9/30/2013 Conflict of Interest Statement Behavioral Interventions - - PDF document

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GARY R. ELKI NS, P H .D., ABP P

D I R E C T O R , M I N D - B O D Y M E D I C I N E R E S E A R C H 1

Behavioral Interventions for Hot Flashes.

, L A B O R A T O R Y D E P A R T M E N T O F P S Y C H O L O G Y & N E U R O S C I E N C E B A Y L O R U N I V E R S I T Y

Conflict of Interest Statement

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The author of this presentation has no financial or commercial conflicts of interest pertinent to this presentation within the last 12 months.

Overview

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Behavioral Interventions for Hot Flashes. Review of clinical trials Next Steps

Behavioral interventions for hot flashes

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Paced Respiration Mindfulness-Based

Stress Reduction

Cognitive-

Behavioral Therapy

Yoga Clinical Hypnosis

Behavioral interventions for hot flashes

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There is a need for a safe and effective treatment

alternatives for women suffer from hot flashes and insomnia.

Hormone therapy may be contraindicated for

Hormone therapy may be contraindicated for some women.

Many women seek options for the treatment of hot

flashes due to concerns over risks and potential side-effects of pharmaceutical therapies.

Advantages of Behavioral Treatments

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Generally considered safe Many are skill-based

N id ff

No side effects May have side benefits (stress) But are they effective in reducing

hot flashes… ?

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The Placebo Effect & Hot Flash Clinical Trials

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Placebo effect can be

quite remarkable in hot flash trials (>30%-40%).

The reason for the size of

this placebo effect is not fully understood.

Establishing clinical

significance (>50%)

Paced Respiration

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Slow measured breathing

intervention, often paired with progressive muscle relaxation or relaxation response training.

Paced Respiration “protocol”:

8 hours, biweekly, laboratory-based, one-

• n-one instruction

Practice, 15 min, 2X day Application at each HF (slow deep

breathing at each HF onset)

Paced Respiration

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Initially combined with progressive muscle

relaxation in a study of 14 healthy midlife women

(Germaine & Freedman, 1984)

Reduced diary-recorded HF after 6 weeks & 6 months.

ll i d f d i i

Follow-up comparative study of paced respiration

(n=11), progressive muscle relaxation (n=11), and attention control (n=11).

(Freedman & Woodward, 1992)

Only paced respiration showed significant reductions in

• bjectively measured hot flashes after 8 weeks.

50% reduction in hot flash frequency by diary and objective

measure.

Paced Respiration

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Subsequently, an early study examining the biochemical

and thermoregulatory effects of paced respiration versus alpha-EEG biofeedback (used as control), found (~50% reduction in HF frequency in paced respiration. (Freedman,

Woodward, Brown, Javiad, & Pandey, 1995)

However, a recent study investigating ‘dose’ compared

two paced-breathing programs to usual breathing found hot flash reduction during the 9 weeks, 52% for paced breathing twice a day, 4 2% for paced breathing once a day, and 4 6% for usual breathing. (Sood et al., 2013).

Paced Respiration… Further Study…

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A 16-week, 3 group, partially blinded, controlled trial

(2:2:1 randomization and stratification: breast cancer/ no cancer), 218 women received either paced respiration, a breathing control group, or usual care.

(Carpenter et al., 2013). Results of this study showed no significant group

differences for HF frequency, severity, and bother at 8

• r 16 weeks post-randomization.

The authors concluded the paced respiration is unlikely

to provide clinical benefit for menopausal symptoms in breast cancer survivors or menopausal women without

• cancer. Small benefits in mood and sleep disturbance.

Mindfulness-Based Stress Reduction

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Learning to recognize and discriminate more

accurately between the components of experience such as thoughts, feelings, and sensations, and developing a non-reactive awareness of these.

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MBSR training teaches mindfulness through

breathing, body awareness exercises, sitting and walking meditation as well as gentle yoga.

Mindfulness-Based Stress Reduction

Shifting emphasis from focus (inward thinking) to

awareness (outward, “seeing the scenery).

Mindfulness-Based Stress Reduction

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Pilot study for hot flashes in 2006.

(Carmody, Crawford, & Churchill, 2006). 15 symptomatic women completed an 8-week MBSR

program, keeping daily diaries of hot flashes and completing hot flash related quality of life instruments at completing hot flash related quality of life instruments at baseline and follow-up.

Significant improvements on quality of life measures and

hot flash severity decreased by 40%.

HF frequency reduced 39%. 15

A randomized controlled study of mindfulness training

for coping with hot flashes was published in 2011. 110 women were randomized to MBSR or wait list control.

(Carmody, Crawford, Salmoirago-Blotcher, Leung, Churchill & Olendzki, 2011)

Primary outcome was degree of bother from hot flashes.

Mindfulness-Based Stress Reduction

y g Secondary outcomes were hot flash intensity, quality of life, insomnia, anxiety & perceived stress.

Results showed within-woman changes in bother from

hot flashes differed significantly by treatment arm, HF bother decreased by 14.7% in MBSR vs. 6.8% in WLC. At 20 weeks, total reduction in bother was 21.6% in MBSR vs 10.5% in WLC. There were no differences in HF intensity.

Cognitive-Behavioral Therapy

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Cognitive behavior therapy (CBT) is a type of

psychotherapeutic treatment that helps patients understand the relationship between thoughts and feelings and develop coping behaviors.

Initial case reports showed substantial

improvements in hot flash frequency, quality of life, depression and anxiety with improvements maintained 6 months post-treatment .

(Allen, Dobkia, Boohar & Woolfolk, 2006)

Cognitive-Behavioral Therapy

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MENOS 2: Randomized, no-treatment control study of

group cognitive behavioral therapy and guided self-help CBT in 140 symptomatic women.

(Ayers, Smith, Hellier, Mann & Hunter, 2012)

Group and self-help CBT reduced hot flashes and night Group and self-help CBT reduced hot flashes and night

sweat frequency at 6 and 26 weeks.

Combined HF/ NS reductions at 26 weeks: 4 0 % for group CBT,

36 % for self-help CBT, 23% for control. Mood, indices of quality of life, indices of emotional

functioning, and physical functioning showed significant improvements for group CBT at 26 weeks.

Yoga

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Pilot study of hatha yoga for hot flashes published in 2007.

(Booth-LaForce, Thurston & Taylor, 2007) Prospective within-group design. Participants were 12 peri- and post-

menopausal women experiencing at least 4 menopausal hot flashes per day, at least 4 days per week. Assessments were administered before and after completion of a 10-week yoga program p y g p g

The authors found significant pre- to post-treatment improvements in

the severity of questionnaire-rated total menopausal symptoms, hot- flash daily interference, and sleep efficiency, disturbances, and quality.

Neither 24 -h physiological m onitoring nor accom panying

diaries yielded significant changes in hot flashes.

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Yoga

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3-arm RCT (walking, yoga,

control) was also published in 2007.

(Elavsky & McAuley, 2007)

Four-month randomized controlled

exercise trial with three arms: walking, yoga and control (n = 164; M age = 49 9) yoga, and control. (n = 164; M age = 49.9)

Structured and supervised walking

program meeting three times per week for 1 hour and supervised yoga program meeting twice per week for 90 minutes.

Results indicated that walking

and yoga were effective in enhancing positive affect and m enopause-related QOL and reducing negative affect.

Yoga

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MSFLASH 3X2 factorial, yoga, aerobic exercise and omega-3 fish oil

supplementation:

(LaCroix AZ. MsFLASH Research Network. Presented at: the North American Menopause Society’s 23rd Annual Meeting; Oct. 3-6, 2012; Orlando, Fla.) The study involved 355 women who had 2+ HF/ day. Participants in

the yoga group took group classes once a week for 12 weeks and practiced yoga at home in between classes Study participants in the practiced yoga at home in between classes. Study participants in the exercise group followed a specific exercise routine, 3 times per week, for 12 weeks at a study exercise center. All participants will be were asked to take 3 study pills (Omega-3 or placebo) each day for 12 weeks.

Null results in HF reductions Secondary endpoints of sleep, depressive sym ptom s and

anxiety sym ptom s showed significant im provem ents with yoga or exercise.

Om ega-3 fish oil results were null.

Clinical Hypnosis for the treatment of hot flashes.

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Hypnosis is a mind-body therapy in which a patient

is provided suggestions for relaxation, mental imagery, an altered state of consciousness, and improvement in symptoms. Pil t i b t i i 8

Pilot in breast cancer survivors in 2008

60 women randomized to clinical hypnosis or no treatment Hot Flash Score (frequency x severity) reduced 68 %. Significant im provem ents in self-reported anxiety,

depression, interference of hot flashes on daily activities, and sleep were observed for patients who received the hypnosis intervention.

Elkins et al., 2008

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Hypnosis

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RCT of clinical hypnosis versus structured attention.

(Elkins, Fisher, Johnson, Carpenter, & Keith, 2013) 187 post-menopausal women randomized to clinical hypnosis

• r structured attention control.

Self-report & physiological measurement of HF At 12 weeks HF frequency reduced 74.16% At 12 weeks HF score reduced 8 0 .32% Secondary outcom es significant for hot flash related

daily interference, sleep, and treatm ent satisfaction.

Hypnosis for hot flashes: Elkins et al., 2013

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10 20 30 40 50 60 70 80 Baseline Week 5 Follow up

MEAN HOT FLASH FREQUENCY

Structured Attention Hypnosis 2 4 6 8 10 12 Baseline Week 5 Follow up

Physiologically Monitored Hot Flashes

Structured Attention Hypnosis 5 10 15 20 25 Baseline Week 5 Follow up

MEAN HOT FLASH SCORE

Structured Attention Hypnosis

Behavioral Interventions : Next steps

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Behavioral interventions have shown generally

positive results.

Hypnosis Intervention shows clinically significant

reduction in hot flashes (daily diaries and h i l i l t) d i l physiological measurement) and improve sleep quality and mood).

It is unknown how hypnosis intervention works.

Deconstruction is the critical next step.

Identifying the effective components could lead to

broader dissemination and reduce patient burden.

Selected references

Allen, L. A., Dobkin, R. D., Boohar, E. M., & Woolfolk, R. L. (2006). Cognitive behavior therapy for menopausal hot flashes: Two case reports. Maturitas, 54(1), 95‐99. Ayers, B., Smith, M., Hellier, J., Mann, E., & Hunter, M. S. (2012). Effectiveness of group and self‐help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): a randomized controlled trial. Menopause, 19(7), 749‐759. doi: 10.1097/gme.0b013e31823fe835 Booth‐LaForce, C., Thurston, R. C., & Taylor, M. R. (2007). A pilot study of a Hatha yoga treatment for menopausal symptoms. Maturitas, 57(3), 286‐295. Carmody, J., Crawford, S., & Churchill, L. (2006). A pilot study of mindfulness‐based stress reduction for hot flashes. Menopause, 13(5), 760‐769. doi: 10.1097/01.gme.0000227402.98933.d0 Carmody, J. F., Crawford, S., Salmoirago‐Blotcher, E., Leung, K., Churchill, L., & Olendzki, N. (2011). Mindfulness training for coping with hot flashes: results of a randomized trial. Menopause, 18(6), 611‐620. doi: 10.1097/gme.0b013e318204a05c Carpenter, J., Burns, D., Wu, J., Otte, J., Schneider, B., Ryker, K., . . . Yu, M. (2013). Paced Respiration for Vasomotor and Other Menopausal Symptoms: A Randomized, Controlled Trial. Journal of General Internal Medicine, 28(2), 193‐200. doi: 10.1007/s11606‐012‐2202‐6 Elavsky, S., & McAuley, E. (2007). Exercise and self‐esteem in menopausal women: a randomized controlled trial involving walking and yoga.

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American Journal of health promotion, 22(2), 83‐92. Elkins, G., Marcus, J., Stearns, V., Perfect, M., Rajab, M., Ruud, C., . . . Keith, T. (2008). Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. Journal of Clinical Oncology, 26(31), 5022‐5026. Elkins, G. R., Fisher, W. I., Johnson, A. K., Carpenter, J. S., & Keith, T. Z. (2013). Clinical hypnosis in the treatment of postmenopausal hot flashes: a randomized controlled trial. Menopause, 20(3), 291‐298. Freedman, R. R., & Woodward, S. (1992). Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring. Am J Obstet Gynecol, 167(2), 436‐439. Freedman, R. R., Woodward, S., Brown, B., Javaid, J. I., & Pandey, G. N. (1995). Biochemical and thermoregulatory effects of behavioral treatment for menopausal hot flashes. Menopause, 2(4), 211‐218. Germaine, L. M., & Freedman, R. R. (1984). Behavioral treatment of menopausal hot flashes: evaluation by objective methods. J Consult Clin Psychol, 52(6), 1072‐1079. LaCroix, A. Z. MsFLASH Research Network. Presented at: the North American Menopause Society’s 23rd Annual Meeting; Oct. 3‐6, 2012; Orlando, Fla. Sood, R., Sood, A., Wolf, S. L., Linquist, B. M., Liu, H., Sloan, J. A., . . . Barton, D. L. (2013). Paced breathing compared with usual breathing for hot flashes. Menopause, 20(2), 179‐184.