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Key Questions to Ask Patients With Somatic Symptom Disorder
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
What ketamine and psilocybin can and cannot do in depression
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
