June 2020 · Mind Medicine Australia
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The Challenges of Depression Treatment in 2020

Trees and the sunset

Over recent years there has been a laudable and impressive effort to reduce the stigma associated with mental health conditions such as depression, and to engage more people with these conditions in treatment, especially here in Australia. However, this has not been accompanied by a clear reduction in the consequences of depression, such as suicide, in our community. There are lots of possible reasons for this failing but a completely under-recognised one concerns the limited effectiveness of the treatments we currently have available.

Whilst there are also issues with access to, and the effectiveness of, psychological treatments, I want to focus here on the limitations of existing antidepressant medication treatments. I want to make really clear up front that some patients are helped extremely well by these medications, they can change the lives of patients who respond to them, restoring their ability to function and lead fulfilling lives.

If you are taking one of these medications, what I am writing is not meant to persuade you to stop the medication, not at all, don’t do this! If your medication is not working, however, talk to your doctor and make sure you actively explore what other options you have. You should set the bar high and aim to get well, to get your old life back.

The main problem with antidepressant medication I want to highlight is that they are just not effective for enough people and this limits the size of the group of people who can get the life changing benefits from them that they deserve.

The largest study that has investigated the effects of antidepressants was the sequenced treatment alternatives to relieve depression (STAR*D) study [1]. This impressive effort was funded by the National Institute of Mental Health in the US, independent of the pharmaceutical industry. It involved the sequential treatment of several thousand patients with depression who received up to 4 different steps of treatment, starting with the standard SSRI antidepressant citalopram. The study examined remission rates: the percentage of the patients who effectively got better with each stage of treatment. In the first round of treatment, ~ 37% of patients became symptom free taking citalopram, only about 30% to the second medication they tried, less than 15% to the third and only 13% to the fourth. There were also significant rates of withdrawal from treatment at each level: 21% after stage 1, 30% after stage 2 and 42% after stage 3.

Although these statistics are concerning, they don’t quite paint a picture as to how bad things were as overall outcomes are determined both by whether you get better on a medication, but also how long this benefit lasts. Unfortunately relapse, a return of depression, was quite common. It was especially striking that patients who had struggled to get better initially, especially those who needed more than one medication to do so, experienced relapse at quite high rates. In fact, if a patient was in the group who didn’t respond to the first medication but then did get better, there was a greater than 50% chance that they would relapse in the next 12 months. Relapse rates were even higher if patients had required three or four courses of initial treatment.

It is possible to take these rates and to estimate the chance that a patient will respond and then remain well over a period of time: the overall value of the medication. In a paper published in 2016, Harold Sackeim did this with data from the STAR*D study [2]. His analysis found the following. The chance you would get better with the first medication, citalopram, and stay well for 12 months was about 27%. However, if a patient failed to respond to 2 initial antidepressant medication trials, the likelihood that they would respond to a subsequent medication trial and then remain well for at least 12 months fell to less than 5%. In other words, once a patient has failed to respond to 2 medications, the likelihood that they will achieve sustained benefit with the third or subsequent medication is going to be less than one in 20.

These results are really sobering and should be a siren call for attention and action. Clearly some patients do wonderfully well with treatment but many don’t and once a few medications have failed, the chances of persistent response to future trials falls substantially. This has several direct and important implications.

First, we need to think more creatively in the treatment of patients who are not getting better with initial medication treatment. Consider other options, things like repetitive transcranial magnetic stimulation (rTMS) — my hobby horse and clearly an effective option in medication non responsive patients — , other forms of psychotherapy and even ECT. If medication treatment is being pursued and especially if the patient has responded, they need to be followed really closely. Everything that is possible from biological, psychological and social perspectives needs to be done, for example mindfulness based cognitive behavioural psychotherapy, to reduce their risk of relapse over time.

Most critically we desperately need a broader range of new accessible and affordable therapies. This is going to take meaningful investment in experimental therapeutics, clinical trials and translational infrastructure. We need to invest in the development and testing of novel medications, but also new non invasive froms of brain stimulation such as transcranial alternating current stimulation and focused ultrasound. We also need to be open to development of other novel forms of therapy, such as psychedelic assisted psychotherapy, which is fortunately now starting to get evaluated carefully. The investment in new treatment development is critical and timely as our patients really deserve that this be taken as seriously as the other major health problems in our community that attract widespread funding.


[1] https://www.nimh.nih.gov/funding/clinical-research/practical/stard/allmedicationlevels.shtml

[2] Sackeim H. Acute continuation and maintenance treatment of Major depressive episodes with transcranial magnetic stimulation. Brain Stimulation 9 (2016) 313–319

Psychedelic-Assisted Psychotherapy to Treat Sexual Abuse Victims

Image of a white flower

By Priscilla Duarte and Dr Alana Roy

Sexual abuse is a safety and health problem all over the world, affecting people of all ages, socioeconomic and demographic groups; in Australia, 1 in 5 women have experienced sexual violence and 1 in 22 men were sexually abused, resulting in severe individual and social impacts. In the Mental Health field, it has been a challenge for professionals to properly help those victims, but recent research on Psychedelic Assisted Psychotherapy is leading us to a paradigm expansion in treatment.

Sexual assault survivors tend to develop a range of chronic psychic illnesses, such as post-traumatic stress disorder (PTSD), depression, anxiety, problems in social adjustment, sleep difficulties, and addiction. Traditional talk therapy can be challenging or even re-traumatizing for the victims as it’s often difficult for them to talk about the trauma, or even access their own feelings. It can also be challenging to establish confidence and therapeutic alliance with professionals.

Psychedelic Assisted Psychotherapy has been used to great success in treatment-resistant mental illnesses. By helping the patient to alter their subjective experiences, substances such as MDMA, Psilocybin, and Ayahuasca can make treatment far more effective and create optimal conditions for psychotherapy.

How do those substances work?


MDMA Assisted Psychotherapy has been successfully tested to treat PTSD, and it’s already been considered a breakthrough treatment for trauma-related conditions; This is a well-known prosocial drug and has been classified as an “entactogen” or “empathogen” due to its role in producing experiences of emotional openness and empathy, not only towards others but to oneself as well, increasing self-compassion and acceptance.

In a psychotherapeutic context, this wellbeing state facilitates building up a strong therapeutic alliance with professionals, and accessing memories and feelings with a decreased sense of anxiety and fear. Findings suggest that at the same time that empathy is stimulated, and fear and anxiety decrease, the prefrontal cortex is stimulated, improving modulating emotions and thought, facilitating the reprocessing of traumatic memories. That may explain why people can approach their worst memories and feelings with psychotherapists without being retraumatized.

Psilocybin and Ayahuasca

In contrast to MDMA, Psilocybin and Ayahuasca are classical psychedelic compounds. Generally, Psychedelic substances help to access repressed feelings and memories, and in a supportive environment can trigger the release of meaningful and cathartic experiences.

Psilocybin is a substance found in some mushroom species, and it stimulates cognitive flexibility due to its capacity to alter communication among brain networks, such as the Default Mode Network, helping the patient to break out rigid styles of thinking, feeling and behaving, and to prospect new perspectives for the future. The therapeutic use of this substance has shown good results to treat Major Depression, Existential Anxiety, OCD, and Addiction.

Ayahuasca is an Amazonian brew made from the combination of two plants, one containing DMT (commonly Psychotria viridis) and the other one containing MAOi (usually Banisteriopsis caapi), which makes the DMT able to be consumed orally as a drink. The use of Ayahuasca creates a dream-like state in the brain, enabling patients to access liminal sub-conscious content. It has been successfully used to treat depression and it is also a promising treatment for addiction.

Psychedelic Assisted Therapy is building new pathways to future mental health practices, and it’s showing a new way to effectively approach what we consider today as “difficult-to-treat” mental illnesses, including sexual abuse trauma. As such, it’s important that we legalize and regulate these kinds of treatments to make them available to people who are struggling with mental suffering, and who cannot find relief in the currently available treatments.

Find out how you can contribute to make that possible here!

Webminar session

Here is a recording of our webinar held on 22 April and facilitated by Dr Alana Roy and Renee Harvey.

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