1. TFP: MID- AND LATE-PHASE; EMPIRICAL STATUS borderlinedisorders.com Session 4: John F. Clarkin, Ph.D.

2. EVOLUTION OF TFP

3. Typical evolution of therapy I The patient tests/challenges the contract Early emphasis on nonverbal and counter- transference channels of communication Decrease in acting out: life settles down while dynamics get focused in the therapy Increasing awareness of the importance of the therapist for the patient, and defenses against this (attachment themes); increase in affect intensity in sessions

4. Typical evolution of therapy II As therapy advances to the midphase: Interpretation of defenses against integration A cycle where the problematic dynamics reappear, but in a more contained and limited way There is evidence of integration, initially tentative and subject to frequent regressions to splitting Practical problems arise stemming from earlier life choices that no longer “fit” well

5. Termination Every separation (end of session, vacation, etc.) can bring up the dynamics of termination For borderline patients, separation is always an issue Narcissistic patients may have difficulty getting involved before separation becomes an issue The dynamics of separation and termination should be addressed throughout the therapy Successful termination involves successful internalization and integration Termination involves the dynamics of healthy vs. pathological mourning

6. In-Session Indications of Integration and Structural Change The patient’s comments indicate reflection on and exploration of the therapist’s interventions The patient is able to accept the exploration and interpretation of primitive defense mechanisms The patient can contain and tolerate the awareness of previously projected affects The patient can experience guilt/remorse and enter into the depressive position The patient can tolerate fantasies and the development of a transitional space The evolution of predominant transferences

7. Clinical Manifestations of Structural Change Change at the level of psychological structures with a more integrated psychological experience will lead to: Better functioning, with a reduction of symptoms and maladaptive behaviors Change in the patient’s sense of self and experience of the world Ability to cope with stress and adversity Living a “full” life with a realistic measure of satisfaction in love and work

8. TFP IS EMPIRICALLY DEVELOPED AND SUPPORTED

9. Steps in Empirical Development of Treatment (Kazdin, 2004)  Conceptualization of the pathology  Conceptualization of the treatment and clinical testing  Manualization of treatment  Therapist training to adherence and competence  Preliminary data with effect sizes  Randomized controlled trial  Investigation of moderators and mediators  Generalizability of treatment (patients not excluded; treatment in community; transport to another setting)

10. Our Progress Conceptualization of the pathology: Theory: Object relations theory: Kernberg, 1975, 1982, 1984; Kernberg & Caligor, 2005 Phenomenology: Attachment: Levy et al, 2006 Measurement: IPO, STIPO (Stern et al, 2010; Hoerz, Clarkin, Stern & Caligor, in press) Borderline subgroups: Lenzenweger, Clarkin, Yeomans, et al, 2008 Neurocognitive functioning: Processing negative affect: Silbersweig, et al, 2007 Attention network (ANT): Posner et al, 2005

11. Our Progress Conceptualization of the treatment and clinical testing: NIMH R21 Grant (PI: J. Clarkin): Clarkin, Foelsch, Levy et al, 2001 Manualization of treatment: Clarkin, Yeomans & Kernberg, 2006 Preliminary data with effect sizes: Clarkin et al, 2001

12. Our Progress  Randomized controlled trial: Clarkin et al, 2007; Doering et al, 2010  Investigation of moderators and mediators: Levy, et al, 2006; Lenzenweger et al, 2012  Generalizability of treatment: transport to another setting: Doering, et al, 2010

13.  Examine efficacy of TFP  N=90; randomized to TFP vs. DBT vs. STP  Primary outcomes:  Improvements in suicidality only in TFP & DBT  Anger and impulsivity in TFP & SPT  Verbal & direct assault only in TFP  Secondary outcomes:  improvements in depression, anxiety and psychosocial functioning in all 3 groups  TFP only improvements in irritability

14. Only in TFP improvements in coherence of AAI narratives, secure attachment, Reflective Functioning (RF; mentalization)

15. Change in RF as a Function of Time and Treatment (Levy et al, 2006)

16.  RCT of TFP vs. treatment by experienced community psychotherapists (ECP)  n=104  Multi-center: Munich, Vienna  1 year  TFP superior in drop out (38.5% vs. 67.3%), suicide attempts, BPD symptoms, psychosocial functioning, and personality organization and inpatient admissions. Both improved in depression and anxiety.

17. Current Empirical Status of TFP TFP is a treatment closely tied to a clinical theory TFP has been articulated and manualized TFP has been taught to therapists from multiple disciplines, levels of experience and across the world (not just at our own location) TFP has been show to be effective in three uncontrolled studies and efficacious in relation to community therapist who are experienced with BPD as well as DBT (comparable results) These findings are consistent with recent meta-analyses TFP not only produces symptom change (e.g, suiciduality) but results in structural changes as shown in changes in reflective functioning, attachment security/narrative coherence and personality organization. The RF finding has been replicated in an independent sample and the attachment finding has been replicated in two additional independent samples These structural changes have been related to both neurocognitive and neuroscience findings

18. LIMITATIONS OF EXISTING BPD TREATMENT RESEARCH

19. Recent Meta-analysis (Levy et al, 2012) Exhaustive search for treatment studies of BPD No differences related to treatment orientation There were differences related to date of study and methodology

20. Summary There are a number of promising therapies for BPD (e.g., DBT, MBT, TFP, SFPT, and DDP) The studies that have compared well delivered bonafide treatments generally suggest few differences between these treatments For example, there is not one study in which DBT is compared with an active treatment that it shows clear superiority Levy, Ellison, Temes, Khalsa (in prep)

21. Major Limitations of Existing Treatment Research Focus on symptom change; outcomes in work and intimate relations are limited Very little focus on mechanisms of change (see Kazdin, 2006) Heterogeneity of BPD patients, in terms of overall severity and domains of dysfunction Treatment packages investigated (e.g., TFP, DBT, MBT, Schema) have multiple elements, much overlap especially in terms of structure and support for improvement

22. Existing Treatments Are Most Effective With Symptoms, Not Functioning Consider McMain et al, 2012, DBT and General Psychiatric Management: Two years after 1-year treatment, effects of treatments persisted in reduced frequency and severity of suicidal and nonsuicidal self- injurious behaviors, health service utilization, symptom severity, general psychopathology However, at follow-up 51.8% were neither working nor in school, compared to 60.3% before treatment. Before treatment, 39.7% receiving disability benefits, and 38.8% on such benefits at the end of follow-up

23. Symptom and Social Functioning in BPD Over Time (Zanarini et al, 2012) Symptom remission is substantially more common in BPD than social and functional recovery Only 40% of BPD patients compared to 75% of axis II comparison patients attained a social and functional recovery lasting 8 years or longer Vocational impairment is the main reason that BPD fail to attain or maintain symptomatic and social/vocational functioning

24. LIMITATIONS OF EXISTING BPD TREATMENT RESEARCH

25. Recent Meta-analysis (Levy et al, 2012) Exhaustive search for treatment studies of BPD No differences related to treatment orientation There were differences related to date of study and methodology

26. Summary There are a number of promising therapies for BPD (e.g., DBT, MBT, TFP, SFPT, and DDP) The studies that have compared well delivered bonafide treatments generally suggest few differences between these treatments For example, there is not one study in which DBT is compared with an active treatment that it shows clear superiority Levy, Ellison, Temes, Khalsa (in prep)

27. Major Limitations of Existing Treatment Research Focus on symptom change; outcomes in work and intimate relations are limited Very little focus on mechanisms of change (see Kazdin, 2006) Heterogeneity of BPD patients, in terms of overall severity and domains of dysfunction Treatment packages investigated (e.g., TFP, DBT, MBT, Schema) have multiple elements, much overlap especially in terms of structure and support for improvement

28. Existing Treatments Are Most Effective With Symptoms, Not Functioning Consider McMain et al, 2012, DBT and General Psychiatric Management: Two years after 1-year treatment, effects of treatments persisted in reduced frequency and severity of suicidal and nonsuicidal self- injurious behaviors, health service utilization, symptom severity, general psychopathology However, at follow-up 51.8% were neither working nor in school, compared to 60.3% before treatment. Before treatment, 39.7% receiving disability benefits, and 38.8% on such benefits at the end of follow-up

29. Symptom and Social Functioning in BPD Over Time (Zanarini et al, 2012) Symptom remission is substantially more common in BPD than social and functional recovery Only 40% of BPD patients compared to 75% of axis II comparison patients attained a social and functional recovery lasting 8 years or longer Vocational impairment is the main reason that BPD fail to attain or maintain symptomatic and social/vocational functioning

30. RECENT FINDINGS BY OUR RESEARCH GROUP

31. Study 1: Different Types of Borderline Patients (Lenzenweger, Clarkin, Yeomans, et al, 2012) A theoretical orientation toward BPD pathology was matched with a sophisticated statistical technique (finite mixture modeling) Three groups of borderline patients emerged. Group 1: low in aggression, paranoia, antisocial; less negative emotion, less childhood abuse, better social/work functioning Group 2: high paranoid and low aggression and antisocial; less affiliative, higher rates of childhood sexual abuse Group 3: aggressive, antisocial, non-paranoid; impulsive, identity diffused, psychopathic This finding of different types of BPD patients has been replicated (Yun et al, 2012; Hallquist & Pilkonis, 2012)

32. Study 2: Effortful Control, Interpersonal Functioning, and Symptom Distress Low effortful control in children is associated with aggression, poor peer relations, lack of moral development Low effortful control in children is predictive of interpersonal difficulties in adults

33. Current Approach to Pathology: Research Domain Criteria Project (NIMH) Focus on pathophysiology that will help identify new targets for treatment development, detect subgroups for treatment selection, provide better match between research findings and clinical decision making RDoC classification rests on three assumptions: 1) mental disorders are disorders of brain circuits, that 2) can be identified with tools of neuroscience, and 3) data will yield biosignatures useful for clinical management Major RDoC domains: negative valence systems, positive valence systems, cognitive systems, systems for social processes, arousal/modulatory systems (Insel, et al., 2010; Insel, 2013)

34. Definition of Effortful Control The ‘voluntary’ aspect of temperament: Successful regulation & conflict resolution among emotions, thoughts and behaviors (Posner & Rothbart, 2007, 2009; Derryberry & Rothbart, 1997) Reflects the maturation & efficiency of executive attention: Ability to inhibit a prepotent response and activate a subdominant one when necessary, according to situational demands and long-term goals (Gerardi-Caulton, 2000; Simonds et al, 2007; Chang & Burns, 2005) Long-term implications: Children’s executive attention predicts self-control abilities in adulthood (Casey et al, 2012; Eigsti et al, 2006)

35. Results De Panfilis, Meehan, Cain & Clarkin. Comprehensive Psychiatry, in press. EC GSI IIP- Distress Causal step strategy for mediation (Baron & Kenny, 1986) : higher interpersonal distress fully mediates the effect of low EC on greater psychopathology severity (Sobel’s test=−4.28, p<.00) Bootstrapping procedure for indirect effects (Preacher & Hayes, 2008) : significant total indirect effect model of EC on GSI through IIP-distress (ab=−.14, 95%CI=−.07- −.24) β=−.38* β=.43* β=−.28* a=−.31* b=.46* (β=−.12) c= −.24* *p<.00 (c’= −.09)

36. Results De Panfilis, Meehan, Cain & Clarkin. Comprehensive Psychiatry, in press. EC GSI IIP- Distress Bootstrapping procedure for indirect effects (Preacher & Hayes, 2008): significant total indirect effect of EC on GSI through IIP-distress ab=−.14, 95%CI=−.07- −.24 a=−.31* b=.46* c= −.24* *p<.00 (c’= −.09)

37. Conclusions 1. Among adults, low EC is associated with increasing distress related to general aspects of psychopathology A basic domain of functioning potentially relevant for various psychiatric disorders, throughout the life span 2. An impairment in interpersonal functioning explains this effect EC may foster psychological adjustment through promoting successful resolution of interpersonal problems De Panfilis, Meehan, Cain & Clarkin. Comprehensive Psychiatry, in press.

38. Study 3: Affect Regulation Before and After TFP Amygdala hyperresponsivity to social and emotional stimuli in BPD patients (Donegan et al, 2003; Herpertz et al, 2001; Silbersweig et al, 2007) BPD show mistrust in tasks involving interpersonal cooperation Attempts to reappraise situations involving reduction of negative affect are deficient in BPD patients

39. Emotional Go-NoGo Task POSITIVE VERBAL STIMULI GoNo-go NEUTRAL VERBAL STIMULI GoNo-go NEGATIVE VERBAL STIMULI GoNo-go

40. Behavioral Results Patients rated negative words more negative Longer reaction times for patients during no-go blocks Greater errors of omission for patients during no-go and negative no-go Greater errors of commission for patients under negative no-go condition

41. Neuroimaging Results  Behavioral inhibition and negative emotion: Patients manifested decreased ventromedial prefrontal (medial orbitofrontal, subgenal anterior cingulate) activity  Behavioral inhibition and negative emotion:  Patients manifested decreasing vetromedial prefrontal & increasing extended amygdalar- venral striatal activities  These activites signficantly correlated with trait measures (MPQ) of decreased constraint and increased negative emotion

42. Discussion OFC lesions/dysfunction associated clinically with socio-emotional dyscontrol In BPD, a bias toward intense negative feelings may dominate the process coupled with failure of top-down control Negative affective memories/states may propel behavior, unchecked by evolving socioemotional contexts

43. Our Latest TFP Treatment Study: Psychological Results BPD (N=10) selected for Diagnosis and Affective Lability Outcome measured over time on symptoms (affective lability), interpersonal behavior (IIP), and performance in love and work We found significant change in patient affective lability, positive affect, interpersonal behavior (sensitivity, paranoia, intrusiveness, vindictiveness), and work At the end of treatment, all patients were working; intimate relations are slower to evolve and improve

44. Our Latest TFP Treatment Study: Neurocognitive Functioning Post Treatment vs Pre Treatment: Affective lability improvement correlated with decreased amygdala activity and increase cingulate activity MPQ constraint correlated with increase in orbital medial prefrontal cortex activity Neurocognitive functioning at baseline as predictor of change: Increased right amygdala functioning predicted affective lability total change Decreased pre-frontal activity predicted improvement in MPQ constraint

45. IN CONCLUSION…

46. Take-Home Message Take empirically supported with a grain of salt: this is only the beginning; we know very little Focus on the individual patient; each borderline is unique; probably one-size treatment does not fit all Develop your own local way of matching borderline patients to a treatment; context (public health system vs. private practice) makes a difference The treatments are growing in number (MBT, TFP, DBT, Schema, General Psychiatric Management, etc); why not take the best from each? Some form of integrated treatment focused on the individual patient may emerge More treatment development focus on work and social functioning is needed Future treatment studies must focus on specific domains of dysfunction most relevant to the broad category of BPD