.

Misu

A recent study of mobile usage and depression found that:

“Participants with depression were found to have fewer saved contacts on their devices, spend more time on their mobile devices to make and receive fewer and shorter calls, and send more text messages than participants without depression.”

Depression screening using mobile phone usage metadata⁷.

There is definitely a link between the use of technology and depression scores, Misu sets out to address this with some clever technology. Misu installs on your computer and works in the background tracking short-lived emotions via facial micro-expressions and organizes an emotional history alongside which apps are used. The intention is to reveal to users how various apps influence their mind and helps a person become aware of his/her mood patterns and preferences. I have been using it for a number of weeks and here is how my happiness rates alongside the various OSX programs I use.

Misu claims the app has an 86% accuracy rate of being able to predict someone’s mood, this came from calibrating the AI with 1⁄4 million people volunteers having their photos captured.

Wuju

Wuju is the brainchild of Eli Finer. Built from Eli’s long, struggle with depression, this app comprises diversified moods with his narration and music in the background which produces a less AI-based visual healing experience and simulates in-person therapy but with a setting of the patient’s choice.

Wuju intends to halt extraordinary runaway thoughts but also uncovers the most mundane and ordinary sensations to heal the uncontrolled minds. While this app can heal transient emotional injuries in a short time, it collects data to evaluate the progress in people’s behaviour which allows for the app’s further improvement. In Eli’s latest tweet, he provided stats as evidence for the app’s effectiveness. Remarkably, there was a maximum drop in anger by 89%, resistance by 74% from 138 samples, shame by 85% and other emotions also showed a significant decrease⁵. It is claimed that For 50% of its users, it worked extremely well and moderately well for a further 25%⁶.

Tethr

Due to an overused idea that men are strong-minded goliaths devoid of sentimental thoughts, they do not disclose their mental health problems nor seek support. In England, 1 in 8 men suffer from mental health problems that are left untreated⁸. To break this conventional image, Tethr , a mhealth app turns to the needs and wellness of the marginalized gender and helps men replenish their internal peace. It engages male peers to share their hollow experiences and consists of mhealth hotlines, coaching and articles for men which make it an effective tool.

Beyond the effectiveness of these apps, the questions get trickier. How do these apps manage users’ privacy and data? MHealth Apps are not only effective in their use but also address their users’ privacy by explaining how this app uses their data and has led to the satisfaction of their users. Do these apps provide the best treatment out of all the mental illness methods? While different techniques work for different patients, mHealth apps are devoid of almost every problem relating to drug treatments and traditional psychotherapies. With increasing consumption of antidepressants in children and older adults along with people who do not receive traditional treatment either because of stigmatization or inaccessible conventional treatments, mhealth apps provide a promising solution and strategy to overcome these barriers. Presently, the smartphone usage is ubiquitous and current covid-19 dynamics have led to an increase in the use of these digital interventions which are easily accessible and inexpensive, have a time-saving user-friendly interface, and are becoming a day-to-day custom for their avid users. Furthermore, they provide supplementary treatment to traditional therapy and are used in combination with these techniques to explore the entire spectrum of mind.

are antidepressant medicines, all of which have been carefully scrutinized in randomised controlled trials before they can be sold to the public as the majority of drugs can cause both harm and good. In the app world, Google and Apple tend to think little harm can occur by using an unproven depression app and do not to delve into medical claims. The NHS on the other hand (the UK national health service) has done a great job of making a list of “Approved Apps” we intend to do the same.

Mobile apps have significant potential to deliver high-efficacy mental health interventions. Given the global shortage of psychiatrists and the lack of mental health care access in rural regions, apps have emerged as a viable tool to bridge the mental health treatment gap. However, the majority of the apps that are currently available lack clinically validated evidence of their efficacy and as such cannot be fully recommended by health care practitioners. Given the number and pace at which mobile Health (mHealth) apps are being released, further robust research is warranted to develop and test evidence-based programs. It has been mentioned elsewhere in the scientific literature⁸, but to reiterate, we implore mHealth organizations, and others, come together to set universal standards for mental health app quality control, and that those standards include at a minimum the review of data security, app effectiveness, usability, and data integration.

References

1. Global Burden of Disease Study 2019 (GBD 2019) Results. Global Burden of Disease Collaborative Network. [Online] Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2020, October 2020. [Cited: November 7, 2020.] http://ghdx.healthdata.org/gbd-results-tool..
2. Antidepressant Drugs Market to Reach $15.98 Bn by 2023, Globally at 2.1% CAGR, Says Allied Market Research. https://www.prnewswire.com/. [Online] PR Newswire, 11 21, 2018. [Cited: 11 7, 2020.] https://www.prnewswire.com/news-releases/antidepressant-drugs-market-to-reach-15-98-bn-by-2023-globally-at -2-1-cagr-says-allied-market-research-873540700.html.
3. Something startling is going on with antidepressant use around the world. https://www.businessinsider.com/. [Online] Business Insider, 2 4, 2016. [Cited: 11 7, 2020.] https://www.businessinsider.com/countries-largest-antidepressant-drug-users-2016-2.
4. Use of mental health services for anxiety, mood, and substance disorders in 17 countries in the WHO world mental health surveys. The Lancet. [ Online] 9 8, 2007. [Cited: 11 2, 2020.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847360/.
5. Finer, Eli. [Online] 10 9, 2020. [Cited: 11 7, 2020.] https://twitter.com/finereli/status/1314784540703899648. 6. Wuju App. Wuju. [Online] [Cited: 11 7, 2020.] http://wujuapp.com/#:~:text=Unlimited%20trial,moderately%20well%20for%20further%2025%25. 7. How Misu Works. Misu. [Online] [Cited: 11 7, 2020.] https://www.misu.app/how-misu-works.
6. Survey of people with lived experience of mental health problems reveals men less likely to seek medical support. www.mentalhealth.org.uk/. [Online] 2016. [Cited: 11 7, 2020.] https://webarchive.nationalarchives.gov.uk/20180328130852tf_/http://content.digital.nhs.uk/catalogue/PUB2174 8/apms-2014-full-rpt.pdf/.
7. Rouzbeh Razavi, Amin Gharipour, Mojgan Gharipour, Depression screening using mobile phone usage metadata: a machine learning approach, Journal of the American Medical Informatics Association, Volume 27, Issue 4, April 2020, Pages 522–530, https://doi.org/10.1093/jamia/ocz221
8. Torous J, Andersson G, Bertagnoli A, Christensen H, Cuijpers P, Firth J, et al. Towards a consensus around standards for smartphone apps and digital mental health. World Psychiatry 2019 Feb;18(1):97-98

It is no secret in the medical sector, that evidence for the efficacy of traditional antidepressants (SSRIs, SNRIs, NASSAs…) is underwhelming. In 2018, the largest-ever meta-analysis concluded that the majority of their effect, if any, can be attributed to placebo¹. That being said, the clinical rationale for taking them is still sound, as prescribing them is thought to offer a harm reduction strategy, enabling the sufferer to seek additional talking therapy to address the underlying causes of the disease. This therapy often takes the form of psychotherapy, however, due to high private costs and the chronically underfunded NHS, it is often difficult for the general public to break out of limbo and fix the root cause of their condition.

Is there an alternative route?

If “Best Practice” care is being followed, something like the NICE CKS guidance on depression should have been carried out. This pathway includes the most up-to-date, proven science on the topic. The starting point will always be a non-drug approach, this includes:

1. Eat a healthy diet – supplementation of Vitamin D3 / Omega, ↓ intake of alcohol.
2. Getting enough sunlight – exercise outside as below can bolster Vitamin D3 as above.
3. Exercising regularly – 3+ times a week get heart rate above resting and maintain.
4. Sleeping well – by increasing exposure to sunlight you can reset your Circadian Rhythm whilst exercise will help you sleep.
5. Not overstimulating – anti rumination, reduce caffeine intake do more mindfulness and meditation.
6. Accessing talking therapy – self-therapy, counselling, cognitive behavioural therapy, increased social contact.

Once these factors have been exhausted, the second stage is to take a medicine, which usually starts with an SSRI such as citalopram or fluoxetine. If this initiation fails (after 6-12 months), there is usually a “switching or augmenting” to different medicines. This can only go so far as there are a limited amount of treatment options. When an inadequate response to at least two antidepressants has been tried this is referred to as Treatment-Resistant Depression (TRD). TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. In the UK alone, 2.7 million people have treatment-resistant depression which accounts for 10% and 30% of all people with depression².

So what else can be done to treat TRD?

There are treatments that have been used in mainstream medicine for almost half a century that have proven clinical safety profiles and high relative efficacy for the treatment of TRD. One of the most common, esketamine, has been discussed at length on this blog in another article, another option which is the subject of this article is the mushroom-derived molecule, psilocybin.

A short history of Psilocybin as a Medicine.

In the 1960s psilocybin was marketed as a medicine by Sandoz (now Novartis) as a “catalyst” for people with treatment-resistant depression. In a systematic review of clinical trials, Rucker³ showed that approximately 80% of patients who are given psilocybin show clinical improvement.

In 1970, in response to a UN convention in 1971, psilocybin was made a schedule 1 drug in the UK, making it nearly impossible to use in clinical trials. The evidence that placed psilocybin into schedule 1 widely seen in the scientific community as flimsy⁴.

Fast track to today and the government’s opinion is now shifting making it possible for clinicians to study psilocybin in the same way as all potential new medicines. A recent Imperial study published the following inclusion and exclusion criteria for a new study on the medicine:

Inclusion criteria:

• Aged between 18-65
• Currently suffering from moderate to severe depression. Mild depression or historical depression are not being looked at in this study
• Willing to take two doses of psilocybin and a six-week course of Escitalopram

Patients, they would exclude from treatment include:

• You have a diagnosis of Emotionally Unstable (Borderline) personality disorder
• You have a personal or immediate family history of psychosis (drug-induced psychosis, Schizophrenia, Bipolar). Bipolar disorder is not being looked at in this study
• You are currently addicted to alcohol or any illicit drugs
• You have taken a full course of Escitalopram in the past (please note that there is a similar medication called Citalopram which is fine to have taken
• You have epilepsy or any serious heart conditions

This criterion is interesting because it indicates what the prescribing requirements may be when a legal psilocybin medicine is launched. However, as of 1st March 2021, psilocybin is still illegal in the UK, the drug belongs to the Class A substance category alongside heroin and cocaine.

When will psilocybin be legally available in the UK?

Unfortunately, unlike esketamine, psilocybin has yet to become a licensed product in the UK (so that it can be prescribed) as it is still criminalised. Decriminalisation is occurring slowly around the world, notably in the State of Oregon in the US. Within the UK, this has been said to be at least 2-3 years away. If you would like to help in the movement to decriminalise psilocybin here is a simple argument for decriminalization and here is a template you can use to send to your MP expressing your support for the cause. However, if you cannot wait there is always another route. First is the use of a legal alternative, there is a lot of evidence to suggest that ketamine, which has over 50 years of clinical use and a strong safety profile has much the same effects as psilocybin. The second route is to recognise that healthcare legality is based upon regionality, i.e. the fact that psilocybin is illegal in the UK does not mean it is illegal worldwide…

Health Tourism

“Health Tourism” is a term used when someone wants to source medical treatment from a country other than where they reside. The most common destinations for general medical conditions include Canada, Singapore and the UK. Health Tourism usually occurs where the country of origin has a high cost associated with healthcare and the destination has a lower cost.

Similarly for psilocybin treatment, health tourism is burgeoning. Instead of travelling to avoid high costs, patients are migrating to avoid criminal prosecution. Some countries including the Bahamas, Jamaica, Netherlands, Samoa and the aforementioned US State, Oregon, either never classified magic mushrooms as illegal or have been through the decriminalisation process.

So flying to these countries and receiving treatment avoids any prosecution action for the originating country. The main issue with this is that the standards of care in the treatment country may not be as regulated as treatment in the UK. Below is a list of attributes you should check before accessing treatment:

• On-site medical team, in case of any medical emergencies.
• Regulated by the national authority with a recent inspection report.
• Third-party, impartial patient feedback submission system.
• Quality Management System.

If you would like our medical team to review the Medical Tourism destination based on their regulation and safety please get in touch with our team.

References

¹Network meta-analysis of antidepressants, published in The Lancet on September 22, 2018, accessed on 23rd February 2021 via: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31783-5/fulltext

² Treatment-resistant depression: what are the options. BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k5354 (Published 18 December 2018) BMJ 2018;363:k5354

³ Rucker JJ, Jelen LA, Flynn S, Frowde KD, Young AH. Psychedelics in the treatment of unipolar mood disorders: a systematic review. J Psychopharmacol 2016;30:1220-9.27856684

⁴Hawkes N. Sixty seconds on . . . psilocybin. BMJ 2016;353:i2775. 10.1136/bmj.i2775 27194646

⁵https://www.independent.co.uk/news/health/magic-mushroom-depression-psilocybin-trials-kcl-mental-health-addiction-a9251451.html

If you would like to watch a short video of how esketamine may work have a look at the video below:

Current availability in Australia

Esketamine was launched in Australia on the 9th of March 2021. Below is a timeline published by the Therapeutic Goods Association of Australia.

Ketamine vs Esketamine in Australia

Obtaining esketamine for psychiatric conditions in Australia is difficult as there are few prescribers and those that do charge a large amount of money for access. Off-label prescribing of ketamine for major depression is a possible alternative however this is uncommon, given regulatory hurdles (esketamine is still classed as a Schedule 8 poison) and uncertainty around efficacy and safety.

The reason for caution is primarily the taboo surrounding “psychedelics” which has been spurred by the Royal Australian and New Zealand College of Psychiatrists (RANZCP) calling on medical practitioners to proceed with caution when treating patients with ketamine.

However, this RANZCP announcement was not out of the blue, it followed a small unsuccessful clinical trail² of Intranasal Esketamine for Treatment-resistant Depression which was completed in 2016, and was ended prematurely because of unexpected side effects suffered by patients. It was found at the dose given, 100mg – over 10 sprays, more than twice the dose of any previous trial – their blood pressure shot up, they became uncoordinated and they suffered “unpleasant” psychotic-like effects. This is in light of other successful international trials seem to indicate not that the drug is ineffective, however, that the dosage range should be below this top threshold of between 50mg-100mg.

Who will be most likely to be prescribed esketamine?

The main inclusion criteria that would allow patients to obtain esketamine in Australia include:

• At least a single-episode major depressive disorder (MDD) that lasted for a minimum of two years.
• must have a MADRS total score of >=22
• nonresponse to 2+ oral antidepressant treatments

Who will be LEAST likely to be prescribed esketamine?

Again, according to the original clinical trial patients who were excluded from use include:

• previously not responded to ketamine in the past.
• MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
• homicidal ideation
• history of moderate or severe substance or alcohol abuse
• neurodegenerative disorder such as Alzheimer’s disease, vascular dementia, Parkinson’s disease)

Alternatives to esketamine

One alternative to esketamine is the original form of the medicine, ketamine. There are some clinicians administering the original drug form as an ‘off-label’ treatment. At these clinics Ketamine, is administered in a variety of ways: via an intravenous ketamine infusion (IV), an intramuscular injection (IM), a subcutaneous injection (SC), intranasally (NAS), sublingually(SL) and orally. Routes vary in the onset of action, bioavailability and clearing time through the system for each individual. While there is generally a predictable response based on past administration, it is possible that patients may experience variable physiological and subjective experiences with the same dose.

There are a variety of dosing protocols in practice. Much research and attention has been focused on the provision of 0.5mg/kg of ketamine by IV infusion over 45 minutes, in a repeated series consisting of 2/week for 3-4 weeks. Other described protocols include the provision of a single infusion, twice weekly, weekly or longer interval dosing as determined by patient need and response.

Another alternative is to investigate the use of other agents (often termed psychedelics) including psilocybin (magic mushrooms) or NDMA. The science surrounding these substance has progressed a long way in recent years, so much so that there is a petition to the organisation which regulates medicines in Australia the TGA to decriminalise their use.

Conclusion

In conclusion, it is now highly likely that in the near future that there will be dedicated esketamine clinics set up in Australia. If you are desperate to access the medicine now, possibly try accessing the medicine “off-label” (potentially very expensive as above). Institute, or wait till the end of the year…

Reference:

1. Ketamine-related drug could be ‘watershed’ in treating depression, 2019,https://www.theguardian.com/society/2019/mar/08/new-ketamine-related-drug-could-be-watershed-in-treating-depression.
2. A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (SUSTAIN-2):  https://www.australianclinicaltrials.gov.au/anzctr/trial/NCT02497287