The document discusses optimizing the use of atypical antipsychotics by reducing variability in patient care and outcomes. It outlines a four-step optimal care process: 1) making a proper diagnosis and communicating it to the patient, 2) considering acute symptom control and long-term goals in medication initiation, 3) adjusting treatment to achieve stability, and 4) maintaining care to minimize relapse. Barriers to optimal care are identified along with expert approaches to address them at each step of the care process.

1. Optimizing the Use of Atypical Antipsychotics

2. Background – Variations in Care Assumption Most physicians will make similar diagnostic and treatment decisions, and will offer care in similar ways Reality A wide variety of factors influence clinical decisions made by physicians leading to high variability of clinical practice High variability in care can lead to poor patient outcomes including unacceptably high rates of side effects and lack of efficacy

3. Process of Care Participants Canada Dr. Pratap R. Chokka Dr. Pierre Chue Dr. Valerie Tourjman Germany Dr. Brita Dorn Dr. Claus-J ürgen Krafczyk Dr. Markus Leweke Italy Dr. Rocco Pollice Spain Dr. Celso Arango Dr. Francesco Colom Dr. Jose M. Olivares United Kingdom Dr. John Cookson Dr. Tonmoy Sharma United States Dr. Joseph Bryer

4. Table of Contents History of Psychosis Management Variations in Care The Optimal Care Process Overview Barriers and Best Practices Elements: Diagnosis, Medication Initiation, Treatment Optimization, Continuation of Care Putting It All Together The Atypical Antipsychotic CareMap ™ Discussion References

5. Objectives To increase awareness of best clinical practices in the management of patients with bipolar disorder or schizophrenia To provide practical information, keys to success, and tools to help practitioners overcome barriers to achieving high quality care

6. Bipolar Disorder and Schizophrenia: A Historical Perspective http://www.mindful-things.com/history_of_psych_home.html#120_70BC 1409 - First asylum in Seville, Spain 1934 - Electroconvulsive therapy (ECT) introduced by von Meduna 1978 - Dopamine hypothesis put forward to explain schizophrenia 1985 - U.S. NIMH's Consensus Conference on ECT concluded risks virtually eliminated and best used for depression and some mania 1300 1400 1900 1990 2005 1330 - Casting out devils in common use 1911 - Bleuler introduced term "schizophrenia" 1932 - Sakel introduced insulin coma therapy for schizophrenia 1952 - French researchers discovered chlorpromazine, marking the beginning of psychopharmacology 1983 - Researchers discover many schizophrenics cannot track moving target visually—close relatives also share this deficiency, even if not schizophrenic

7. Bipolar Disorder and Schizophrenia: A Historical Perspective 1990 2005 1990 - First atypical antipsychotic introduced-clozapine 1992 - APA and CPA establish clearer guidelines and standards for using ECT 1993 - Neuroimaging studies showed frontal, temporolimbic and basal ganglia involved in schizophrenia — Same abnormalities observed with other conditions, though to a lesser degree 1994 - Saykin, et al discover temporolimbic deficits of unmedicated, first-episode schizophrenic patients 2000 - American Psychiatric Association published the DSM-IV-TR , Diagnostic and Statistical Manual of the Mental Disorders Fourth Edition, Text Revision http://www.mindful-things.com/history_of_psych_home.html#120_70BC 2005 - Genetic biomarkers identified as basis for future blood test to confirm diagnosis of schizophrenia or bipolar disease

8. Factors Influencing the Variability of Clinical Practice Clinical Decision Clinical data Beliefs Peers Experience and training Competence Habits Emotions Comfort level

9. Factors Influencing the Variability of Clinical Practice External Influences

10. Variations in Care Can result from the following: The capacity of the local health care system influencing how much care is given The practice styles of local physicians determining the type of care delivered Local medical opinion and resources appearing to be more important than science in determining how medical care is delivered (Wennberg, 2002)

11. Variations in Care Can lead to: An average 17 year lag between the discovery of more effective forms of treatment and their incorporation into routine patient care (Balas, 2003) Avoidable deaths of roughly 79,000/year in U.S. (National Committee for Quality Assurance, 2004) Only 55% of patients receiving recommended care (McGlynn, 2003)

12. Variations in Mental Illness Care 70% of bipolar patients are misdiagnosed before receiving a correct diagnosis (Hirschfeld, 2003) On average, patients with bipolar disorder wait more than 8 years from the start of symptoms before receiving a correct diagnosis (Hirschfeld, 2003) Patients get the correct mental healthcare only about 50% of the time (National Committee for Quality Assurance, 2004)

13. Approaches to Reducing Variability Identify problems and intervene Chart audits and compliance reports Treatment protocols OR Identify best practices as a model Attending physicians teaching residents Experienced clinicians educating others

14. Reducing Variability of Care Through Best Practices Best clinical practices Effective techniques Useful tools Reduced variability in patient care & outcomes through Delayed patient treatment Incomplete diagnostic assessments Diverse treatment initiation strategies Degree of intensity of follow-up Lack of continuity of care from inpatient to outpatient Inadequate patient education Environmental stressors Variations in the quality of the patient/physician relationship High variability in patient care & outcomes due to Knowledge and Experience

15. Observed Barriers and Expert Approaches to Achieving Optimal Performance with Atypicals Assure continuity and coordination of care, including offering intermediate care Break in continuity of care following discharge Rational approach to medication selection based on patient profile Ad hoc medication selection Rapid dose initiation to gain early control over acute symptoms Slow initial dose titration to avoid side effects Heightened vigilance for early psychosis symptoms Delaying the initial diagnosis Stay alert for first sign(s) of relapse Lack of vigilance around relapse Commit to a treatment and stick with it Failure to give adequate therapeutic trial Think long term when selecting your acute medication Focus on acute management Build rapport beginning with first interaction Neglecting to establish a relationship with the patient Expert Approach (Pearls) Barrier (Perils)

16. Overview of the Optimal Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse

17. Overview of the Optimal Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse Objective: Consider acute symptom control with long-term goals Objective: Adjust treatment program to achieve stability Objective: Maintain care to minimize relapse Objective: Make proper diagnosis, communicate it to patient

18. The Care Process: Diagnosis Objective: Make proper diagnosis and communicate it to the patient Perils Delayed ⁄ Inappropriate diagnosis Patients rarely volunteer information about mania, mood, or anxiety symptoms Cognitive deficits that predict poor outcomes often overlooked Limited patient insights

19. The Care Process: Diagnosis Objective: Make proper diagnosis and communicate it to the patient Pearls Perform comprehensive diagnostic work-up for organic causes and make transparent to patient to establish trust Assess role of drugs, alcohol, and non-adherence as contributing factors If patient is admitted, minimize trauma of the admission process Communicate using effective approaches Establish a treatment plan that includes long-term goals (e.g., medication compliance)

20. Key to Success Build trust beginning with first interaction

21. Diagnosis: Support Resources Many existing resources support diagnosis and overall management strategies Guidelines APA, NICE Regional, local guidelines Assessment instruments Websites DSM and ICD criteria

22. Overview of the Optimal Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse Objective: Consider acute symptom control with long-term goals Objective: Adjust treatment program to achieve stability Objective: Maintain care to minimize relapse Objective: Make proper diagnosis, communicate it to patient

23. The Care Process: Medication Initiation Objective: Consider acute symptom control with long- term goals Perils Lack of documentation of previous of medications, their effectiveness, reported side effects, etc. Failure to identify patients at increased risk for some side effects Selecting medication only for controlling acute symptoms rather than best choice for long-term management Perception of need for slower titration to avoid side effects may lead to sub-therapeutic dosing Failure to reach therapeutic range and maximize the dose of first medication

24. The Care Process: Medication Initiation Objective: Consider acute symptom control with long- term goals Pearls Rapid initiation and sustained use of antipsychotic medication is the cornerstone of successful management Rationally select medication, keeping the end in mind Target most problematic symptoms, but side effect profile may be prime determinant of drug choice Atypical antipsychotics are a medication choice Select medication addressing predominant symptom and having lowest risk of long-term side effects

25. The Care Process: Medication Initiation Objective: To consider acute symptom control with long-term goals Pearls Build early rapport with patient Set expectations regarding side effects, effectiveness, etc. Involve patient in medication selection process Gain early feedback on effects of medication

26. Rational Medication Selection Criteria Benefits Primary diagnosis Severity of acute symptoms Long-term adherence Functional outcome(s) Risks Relative severity of possible adverse events Patient risks for selected side effects (see slide 27) Benefit-risk ratio Effectiveness and side effects of past medication(s)

27. Rational Medication Selection: Potential Adverse Events to Consider Symptoms to consider EPS/Tardive Dyskinesia Akathisia Nausea and vomiting Prolactin elevation/ sexual dysfunction Weight gain Sedation Signs to consider Glucose abnormalities Lipid abnormalities QTc prolongation Hypotension Anti-cholinergic side effects When selecting a medication, a clinician should consider both the patient’s needs in the short and the long term and the efficacy and side-effects of various medications References: American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition: February, 2004. Bagnall AM, et. Al. A systematic review of atypical antipsychotic drugs in schizophrenia. Health Technology Assessment . 2003;7(13). National Institute for Clinical Excellence. Schizophrenia: Core interventions in the treatment and management of schizophrenia in primary and secondary care. Clinical Guideline 1, December 2002.

28. External Factors Affecting Medication Selection Drug formulary committee Anecdotal experience Availability of samples Patient preference

29. Key to Success Think long term when selecting your acute medication

30. Medication Initiation Tool: Medication Schedule

31. Overview of the Optimal Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse Objective: Balance acute symptom control with long-term goals Objective: Adjust treatment program to achieve stability Objective: Maintain care to minimize relapse Objective: Make proper diagnosis, communicate it to patient

32. The Care Process: Treatment Optimization Objective: Adjust treatment program to achieve stability Perils Medication prematurely deemed ineffective before completing adequate therapeutic trial of 4-6 weeks Unable to identify what information to provide to cognitively challenged patients, and when to provide it Lack of communication and inconsistency of care between inpatient to outpatient settings Especially before first follow up visit for severe, chronic patients

33. The Care Process: Treatment Optimization Objective: Adjust treatment program to achieve stability Pearls Monitor medication effectiveness over adequate therapeutic trial of 4-6 weeks (APA, 2004) Adjust medications to reduce target symptoms residual symptoms emerging side effects Titrate between side effects and symptoms Establish tracking methodology

34. The Care Process: Treatment Optimization Objective: Adjust treatment program to achieve stability Pearls Cognitive therapy and psychoeducation should be continuous, but staged Continue building physician-patient relationship Involve caregiver ⁄ family and monitor environment for stressors (e.g., psychosocial, substance abuse, financial, etc.) Assess and anticipate reasons for non-adherence Prepare patient for return to community and orchestrate continuity of care with outpatient care providers

35. Key to Success Commit to a treatment and stick with it

36. Treatment Optimization Tool: Treatment Plan Checklist

37. Treatment Optimization Tool: My Action/Monitoring Plan

38. Overview of the Optimal Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse Objective: Balance acute symptom control with long-term goals Objective: Adjust treatment program to achieve stability Objective: Maintain care to minimize relapse Objective: Make proper diagnosis, communicate it to patient

39. The Care Process: Continuation of Care Objective: Maintain care to minimize relapse Perils Failing to make plans for continued care after hospitalization leading to early relapse Strong propensity for substance and/or alcohol abuse Bipolar patients may seek to achieve mood elevation Isolation/lack of a caregiver support system

40. The Care Process: Continuation of Care Objective: Maintain care to minimize relapse Pearls Provide appropriate degree of intervention for patients prone to relapse Assure caregiver education and involvement Maintain a high trust relationship Make crisis management resources available Assure strict vigilance to early recognition of relapse symptoms Reinforce medication adherence and avoidance of drugs and alcohol Target optimizing functional outcomes

41. Key to Success Stay alert for first sign(s) of relapse

42. Continuation of Care Tool: Tips for Staying Well

43. Putting It All Together: The Care Process Goal: Achieve best functional outcomes by reducing frequency of relapse Objective: Balance acute symptom control with long-term goals Objective: Adjust treatment program to achieve stability Objective: Maintain care to minimize relapse Objective: Make proper diagnosis, communicate it to patient

44. Putting It All Together: The CareMap ™ Pierre Chue, F Markus Leweke, Ana González-Pinto on behalf of the CareMap Research Team. Sharing best practice in the management of schizophrenia and bipolar disorder: development of an atypical antipsychotic CareMap. Int J Neuropsychopharmacol 2006; 9 (Suppl 1): S261. Abstract number P03.124

45. Summary Goal: Achieve best functional outcomes Keys to success Build trust beginning with first interaction Think about the long term when selecting your acute medication Commit to a treatment and stick with it Stay alert for first sign(s) of relapse Best practices Resources

46. Discussion

47. References American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition: February, 2004. Bagnall AM, et. Al. A systematic review of atypical antipsychotic drugs in schizophrenia. Health Technology Assessment . 2003;7(13). Balas EA. Information Systems Can Prevent Errors and Improve Quality. J Am Med Inform Assoc . 2001;8:398-99. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and Impact of Bipolar Disorder: How Far Have We Really Come? Results of the National Depressive and Manic-Depressive Association 2000 Survey of Individuals With Bipolar Disorder. J Clin Psychiatry . 2003;64:161-74. Institute of Medicine. Health Professions Education: A Bridge to Quality. Washington, D.C.: National Academy Press, 2003. McGlynn EA, Asch SM, Adams J, et al. The Quality of Health Care Delivered to Adults in the United States. N Engl J Med . 2003;348:2635-45. National Committee for Quality Assurance. The State of Health Care Quality: Industry Trends and Analysis. Washington, D.C.: NCQA, 2004. National Institute for Clinical Excellence. Schizophrenia: Core interventions in the treatment and management of schizophrenia in primary and secondary care. Clinical Guideline 1, December 2002. Tsuang MT, Nossova N, Yager T, et al. Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: A preliminary report. Part B: Neuropsychiatric Genetics. Am J Med Genetics. 2005;133B:1-5. Wennberg JE. Unwarranted Variations in Healthcare delivery: Implications for Academic Medical Centres. BMJ . 2002;325:961-64.