Peter F. Buckley, MD

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In this video clip, Dr Peter Buckley addresses 2 questions:

• What factors do you consider when you offer depot medications to a patient with schizophrenia?
	• What can be done to encourage the use of depot medications?

This video was originally posted on June 19, 2012 and has since been updated with permission from Dr Buckley. -Ed

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In this video segment, Dr. Peter Buckley addresses 2 questions:
	• What factors do you consider when you offer depot medications to a patient with schizophrenia?
	• What can be done to encourage the use of depot medications?

Schizophrenia Q&A: Depot Medications in Schizophrenia Therapy

Our understanding of schizophrenia has deepened and evolved, although perhaps not as much in its treatment as in its neurobiology. The Special Report articles on schizophrenia illustrate well this current state of play. Much is known about the biology and pharmacodynamics of drug metabolism, which has influenced the choice of many drugs and has pointed out greater risks and synergies with drug-drug interactions based on inhibitory effects on the P450 system. While some studies suggest that this approach might be beneficial in the clinical treatment of schizophrenia, the effect remains limited and the results from other studies have been modest at best.

The results from recent studies suggest that the neurobiology of schizophrenia converges more with other psychiatric conditions than might otherwise be considered. The historical antecedents of this are described in a fascinating “re-read” of the original writings of Emil Kraepelin from 1870 through 1920 by one of today’s luminaries in psychiatric genetics, 

 A contemporary evaluation of neurobiological overlap among schizophrenia, bipolar disorder, major depression, autism, and alcoholism suggests a shared genetic vulnerability across these conditions rather than an independence for genetic effects for schizophrenia.

 These findings are reflected in a large genetic analysis of 25 neurological conditions-

-comprised of psychiatric and neurological disorders, which showed even greater congruence among mental health disorders than neurological disorders.

There has been much written recently of the legalization of cannabis use and also the use of cannabidiol oil in medicine. It is well known that cannabis use heightens the risk for schizophrenia as well as worsening its course.

 Yet, it is intriguing that cannabidiol oil is being tested as a potential treatment for schizophrenia. In an 8-week, placebo-controlled study, 

 found a modest beneficial effect of cannabidiol oil as an adjunct to antipsychotic therapy. Equally importantly, there were no significant adverse effects from this “neuroscience-informed” innovative treatment approach.

The quest for individualized treatments continues. A seminal European 

of first episode schizophrenia shows how far we have come and how far we have yet to go.

 of 450 patients with first-episode psychosis suggested a 76% remission rate through 3 phases of antipsychotic treatment that spanned 3 months: with initial exposure to low-dose amisulpride; randomization, if needed, to either higher-dose amisulpride or olanzapine; and thereafter, if needed, treatment with clozapine. The overall remission rate is similar to earlier US first-episode treatment studies. The second phase of treatment with either higher dose of amisulpride or olanzapine was deemed redundant with the recommendation that clinicians should go directly to clozapine once an appropriate first-line therapy has failed-a provocative and important conclusion from this study.

We hope this collection of articles in this two-part Special Report is helpful to you in illuminating contemporary themes in schizophrenia.

Dr Buckley is Dean, School of Medicine, Virginia Commonwealth University, Richmond, VA.

 Gandal M, Haney JR, Parikshak NN, et al. 

Shared molecular neuropathology across psychiatric disorders parallels polygenic overlap

 Antila B, Bulik_Sullivan B, Finucane HK, et al, for the Brainstorm Consortium. 

Analysis of shared hereditary in common disorders of the brain

Cannabis and psychosis: what we know and what we should do about it

Cannabidiol oil as an adjunct treatment for schizophrenia

 Kahn RS, Winter van Rossum I, Leucht S, et al. 

Amilsulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three phase switching study

Peter F. Buckley, MD introduces part 1 of our Special Report on schizophrenia.

Introduction: Convergence of Thought?

 has posed 3 questions to Dr Peter F. Buckley, a psychiatrist and expert on schizophrenia. He will be speaking on “Reliable Biomarkers, Personalized Medicine, and the Treatment of Schizophrenia: Will Science (Ever?) Trump Clinical Trial and Error?” at APA 2016 on Tuesday, May 17 at 9:00 AM.

 Personalized medicine is a term now ever increasingly used to describe the evolution of medicine in being able to individualize and/or tailor our treatments in a targeted, individualized way for each patient. This approach is predicated upon a greater understanding of the biology of illness and how it plays out-uniquely and specifically-for each individual patient. Other terms that are considered relatively synonymous with personalized medicine include precision medicine and preventative medicine.

Q: How does psychiatry fare compared with other areas of medicine with respect to personalized medicine?

 In many ways, cancer research and clinical care is leading the way in advancing personalized medicine. The genetic risk-and treatment sensitivity-of several cancers is now better known. For example, whether a female with breast cancer possesses the BRCA gene now powerfully determines which drugs should be selected to tailor care to her. Another example is the selection and dosing of anticoagulant medications based upon the genetic makeup of the patient as it relates to the slow or fast metabolism of these drugs.

Continued advances in our understanding of mental illnesses as well as the development and validation of biomarkers could be a game changer.

In psychiatry, we are also advancing these approaches. We are now aware, due to the work of Dr Charles Nemeroff and many others, that genetic susceptibility to stress powerfully contributes to whether people develop depression when exposed to life stressors during adulthood.1 In another exciting initiative, Dr Carol Tamminga and colleagues

 have conducted a comprehensive study of the neurobiology (or “neurobiologies”) of psychoses-across schizophrenia, schizoaffective disorder, and bipolar disorder.

[[{"type":"media","view_mode":"media_crop","fid":"45724","attributes":{"alt":"schizophrenia","class":"media-image","id":"media_crop_1489146643962","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5798","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 176px; height: 176px; float: right","title":"Â©Lightspring/Shutterstock","typeof":"foaf:Image"}}]]Interestingly, our colleagues have found 3 distinct “biotypes”-that is, neurobiologically-defined patient groups, as opposed to the more “traditional” distinctions of psychosis as schizophrenia, schizoaffective disorder, and mood disorder.

 Exciting stuff. Several other groups across the US and globally are working on similar approaches.

There’s also a lot of emphasis on developing and validating biomarkers for mental illnesses. Our field is grateful to Dr Thomas Insel, immediate past director of the NIMH for his strategic leadership in advancing us toward personalized medicine.

Q: What might mental health care look like in 5 years?

 Well, like all other areas of medicine, the extent to which healthcare reform will be fully implemented will powerfully influence how mental healthcare will be delivered. The increased insurance coverage is already a major accomplishment and of course people with mental illness and/or addiction problems are also represented in this success. The extent to which the implementation of healthcare reform will 

 encompass mental health parity will also be another key determinant. Furthermore, psychiatry will need to embrace value-based reimbursement and, in doing so, agree upon and promulgate quality metrics that are appropriate for the major mental health conditions.

Finally, continued advances in our understanding of mental illnesses as well as the development and validation of biomarkers could be a game changer for early identification, assessment, and targeted treatments for mental illnesses. Collectively, these are great opportunities for psychiatry and will shape where and how we deliver mental health care into the future. Time will tell.

Dr Buckley is the Dean of the Medical College of Georgia at Augusta University, Augusta, Georgia, and a member of the 

1. Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. 

 2016;89:892-909.
2. .Clementz BA, Sweeney JA, Hamm JP, et al. Identification of distinct psychosis bio types using brain based bio markers. 

 2016;173:373-384.
3. De Leon J. Is psychiatry only neurology? Or only abnormal psychology? Deja Vu after 100 years. 

The personalized medicine approach is predicated upon a greater understanding of the biology of illness and how it plays out-uniquely and specifically-for each individual patient. 

Biomarkers, Personalized Medicine, and Schizophrenia

by Jeffrey A. Lieberman, MD, and Ogi Ogas; New York: Little Brown and Company;2015 352 pages • $28 (hardcover)

, Immediate Past President of the American Psychiatric Association, Chairman of Psychiatry at the Columbia University of College of Physicians and Surgeons, and preeminent schizophrenia researcher has hit a home run with the 2015 publication of his book, 

Dr Lieberman tells the story of the evolution of psychiatry from a place of skepticism and distain to its more recent emergence as a modern neuroscience. His stories about the pervasive effect of stigma are compelling and remind us of the ever-present need to emphasize-where we can-the real progress in our understanding of the brain and of the mind. I particularly like the provocative titles and quotations of each chapter-for example, Mother’s Little Helper: Medicine at Last:

Mother needs something today to calm her down
And though she’s not really ill
There’s a little yellow pill
She goes running for the shelter of a mother’s little helper

Moreover, Dr Lieberman has skillfully managed to interweave the story of psychiatry with his own experiences, starting as a trainee, to his current leadership roles, and to do so in a self-effacing manner that personalizes the journey for us as readers.

At one level of course, the story is a damning one-societal responses to mental illness are variously characterized as fear, ignorance, condemnation and, at best, apathy. Dr Lieberman paints the picture that psychiatry gains credence and momentum as its science gains greater foothold-thus, the benefits of discovery in mental illness as well beyond the (mere) molecules and synapses and the availability of new information constitutes the most powerful antidote to societal inertia and stigma. In its own way, this book fittingly adds to this advocacy.

Dr Buckley is Dean of the Medical College of Georgia of Georgia Regents University in Augusta.

The author of this book tells the story of the evolution of psychiatry from a place of skepticism and distain to its more recent emergence as a modern neuroscience.

A Tour de Force of the History of Psychiatry

What progress has been made in controlling negative symptoms in schizophrenia?

The short answer. . .the management of negative symptoms still remains a substantial challenge. Here, Dr. Peter Buckley explains why these disabling manifestations that overlap with cognitive functioning are a "tough nut to crack." Psychological and medication treatments can help address secondary negative symptoms, such as hyper-religosity, However, in this population, newer drugs, such as clozapine, haven't effected significant change.

Dr Buckley, a noted schizophrenia expert, is Dean of the Medical College of Georgia.

Has any progress been made in our ability to manage negative symptoms of schizophrenia?

Controlling Negative Symptoms in Schizophrenia (Video: 2:54 minutes)

What antipsychotic-if any-is most effective in a patient with schizophrenia whose chief symptom is hyper-religiosity? Does clozapine play a special role in this kind of setting?

Might an isolated symptom such as hyper-religiosity be a manifestation of a delusional disorder instead? Is it possible to target therapy with a particular antipsychotic? 

Here, noted schizophrenia expert Peter Buckley, MD, addresses these questions. Dr Buckley is Dean of the Medical College of Georgia. 
 

In schizophrenia therapy, the question arises whether a patient with hyper-religiosity as a main symptom can be treated with an antipsychotic (like clozapine) that targets that symptom.

Treating Schizophrenia, One Symptom at a Time: Is it Feasible?(Video: 1:40 minutes)

In this short video clip, Dr. Peter Buckley talks specifically about the new antipsychotic Latuda (lurasidone), as well as the use of mood stabilizers as adjunctive therapy in schizophrenia.

Latuda has been shown to be an effective antipsychotic agent. It appears to be effective in preventing relapse and in long-term therapy.  It is important to dose at appropriate levels.

It is not always necessary to give a mood stabilizer as an adjunctive therapy.
 • A good proportion of patient take an antipsychotic plus other medications to manage mood problems, depression, or sleep disorders.
 • People with schizophrenia may have highs and lows, indicative of schizoaffective disorder; a mood stabilizer may help control common features of the illness.
• In general, go about approaching treatment with the simplest regimen possible. Start with a single drug and get the best out of it before adding another drug or before switching to a different agent.

What effect has the new antipsychotic Latuda had in patients with psychosis? Is a mood stabilizer as an adjunctive therapy necessary for schizophrenia or is the use of an antipsychotic alone sufficient?

Effects of New Antipsychotics and Adjunctive Therapy for Schizophrenia (Video: 4:05 minutes)

What strategies help prevent and manage medication-associated weight gain in patients with schizophrenia?  Peter Buckley, MD, discusses these issues here:

Before starting medication:

. Get a good baseline weight measurement 
. Get a range of metabolic tests (cholesterol, lipids, glucose)
. Re-measure periodically to measure weight trajectory

. Monitor the pattern of weight gain after starting a new medication. Early moderate weight gain is a strong predictor of future weight gain. 

. Diet and exercise, especially early-on before weight gain occurs, is important, and far easier than losing weight once pounds have been added.

. In general, instead of reaching for antiobesity drugs, consider substituting an 

to manage underlying schizophrenia symptoms.

More: Nutritional and OTC Supplements in Schizophrenia

Weight gain is a known side effect of some medications for schizophrenia. Here: strategies to prevent and manage weight gain.

Weight Gain in Schizophrenia: Tips for Prevention and Management (Video: 2:37 minutes)

In schizophrenia therapy, perphenazine can play in combating symptoms and in preventing relapse, though it can be associated with metabolic side effects.

Perphenazine was used in the CATIE study. Here, Dr. Peter Buckley addresses: 
• The current role of perphenazine in the management of schizophrenia.   
• The drug’s association with weight gain. 
• The metabolic side effect profile of perphenazine.