Christoph U. Correll, MD; John Kane, MD; Nassir Ghaemi MD, MPH

Disclosures

June 04, 2015

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Christoph U. Correll, MD: Hello. I am Dr Christoph Correll, professor of psychiatric and molecular medicine at Hofstra North Shore-LIJ School of Medicine in Hempstead, New York. With me is Dr John Kane, chair of the department of psychiatry at the Hofstra North Shore-LIJ School of Medicine and Zucker Hillside Hospital; and Dr Nassir Ghaemi, professor in the Department of Psychiatry, and director of the Mood Disorders Program at Tufts Medical Center in Boston, Massachusetts.

We are in Toronto attending the 168th American Psychiatric Association (APA) Annual Meeting and are here today to discuss highlights from the conference. John, this has been a very lively meeting. One area that has gotten a lot of coverage is research on the psychedelics, ketamine, and marijuana.[1,2] Can you maybe summarize some of your impressions of those presentations?

John Kane, MD: This is a very exciting area. We are seeing a resurgence of interest in some of these compounds. We now have studies of psilocybin for treating anxiety in cancer patients,[2] and we are seeing the medical use of marijuana now for several different indications. We need a lot more research, but I believe it is good to see this growing interest in learning more about these interesting compounds. Ketamine is being used now to treat depression. Obviously we still have a lot to learn about that, the long-term use, but it is very exciting.

Dr Correll: In the United States, there has always been a push-back to any research with these agents because of the belief that legalizing them could be bad for the brain or because of other biases. What is your take on that? Why have those attitudes changed and can it ultimately help science and patients?

Dr Kane: I believe we have to separate the politics from the science and make sure that our political decisions are informed by data and by evidence. That has been lacking in recent years. We need much more information that people can use. There are always risks and benefits. We have compounds that may have abuse potential but may also have some valuable therapeutic indications.

Dr Correll: One point with marijuana is that tetrahydrocannabinol, or THC, may actually promote psychosis, but some other compounds in the cannabinoid may minimize it. Nassir, what is your take on that area?

Nassir Ghaemi, MD, MPH: I believe that much of the discussion in this conference is being driven by the fact that marijuana is being legalized medically, and in some states, in general. This trend is raising questions in the field of whether this is good or bad and how it may impact practice. There is some concern that it may increase the rates of substance abuse and may cause more problems than not, which we may not be able to predict ahead of time.

Dr Kane: But it does provide an opportunity for us to study those things and perhaps learn who is vulnerable to abuse and who is likely to get some therapeutic benefit.

Culture and Psychiatric Illness

Dr Correll: Another popular topic has been the cultural differences in the expression of psychiatric disorders.

Dr Kane: One presentation addressed differences in the way depression is diagnosed in different countries.[3] In some cultures, people are much more likely to focus on their symptomatic complaints when they are depressed, rather than talking about feeling down or sad. Thus, we as psychiatrists need to be sensitive to the differences. Certainly in the United States now there are people from many different cultures, so when we interview patients we need to be sensitive to the different ways that depression might present.

Dr Correll: Nassir?

Dr Ghaemi: This is another example of cultural trends affecting the conference. We are obviously becoming a much more multicultural society. I do not believe any new, groundbreaking data about cultural differences are being presented at this conference, but we have more awareness that it matters. And I think that is relatively new.

Dr Correll: Yes. For example, some Hispanic populations interpret anxiety and depression differently, and clinicians need to be aware of that. We also need to teach our residents more about that culture awareness. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has also put some emphasis on that. I believe we are all moving in the same direction, emphasizing that the brain and its expressions are varied based on the patient's environment.

Dr Kane: We also hope to enhance mental health literacy so that people from different cultures can understand what mental illness is, what it may mean for them or their families, so that we can have a more informed discussion with patients.

Psychodynamic Psychotherapy

Dr Correll: Another area of discussion has been psychodynamic psychotherapy. It is a bit strange to see so many of these presentations at this meeting because this is such an old and accepted kind of treatment. What is your take on psychodynamic psychotherapy and the presentations here?

Dr Kane: There is certainly a lot of continued interest in psychodynamic psychotherapy among many of our colleagues. I also see a burgeoning interest and awareness of some of the more specialized psychosocial interventions and cognitive-behavioral therapies. We certainly need to try to deliver evidence-based treatments for our patients and also be flexible and eclectic, and understand that certain kinds of therapy may be appropriate for certain kinds of patients.

Dr Correll: Nassir?

Dr Ghaemi: Yes. We are seeing something that is descriptively interesting for the profession—that there are many meetings and discussions about psychodynamic and psychoanalytic approaches in psychiatry, and it is not going away, for good or for ill. That could be debated, but certainly clinicians must be seeing some benefits in practice in different kinds of ways that lead them to continue to be interested in psychodynamic approaches, personality conditions, and so on. I believe we need more research to clarify when we should use these various approaches and when to use them less so. But it is descriptively interesting that a large interest in the psychoanalytic approaches continues.

Dr Correll: It is clear that medications have limitations and the psychotherapeutic approaches have limitations. We need to define more subgroups of who benefits from which approach and which combination. That is why it is important to see that some of the schools are becoming more open to choosing different techniques from different approaches, so that we not only match the patient to a certain therapy but match the therapy to the patient.

Dr Kane: And also, as you implied, the integration of approaches is important. We may use a combination of medication and a certain type of psychotherapy or psychosocial treatment. For many conditions, that combination, that integration, is very important.

The Mind-Body Connection

Dr Correll: Right. On the other end of the spectrum, we are also seeing much more of medical conditions being joined with psychiatry, so that we are not just talking about the brain but also the body. Nassir, you were part of a symposium on this topic. Perhaps you can share some of the directions of where the field is going.

Dr Ghaemi: That is definitely a central theme to this conference. I participated in organizing the presidential symposium on the mind and the body[4]; how the body affects the mind, how the mind affects the body. There was a lot of interest in that topic and multiple presentations. These were driven in part by the current president of the APA and the scientific committee's interest this year. A general theme is the concept of inflammation associated with the pathophysiology of depressive illnesses in particular.

For example, we have discussed research on how insulin receptor sensitivity is an important aspect of the pathophysiology of depression in the brain. We think about the pancreas in diabetes, but depression and the brain are just as important. And, of course, the conditions are linked. If you have diabetes you are more at risk for depression. If you have both diabetes and depression, you are more at risk for dementia, all of which are part of the same neurotoxic pathophysiology that occurs with a lot of other inflammatory processes in the body.

Some research was presented looking at nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of depression. The meta-analysis[5] suggests that there is some benefit; but then there was a discussion about whether that meta-analysis may not have examined the limits of that benefit. The general consensus was that NSAIDs as a whole probably are not effective for depression, but that there are more subtypes of depression that are associated with high levels of inflammation. For example, some have suggested that a C-reactive protein level above 5 may be a predictor of an inflammation-related depression. In fact, in one study, some patients with depression responded to interferon, but when including major depressive disorder as a whole, the benefit of interferon was no different than that of a saline infusion. So it gets back to the concept of differentiating subtypes of illness as opposed to general, large groupings.

Dr Correll: Right. Inflammation is currently in vogue, and it has been shown to be higher in almost all conditions where it was looked at, including depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, obsessive-compulsive disorder, and suicidality.[6]Many of these psychiatric disorders are also associated with higher body mass index (BMI) and smoking, conditions that also can jack up inflammation. We conducted a meta-analysis[7] in patients with anorexia whose BMI is much, much lower, and we found more inflammation, with elevated IL-6 levels, for example.

Thus, it seems to me that this cannot be specific; it is most likely more of a nonspecific vulnerability marker that may bring out some of the other genetic underpinnings. But if we can lower that stress that is coming or that is bringing out some of the psychiatric disorders that may help a certain subgroup, especially in the inflammation area, it may help the treatments.

Medical Illness in the Mentally Ill

Dr Correll: Another topic that has been discussed at this meeting is medical illness in the mentally ill and how we can address that. These days, the integration of care is very important to reduce morbidity and mortality. John, what is your opinion on that?

Dr Kane: Absolutely. For example, work you have done on the metabolic side effects of antipsychotic drugs[8] shows that we need to be able to prevent some of the consequences of our own treatments in terms of how it affects people's medical well-being. We also need to help people with smoking cessation. We have not devoted enough attention to integrated care, whether it involves providing the primary medical care that people with mental illness need, or providing the psychiatric consultation that people with medical illness need. With the emphasis on cost containment and affordable care, we see an increase in the recognition that if someone has a medical condition such as congestive heart failure or diabetes and that person also has depression or a substance abuse disorder, this adds a tremendous amount to the cost and the challenge of treating the patient. We need to make sure that we are working very closely with our medical colleagues to ensure that everyone is getting the kinds of integrated care that they need.

Dr Correll: Right. Nassir?

Dr Ghaemi: This general concept that medical illness is connected to psychiatric illness is very important and is being recognized more and more. In our symposium,[4]for example, I presented a systematic review on lithium and the prevention of dementia. It turns out that if you have depression or bipolar, your risk of developing dementia is about fourfold higher. According to four or five randomized studies, lithium may protect against that, epidemiologically at least. This could be important for Alzheimer's dementia and vascular dementia and is a relatively simple intervention. The toxicities can be limited with low doses.

Another aspect of this is mortality related to cardiovascular disease. Most people do not realize that the main cause of death for people with affective illness, for example, is cardiovascular mortality, not suicide. Suicide is the highest relative risk, but cardiovascular mortality also goes up and is the most common cause of death. We have reviewed some of the literature on selective serotonin reuptake inhibitors that suggest some reduction in mortality, but also there are data on lithium in the general population that show a reduction in cardiovascular mortality. I believe we are coming back to the notion of saying, in a patient with manic depressive illness, not just "How can we make your mood better?" but also "How can we keep you alive?"

Dr Correll: So psychiatry is really just a medical specialty again. There is also the integration of care, as we have discussed, between medication and psychosocial interventions. John, you are the principal investigator of the RAISE study where this has been very important to change the trajectory of the illness. Can you review that for us?

Improving the Schizophrenia Trajectory

Dr Kane: We presented data on the RAISE project during two symposia[9,10] at the APA. This was an National Institutes of Health-funded program developed to try to improve the trajectory of early schizophrenia. One key element was to integrate psychosocial and psychopharmacologic treatment. There is an emphasis on individual therapy, which we call individual resiliency training of families; psychoeducation of family therapy; support for education; and support for employment as well as psychopharmacologic treatment. All of this is team-based, with a focus on shared decision-making, etc. This approach resulted in a significant improvement in the quality of life from the portion of young people working and going to school, so we are pleased with the results of that. Moreover, there is a lot more interest in setting up programs across the country to facilitate the early identification and treatment of psychotic disorders, so that is very welcome.

Dr Correll: It is important to point out that quality of life was the primary outcome, so this was not our usual symptom-based treatment or even recovery, but it was very much patient-centric. In addition, although it sounded like a lot of interventions, the impetus was to deliver these therapies in usual care settings and under a reimbursement structure that can be translated into usual care settings.

Dr Kane: Exactly. We worked with 34 community clinics in 21 states across the United States. That is a key element, because if we develop a comprehensive care model that can only be delivered in an academic center with a lot of additional funding, it will not help the people who need the treatment.

Dr Correll: That is wonderful that the National Institute of Mental Health puts such an emphasis on the early phase and support of this.

Dr Correll: Thanks very much to my two colleagues, and thanks to you listening. We hope to see you again at a different program. Take care.

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