Ketamine back in the news cycle...

 

The New York Times came out with a report a few days ago describing potential problems that presidential advisor Elon Musk was having with substances (1).  The report included concerns of other observers and his self-report of patterns of use of stimulants, a sedative hypnotic (zolpidem), psychedelic mushrooms, an unknown weight loss drug, and ketamine.  He described bladder complications of ketamine, that do not typically occur with supervised medical use.

The NYT report also includes concerns about erratic behavior by some high-profile individuals and some general concerns about drug use. There are quotes where Musk acknowledges recreational drug use, using ketamine at a frequency of every 2 weeks, and denouncing “traditional therapy” for depression – but it is never clear whether the ketamine is prescribed and supervised by any physician. He is described as having a history of “grandiose statements and a mercurial personality” but some have observed further changes.  All of this occurs on a backdrop of relationship conflicts and a recent goal of maximizing childbirths in the US.

My previously stated adherence to the Goldwater Rule – precludes me from making any armchair diagnoses based on a newspaper article.  But I think it does provide an opportunity for education and ties with some of my previous posts. On the ketamine issues – I reviewed Rasmussen’s book on ketamine and posted a review of it on Amazon.  In the book (p. 45-55) he describes 3 famous “ketamine celebrities” and likens them to modern “influencers”. All three were interested in the altered states induced by the drug.  All three were active from the 1970s to 1990s.  One died by drowning while under the influence of ketamine and another had several close calls with drowning.  The third person may have taken a significant amount of ketamine and wandered into the woods where she died of exposure (although there is an alternate theory of homicide).  In all three cases, these influencers idealized the psychedelic effects of ketamine.  All three had uncontrolled use of ketamine, but only one acknowledged an addiction and warned of that danger.  One of them injected ketamine every hour around the clock for 3 weeks or a total of 500 injections.   

My professional experience with ketamine and the related compound phencyclidine or PCP came at two points in my career.  Initially during my tenure as an acute care inpatient psychiatrist in the late 1980s and early 1990s – I would see people who were acutely psychotic from the effects. The reason why they were transferred to my unit rather than being detoxed in the emergency department was severe agitation, psychosis, and in some cases self-injury.  This represented an acute intoxication delirium and it resolved with symptomatic care and detoxification.  The second point was during my employment at a large substance use treatment center.  Toward the latter half of that employment ketamine was heavily hyped in the press.  There were typically storied about how club drugs were now psychiatric drugs.  I would see people who were using excessive amounts of ketamine often rationalized as a psychiatric treatment or a treatment for chronic pain. Some were using unusual forms of the drug like tablets.  Oral ketamine has a very low bioavailability.  Others were using preparations formulated for sublingual use or the or more typical use by insufflation or inhalation.  I got used to seeing people tell me that many of the substances they were using were for a psychiatric treatment even though they had never been seen or evaluated for a mental health problem.

Supervised medical use of ketamine is necessary because of two risks – hypertension and the neuropsychiatric effects most notably the K-Hole experience.  During that episode of extreme dissociation and delirium – a person has extreme detachment.  Some people feel like it is a near death experience and they are unable to respond to the environment.  In a semi phenomenological study of infrequent, frequent, and former users (3) – more specifically describe the disliked effects as cognitive disorganization, paranoia, dissociation, body/sensation distortion, auditory and visual hallucinations, loss of control, depression, introversion, nausea, vomiting, and restlessness. The subjects who like the experience basically endorsed similar experiences, but felt more relaxed, social and sociable and did not have any of the physical side effects. Half of the frequent users sought medical attention for stomach pain or “K-cramps (30%) and bladder complications (20%).  Half of the frequent users also reported a decline in mental health.  The authors also expressed a concern that there was a signal for compulsive use in their survey question 80% reported using whatever ketamine they had on hand until it was gone rather than saving some for future administration.

As a clinical psychiatrist seeing people who may be using multiple drugs and are often not using the drugs they think they are – the two long term consequences I have seen are severe anxiety and panic attacks and hallucinogen persisting perceptual disorder (HPPD).  The HPPD is technically the result of taking classical psychedelics, but many of these people will also be taking drugs that they think may approximate those effects like ketamine.  Many people compulsively take ketamine and/or stimulants while taking other hallucinogens (Mushrooms or LSD). 

I have included several references on the bladder complications of ketamine (4-9).  Most of them are available online.  In trying to determine the bladder toxic dose of ketamine – the closest I could come was reference 9 at 3 grams/month to 3 grams per week.  Estimates like this assume that the drug ingested is pure pharmaceutical grade ketamine – a likely invalid assumption. I have attended numerous conferences on ketamine infusions administered under medical supervision and have never found any descriptions of bladder complications even though they are listed in the FDA package inserts on ketamine.

In terms of the self-reinforcing property of ketamine – the question is the mechanism.  Many authors write that it causes psychological dependence and those properties may depend on baseline psychological and personality characteristics. There is also the intensity of the spiritual experience if there is a psychedelic experience.  In some studies subjects are asked to rate that experience in terms of similar experiences in their life and in the case of psilocybin they rank it in the top 5 most meaningful (58%) or spiritual significant experiences (67%) in their life (11).  Although ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist it also activates mu opioid receptors and has been suggested as a treatment for opioid use disorder (12) suggesting another reinforcing mechanism. 

Ketamine has several properties outlined so far that highlight its problems and potentials.  It is hyped as an antidepressant but also a general approach to “well-being.”  The influencers of the 1970s emphasized the spirituality and consciousness expanding potential for the drug and they experienced uncontrolled use, medical complications, and deaths and near deaths during periods of intoxication.  Even though many frequent users surveyed required medical help and were concerned about their mental health – the downsides are never mentioned in the media.

This cultural profile is like drugs that people take as performance enhancers believing that their subsyndromal symptoms of anxiety, depression, insomnia, and appetite problems may improve. Beyond that there is an idea that certain drugs may enhance cognition, delay aging, and cause neurobiological changes consistent with both.  As I reported earlier on LSD these effects are unlikely to happen and it becomes a coin toss between whether you are a person who will value any psychedelic experience you get from the drug or not.

For the purposes of the NYT article – it is a fair question to ask if a person making major changes to the federal government affecting millions of people is doing that while using intoxicants and whether that person was screened with the required drug tests according to their policy.   

 

   George Dawson, MD, DFAPA

 

1:  Grind K, Twohey M, On the campaign trail, Elon Musk juggled drugs and family drama.  New York Times May 30, 2025.

2:  Rasmussen KG.  Ketamine: The Story of Modern Psychiatry's Most Fascinating Molecule.  Washington DC.  American Psychiatric Publishing.  2024; 295 pp.

3:  Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJ, Curran HV. Journey through the K-hole: phenomenological aspects of ketamine use. Drug Alcohol Depend. 2008 Jun 1;95(3):219-29. doi: 10.1016/j.drugalcdep.2008.01.024. Epub 2008 Mar 19. PMID: 18355990.

4:  Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007 May;69(5):810-2. doi: 10.1016/j.urology.2007.01.038. PMID: 17482909.

Original series of 9 daily ketamine users with severe ulcerative cystitis.

5:  Meng E, Wu ST, Cha TL, Sun GH, Yu DS, Chang SY. A murderer of young bladders: Ketamine-associated cystitis. Urological Science. 2013 Dec 1;24(4):113-6.

6:  Jhang JF, Birder LA, Kuo HC. Pathophysiology, clinical presentation, and management of ketamine-induced cystitis. Tzu Chi Medical Journal. 2023 Jul 1;35(3):205-12.

This review suggests that conservative measures such as medications may be successful if the patient is able to completely discontinue ketamine.  In refractory cases bladder reconstruction is required.  They describe enterocystoplasty using the ileum to reconstruct the bladder. 

7:  Chen CL, Wu ST, Cha TL, Sun GH, Meng E. Molecular pathophysiology and potential therapeutic strategies of ketamine-related cystitis. Biology. 2022 Mar 24;11(4):502.

Authors suggest 19 possible pathophysiological mechanisms leading to bladder damage from ketamine and reviewed available treatments suggested by other case series.

8:  Jhang JF, Hsu YH, Kuo HC. Possible pathophysiology of ketamine‐related cystitis and associated treatment strategies. International Journal of Urology. 2015 Sep;22(9):816-25.

Authors suggested 7 possible pathophysiological mechanisms for bladder injury including a pathway to neoplastic change.

9:  Chen CH, Lee MH, Chen YC, Lin MF. Ketamine-snorting associated cystitis. Journal of the Formosan Medical Association. 2011 Dec 1;110(12):787-91.

Case series of 4 patients using ketamine by insufflation at a rate of 3 g/week (3 patients) to 3 g/month.  All had severe hemorrhagic cystitis.  Patients typically present with lower urinary tract symptoms (LUTS) including urinary frequency, urinary urgency, straining to urinate, weak stream, and post void leakage. Patients also have bladder pain and may have gross hematuria.  If they are able to stop using ketamine the symptoms can persist for up to one year.  Urinalysis shows hematuria and pyuria, with negative cultures for bacteria. Imaging of the bladder can show a thickened bladder wall with smaller volume. Hydronephrosis and hydroureter can also be present. 

10:  Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction. 2012 Jan;107(1):27-38. doi: 10.1111/j.1360-0443.2011.03576.x. Epub 2011 Jul 22. PMID: 21777321.

11:  Yaden DB, Newberg AB.  The Varieties of Spiritual Experience: 2st Century Research and Perspectives. New York. Oxford University Press. 2022; p. 353.

12:  Levinstein MR, Michaelides M. Exploring the role of mu opioid receptors in the therapeutic potential and abuse liability of (S)-ketamine. Neuropsychopharmacology. 2024 Jan;49(1):315-316. doi: 10.1038/s41386-023-01652-x. PMID: 37438422; PMCID: PMC10700302.

Compartmentalization In Psychotherapy

 

I had this thought after my post about supportive psychotherapy in psychiatry.  In the experience of most psychiatrists, it plays a major role.  The related questions are – why isn’t that role acknowledged and why are psychiatrists even reluctant to use the term.  I had the thought that it is due to compartmentalization and before I research that concept to see if anything has been written about it - I thought I would write down my observations.  

The first thing that comes to mind is the idea that psychotherapy needs to be provided according to a specific formal or informal protocol and a prescribed number of sessions. Psychoanalysis is the obvious prototype of a specific method that can include the number of sessions and approximate duration of therapy.  Over the years the method has been adapted to shorter courses including crisis intervention and both transference- based and non-transference-based psychotherapies.  Psychodynamic therapy has been manualized (Klerman, Strupp, Luborsky) and adapted to both crisis intervention (Viederman) and short-term settings (Sifenos, Gustafson).  Hybrid versions such as psychodynamic and cognitive behavioral therapy (Garret) and existential-psychodynamic therapies (Yalom) have been developed. Complex developments like this probably have many people questioning where to draw the lines.

The second issue is how all these developments fit into psychiatric practice.  You can be a psychoanalyst and maintain well defined courses of therapy and a consistent technique. Some psychoanalysts practice part time and have a separate psychiatric practice.

A third issue is how supportive psychotherapy gets implemented in more common types of practice.  The most common expectation of employed psychiatrists these days is seeing 3 or 4 new patients a day and another 8-10 follow up patients.  Most of the practice includes patients with severe psychiatric disorders that require medical treatment and ongoing assessment and treatment of both medical and psychiatric disorders.

An exciting idea is the ability to provide supportive psychotherapy to all people seen in those settings.  A common stereotype promoted in the press is the idea that people are seen for medications only.  The usual reasons given is that this is the best way for psychiatrists to make money and/or it is a sign that pharmaceutical companies have manipulated psychiatrists into providing care this way.  I have illustrated many times on this blog that all those ideas are incorrect.  Today I want to approach the issue form the perspective of psychotherapy.

It is very difficult to maintain any kind of useful relationship with a patient solely discussing medications. That is true for any physician but most importantly psychiatrists. What else happens in those appointments? Non medication related situations are discussed.  Life is inevitable and people who are stabilized on medications still encounter stressors and crises just like everyone else.  The main difference is that most of the people seeing psychiatrists have major psychiatric disorders that can be destabilized by stress.  They also have first-hand experience with medications that have been useful in the course of their illness.  In those situations, there needs to be a detailed discussion of whether the crisis represents an exacerbation of the primary disorder or something else. That appointment will typically require more than an answer to that question. The patient wants to feel understood by a person who knows them well, wants to leave the appointment feeling better then when they arrived, and wants some ideas about what can be done to alleviate their suffering. A prescription may be added or changed but it is not the primary intervention in that scenario – supportive psychotherapy is. 

Even in scenarios where consultations are done in high acuity settings – there needs to be enough flexibility to recognize the true nature of the problem and intervene psychotherapeutically.  The following vignette illustrates that point:

The patient is a 70-yr old woman who was acutely admitted to the CCU with chest pain to rule out a myocardial infarction. On day 2, the Cardiologist caring for her sends a psychiatry consult because he is concerned that she is depressed and a possible suicide risk.  The psychiatric consultant sees her and observes a depressed appearing women who seems healthy and vigorous.  The consultant notes she recently retired as the CEO of a large company and is having some difficulty adapting to that transition.  She had anticipated travelling in retirement but her husband has a chronic illness and she is the primary caregiver.  The discussion focused on the role transition and existential issues associated with retirement.  She agreed to follow up discussions in the outpatient clinic.  Following the consultation – the consultant met with the Cardiologist and explained the formulation, that antidepressants did not seem to be indicated, and that a suicide risk assessment had been done and that the risk was low and that inpatient treatment was not indicated. 

In the example above this was a typical extensive consultation done on medical-surgical patients.  Psychiatric consultation is critical in these situations because it affects the discharge process of beds with rapid turnover and keeping a patient there longer than necessary can be a major problem. Despite the intensity of that information gathering the consultant can do a supportive psychotherapeutic intervention that the patient was interested in pursuing. It requires a consultant who can quickly identify the relevant theme for psychotherapeutic intervention. I would see this as a problem in pattern recognition that does not seem to be discussed very much in the psychotherapeutic literature.  Most of the discussion of patterns is focused on object relations and the recurrent themes in relationships, although Klerman, et al discuss role transitions as a potential cause of depression. The existentialist may say that meaningfulness may be a better conceptualization.

This is one of many examples of how psychotherapy does not need to be compartmentalized as a separate intervention and can be added into the assessment or any scheduled appointment.  Instead of thinking of psychotherapy as a 40-50 minute block of time once a week – can it be 10-20 minutes weekly in addition to everything else occurring in that appointment? 

People tend to think of psychiatric appointments these days as “med checks”.  This was modified slightly a few years ago when psychiatrists were allowed to use standard E&M (Evaluation and Management) billing codes like all medical and surgical specialists.  There is a complexity dimension and even a psychotherapy dimension.  The main problem with all these billing codes is that they are not reality. They need to be completed to get reimbursement and they need to be completed in a rigid stereotyped way – but they cannot be counted on to reflect the reality of the session. They are constructed for business purposes and not clinical purposes and that is evident if you read a handful of the notes.  You are likely to see a template of required bullet points that are generally headings of evaluations or symptom lists.  They contain limited useful information and nothing about the real exchange between the patient and the psychiatrist.  They say nothing about the shared experience in the room or the quality of that relationship. 

That also suggests a lesser-known form of supportive psychotherapy and that is existential therapy.  In psychiatry, existential psychotherapy leads to association to work by Victor Frankl, Ludwig Binswanger, Leston Havens, and Irwin Yalom.  Although there are some academic psychology departments that specialize in it, most of the psychiatrists and psychologists I know who were self-identified were trained as psychodynamic therapists or psychoanalysts first. Yalom had stated that is probably the best training for existential therapy and most available. For this post, an interesting adaptation of existential therapy is the application to brief visits suggested by Ghaemi and co-authors.      

As you study existential psychotherapy – arriving at a coherent current approach and strategy may seem like an impossible task. Some of the early work by Minkowski and that work reviewed by Havens includes some techniques that I have encountered in other therapies – like paradoxical intention. Binswanger’s description of approaching a patient with mania is probably the most accessible.  The best distillation of the process is probably Ghaemi’s 2018 description of existential psychopharmacotherapy.  He suggests an open-ended interview style – even in patients being seen for brief medication-based visits. The goal is to encourage spontaneity and expression.  Allow the patient to provide the narrative that they think is the most important.  Questions relevant to the medication can be asked later in the interview – but the more open format allows the patient to describe their current problems, symptoms, and adverse effects in their own terms rather than the rigid descriptors of the DSM or associated checklists. Most importantly the interview is focused on phenomenology or the personal internal state of that patient rather than group averaging that may not apply. In the context of empathic understanding by the psychiatrist – the patient feels understood and the therapeutic alliance is enhanced. The alliance is necessary for discussions of the treatment plan, its modification, and informed consent. This is a common form of psychiatric practice, although most practitioners would be hard pressed to discuss it as an existential approach. Many do describe it as supportive or humanistic. Consistent with the compartmentalization theme of this post – most psychiatrists do not think of it as therapy even though it is a critical aspect of psychiatric practice.

Psychodynamic therapies also have several short-term approaches and like existential psychopharmacology.  Some of those authors have described approaches that can be used in crisis intervention with or without medication and during brief visits with a medication focus.  Gustafson discusses specific implementations as common dynamics in psychiatry.  He discusses a trial intervention that can be done in less than 10 minutes.  It is primarily a clarification that makes sense of the current anxiety or depressive state as a natural consequence of what they may be trying to avoid and provides a theory for the mood state.  I have seen similar interventions used in cognitive behavioral therapy.

I hope that I have been clear about the issue of compartmentalization in psychotherapy.  It can occur at the macro level with the silos of major therapies (some 200 by one estimate). Thise silos are often reinforced by practitioners engaged in debates about the design of trials, efficacy, and who is the most “evidence-based”.  Even after those technical and political issues are brushed aside, practitioners are faced with rigid ideas about how psychotherapy needs to be provided. The reality is that every encounter with a psychiatrist should be conducted as though it is psychotherapeutic and there are plenty of options to consider.  The good news is that I am sure a lot of it is occurring already – but because of the classification problem – it is not being counted.  

 

George Dawson, MD, DFAPA

Supplementary 1:  I omitted one of the main factors responsible for compartmentalized psychotherapy to improve the readability of the post and that is managed care constraints.  Managed care is an insidious force that affects all aspects of psychiatric and mental health care.  In psychotherapy when I worked in a CMHC - our therapists had to complete pages of documentation just to provide indicated psychotherapy to people with chronic mental illnesses.  Later when I worked for a managed care company - they had reviewers that approved psychotherapy on a session by session basis.  In some cases they would decide that 3 sessions of psychotherapy were enough and stop payments at that point.  I have also been told that they do not cover psychotherapy provided by a psychiatrist and that I needed to refer to the patient to a counselor.  Even in the ideal world where a course of brief therapy is recommended for a duration of 8-12 session (from the research) it was rare to see a patient receive that many sessions.  Billing, coding, and utilization review are all impediments to psychotherapy. 

References:

Frankl VE. Logotherapy and existential analysis—a review. American Journal of Psychotherapy. 1966 Apr;20(2):252-60.

Binswanger L.  On the manic mode of being-in-the-world.  In:  Strauss E. Phenomenology Pure and Applied.  Pittsburgh.  Duquesne University Press; 1964.

Yalom ID.  Existential Psychotherapy. New York: Basic Books; 1980.

Längle A. From Viktor Frankl’s logotherapy to existential analytic psychotherapy. European psychotherapy. 2015 Feb 18;12:67-83.

Havens LL. The existential use of the self. Am J Psychiatry. 1974 Jan;131(1):1-10. doi: 10.1176/ajp.131.1.1. PMID: 4808428.

Havens LL. The development of existential psychiatry (Karl Jaspers, E. Minkowski, and Otto Binswanger). J Nerv Ment Dis. 1972 May;154(5):309-31. doi: 10.1097/00005053-197205000-00001. PMID: 4554757.

Ghaemi SN. Rediscovering existential psychotherapy: the contribution of Ludwig Binswanger. Am J Psychother. 2001;55(1):51-64. doi: 10.1176/appi.psychotherapy.2001.55.1.51. PMID: 11291191.

Ghaemi SN. Feeling and time: the phenomenology of mood disorders, depressive realism, and existential psychotherapy. Schizophr Bull. 2007 Jan;33(1):122-30. doi: 10.1093/schbul/sbl061. Epub 2006 Nov 22. PMID: 17122410; PMCID: PMC2632297.

Ghaemi SN, Glick ID, Ellison JM. A Commentary on Existential Psychopharmacologic Clinical Practice: Advocating a Humanistic Approach to the "Med Check". J Clin Psychiatry. 2018 Apr 24;79(4):18ac12177. doi: 10.4088/JCP.18ac12177. PMID: 29701934.

Gustafson JP.  Reading the ability of the patient to change his or her life.  Psychiatric Times.  February 2007, Vol. XXIV, No. 2    https://www.psychiatrictimes.com/view/reading-ability-patient-change-his-or-her-life

Photo Credit:

Many thanks to Eduardo Colon, MD for allowing me to use his photos. 

Supportive Psychotherapy - The Clinical Language of Psychiatry

 

 

An interesting topic came up a few days ago – how do you decide if what the patient is describing is just reality-based anxiety as opposed to a more global psychodynamic issue?  It sounds like a basic problem but it is not. A common example is the scenario where one person in a couple (married or not) decides to leave the other precipitating an emotional crisis in the remaining person.  In daily living there are a large array of acute and subacute stressors related to losses, conflicts, accidents, illnesses, moral injury, and other life transitions.  In psychiatric practice they occur across settings including emergency departments, acute care units, and even in patients who are considered stable and being seen on a long-term basis.  These situations are generally context dependent and require psychotherapy skills as the primary intervention.

In all the debate about the role of psychotherapy in psychiatry over the years – the obvious problem of emotional crisis gets left out.  It is as if psychiatrists are calmly assessing people for medical treatment – like an internist would assess somebody for hypertension and then advise them about the treatment.  The reality of psychiatry is that people are in a highly emotional and at times agitated state.  It is impossible to proceed with any kind of evaluation unless you can help them calm down, organize their thoughts, see the psychiatrist as a relative ally, and proceed with the interview.  There is no guarantee that will happen, but being trained in crisis situations and evaluations greatly increases the likelihood that a positive working relationship with the distressed person can be developed and used to help them. 

How do I know that to be true?  I have been in that situation thousands of times and rarely found myself in a non-productive interview. I have successfully done crisis intervention with psychotherapy alone and no medication prescriptions. No prescriptions is not a definitive marker for success – but I have seen the other end of the spectrum.  People in acute distress from being fired, separated from their spouse, or acute bereavement who were suddenly started on antidepressants or anxiolytics after a few days of anxiety or depression and a very brief assessment. I have stopped many of those medications by the time the patient was done seeing me.

What exactly is a crisis and how does talking help?  I go back to the very first book I read on supportive psychotherapy (1).  Werman defines a crisis as an acute deficiency of mental functions that allow people to tolerate the demands of the external world and the inner psychological world.  More specifically:

“The acute deficiency which we call a crisis, occurs when a patient whose life may previously have been in a state of reasonable equilibrium has more or less suddenly become deeply disturbed by a stressful event that may be real, symbolic, or fantasized, and that has precipitated a condition of psychological insufficiency.” (p. 5).

It would follow that the stressful event could be a combination of reality, symbolism, and fantasy.   

Most of these crises resolve without psychiatric or mental health intervention with varying durations.  They also happen commonly across all aspects of psychiatric practice including inadequately resolved crises that can present years later after transitioning to a more permanent psychiatric disorder.  A common example is sudden unemployment. That crisis is most commonly resolved by getting support during the period of unemployment and transitioning back into the work force. But some people have a difficult time with that transition and develop mood or anxiety disorders.  In some cases, it can result in permanent disability.

The correct approach when seeing someone in a crisis is knowing what can be done to restore their psychological equilibrium.  There are suggestions about how to approach that problem in supportive psychotherapy from various schools.  From a technical perspective, supportive psychotherapy originating from psychodynamic schools of thought requires an understanding of those dynamics from the patient but in the short time horizon of the crisis does not usually involve interpretation of the underlying unconscious conflicts.  It also tends to focus on affect rather than cognition or behavior.  It may involve reinforcing defenses or suggesting defenses and generally clarifying some restricted thinking that is an artifact of the effect of the crisis.  People in crisis often exhibit catastrophic or similar forms of restricted thinking that can be reviewed and discussed during an empathy-based interview.  Alternate interpretations can be discussed with the patient and the effect on their affect noted.  Listening and empathic responses are very useful interventions in decreasing patient distress.

To perform this kind of intervention it assumes certain requirements on the part of the therapist.  An empathic interview style is required.  In medical schools - empathy and an associated non-directive interview style is typically taught in the second year before the clinical years start.  Since this is a psychiatry blog, I want to add a psychiatric definition of empathy and that is:

“Empathy is achieved by precise, insightful, persistent, and knowledgeable questioning until the doctor is able to give an account of the patients subjective experience that the patient recognizes as his own.” (2)

Subsequent editions (3) are more specific in how this is achieved but also describe the concept as controversial.  This is how I would understand it.  The basic problem is communication between two people with unique but also similar conscious states.  The person in crisis understands at some level that the psychiatrist can understand them based on that shared humanity. They want to say what happened and be understood. That requires the psychiatrist to be genuinely interested in the mental life of the other person and to avoid any potential obstructions to the flow of information. Therapeutic neutrality is a goal as well as the psychiatrist being aware of any personality characteristics that may get in the way – like impatience or getting bored or annoyed.  The psychiatrist experiences some of the detailed descriptions of what happened to the patient and can resonate with them based on life experience.  Based on that recreation of patient experience the psychiatrist can comment on the associated affect and confirm with the patient that it is their subjective experience.  The controversy about this approach involves the fact that not every experience the patient has (eg. psychosis) has been experienced by the psychiatrist – there are therefore limits to this method.

The concept of phenomenology is also relevant here. It refers to an examination of the patient’s conscious processes – specifically the events that brought them in for consultation- and the associated behavior.  It is a detailed description without any attention paid to theories about how the state occurred or evolved.  It is based on an empathic understating of the patient’s internal state.  Both concepts – empathy and phenomenology are tools for developing an understanding of the patient and communicating that understanding to them. 

In a crisis, there is a time constraint that is also a factor. To use empathic and phenomenological methods typically requires a significant amount of time for the initial descriptions of the patient’s mental state and additional clarifications. In many settings there is an emphasis on a diagnosis and more specifically – a diagnosis as an explanation rather than an initial understanding of the problem.  A supportive psychotherapy approach will be focused on the former rather than the latter. 

An additional part of any crisis assessment includes an evaluation for safety and whether the patient is at risk for self-injury, injury to others, or not being able to provide basic self-care. There are many considerations for the safety assessment that cannot be covered in this post.  For this post - assume there are no significant safety concerns following that assessment.  

There are a wide variety of interventions available.  A few are listed in the box below referenced by some of the authors I have listed. 

 

An important concept in supportive psychotherapy is that many of the current manualized or structured therapy approaches were taught as supportive psychotherapy before they became what appear to be separate schools of thought. For example, when I first read about interpersonal therapy for depression (4) and cognitive behavioral therapy for depression and anxiety (5) – I realized that I had been using these approaches in what I called supportive psychotherapy.  During the period I was trained my psychotherapy supervisors had varied theoretical backgrounds and had Rogerian, psychoanalytical, psychodynamic, existential, and behavioral orientations.  They worked in practice environments where people presented with severe problems. Some had experience in shifting from one paradigm to another based on whether the patient was making progress or tolerating the current interventions.  The best example in that case is this diagram from Kroll (6) on treating patient with borderline personality disorder. 

 

Modalities of Psychotherapy
	Supportive	Exploratory
Content	WINDOW A Openly supportive Behavioral-didactic focus Problem-solving Competency based	WINDOW B Explores patterns in life-events
Process	WINDOW C Identifies process occurring in therapy Provides support for changing the process toward competency	WINDOW D Explores process occurring in therapy Explores relationship of therapy to life patterns

    

Kroll begins his discussion of the diagram by this disclaimer that anticipates philosophical criticisms of psychiatry for the next 40 years: “The reader and the author must keep in mind that a schematic model is an artificial device having heuristic value and ought not to be mistaken as transmitted truth or a piece of reality. It is a way of organizing our observations and thoughts; too literal an adherence to any schema, especially a simplified one, will result in greater problems than benefits.” (p. 103).

He then goes on to illustrate by example how a young patient with parental conflict could be addressed in any of the 4 windows in his table.  He points out that are therapies have elements of supportive and exploratory therapy and that in a typical therapy session the therapist can move between windows based on their experience and judgment about timing.  I plan to illustrate this with an example from Viederman and his original psychodynamic life narrative in a subsequent post.  I also plan to illustrate additional supportive therapies based on the common factors model in psychotherapy and behavioral activation as a supportive psychotherapy for depression.    

It is not very common knowledge that supportive psychotherapy has historical roots in psychiatry and is both evidence and empirically based.   The first physician to use the term psychiatry was Johann Reil (1759-1813) a German physician described as a physiologist, anatomist, and psychiatrist. In 1803 he wrote Rhapsodien uber die Anwendung der psychischen Kurmethode auf Geisteszerrüttungen ('Rhapsodies about applying the psychological method of treatment to mental breakdowns') that included a method of supportive psychotherapy (11,12). Modern techniques of supportive psychotherapy have be used in clinical trials in some cases as placebo but in many of these trials the performance of supportive psychotherapy is equal to or superior to the psychotherapy intervention being studied (13).

Supportive psychotherapy has come a long way since the time I learned it nearly 40 years ago.  Like most things in psychiatry the issue of psychotherapy is always highly politicized due to several factors. When I learned it – polarization between the psychiatrists who considered themselves therapists as opposed to biological psychiatrists was at an all time high.  I can still recall walking into the room with those biological psychiatrists when I had to staff patients with them and listening to what they were saying to the patient.  I would end up thinking: “Wait a minute this biological psychiatrist is doing supportive psychotherapy!”  That is an oversimplification – I was taught by some of the best psychiatrists in the country if not the world and most of them were clear that both psychotherapy and biomedical psychiatry were skills that all psychiatrists needed to have. Supportive psychotherapy is a language for communicating with patients and it alway has been.

 

George Dawson, MD, DFAPA

 

References:

1:  Werman DS.  The Practice of Supportive Psychotherapy.  New York: Brunner/Mazel Publishers; 1984.

2:  Sims A.  Symptoms in the Mind: An Introduction to Descriptive Psychopathology. 3^rd ed. London: Saunders; 1995.

3:  Oyebode F.  Sims’ Symptoms in the Mind: Textbook of Descriptive Psychopathology. 6^th ed. London: Elsevier; 2018.

4:  Klerman GL, Weissman MM, Rounsaville BJ, Chevron ES.  The Interpersonal Psychotherapy of Depression.  New York; Basic Books; 1984.

5:  Beck AT, Rush AJ, Shaw BF, Emery G.  Cognitive Therapy of Depression.  New York; Guilford Press; 1979.

6:  Kroll J.  The Challenge of the Borderline Patient. New York; WW Norton and Company.  1988:  p. 104.

7:  Viederman M. The psychodynamic life narrative: a psychotherapeutic intervention useful in crisis situations. Psychiatry. 1983 Aug;46(3):236-46. PMID: 6622599.

8:  Viederman M.  Clarification: A Powerful Therapeutic Strategy in Psychodynamic Psychotherapy. Psychodynamic Psychiatry.  2025; 53(2), 172–183.

9:  Dewald PA.  Psychotherapy: A Dynamic Approach.  2^nd ed. New York: Basic Books; 1969.

10:  Battaglia J.  Doing supportive psychotherapy.  Washington, DC: American Psychiatric Press: 2020.

11:  Novalis PN, Rojcewicz SJ, Peele R.  Clinical Manual of Supportive Psychotherapy.  Washington, DC: American Psychiatric Press; 1993.

12:  Novalis PN, Singer V, Peele R.  Clinical Manual of Supportive Psychotherapy.  2^nd ed.  Washington, DC: American Psychiatric Press; 2020.

13:  Markowitz JC. Supportive Evidence: Brief Supportive Psychotherapy as Active Control and Clinical Intervention. Am J Psychother. 2022 Sep 1;75(3):122-128. doi: 10.1176/appi.psychotherapy.2021.20210041. Epub 2022 Mar 2. PMID: 35232221.

Real World Evidence and Cannabis Psychosis

 

As readers of this blog know – I am not high on cannabis.  That is based on my experience as an acute care psychiatrist and an addiction psychiatrist. That real world experience was associated with treating hundreds of people for exacerbations of preexisting psychotic disorders as well as seeing psychosis develop in people with no risk factors of family history of psychosis. A significant number of thise people need ongoing treatment for psychosis to stay out of the hospital.  Their course is complicated by cannabis use disorder.  Contrary to the hype – addiction can occur to cannabis with all of the associated problems.

Rhetoric is always a significant factor in the United States, especially when there are large sums of money at stake. Depending on who you read the $38.5B cannabis industry is part of the $1.8T health and wellness industry compared with the total pharmaceutical industry value of $602B.  For twenty years we heard about medical cannabis as though it was a miracle drug.  The first medical application of cannabis may have occurred in the second century AD when a famous Chinese physician mixed it with wine and used it as an analgesic.  The use of cannabis as an intoxicant preceded this medical use by about 800 years (1).  The rise of Taoism, Chinese culture, and the availability of alcohol and opium are thought to have limited its widespread use for that purpose. Hemp was also cultivated as a seed crop but that was supplanted by more effective seed crops much like medical use.  The 20^th century medical rhetoric always ignored that history. I attended many seminars where there was a discussion of the endogenous cannabinoid system as a backdrop to talking about medical applications.  In my home state there was a tortured effort to invent a system parallel to the FDA to approve medical cannabis for certain indications. I use the word tortured because the evidence including collected data was very thin to non-existent.  All of this was an obvious prelude to legalization of cannabis and being able to market it as an intoxicant. The psychiatric side effects and the fact that any intoxicant has major problems associated with it – were minimized. Common minimization rhetoric included the ideas that alcohol was much more dangerous, that cannabis-based crimes were discriminatory, and that the War on Drugs was a failure. There was also the idea that the United States was lagging behind the rest of the world in legalization, when it is only fully legal in 9 countries in the world.

That brings me to a recent paper characterizing the real-world evidence of antipsychotic use to treat cannabis induced psychosis.  I follow two of the authors of this paper (Tiihonen and Taipale) because they are experts in designing observational studies based on registry data that typically does not exist in the US.  In this case they selected a cohort of 1772 patient with a diagnosis of cannabis induced psychosis (CIP) from Swedish registry and insurance data between January 2006 and December 2021.  Exclusion criteria included any previous diagnosis of substance induced psychosis, schizophrenia, or bipolar disorder.  Medication data was collected according to the Anatomical Therapeutic Chemical (ATC) classification.  Medication exposure to antipsychotic and antimanic medications was based on exposures as prescription refills and less than 5 exposures was not counted as an exposure.  Additional psychiatric medications – antidepressants, medications for ADHD and addictions, benzodiazepines and related drugs were also extracted.  The resulting medication list from the supplementary information is listed below along with the effect on the primary outcome (rehospitalization for CIP) by Hazard Ratio.

	Events	Users	Person-years	aHR (95%CI)
Antipsychotics
No exposure	1892	1754	10617,19	Reference
Levomepromazine	30	131	49,64	0.92 (0.59-1.44)
Perphenazine	NA	NA	NA	NA
Perphenazine LAI	9	26	28,58	0.55 (0.25-1.22)
Haloperidol	35	125	69,09	1.01 (0.66-1.54)
Haloperidol LAI	14	22	18,37	1.14 (0.61-2.15)
Flupentixol	5	22	20,42	0.88 (0.31-2.50)
Flupentixol LAI	NA	NA	NA	NA
Zuclopenthixol	10	41	41,29	0.71 (0.32-1.61)
Zuclopenthixol LAI	26	47	45,7	0.77 (0.47-1.26)
Clozapine	28	54	119,25	0.56 (0.34-0.90)
Olanzapine	404	1013	1031,96	0.82 (0.70-0.96)
Olanzapine LAI	13	57	50,1	0.29 (0.16-0.55)
Quetiapine	91	385	405,41	0.94 (0.69-1.27)
Risperidone	72	261	210,27	0.91 (0.66-1.26)
Risperidone LAI	18	40	45,46	0.55 (0.28-1.10)
Aripiprazole	62	331	283,83	0.61 (0.43-0.88)
Aripiprazole LAI	15	69	83,45	0.26 (0.14-0.49)
Paliperidone LAI 1M	32	74	63,03	0.69 (0.45-1.08)
Paliperidone LAI 3M	6	8	10,39	0.43 (0.09-2.03)
AP Polytherapy	423	675	727,23	0.75 (0.64-0.89)
Cariprazine	5	19	9,32	20.88 (1.99-218.64)
Paliperidone oral	5	42	14,8	1.38 (0.48-3.95)
Other SG oral	NA	NA	NA	NA
Other FG oral	NA	NA	NA	NA
ADHD medications
No exposure	3127	1767	13312,32	Reference
Dexamfetamine	NA	NA	NA	NA
Methylphenidate	30	206	307,89	0.67 (0.41-1.11)
Modafinil	NA	NA	NA	NA
Atomoxetine	16	85	59,31	0.64 (0.32-1.26)
Lisdexamphetamine	27	168	223,14	1.10 (0.61-1.98)
ADHD polytherapy	NA	NA	NA	NA
SUD medications
No exposure	3145	1767	13749,18	Reference
Disulfiram	25	79	41,09	0.94 (0.48-1.82)
Acamprosate	NA	NA	NA	NA
Naltrexone	10	60	36,73	1.39 (0.55-3.50)
Buprenorphine	15	24	55,87	0.83 (0.27-2.56)
Methadone	11	17	68,81	3.05 (0.80-11.69)
Multiple SUD drugs	NA	NA	NA	NA
Antidepressants
No exposure	2704	1742	11565,26	Reference
Clomipramine	5	24	30,15	0.57 (0.15-2.12)
Amitriptyline	NA	NA	NA	NA
Nortriptyline	NA	NA	NA	NA
Fluoxetine	22	118	164,43	0.75 (0.41-1.34)
Citalopram	15	109	114,94	0.56 (0.29-1.10)
Paroxetine	12	30	50,26	1.60 (0.67-3.77)
Sertraline	104	447	538,89	0.75 (0.56-1.00)
Fluvoxamine	NA	NA	NA	NA
Escitalopram	60	249	277,43	1.03 (0.71-1.49)
Moclobemide	NA	NA	NA	NA
Mianserin	NA	NA	NA	NA
Mirtazapine	122	449	387,9	0.89 (0.69-1.15)
Bupropion	13	155	86,75	0.94 (0.48-1.82)
Venlafaxine	48	170	217,67	1.15 (0.75-1.76)
Reboxetine	NA	NA	NA	NA
Duloxetine	25	91	101,98	1.30 (0.75-2.27)
Agomelatine	<5	20	9,38	5.28 (0.41-67.42)
Vortioxetine	6	48	36,58	0.67 (0.26-1.73)
Rare antidepressants	NA	NA	NA	NA
Antidepressant polytherapy	65	364	364,42	0.93 (0.62-1.39)
Benzodiazepines and related drugs
No exposure	2817	1755	12756,76	Reference
Any benzodiazepine or related drug	390	732	1231,3	1.19 (1.01-1.40)
Mood stabilizers
No exposure	3020	1768	13280,77	Reference
Carbamazepine	11	41	42,23	0.93 (0.44-1.99)
Valproic acid	89	168	206,7	0.93 (0.70-1.25)
Lamotrigine	15	115	159,81	0.68 (0.34-1.37)
Topiramate	NA	NA	NA	NA
Lithium	60	107	217,85	0.98 (0.67-1.43)
Mood stabilizer polytherapy	8	66	64,51	0.46 (0.20-1.07)

 

The data was analyzed using a stratified Cox regression model.  The advantage to this model is that the assumption that hazard ratios are constant over time are restricted to the stratum occupied by each individual so that hazard ratios between strata may differ based on genetics, age and other factors but they are constant in each stratum.

Of the final sample 84.7% were men and the mean age of onset of the first diagnosis was 26.6 (± 8) years.  About half of the sample had work income at baseline but 5.4% had 90 days sick leave from work in the year before the study and 6.9% were on disability pensions.  

In terms of the primary rehospitalization endpoint – any antipsychotic use was associated with a decreased risk of readmission (aHR 0.75; 95%CI 0.67–0.84).  Some of the antipsychotics associated with less risk like aripiprazole, aripriprazole LAI, olanzapine, olanzapine LAI, and clozapine clozapine,  Any antipsychotic use also reduced the risk of secondary endpoints including hospitalization due to a medical problem (aHR 0.58; 95% CI 0.38–0.89) and hospital admission caused by a substance use disorder (aHR 0.78; 95% CI 0.71–0.87).

The authors include a Forest plot of antipsychotic medications and risk of relapse (see Fig 1.)  The SGA drugs olanzapine, clozapine, and aripiprazole had the best results in both LAI and oral short acting forms.  FGA drugs (pooled) and paliperidone, risperidone, and quetiapine (all SGAs) did not have a statistically significant result.

The authors conclude that AP drugs – especially the LAI version may be effective in preventing rehospitalization following an episode of cannabis induced psychosis – a condition that as a high risk of relapse.  The reduction in risk was about 72%.  Medication effectiveness mirrored effectiveness noted in psychotic disorders for clozapine.  FGA were less effective than noted in studies of first episode psychosis without cannabis use and this may be due to the small numbers being treated with these medications.  They speculate that the effectiveness of aripiprazole may be due to partial dopamine agonist activity with improved cognition and less craving.  They cite one of their previous papers suggesting that the combination of clozapine and aripiprazole may be the best to prevent relapse prevention in schizophrenia and substance use (3).     

In terms of limitations, the authors cite the small subject numbers in some of the studied groups.  They also lacked data on ongoing cannabis use if rehospitalization did not occur. It is always interesting to consider what an ideal randomized controlled clinical trial of this problem would look like.  At the minimum it would involve structured interviews for psychiatric diagnoses, detailed structured interviews on substance use, and possible toxicology screens and measures of medication adherence for oral medications (typically pill counts).  That may be a fundable grant at some point – but the current political atmosphere in the US suggests otherwise. This is a significant strength of the studies from this group.  As I noted in a recent post it also reflects the clinical experience of acute care psychiatrists in the US where substance use is a significant complication of care.   

 This is an excellent observational study of how cannabis use and cannabis use disorder complicates the lives of people. Obviously not everyone who uses cannabis is at risk for these complications – but if they occur and result in hospitalization and the prescription of medications for treating an ongoing psychosis that results in major life disruption and disability.  The less obvious disruption is how both psychosis and cannabis in can impair the insight of the affected individual. Psychosis generally leads to a conscious state where the affected individual cannot accurately assess how they are doing in the environment and take corrective action. With a cannabis use disorder, an individual can experience reinforced use by the biological properties of THC, and continue to use the substance despite negative consequences.  People with those impairments have a much harder time stopping cannabis use often despite very negative consequences.  That pattern of behavior is always a good reason to avoid intoxicants of any kind.  

George Dawson, MD, DFAPA

 

References:

1:  Booth M.  Cannabis – A History. New York. Picador, 2003: 23.

2:  Mustonen A, Taipale H, Denissoff A, Ellilä V, Di Forti M, Tanskanen A, Mittendorfer-Rutz E, Tiihonen J, Niemelä S. Real-world effectiveness of antipsychotic medication in relapse prevention after cannabis-induced psychosis. Br J Psychiatry. 2025 May 6:1-7. doi: 10.1192/bjp.2025.72. Epub ahead of print. PMID: 40326094.

3:  Tiihonen J, Taipale H, Mehtälä J, Vattulainen P, Correll CU, Tanskanen A. Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA Psychiatry. 2019 May 1;76(5):499-507. doi: 10.1001/jamapsychiatry.2018.4320. PMID: 30785608; PMCID: PMC6495354.

Graphic Credit:

The table and figure used in the above post is taken directly from the authors Supplementary data and original paper per the CC license (reference 2):

Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.