Are psychological treatments of panic disorder efficacious?

Transcription

1 Are psychological treatments of panic disorder efficacious? Peter Wilhelm PD Dr. Peter Wilhelm, Spring

2 Efficacy of Behavioral Treatment of Panic Disorder First randomised controlled trial Barlow and colleagues Barlow, D. H., Craske, M. G., Cerny, J. A. & Klosko, J. S. (1989). Behavioral treatment of panic disorder. Behavior Therapy, 20, Craske, M. G., Brown, T. A. & Barlow, D. H. (1991). Behavioral treatment of panic disorder: A two-year follow-up. Behavior Therapy, 22, PD Dr. Peter Wilhelm, Spring

3 Background: Panic Disorder, DSM 5 (p. 190) Individual experiences recurrent unexpected panic attacks, and is persistently concerned or worried about having more panic attacks, or changes his or her behavior in maladaptive ways because of the panic attacks (e.g., avoidance of exercise or of unfamiliar locations). Panic attacks are abrupt surges of intense fear or intense discomfort that reach a peak within minutes, accompanied by physical and/or cognitive symptoms: e.g. accelerated heart rate, sweating, trembling or shaking, shortness of breath, chest pain or discomfort.., fear of loosing control, fear of dying. 12 month prevalence: 2-3%, women vs men: 2:1 High comorbidity PD Dr. Peter Wilhelm, Spring

4 Background State of the art treatment for panic disorder, in the1980s, when the study was conducted: Panic attacks can effectively be treated with psychoactive drugs (Benzodiazipines) Behavioral therapy is effective in treating avoidance behavior (via in vivo confrontation) Implicit assumption: Behavioral therapy is not an efficacious treatment for panic disorder without agoraphobic avoidance PD Dr. Peter Wilhelm, Spring

5 Background Is cognitive behavioral therapy (CBT) efficacious for the treatment of panic disorder without agoraphobic avoidance? State of research Several case studies in which CBT led to an improvement (e.g. Gitlin et al., 1985; Clark, Salkovskis & Chalkley, 1985) 1 controlled pilot study (Biofeedback, PMR & cognitive Therapy vs. waiting list control group), with 11 patients (Barlow, Cohen et al., 1984) PD Dr. Peter Wilhelm, Spring

6 Aim of the studie Objective: Evaluating the efficacy of a newly developed CBT for the treatment of panic disorder PD Dr. Peter Wilhelm, Spring

7 Treatment conditions Exposition & cognitive Therapy (E&C) Cognitive restructuring: Acquiring skills for re-evaluating beliefs and appraisals about environmental and internal physiological cues analysis of faulty logic, reattribution, decatastrophizing, self instruction Interoceptive exposure after the 5 th session: Anxiety hierarchy. Cognitive skills were applied to anxiety provocing situations through visualisation of anxiety scences and overbreathing. Progressive Muscle Relaxation (R) 2x exercises per day. After 5th session: exercising the use of relaxation as a coping skill Relaxation combined with exposition und cognitive therapy (Comb) Wait list control group PD Dr. Peter Wilhelm, Spring

8 Application of treatments Single Therapy: 1 x per week, 15 weeks Treatment manuals: detailed description for evry session Therapist: 10 doctoral students and psychologists, who were trained for all interventions Weekly supervision Treatment Integrity All sessions were audiotaped 35 tapes were randomly selected: Two 5 min segments were selected and therapist behavior was rated Patients rated credibility and Logic of treatment (after 1. and last session, follow up) PD Dr. Peter Wilhelm, Spring

9 Participants Patients of Phobia and Anxiety Disorder Clinic, State University of New York Panic Disorder without or only slight Agoraphobia PD Dr. Peter Wilhelm, Spring

10 Sample: Inclusion and exclusion criteria Inclusion Criteria DSM III-R: Panic disorder, no or slight agoraphobic avoidance Therapist Rating: Severity of disorder > 4 (Scale 0 to 8) (Anxiety Disorder Interview Schedule-Revised; ADIS-R) At least 1 attack within the last 2 weeks (diary, 4 times daily) Patients who already got other treatments not related to anxiety Stable medication Exclusion Criteria Age 18 to 65; Alcohol- or substance abuse Major depression, psychosis, organic brain syndrome Other therapies of anxiety / Begin of Psychopharmacological treatment less than 3 Mon. benzodiazepines, less than 6 Mon. MAO-Hemmer, tricyclic antidepressants) PD Dr. Peter Wilhelm, Spring

11 Meassurements Standardized Interviews (blind judges) Hamilton Anxiety and Depression Scales Standardized Self-Reports State-Trait Anxiety Inventory (Spielberger, Gorusch, & Lushene, 1970) Cognitive Somatic Anxiety Questionnaire, (Marks & Mathews, 1979), Fear Questionnaire (Marks & Mathews, 1979) Beck Depression Inventory (Beck et al., 1961) Psychosomatic Rating Scale (Cox, Freundlich & Meyer, 1975) Subjective Symptom Scale (Modification, Hafner & Marks, 1978) Self-Observation: Structured diary (4 times daily) Anxiety Rating from 0 to 8; Panic yes/no; stressful events? PD Dr. Peter Wilhelm, Spring

12 Composite measures of clinically significant change Treatment responder 20% Improvement in three of four measures: Clinical rating of severity (> 2 points) Fear Questionnaire (> 2 points) Number of panic attacks per week Subjective Symptom Scale Total score (> 8 points) Treatment non-responder Deterioration of 20% (Pre-Post) in any of the measures (independent of improvement in other variables) End state functioning absolute level of functioning at Post-Assessment(only completers) low end state (LES) vs high end state (HES) PD Dr. Peter Wilhelm, Spring

13 Research Design Patients were randomly assigned to 4 conditions Assessment : Pre Post Follow up: 3, 6, 12, 24 months PD Dr. Peter Wilhelm, Spring

14 Sample size and drop-outs (in %) Pre Post 6-Month 24-Month Wait-list (6%) - - Exposition (E) & Cognitive Therapie (C) (6%) 8 15 Relaxation (R) (33%*) 9 9 Combined (E & C & R) (17%) 6 10 Comparison drop-outs vs. completers (ANOVAS) Drop-outs: lower severity at pre treatment Higher consumption of anxiolytics * signifikant PD Dr. Peter Wilhelm, Spring

15 Change in sample size over time PD Dr. Peter Wilhelm, Spring

16 Treatment Responders at Post-Assessment significant PD Dr. Peter Wilhelm, Spring

17 High End-State Functioning at Post-assessment significant PD Dr. Peter Wilhelm, Spring

18 Comparison: Pre-Post Assessment Reduction in clinical rating of severity All treatment groups significantly improved but not CG All treatment groups were significantly better than CG Reduction in Hamilton Anxiety Score All treatment groups significantly improved but not CG R and Combined G were significantly better than control group Psychosomatic Symptoms Only relaxation group significantly improved Only R was significantly better than CG No significant differences in the other measures PD Dr. Peter Wilhelm, Spring

19 Patients without panic attacks. Post-Assessment (Study completers) PD Dr. Peter Wilhelm, Spring

20 Patients without panic attacks. Post-Assessment (Intent to Treat analysis with total sample) PD Dr. Peter Wilhelm, Spring

21 24 Month Follow-Up: Summary Maintainance of therapy success Decrease of trait-anxiety and somatic symptoms (Post vs. 24 months) BDI-Scores Increase in R-group Decrease in E & C-group PD Dr. Peter Wilhelm, Spring

22 Participants with high end state and without panic (Study completers) PD Dr. Peter Wilhelm, Spring

23 Participants with high end state and without panic (Total Sample) significant for Panic-Free PD Dr. Peter Wilhelm, Spring

24 24 months Follow-Up: Other Psychological Treatments Alternative Psychotherapy: R 83%, E&C 33%, COMB 40% Psychopharmaca R 71%, E&C 17%, COMB 43% PD Dr. Peter Wilhelm, Spring

25 Summary of results Post Assessment: (R, E&C, E&C&R) > Wait list In relaxation group, less patients were panic free, However anxiety and psychosomatic symptoms were reduced. Follow up: Maintenance of therapy success over 2 years For patients with interoceptive exposer and cognitive restructuring Patients in relaxation group less stable patterns Highest drop out rate Highest rate of additional treatment Cognitive behavioral therapy with relaxation (E&C&R) was not more efficacious than E&C PD Dr. Peter Wilhelm, Spring

26 Conclusions Panic disorder without agoraphobic avoidance can be efficaciously treated with a combination of interoceptive exposer + cognitive restructuring Directly after treatment, relaxation is as efficacious as interoceptive exposer + cognitive restructuring, but in the long run it is less efficacious. Relaxation is not a necessary component of an efficacious treatment of panic disorder. Interoceptive exposer + cognitive restructuring is sufficient. Compared to results in the literature, long term effects of interoceptive exposer and cognitive restructuring are better than pharmacological treatment PD Dr. Peter Wilhelm, Spring

27 Conclusions Panic disorder without agoraphobic avoidance can be efficaciously treated with a combination of interoceptive exposer + cognitive restructuring Directly after treatment, relaxation is as efficacious as interoceptive exposer + cognitive restructuring, but in the long run it is less efficacious. Relaxation is not a necessary component of an efficacious treatment of panic disorder. Interoceptive exposer + cognitive restructuring is sufficient. Compared to results in the literature, long term effects of interoceptive exposer and cognitive restructuring are better than pharmacological treatment PD Dr. Peter Wilhelm, Spring

28 Cognitive-behavioral therapy, pharmacotherapy, or their combination for treating panic disorder (PD): A randomized controlled trial (RCT) (Barlow, Gorman, Shear, & Woods, 2000) PD Dr. Peter Wilhelm, Spring

29 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Background Background: Well established efficacy for two PD treatments Psychological treatment: CBT Pharmacological treatment with Imipramine (Tofranil) First tricyclic antidepressant, discovered 1951 by Ciba Geigy (today Novartis) increases the extracellular level of neurotransmitters (serotonin, norepinephrine ) by limiting their reabsorption (reuptake) into the presynaptic cells Broad range of effects Improves mood, reduces symptoms of agitation and anxiety side effects: dry mouth, drowsiness, dizziness, blurred vision, low blood pressure, rapid heart rate, increased sweating, diarrhea, stomach cramps, increase of appetite, weight gain PD Dr. Peter Wilhelm, Spring

30 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Objectives Relative and combined efficacies of drug and PT treatment for PD have not been evaluated Objectives: To evaluate, whether drug and PT for PD are each more efficacious than placebo one treatment is more efficacious than the other combined therapy is more efficacious than either therapy alone? PD Dr. Peter Wilhelm, Spring

31 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Study design 312 panic disorder patients were randomly assigned to five groups (double blind) CBT Imipramine Drug placebo CBT + Imipramine CBT + Drug placebo PD Dr. Peter Wilhelm, Spring

32 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Treatments (acute phase) Treatments were manualized for each condition Acute treatment phase: 11 sessions during 12 weeks for each condition CBT individual 50-minute sessions Interoceptive exposure, cognitive restructuring, and breathing training Psychopharmacotherapy (Imipramine or Placebo) + Clinical Management individual 30-minute contacts monitor adverse effects, clinical state, and physical/mental condition maximize compliance proscribe specific interventions included in CBT (cognitive restructuring of anxiety and panic symptoms) Imipramine treatment was slowly titrated up to a maximum of 300 mg/day Blood levels were assessed at 6 and 12 weeks Combined Treatment (Imipramine or Placebo + CBT) individual contacts with 2 therapists for about 75 minutes per week. Benzodiazepine screening of urine samples PD Dr. Peter Wilhelm, Spring

33 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Treatments (maintenance phase) Responders to acute treatment entered a 6-month maintenance phase without breaking the study blind. 6 monthly appointments in which treatment similar to the acute treatment was continued After maintenance phase treatment was stopped PD Dr. Peter Wilhelm, Spring

34 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Therapists Therapists providing CBT were doctoral level clinicians who underwent extensive training Pharmacotherapists were experienced psychiatrists who underwent additional training Ongoing supervision, biweekly Adherence and competence ratings were collected after listening to a sample of audiotaped sessions PD Dr. Peter Wilhelm, Spring

35 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Assessment at baseline after acute phase (3 months after baseline) after maintenance phase (9 months after baseline) after follow-up phase (15 months after baseline) Trained evaluators (blind to treatment assignment) judged patients on Panic Disorder Severity Scale (PDSS) clinician-rated scale of PD severity Response was defined > 40% reduction of PD symptoms Clinical Global Impression Scale (CGI), 7-point ratings on 2 items: overall improvement and severity Definition of responders: CGI much improved ( 2) while being rated as mild or less ( 3) on CGI severity Patients who received nonstudy treatment for anxiety = nonresponders PD Dr. Peter Wilhelm, Spring

36 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Patients Inclusion criteria: Potential participants met DSM-III-R or DSM-IV criteria for PD with no more than mild agoraphobia (ADIS-R avoidance scale 18) Panic attack(s) in the 2 weeks before treatment Patients with comorbid unipolar depression were not excluded Patients were permitted to take benzodiazepines until end of acute phase Exclusion criteria psychotic, bipolar, or significant medical illnesses, suicidality, significant substance abuse, contraindications to either treatment, prior nonresponse to similar treatments, concurrent competing treatment or pending disability claims PD Dr. Peter Wilhelm, Spring

37 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Allocation of Patients PD Dr. Peter Wilhelm, Spring

38 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Drop outs during acute phase PD Dr. Peter Wilhelm, Spring

39 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Drop outs during acute phase PD Dr. Peter Wilhelm, Spring

40 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

41 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * * Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

42 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * * n.s. Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

43 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * n.s. * n.s. Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

44 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * n.s. n.s. * n.s. Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

45 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of acute phase (3 months) (intent to treat) Response was defined > 40% reduction in symptoms on Panic Disorder Severity Scale (PDSS) rated by trained evaluators * n.s. n.s. n.s. * n.s. Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

46 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at the end of 6-month maintenance phase (intent to treat) After 6-month maintenance phase: responders continued medication or monthly CBT * * * * Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

47 Percent CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Responders (%) at follow up 6 months after maintenance (intent to treat) After 6-month follow up without treatment * # # Placebo CBT Imipramine IPT CBT + Placebo CBT + Imipramine PD Dr. Peter Wilhelm, Spring

48 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) Summary and conclusions both imipramine and CBT are better than pill placebo for treatment of PD (post acute, post maintenance) Imipramine produced a superior quality of response until end of maintenance CBT had more durability and was somewhat better tolerated Relapse 4% for CBT, 25% for Imipramine High attrition in placebo group; weak and non durable response Coadministration of Imipramine and CBT resulted in limited benefit over monotherapy Improvement after maintenance addition of imipramine appeared to reduce long-term durability of CBT Potential underestimation of benefits of medication by using a tricyclic antidepressant instead of an SSRI PD Dr. Peter Wilhelm, Spring

49 CBT, pharmacotherapy, or their combination? (Barlow et al., 2000) What are limitations and problems of this study? PD Dr. Peter Wilhelm, Spring