Annual Meeting Point-Counterpoint Keynote Speakers Begin the Debate on
Efficacy vs. Tolerability: Which Trumps?

By Dean Najarian, PharmD, BCPP

Do the findings from CATIE surprise you and has it changed your clinical decision process based on the results over the last few years?

Buckley: Dr. Buckley is not so surprised with the outcomes from the CATIE trial and states, “This is an important study which, however, has to be taken in context with other studies and clinical information.” His clinical decisions based on this trial have not changed.

Nasrallah: Dr. Nasrallah points out, “Staying on a medication is hard and switching was a common theme, perhaps due to the dynamics of the study design.” He feels perphenazine was a surprise overall but quickly points out, even in the most select patients, perphenazine still had the highest rate of movement disorders since patients with profound movement disorders were excluded from using perphenazine due to ethical reasons. He states, “Perhaps there was a missed opportunity to look at this issue.” The CATIE results have not changed his clinical decision making process.

 

In your opinion, do you think the risk of permanent movement disorders with the typicals is more or less profound than the risk of developing metabolic disorders with the atypicals in today’s patients and has this been addressed adequately in clinical trials?

Nasrallah: “The concern for developing tardive dyskinesia exceeds the concerns for developing metabolic disorders.” says Dr. Nasrallah. “Permanent movement disorders cause harm to the functioning brain and for which there is no treatment and leads to a poorer outcome. Metabolic concerns can be controlled or even prevented to a greater degree than the increased risk of typicals causing permanent movement disorders”.

Buckley: Dr. Buckley states, “Neither consequence is acceptable, we need to better understand the individual patient risk profile in making treatment decisions.”

 

Which atypical(s) antipsychotic offers both the best efficacy and tolerability profile for the maintenance therapy of schizophrenia in your opinion and why?

Nasrallah: All atypicals have similar efficacy (excluding clozapine) especially when the doses are optimized. According to CATIE it appeared risperidone had both a more efficacious and tolerable profile than others according to Dr. Nasrallah.

Buckley: In contrast, Dr. Buckley states “It’s just not as simple as that; it is still ‘trial and error’ for each patient.”

 

Does your choice of antipsychotic differ in treating the acute versus maintenance phase of schizophrenia and why or why not?

Both clinicians agree there are times where different antipsychotics are chosen for each phase.

Buckley: Dr. Buckley perhaps may choose a sedating antipsychotic in the acute phase if necessary and long term treatment may come down to ease of use.

Nasrallah: Dr. Nasrallah may chose an antipsychotic that he feels the patient will tolerate for the long-term since this is a lifelong illness which may differ from treating the acute phase to gain symptom control.

 

Since clozapine was the most efficacious antipsychotic in CATIE and potentially reduces suicide, should clozapine still be reserved for refractory cases after failure of several other trials?

Nasrallah: Dr. Nasrallah believes lowering the bar to “two adequate trials” (optimal dose and duration) of antipsychotics would be a reason to introduce clozapine. According to Dr. Nasrallah, a recent Finnish study showed there was not a higher rate of mortality or cardiovascular events with clozapine compared to others, though its only one study.

Buckley: “Evidently not, but this is also very complex and now also incorporates the lesser experience of newer clinicians with using clozapine”, states Dr. Buckley.

 

Do you feel prior authorizations and tiered availability (fail first) of atypical antipsychotics help or hurt your ability to treat patients appropriately (based on efficacy and tolerability) and does the potential cost savings for the medications really help reduce overall costs?

Nasrallah: Dr. Nasrallah seriously objects against any fail first policies and states, “This is strictly a monetary decision rather than the prescriber’s decision. A more successful metric should be the outcome for the patient to avoid rehospitalization.”

Buckley: Dr. Buckley thinks this topic of conversation is very complex and there are many factors to be considered.

 

Since partial adherence has such a profound effect on disease progression and additional health systems costs, why are the long acting injectables for maintenance therapy only utilized about 5% in the US and reserved for the worst off patient in your opinion?

Nasrallah: Dr. Nasrallah believes long acting injectable antipsychotics “need more respect” and is optimal treatment for patients that suffer one relapse because partial adherence to medications is part of the disease. It is more compassionate, rational and humane. Allowing patients to relapse is toxic to the brain and patients become treatment refractory.

Buckley: Dr. Buckley also believes this treatment paradigm is “likely underutilized”.

 

How often does patient/family preference guide your treatment selection? If you don’t agree, what type of approach would you take?

Buckley: Dr. Buckley believes these conversations with patients and families are “key,” especially since everyone checks out information about their medications on the web.

Nasrallah: The patient/clinician relationship is vital. “It’s critical to get buy in from the family”, says Dr. Nasrallah. He believes the prescriber is more suited to make the decision to evaluate the risks and he is not ready to relinquish this authority. Proper and respectful psychoeducation needs to occur.

 

 

Biographies:

Peter F. Buckley, MD, is Professor and Chairman in the Department of Psychiatry and Associate Dean for Leadership Development at the Medical College of Georgia in Augusta. Dr. Buckley immigrated to America in 1992 after completing his medical degree and postdoctoral training at the University College Dublin School of Medicine in Ireland. His thesis was on the subject of neuroimaging and neurodevelopment in schizophrenia. Before joining the Department of Psychiatry at the Medical College of Georgia, Dr. Buckley was Professor of Psychiatry and Vice Chair in the Department of Psychiatry at Case Western Reserve University School of Medicine in Cleveland, Ohio and served as Medical Director at Northcoast Behavioral Healthcare System (NBHS), the adult state psychiatric services for Cleveland and Toledo, Ohio.

Dr. Buckley conducts research on the neurobiology and treatment of schizophrenia. He is author of a textbook on psychiatry and has edited seven specialist books on schizophrenia, as well as publishing widely in major psychiatric journals with over 250 book chapters, articles, and abstracts. Buckley is also Editor-in-Chief of Clinical Schizophrenia & Related Psychoses and of the Journal of Dual Diagnosis. Dr Buckley is on the editorial board of six other journals. Dr Buckley has been a contributor to several expert consensus guidelines and is a federally funded investigator in the treatment of schizophrenia. Dr Buckley is chair of the schizophrenia spectrum disorders and late life review committee of the National Institute of Mental Health. Dr Buckley is on the board of several professional organizations, is a member of the Scientific Board of the National Alliance for the Mentally Ill, is subcommittee member of a gubernatorial task force for mental health in Georgia, and he is listed in Best Doctors in America. He is the recipient of several awards for his work, including an Exemplary Psychiatrist Award from the National Alliance for the Mentally Ill and the 2006 Georgia Psychiatrist of the Year Award. Dr. Buckley is also the recipient of the American Psychiatric Association Administrative Psychiatric Award for his work on State-University Collaborations.

Dr. Henry Nasrallah is a widely recognized psychiatrist, educator and researcher. He received his BS and MD degrees at the American University of Beirut (AUB). Following his psychiatric residency at the University of Rochester and neuroscience fellowship at the NIH, he served as a faculty member at the University of California at San Diego and the University of Iowa before assuming the chair of the Ohio State University Department of Psychiatry for twelve years. In 2003, he joined the University Of Cincinnati College Of Medicine as Associate Dean and Professor of Psychiatry and Neuroscience.

Dr. Nasrallah is the Director of the Schizophrenia Program, and his research focuses on the neurobiology and psychopharmacology of schizophrenia and related disorders including bipolar disorder. He has published over 350 scientific articles and 400 abstracts, as well as 11 books. He is Editor-In-Chief of two journals (Schizophrenia Research and Current Psychiatry) and is the co-founder of the Schizophrenia International Research Society (SIRS). He has been board-certified in both adult and geriatric psychiatry. He is a Fellow of the American College of Neuropsychopharmacology [ACNP], Fellow of the American College of Psychiatrists, distinguished Fellow of the American Psychiatric Association, and past President of the Cincinnati Psychiatric Society and the American Academy of Clinical Psychiatrists, and is currently the President of the Ohio Psychiatric Physicians Education and Research Foundation. He has twice received the NAMI Exemplary Psychiatrist Award and was recognized as the U.S. Teacher of the Year by The Psychiatric Times. He has received over 75 research grants and is listed in several editions of the book “Best Doctors in America”.