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Fast-tracking psilocybin for refractory depression makes sense
A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.
In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.
In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),1 which enable opportunities for various treatment methods.2 Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.3 VNS4 remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.
It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.
Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”5 and in his book, “How to Change Your Mind,”6Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.
With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study8 with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.
Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,9 as the study and FDA trials for ketamine have as well.10 It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.
The process will take some time. And it is worth remembering that, although research has been promising,11 the number of patients studied, research design, and outcomes are not yet proven for psilosybin.12 The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide13 (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.
Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.
References
1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.
2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.
3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.
4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.
5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.
6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).
7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.
8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.
9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.
10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.
11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.
12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.
13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.
*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.
A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.
In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.
In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),1 which enable opportunities for various treatment methods.2 Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.3 VNS4 remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.
It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.
Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”5 and in his book, “How to Change Your Mind,”6Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.
With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study8 with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.
Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,9 as the study and FDA trials for ketamine have as well.10 It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.
The process will take some time. And it is worth remembering that, although research has been promising,11 the number of patients studied, research design, and outcomes are not yet proven for psilosybin.12 The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide13 (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.
Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.
References
1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.
2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.
3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.
4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.
5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.
6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).
7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.
8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.
9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.
10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.
11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.
12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.
13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.
*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.
A significant proportion of patients with major depressive disorder (MDD) either do not respond or have partial responses to the currently available Food and Drug Administration–approved antidepressants.
In controlled clinical trials, there is about a 40%-60% symptom remission rate with a 20%-40% remission rate in community-based treatment settings. Not only do those medications lack efficacy in treating MDD, but there are currently no cures for this debilitating illness. As a result, many patients with MDD continue to suffer.
In response to those poor outcomes, researchers and clinicians have developed algorithms aimed at diagnosing the condition of treatment-resistant depression (TRD),1 which enable opportunities for various treatment methods.2 Several studies underway across the United States are testing what some might consider medically invasive procedures, such as electroconvulsive therapy (ECT), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT often is considered the gold standard of treatment response, but it requires anesthesia, induces a convulsion, and needs a willing patient and clinician. DBS has been used more widely in neurological treatment of movement disorders. Pioneering neurosurgical treatment for TRD reported recently in the American Journal of Psychiatry found that DBS of an area in the brain called the subcallosal cingulate produces clear and apparently sustained antidepressant effects.3 VNS4 remains an experimental treatment for MDD. TMS is safe, noninvasive, and approved by the FDA for depression, but responses appear similar to those with usual antidepressants.
It is not surprising, given those outcomes, that ketamine was fast-tracked in 2016. The enthusiasm related to ketamine’s effect on MDD and TRD has grown over time as more research findings reach the public. While it is unknown how ketamine affects the biological neural network, a single intravenous dose of ketamine (0.5 mg/kg) in patients diagnosed with TRD can lead to improved depression symptoms outcomes within a few hours – and those effects were sustained in 65%-70% of patients at 24 hours. Antidepressants take many weeks to show effects. Ketamine’s exciting findings also offered hope to clinicians and patients trying to manage suicidal thoughts and plans. Ketamine was quickly approved by the FDA as a nasal spray medication.
Now, in another encouraging development, the FDA has granted the Usona Institute Breakthrough Therapy designation for psilocybin for the treatment of MDD. The medical benefits of psilocybin, or “magic mushrooms,” has a long empirical history in our literature. Most recently, psilocybin was featured on “60 Minutes,”5 and in his book, “How to Change Your Mind,”6Michael Pollan details how psychedelic drugs where used to investigate and treat psychiatric disorders until the 1960s, when street use and unsupervised administration led to restrictions on their research and clinical use.
With protocol-driven specific trials, they might become critical medications for a wide range of psychiatric disorders, such as depression, PTSD, anxiety, and addictions. Exciting findings are coming from Roland R. Griffiths, PhD, and his team at Johns Hopkins University’s Center for Psychedelic and Consciousness Research. In a recent study8 with cancer patients suffering from depression and anxiety, carefully administered, specific and supervised high doses of psilocybin produced decreases in depression and anxiety, and increases in quality of life and life meaning attitudes. Those improved attitudes, behavior, and responses were sustained by 80% of the sample 6 months post treatment.
Dr. Griffiths’ center is collaborating with Usona, and this collaboration should result in specific guidelines for dose, safety, and protection against abuse and diversion,9 as the study and FDA trials for ketamine have as well.10 It is very encouraging that psychedelic drugs are receiving fast-track designations, and this development reflects a shift in the risk-benefit considerations taking place in our society. Changing attitudes about depression and other psychiatric diseases are encouraging new approaches and new treatments. Psychiatric suffering and pain are being prioritized in research and appreciated by the general public as devastating. Serious, random assignment placebo-controlled and double- blind research studies will define just how valuable these medications might be, what is the safe dose and duration, and for whom they might prove more effective than existing treatments.
The process will take some time. And it is worth remembering that, although research has been promising,11 the number of patients studied, research design, and outcomes are not yet proven for psilosybin.12 The FDA fast-track makes sense, and the agency should continue supporting these efforts for psychedelics. In fact, we think the FDA also should support the promising trials of nitrous oxide13 (laughing gas), and other safe and novel approaches to successfully treat refractory depression. While we wait for personalized psychiatric medicines to be developed and validated through the long process of FDA approval, we will at least have a larger suite of treatment options to match patients with, along with some new algorithms that treat MDD,* TRD, and other disorders just are around the corner.
Dr. Patterson Silver Wolf is an associate professor at Washington University in St. Louis’s Brown School of Social Work. He is a training faculty member for two National Institutes of Health–funded (T32) training programs and serves as the director of the Community Academic Partnership on Addiction (CAPA). He’s chief research officer at the new CAPA Clinic, a teaching addiction treatment facility that is incorporating and testing various performance-based practice technology tools to respond to the opioid crisis and improve addiction treatment outcomes. Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He has written several books and published more than 1,000 peer-reviewed scientific articles, texts, and practice guidelines.
References
1. Sackeim HA et al. J Psychiatr Res. 2019 Jun;113:125-36.
2. Conway CR et al. J Clin Psychiatry. 25 Nov;76(11):1569-70.
3. Crowell AL et al. Am J Psychiatry. 2019 Oct 4. doi: 10.1176.appi.ajp.2019.18121427.
4. Kumar A et al. Neuropsychiatr Dis Treat. 2019 Feb 13;15:457-68.
5. Psilocybin sessions: Psychedelics could help people with addiction and anxiety. “60 Minutes” CBS News. 2019 Oct 13.
6. Pollan M. How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (Penguin Random House, 2018).
7. Nutt D. Dialogues Clin Neurosci. 2019;21(2):139-47.
8. Griffiths RR et al. J Psychopharmacol 2016 Dec;30(12):1181-97.
9. Johnson MW et al. Neuropsychopharmacology. 2018 Nov;142:143-66.
10. Schwenk ES et al. Reg Anesth Pain Med. 2018 Jul;43(5):456-66.
11. Johnson MW et al. Neurotherapeutics. 2017 Jul;14(3):734-40.
12. Mutonni S et al. J Affect Disord. 2019 Nov.1;258:11-24.
13. Nagele P et al. J Clin Psychopharmacol. 2018 Apr;38(2):144-8.
*Correction, 1/9/2020: An earlier version of this story misidentified the intended disease state.