James Lake M.D. IntegrativeMentalHealth Clinical Asst. Professor, Stanford Psychiatry

1. Establishing a Methodology for Integrative psychiatry: from research to clinical applicationsGroningen, The Netherlands3 December, 2008 James Lake M.D. www.IntegrativeMentalHealth.net Clinical Asst. Professor, Stanford Psychiatry Clinical Asst. Professor, Program in Integrative Medicine, University of Arizona

2. Third Conference on Integrated Psychiatry—New Perspectives on Body and Mind 3 December 2008 James Lake M.D. www.IntegrativeMentalHealth.net Clinical Assistant Professor, Stanford Psychiatry Clinical Assistant Professor, University of Arizona Program in Integrative Medicine

3. The future of psychiatry and the evolution of integrative medicineThird Conference on Integrated Psychiatry—New Perspectives on Body and Mind 3 December 2008 James Lake M.D. www.IntegrativeMentalHealth.net Clinical Assistant Professor, Stanford Psychiatry Clinical Assistant Professor, University of Arizona Program in Integrative Medicine

4. Financial interests • none

5. Methodology in integrative psychiatry I. Premises—framing the issues II. Philosophical problems III. Evidence in medicine IV. Research methodology issues V. Clinical integrative methodology VI. Integrative management of depression VII. Integrative management of anxiety

6. Starting points • Premises: the emerging context of integrative psychiatry • Philosophical issues determine meanings of evidence • Evidence standards determine methodology • Methodology biases beliefs and understandings about specific clinical approaches

7. Premises One person’s assumptions about how things are today

8. Premises • Integrative mental health care is now the de factostandard approach used by the majority of mentally ill patients in the U.S. • Context—limited conventional choices, increasing safety and efficacy concerns • Decisions about non-drug Rx are made with little or no evidence • There is no established methodology for planning integrative treatments

9. Integrative perspective • Many conventional Rx are often beneficial and safe • Some conventional Rx are not effective and have signicant safety problems • Many non-conventional Rx are beneficial and safe • Some non-conventional Rx are not effective and have significant safety issues

10. The emerging context for integrative psychiatry • Integrative healthcare is patient-centered and individualized • Integrative medicine engages patient’s active participation to improve wellness rather than treat a “disorder” (Barrett 2003). • Limitations of conventional Rx of mental illness invite rigorous evaluation of promising CAM Rx

11. Context for integrative Rx • Integrative medicine offers a reasonable “middle way” in mental health care incorporating advantages of conventional and non-conventional approaches while ideally minimizing limitations and risks of either approach alone.

12. Philosophical issues implications for integrative medicine and psychiatry

13. Philosophical issues • Methodologies in medicine reflect a priori epistemological and ontological assumptions about health and illness • Beliefs and traditions in medicine are implicit in methodologies used in research and clinical practice • Therefore, there is no objective methodology: clinical approaches in disparate systems of medicine are not and cannot be validated using objective empirical means alone

14. In other words… • Many systems of medicine do not use or require “objective methods” to demonstrate the existence of a putative mechanism of action or verify claimed outcomes because the truth of a claim that a mechanism of action is present or that an outcome takes place is implicit within the conceptual framework that embodies the system of medicine.

15. What is “true” depends on accepted methodology • Truth claims of some non-conventional modalities have not been verified by contemporary Western science (eg, Acupuncture, “energy medicine”) • The same is also true of some conventional treatments in widespread use (eg, Buproprion, anti-seizure medications for Bipolar Disorder)

16. Consensus vs “objective” methods • Beliefs about the effectiveness of treatments in medicine have as much to do with professional consensus and economic factors as with rigorous “objective” methods for assessing empirical evidence (Kuhn, Structure of Scientific Revolutions).

17. Philosophical problems have practical consequences • These philosophical and ideological issues must be taken into account when developing a methodology for constructing practical integrative strategies combining approaches from disparate non-Western systems of medicine.

18. Philosophical problems of nosology and evidence • Establishing ontology of phenomena associated with illness or health and corresponding typology of legitimate medical practices (ie, for which verifiable truth claims can be made). • Establishing standards of evidence for verifying claims of a putative mechanism of action or a reported outcome. • Establishing a framework for a “hierarchy of evidence” for comparing disparate modalities on the basis of objective and subjective criteria.

19. Evidence in medicine EBM and beyond NOTE: following slides need major edits and shortening

20. Evidence-based medicine (EBM) • Uses “hierarchy of evidence” model to assess significance of findings viz study design • Relies on systematic reviews of peer-reviewed literature to “guide judicious use of current best evidence in making decisions about the care of individual patients (Sacket 1996)” • Derives Rx decisions on a case-by-case basis following review of “best evidence” in the context of physician’s expertise and patient preferences

21. Limitations of EBM • Brings rigor to analysis of findings and offers valuable Rx planning tool • However…most biomedical Rx do not adhere to EBM standards • Few M.D.s practice EBM because they don’t know methods or don’t have time or resources to review literature • Most M.D.s recommend Rx based on clinical experience or expert opinions

22. EBM—limitations • Evidence-based Complementary and Alternative Medicine (CAM) working group created to find ways to apply EBM to the evaluation of CAM modalities…however… • EBM excludes relevant research and clinical data and uses hierarchy of evidence biased in favor of traditional biomedical research designs

23. EBM—limitations • Assumes relevant data only obtained using statistical measures describing directly observable “outcomes” isolated from all possible confounding variables • Assumes “legitimate” Rx have discrete identifiable mechanisms of action and causal relationship between Rx effects, mechanism of action, and statistical measures of “outcomes.” • Equates “causes” and “effects” with mechanisms

24. EBM—limitations • Does not acknowledge relevance of emerging paradigms to medicine • Claims findings “rigorous” only after sequential “significant” outcomes obtained from identical study designs using identical statistical methods. • Assumes averaged results of systematic reviews of several “well designed” studies can be generalized to individuals to guide Rx planning

25. EBM implicitly biased against CAM • EBM assumptions about valid methods for obtaining data implicitly biased against CAM • Consequence: most CAM Rx ranked at lowest “level” of evidence hierarchy and many CAM Rx dismissed before the “evidence” appraised

26. Integrative medicine optimizes EBM methodology Utilizing both quantitative and qualitative information

27. Quantitative criteria used to assess evidence • Numbers and kinds of studies (in vitro studies, RPCT, cohort studies, case series, etc.) and significance ratings • Systematic reviews or narrative reviews and significance ratings • Studies in progress, objectives and preliminary findings • Specificity of findings by symptom (ie, does Dx or Rx enhance Dx accuracy or improve Rx outcomes?)

28. Qualitative criteria used to evaluate evidence • Unresolved research issues influencing study design • Safety, availability, cost, insurance coverage, etc. • Described uses of specified modality in conjunction with other Rx for specified symptom • Best information resources for patients or clinicians • Patient preferences and attitudes toward Rx

29. Kinds of evidence: creating evidence hierarchies • Efficacy verified and mechanism of action verified • Efficacy verified and mechanism of action not verified • Efficacy verified and mechanism of action refuted • Efficacy refuted and mechanism of action refuted • Efficacy verified and mechanism of action unverifiable • Efficacy unverified and mechanism of action unverifiable • Efficacy refuted and mechanism of action unverifiable

30. Levels of evidence • “N of 1” trials or systematic reviews of RCTs • RCTs where follow-up is greater than 80% • Cohort studies • Case control studies or observational studies • Expert opinion (often most authoritative)

31. Combined quantitative/qualitative evidence • Four “levels” of evidence viz combinations of different quantitative and qualitative evidence for use of particular Rx for specified sx • In some cases quality studies done but not analyzed in systematic review • In some cases studies on-going, recently concluded but not published, or published but not reviewed

32. Quantitative-qualitative model • Quantitative-qualitative model provides balanced methodology for weighing evidence for both conventional and CAM Rx when different levels and kinds of evidence support different Rx

33. Integrative methodology expands EBM methods • Includes rigorous analysis of quantitative findings • Includes analysis of qualitative findings • Takes into account both limitations and relevance of quantitative and qualitative, objective and subjective information

34. Three kinds of modalities • Conventional and non-conventional modalities fall into three general classes: • empirically-derived—relies on empirical test of truth claims • consensus-based—relies on shared professional agreement about mechanism or outcomes • intuitive—shared agreement and not susceptible to empirical validation.

35. Integrative medicine will incorporate empirically-derived, consensus-based and intuitive Rx • Novel empirically derived, consensus-based and intuitive methods will continue to emerge • Certain consensus-based methods will become validated, others refuted • Certain intuitive methods will become validated, others refuted

36. Examining quantitative and qualitative evidence when planning integrative management 4 levels

37. Substantiated—IN CURRENT USE AND EFFECTIVE • Systematic review findings strongly support claims that the treatment results in consistent positive outcomes for a specified symptom • OR three or more rigorously conducted double-blind randomized controlled trials support claims of outcomes of the modality for a specified symptom • AND the modality is in current use for the treatment of a specified symptom • AND the use of the modality for a specified symptom is endorsed by a relevant professional association.

38. Provisional—in current use and probably effective • Systematic review findings are positive but not compelling, or have not been conducted because of insufficient numbers of studies or uneven quality of completed studies • OR three or more rigorously conducted double-blind randomized controlled trials yield positive but not compelling findings • AND the modality is in current use for the treatment of a specified symptom pattern • AND the use of the modality with respect to a specified symptom pattern may be endorsed by a relevant professional association.

39. Possibly effective—in current use and possibly effective • Fewer than three studies or poorly designed studies have been done to determine whether a particular modality results in consistent positive outcomes with respect to a specified symptom. • AND research findings or anecdotal reports are limited or inconsistent • AND there are insufficient quality studies on which to base a systematic review or meta-analysis • AND the modality is in current use but remains controversial • ANDmay be endorsed by a relevant professional association.

40. Refuted—may be in current use but refuted by evidence • For a particular treatment modality findings of three or more rigorously conducted studies or at least one systematic review consistently show that the modality does not result in beneficial outcomes with respect to a specified symptom • OR the conclusions of one or more systematic reviews or meta-analyses refute claims made for the treatment modality with respect to a specified symptom. • AND usually not in current use or use is highly controversial • AND not endorsed by a relevant professional society

41. Research methodology issues Verifying mechanisms of action and measuring outcomes

42. Verifying outcomes—not mechanism of action • The same methodology can be used to establish the effectiveness of any modality regardless of differences between parent systems of medicine. • This is true because effectiveness is determined on basis of (subjective or objective) outcomes only—ie, there is no epistemological requirement of a proof of a postulated mechanism of action.

43. Problems inherent in measuring symptoms and outcomes • Mental and emotional complaints are intrinsically subjective • Diagnostic criteria continue to change • Limitations of study designs • High placebo response rates of most psychiatric disorders to conventional treatments are consistently high

44. Rigor and Relevance • Because of unreliability of quantitative methods for comparing outcomes, measures of rigorand relevance can be used (Richardson 2002). • “Rigor” is strength of evidence used to establish claims that a specified modality actually works—ie, outcomes claims are true. • “Relevance” is appropriateness of a specified modality viz needs and preferences of a particular patient.

45. Rigor and Relevance • In integrative medicine the clinician’s goal is to find a “balance” between rigor and relevance that adequately addresses the presenting complaint, is realistic, and is acceptable to the patient.

46. Clinical integrative psychiatry The intake, assessment, formulation, treatment and follow-up

47. Planning integrative Rx involves • Making practical clinical recommendations • Based on “highest level” of quantitative and qualitative evidence • While taking into account • Practitioner training and skill level • patient preferences • Patient cultural and social beliefs and values • Cost and insurance coverage • Available resources

48. The integrative clinician must address five basic issues: • Obtain complete hx: clarify sx that are focus of clinical attention; prev Rx and response; medical, psychiatric, psycho-social, cultural and spiritual factors • Determine causes or meanings of core symptoms • Determine reasonable treatment approaches based on evidence review • Identify practical constraints: cost, availability, preferences and values that constrain the “shape” of a realistic and acceptable integrative strategy • Implement rx plan, schedule follow-up care, and make appropriate changes depending on progress and assessment findings

49. The intake interview In integrative mental health care

50. The integrative intake • Chief complaint (sx type, severity & duration) • Nutrition, exercise, life style • Medical, social and family hx • Previous Rx and response (conventional and CAM) • Relationship history and problems • Cultural, religious and spiritual issues • Medications and supplements