Suboptimal Response in Psychotic & Mood Disorders: Causes, Consequences, and Management Strategies

Transcription

1 Suboptimal Response in Psychotic & Mood Disorders: Causes, Consequences, and Management Strategies Henry A. Nasrallah, MD Sydney W. Souers Professor and Chair, Department of Psychiatry, Saint Louis University, St. Louis, MO Editor-in-chief Schizophrenia Research and Current Psychiatry Peter J. Weiden, MD Professor of Psychiatry University of Illinois Medical Center, Chicago, IL Chief Medical Officer Uptown Research Institute, Chicago, IL Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD Lundbeck, LLC March 2016 MRC2.CORP.D advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.

2 Henry A. Nasrallah, MD Position: Dr. Nasrallah is the Sydney W. Souers Professor and Chair of the Department of Psychiatry at Saint Louis University (St. Louis, MO), and he is the editor-in-chief of Schizophrenia Research and Current Psychiatry. Education: Dr. Nasrallah earned his MD from the American University of Beirut, School of Medicine (Beirut, Lebanon). He completed a psychiatry residency at the University of Rochester Medical Center (Rochester, NY) and a neuroscience research fellowship at the National Institutes of Health (National Institute of Mental Health) Laboratory of Clinical Psychopharmacology (Washington, DC). Peter J. Weiden, MD Position: Dr. Weiden is a Professor of Psychiatry at the University of Illinois Medical Center (Chicago, IL) and the Chief Medical Officer at Uptown Research Institute (Chicago, IL). Education: Dr. Weiden earned his MD from the State University of New York at Stony Brook (Stony Brook, NY) and a Master s degree in Psychiatric Epidemiology at the Columbia University Mailman School of Public Health (New York, NY). He completed a psychiatric residency and a schizophrenia research fellowship at the Payne Whitney Clinic, New York Hospital Cornell Medical Center (New York, NY), and also completed a psychiatric epidemiology fellowship at the Columbia University Mailman School of Public Health (New York, NY). 2

3 This program was developed with the support of Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck, LLC. The speakers are compensated contractors of Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD 3 advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.

4 PsychU Virtual Forum Rules of Engagement: Otsuka Pharmaceutical Development and Commercialization, Inc. (OPDC) and Lundbeck, LLC. have entered into collaboration with Open Minds, LLC. to explore new ways of bringing/increasing awareness around serious mental illness. OPDC/Lundbeck s interaction with Open Minds is through PsychU, an online, non-branded portal dedicated to providing information and resources on important disease state and care delivery topics related to mental illness. One of the methods employed for the sharing of information will be the hosting of virtual fora. Virtual fora conducted by OPDC/Lundbeck are based on the following parameters: When conducting medical dialogue, whether by presentation or debate, OPDC/Lundbeck and/or its paid consultants aim to provide the viewer with information that is accurate, not misleading, scientifically rigorous, and does not promote OPDC/Lundbeck products. OPDC/Lundbeck and/or their paid consultants do not expect to be able to answer every question or comment during a PsychU Virtual Forum; however, they will do their best to address important topics and themes that arise. OPDC/Lundbeck and/or their paid consultants are not able to provide clinical advice or answer questions relating to specific patient s condition. Otsuka and Lundbeck employees and contractors should not participate in this program (e.g., submit questions or comments) unless they have received express approval to do so from Otsuka Legal Affairs. OPDC and Lundbeck operate in a highly regulated and scrutinized industry. Therefore, we may not be able to discuss every issue or topic that you are interested in, but we will do our best to communicate openly and directly. The lack of response to certain questions or comments should not be taken as an agreement with the view posed or an admission of any kind. 4

5 Objectives Explore the negative impact and potential causes of suboptimal response in serious mental illness Discuss the various definitions of remission and recovery in major depressive disorder, bipolar disorder, and schizophrenia Understand pharmacological approaches to suboptimal response 5

6 Defining Suboptimal Response in Serious Mental Illness Optimal Expected Suboptimal Treatmentresistant Suboptimal response, which refers to any clinical state where a patient is not completely well, symptomatically or functionally, 1 is a common challenge in psychiatric practice 2 5 Suboptimal response has been consistently associated with worse clinical outcomes 2,6,7 1. Volavka J, et al. Am J Psychiatry. 2002;159: Lehman AF, et al. Am J Psychiatry. 2004;161: Rush AJ, et al. Am J Psychiatry. 2006;163: Levine SZ, et al. Schizophr Res. 2011;133: Perlis RH, et al. Am J Psychiatry. 2006;163: Gelenberg AJ, et al. Am J Psychiatry. 2010;167: Hirschfeld RMA, al. Am J Psychiatry. 2002;159:

7 First Consider Possible Non-pharmacologic Causes of Suboptimal Response Incorrect diagnosis 1,2 Substance use comorbidities 2 Adherence problems 1,2 Variability in drug activity due to environmental factors 3 Treatment access barriers 1 1. Goldman LS, et al. J Gen Intern Med. 1999;14: Argo TR, et al. Texas Medication Algorithm Project: Schizophrenia Treatment Algorithms Available online at Accessed Feb 8, Spina E, de Leon J. Basic Clin Pharmacol Toxicol. 2007;100(1):

8 Polling Question In your experience with psychotic and/or mood disorders, what is the most common cause of suboptimal response in patients? A. Incorrect diagnosis B. Substance use comorbidities C. Adherence problems D. Treatment access barriers E. Other 8

9 Working Definitions of Remission and Recovery: Major Depressive Disorder Because treatment goals vary in serious mental illness, working definitions of recovery also vary Major Depressive Disorder 1,2 REMISSION Conceptual definition Operational definition Symptoms present, but do not meet full criteria, or <2 months without significant symptoms of a major depressive episode (MDE; partial remission) No significant signs and symptoms for 2 months (full remission) Hamilton Depression Rating Scale-17 items score 5 or 7 or Montgomery- Åsberg Depression Rating Scale 7 or 9 (based on the precedent in the literature) 3 weeks with an absence of both sad mood and reduced interest, and fewer than 3 of the 7 additional core criterion symptoms may be present Relationship to full recovery Distinction between remission and recovery depends on the interval following symptom reduction RECOVERY Conceptual definition Operational definition An extended period of remission such that an MDE is unlikely to occur in the near future 4 consecutive months of remission 1. APA. DSM Rush AJ, et al. Neuropsychopharmacology. 2006;31:

10 Working Definitions of Remission and Recovery: Bipolar Disorder Because treatment goals vary in serious mental illness, working definitions of recovery also vary Bipolar Disorder 1,2 REMISSION Conceptual definition Operational definition Signs and symptoms of a specified episode (eg, manic) present, but do not meet full criteria, or <2 months without significant signs and symptoms of an episode (partial remission) No significant signs and symptoms for 2 months (full remission) Hamilton Depression Rating Scale-17 items score 5 or 7 or Montgomery- Åsberg Depression Rating Scale 7 or 9 (based on the precedent in the literature) Young Mania Rating Scale <8 or <5 (based on the precedent in the literature) Relationship to full recovery Remission may or may not be associated with a return to premorbid day-today functioning RECOVERY Conceptual definition Operational definition Recovery refers to recovery relative to the last mood episode, not from the illness 8 consecutive weeks with virtual absence of depressive and manic or hypomanic symptoms 1. APA. DSM Tohen M, et al. Bipolar Disord. 2009;11:

11 Suboptimal Outcome in Schizophrenia Refers to Persistent Symptoms or Functional Impairment Between Acute Episodes Symptoms Accelerate Diagnosis Mild Clinical deterioration may begin early and can occur throughout the first 5 10 years after the first episode A long period of untreated psychosis has correlated with poor prognosis 1. Lieberman JA, et al. CNS Spectr. 2007;12(10)(suppl 18): Emsley R, et al. BMC Psychiatry. 2013;13:50. Number of relapses may be related to greater deterioration Illness-driven decline in functioning plateaus Premorbid Prodromal Psychotic Prodromal Residual Childhood Functional impairment occurs and is difficult to distinguish from other causes Events may trigger disease development Adolescence to early adulthood Approximately 2 5 years Negative symptoms usually develop first, followed by slight positive symptoms Critical years Approximately 5 years Majority of clinical deterioration occurs High risk of relapse Remainder of life Disease severity and level of functioning vary; risk of relapse 3. McGlashan TH. Schizophr Bull. 1988;14(4): Lehman AF. Am J Psychiatry. 2004;161(suppl 2):1 56. Symptoms, Level of Functioning Severe 11

12 Symptoms of Schizophrenia Positive (Psychosis) Unusual thought content (delusions) 1,3 Hallucinations 1,3 Conceptual disorganization 1,3 Negative Affective flattening 1,2 Apathy 3 Anhedonia 3 Avolition 1,2 Asociality 5 Alogia 5 Cognitive Impaired attention 3,4 Impaired working memory 3,4 Impaired executive functioning 3,4 1. American Psychiatric Association. DSM American Psychiatric Association. Am J Psychiatry. 2004;161 (suppl 2): NIMH Web site. Accessed October 3, Velligan DI, et al. Schizophren Res. 2004;71: Nasrallah HA, et al. Contemporary Diagnosis and Management of Schizophrenia

13 Working Definitions of Remission and Recovery: Schizophrenia Because treatment goals vary in serious mental illness, working definitions of recovery also vary Schizophrenia 1-5 REMISSION Conceptual definition Operational definition Improvement in core signs and symptoms and only partial fulfilment of the defining criteria of the disorder (partial remission) Absence of disorder-specific symptoms (full remission) Ratings of mild or less (PANSS, BPRS [using the 1-7 range] scores 3; SAPS and SANS scores 2) on all items, maintained for 6 months Severity score 3 on CGI-Schizophrenia rating scale Relationship to full recovery Remission necessary but not sufficient step toward recovery RECOVERY Conceptual definition Operational definition Ability to function socially and vocationally Being relatively free of disease-related psychopathology Consensus lacking; normative levels of social and occupational functioning; independent living; and remission or non-intrusive levels of psychiatric symptoms BPRS, Brief Psychiatric Rating Scale; PANSS, Positive and Negative Syndrome Scale; SAPS, Scale for the Assessment of Positive Symptoms; SANS, Scale for the Assessment of Negative Symptoms. 1. APA. DSM Andreasen NC, et al. Am J Psychiatry. 2005;162: Pinna F, et al. Ann Gen Psychiatry. 2015;14:6. 4. Liberman RP, et al. Int Rev Psychiatry. 2002;14: Liberman RP, Kopelowicz A. Psychiatr Serv. 2005;56:

14 Despite Guideline-based Treatment, Suboptimal Outcomes Remain a Challenge in Serious Mental Illness Major Depressive Disorder Schizophrenia Bipolar Disorder STAR*D study Of >3500 patients, 63% to 70% patients did not achieve remission 1,2 CATIE study Of >1400 patients, 12% attained and maintained remission for 6 months 3 21% attained and maintained remission for at least 3 months 3 56% had no symptom remission at any visit 3 74% discontinued treatment before 18 months 4 STEP-BD study Of >1400 patients, less than one-third of symptomatic bipolar patients achieved recovery without recurrence over 2 years of follow-up 5 Note: All of these studies are NIMH-funded. Suboptimal response is quite common and is a challenge across major psychiatric syndromes CATIE, Clinical Antipsychotic Trials of Intervention Effectiveness; STAR*D, Sequenced Treatment Alternatives to Relieve Depression; STEP-BD, the Systematic Treatment Enhancement Program for Bipolar Disorder. 1. Rush AJ, et al. Am J Psychiatry. 2006;163: Trivedi MH, et al. N Engl J Med. 2006;354: Levine SZ, et al. Schizophr Res. 2011;133: Lieberman JA, et al. N Engl J Med. 2005;353: Perlis RH, et al. Am J Psychiatry. 2006;163:

15 Several Factors Contribute to Suboptimal Outcomes in Serious Mental Illness Poor Therapeutic Alliance 1 Inaccurate Diagnosis 1 Comorbidities 1 Psychosocial Factors 1,2 Side Effects 1,2 Factors Contributing to Suboptimal Outcomes Poor or Nonadherence 1,2 Inappropriate Therapeutic Modalities 1 Inadequate Dose 1-3 Inadequate Duration 1 PK/PD Factors 1,2 PD, pharmacodynamics; PK, pharmacokinetic. 1. Gelenberg AJ, et al. Am J Psychiatry. 2010;167: Lehman AF, et al. Am J Psychiatry. 2004;161: Hirschfeld RMA, et al. Am J Psychiatry. 2002;159:

16 Polling Question Assuming that you did not identify any secondary reason for suboptimal response in a patient with Major Depressive Disorder, who has been on an adequate therapeutic dose of an approved first-line monotherapy, your preferred next step for a partial but suboptimal responder after 6 weeks of treatment is: A. Continue with watchful waiting without any changes B. Raise the dose higher than your usual target dose C. Suggest adding a psychotherapy targeting remaining symptoms D. Change to your next antidepressant choice E. Add an adjunctive therapy 16

17 Pharmacologic Approaches to Suboptimal Response 1 Strategy Make no changes Optimize current dose Change primary medication Add an adjunctive medication Discontinue a medication Definition Decide that the best option is to continue with the current medication regimen Change the dose of the current medication Change the primary medication for the given diagnosis (usually change within the same class of medication) Add a new medication to the regimen either within class or in a new class Discontinue one or more medications from the current regimen 1. Argo TR, et al. Texas Medication Algorithm Project: Schizophrenia Treatment Algorithms Available online at Accessed Feb 8,

18 Consideration of Multiple Outcome Categories in Serious Mental Illness Psychiatric Outcomes Coexisting depression / anxiety Symptom severity Suicidal ideation Adherence Substance abuse Homelessness Incarceration Patient-centered Outcomes Community engagement Psychosocial functioning Personal empowerment Quality of life Employment Side effects Multiple Outcome Considerations in Serious Mental Illness Medical Outcomes Weight management Complications Managing comorbidities Preventive screening Smoking status 1. Gaynes B, et al. Agency for Healthcare Research and Quality Publication No. 15-EHC003-EF. 18

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20 CLOSING 20

21 Suboptimal Response in Psychotic & Mood Disorders: Causes, Consequences, and Management Strategies Henry A. Nasrallah, MD Sydney W. Souers Professor and Chair, Department of Psychiatry, Saint Louis University, St. Louis, MO Editor-in-chief Schizophrenia Research and Current Psychiatry Peter J. Weiden, MD Professor of Psychiatry University of Illinois Medical Center, Chicago, IL Chief Medical Officer Uptown Research Institute, Chicago, IL Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD Lundbeck, LLC March 2016 MRC2.CORP.D advice or professional diagnosis. Users seeking medical advice should consult with their physician or other healthcare professional.