Treatment‐resistant depression
Ivan Darby
Australian Dental Journal November 13, 2023 DOI: 10.1111/adj.13001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Intranasal esketamine Psilocybin MDMA |
| Topics | Depression |
| Keywords | Conceptualization Periodontology Library science Citation Medical education Dentistry |
| Citations | 8 |
| Key findings | Intranasal esketamine and psychedelics (psilocybin, MDMA) are emerging treatments for treatment-resistant depression, but evidence on their dental side effects is limited. |
Abstract
Treatment-resistant depressionGiven the current focus on mental health especially among dental practitioners, one of the issues we may see is an increase in treatment-resistant depression (TRD).In the management of depression, the ultimate therapeutic goal is remission, but Souery et al (J Clin Psych 2006, 67 (suppl 6): 16-22) suggested that only 60%-70% of patients respond to the first line therapy.TRD is defined as patients with major depressive disorder who do not respond adequately to a course of care with an antidepressant.However, there is some debate around whether it is TRD, a dose that is too low or a reflection of the effectiveness of the medication.The Royal Australian and New Zealand College of Psychiatrists defines TRD as the failure of two medications of adequate dose and duration.In addition, there is a possibility of relapse with prolonged use of anti-depressants.Recently, two forms of treatment have 'hit the headlines'.These are nasal application of ketamine and psychedelics.On the day of writing, the ABC published an article titled 'I took part in a ketamine clinic hoping it would ease my treatment-resistant depression' describing a patient's experience.Although these treatments are currently limited and costly, we as clinicians will most likely see an increase over time in patients using these.The onus is on us to understand the indications, method of administration, pharmacology and treatment outcomes.One starting point is the information available from the Royal Australian and New Zealand College of Psychiatrists (https://www.ranzcp.org).We are all aware of the use of ketamine as an anaesthetic and may also be for recreational use.Ketamine has now been approved for the treatment of TRD by the Therapeutic Goods Administration in the form of intranasal esketamine (Spravato) and doses may be repeated weekly or fortnightly for a period of time.It is a controlled medication and must be taken under supervision with monitoring up to 2 h post-use.Side effects such as hypertension, nausea, headache and dizziness to name a few and these usually pass within this period.Currently, evidence is limited to adults, where it has shown some effectiveness, although evidence is increasing.My understanding is that the approval for use requires prescription of an additional antidepressant.The second that was registered for use in July are psychedelics, 3,4-methylenedioxy-methamphetaime (MDMA) and psilocybin.Information from the RANZCP lists MDMA for use in PTSD and psilocybin in TRD.Psilocybin is a naturally occurring hallucinogen produced by over 200 species of fungi and is commonly known as magic mushrooms.It has a strong affinity for serotonin receptors and is able to activate 5HT receptors.There are a number of different methods reported for administration including capsules and powder.The efficacy of psilocybin is less clear than esketamine, but recent research does suggest a positive response (https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370%2822%2900538-7/fulltext).Again, it has to be administered in a controlled situation with a number of serious side effects including delirium and panic attacks.Again, my understanding is that it must be used with additional intensive therapy.Lastly, the dental side effects of illicit use have been documented, but there seems to be little reported in the medical research on the dental side effects of nasal ketamine and psilocybin.This is an area we need know more about.Please note that the information provided here is correct to the best of my knowledge.I am not a psychiatrist, but have had some experience with patients on these.It is necessarily brief.Readers are directed to the appropriate resources to get more information.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 2
- The post-marketing safety of Esketamine among older adults(≥ 65): an real-world pharmacovigilance study. BMC Pharmacology and Toxicology August 29, 2025
- Effect of esketamine and etomidate anesthesia on neuroplasticity in electroconvulsive therapy for treatment-resistant depression. World Journal of Psychiatry September 19, 2025