Anxiety and Depression in the COPD patient - PowerPoint Presentation

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Anxiety and Depression in the COPD patient

Aaron Pierce, DO

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Disclosure

I have no relevant financial relationships or affiliations with commercial interests to disclose.

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Objectives

Briefly review COPD pathology and treatment

Review

Prevalence of anxiety and depression in COPD

Possible effect of anxiety and depression on COPD and vice versa

Explore treatment options

Briefly review smoking cessation in COPD

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Chronic Obstructive Pulmonary Disease

Progressive obstruction of small airways

Chronic bronchitis

Excessive mucous production and inflammation

Emphysema

Destruction of elastic tissue and enlargement of airspace

Most patients have elements of both

80-90% secondary to smoking

4

th

leading cause of death

Diagnosis confirmed by FEV

1

/FVC less than 0.7

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Modified from Fletcher C. and

Peto

R.: The natural history of chronic airflow obstruction. Br Med J. 1977;1(6077):1645–1648

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COPD exacerbations

Global Initiative for Chronic Lung Disease (GOLD)Acute event characterized by worsening of respiratory symptoms that is beyond day-to-day variations and leads to a change in medicationIncrease in cough frequency or severityIncrease in sputum production Worsening of dyspneaSeverity based on treatment required

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Wedzicha

J, Mackay A, Richa S. COPD exacerbations: impact and prevention. Breathe. 9:434-440, 2013.

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COPD treatment

Treatment

Smoking cessation

Pharmacotherapy with inhaled bronchodilators and corticosteroids

Vaccinations

Oxygen therapy

Pulmonary rehabilitation

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Anxiety disorders in COPD

Generalized anxiety disorder 6-33%1.9-5.15 general populationPanic disorder 6-67%Even with conservative estimates >10X general populationSocial phobia 5-11%1-2% general elderly population

Livermore N, Sharpe L, McKenzie D. Panic attacks and panic disorder in chronic obstructive pulmonary disease: A cognitive behavioral perspective. Respiratory Medicine. 104:1246-1253, 2010 2)

Willgoss

T,

Yohannes

A. Anxiety Disorders in Patients with COPD: A Systematic Review. Respir Care. 2013;58(5):858 –866.

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Effect of anxiety

Difficulty with smoking cessationAlcohol abuseAvoidance of physical activityTreatment complianceWorsened dyspnea and exercise toleranceOverall worsening of QOL independent of COPDAt greater risk of exacerbations

Pumar M, et al. Anxiety and

depression-Important

psychological comorbidities of COPD. J

Thorac

Dis 2014;6(11):

1615-1631.

2)

Laurin

C et al. Impact of Anxiety and Depression on Chronic Obstructive Pulmonary Disease Exacerbation Risk. Am J

Respir

Crit

Care Med. 185(9):918-923. 2012

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Biological factors of panic in COPD

CO2/H+ sensitive neurons involved with ventilation and panic symptomsInduction of panic by infusion of lactate or inhaled CO2 in PD pts. Low intracellular pH trigger for NE release Anxiety Hyperventilation Hyperinflation Increased dyspnea AnxietyBeta agonists and oral corticosteroidsNicotine withdrawal

 

Pumar M, et al. Anxiety and depression-

Improtant

psychological comorbidities of COPD. J

Thorac

Dis 2014;6(11):1615-1631

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Biological factors of panic in COPD

Increased sensitivity to CO2 associated with more dyspnea in COPD39 COPD patients exposed to increased CO2 tensionFEV1 not significantly different Normal CO2 sensitivitySevere dyspneaNormal blood gasesDecreased CO2 sensitivityMild dyspneaIncreased PaCO2Hypoxemia

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Biological factors of panic in COPD

SerotoninMay modulate respiration in part by decreasing sensitivity to CO2Sertraline shown to improve dyspnea without change in objective parametersDirect or indirect effect

Smoller J, et al. Sertraline Effects on Dyspnea in Patients with Obstructive Airways Disease. Psychosomatics. 39:24-29, 1998.

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Cognitive factors of panic in COPD

Cognitive model

Panic arises from catastrophic misinterpretation of bodily or mental sensations

Interaction of belief and trigger

Trigger- slight increase in dyspnea when walking to mailbox

Belief- “worsening SOB means that I will certainly be hospitalized

again and need to be intubated”

Result- panic symptoms and worsening SOB and future avoidance of activity

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This figure was published in Principles and Practice of Pulmonary Rehabilitation, Haas F, Salazar-Schicci J, Axen K. Desensitization to dyspnoea in chronic obstructive pulmonary disease, 241-251, Copyright Elsevier 1993.

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Cognitive factors of panic in COPD

Dyspnea

Similarity to pain

Neurological and emotional aspects

No external reference to measure by

Influenced by beliefs and sense of control

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Differences in pulmonary function with anxiety in COPD

No difference in PFT’s and response to bronchodilators in COPD with panic attacks and those without Moore and Zebb (1999)28 pts with COPD or asthma32% with panic disorderNo significant difference in FVC or FEV1 versus non-panic groupRegvat et al. (2011)50 pts hospitalized with AECOPD50% with anxiety and/or depressionNo difference in FEV1Those with anxiety and/or depression had significantly higher PaO2, lower PaCO2, and higher pH

1)Livermore N, et al;. Panic attacks and panic disorder in chronic obstructive pulmonary disease: a cognitive behavioral perspective. Res Med. 104:1246-1253. 2010 2) Moore M,

Zebb

B. The catastrophic misinterpretation of physiological distress.

Behaviour

Research and Therapy. 37:1105-1118, 1999 3)

Regvat

J, et al. Anxiety and Depression during Hospital Treatment of Exacerbation of Chronic Obstructive Pulmonary Disease. The Journal of Int. Med Research. 39:1028-1038, 2011.

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Differences in pulmonary function with anxiety in COPD

Vogele and Leupoldt (2008)20 hospitalized pts mild/mod COPDNo significant difference in FEV1/FVC or PaO2 in those with and without anxietySelf-report Inventory of Somatic SymptomsHigher somatic symptom perception in several domains in anxious group

Vogele C, Leupoldt A. Mental disorders in chronic obstructive pulmonary disease. Respiratory Medicine. 102:764-773. 2008

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Usmani Z, et al. Systematic meta-analysis of pharmacological interventions for the treatment of anxiety in patients with chronic obstructive pulmonary disease. 2(7);2018

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Treatment of anxiety in COPD- Medications

Momtaz et al. (2014)50 pts with severe COPD with depression and/or anxietyGroup I- Prozac 20mg daily X 3monthsGroup II- TAUGroup I- Dyspnea scale, oxygenation, and PFT’s significantly improved from baseline and not in Group IIHAM-A 24.45 → 20.56 (p=0.01)Significantly negative correlation with FEV1 (r: -0.74, p=0.001)

Momtaz O, et al. Effect of treatment of depression and anxiety on physiological state of severe COPD patients. Egyptian Journal of Chest Diseases and Tuberculosis. 64:29-34. 2015

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Treatment of anxiety in COPD- Medications

BenzodiazepinesMay blunt response to hypoxia which may worsen hypercapniaLow doses (<1/3 of usual dose)Not associated with increased admissions or mortalityHigher dosesNot associated with increased admissionsMortality was increased in a dose-dependent fashionMay help respiratory efficiency Short acting benzodiazepines preferredGabapentoidsLower dosage range safe

1)

Ekstrom

M et al. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study.

BMJ

 2014;348:g445 2)

Savelloni

J, et al. Risk of respiratory depression with opioids and concomitant

gabapentoids.Journal

of Pain Research. 10:2635-2641. 2017

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Treatment of anxiety in COPD- Psychotherapy

Heslopp-Marshall et al (2018)RCT of cognitive behavioral therapy 279 COPD patients with anxiety Randomized to brief CBT or self-help leafletsOutcome based on anxiety subscale of Hospital Anxiety and Depression ScaleMinimal clinically important difference = 1.32Mean difference in CBT group vs. control = 1.52 (p=0.003)Fewer hospital admissions and and ED visits in CBT group

Heslop-Marshall K, et al.

Randomised

controlled trial of cognitive

behavioural

therapy in COPD. ERJ Open Res. 4:94-2018.

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Treatment of anxiety in COPD- Progressive Muscle Relaxation

Progressive muscle relaxationTensing specific muscle groups and slowly relaxing them in orderBreathing exercises and guided imagery may also be usedRenfroe (1988)RCT of 20 COPD patientsPMR group given instruction and audio tape of relaxation exercise, encouraged to practiceEvidence of masterySignificantly greater decrease in HR, 6.76 and RR, 3.33 versus controlReduction in anxiety, dyspnea, and FVC compared to control group

Renfroe KL. Effect of progressive relaxation on dyspnea and state

anx

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Treatment of anxiety in COPD- Progressive Muscle Relaxation

Gift et al. (1992)RCT of 26 ptsPMR group used prerecorded instruction and encouraged to practice at home Mastery demonstrated by increase in temp of 2.2◦C, decrease in HR and RR of 6.5 and 4.8 respectivelySignificantly decreased anxiety, dyspnea, and increased peak flow

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Treatment of anxiety in COPD- Pulmonary Rehab

Pulmonary rehabilitation

Exercise program

Breathing exercises

Education

Managing

exacerbations

Proper use of medications and oxygen

Nutrition counseling

Stress management

Smoking cessation

Several mechanisms of change in anxiety

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Treatment of anxiety in COPD- Pulmonary Rehab

Coventry and Hind (2007)Systematic review and meta-analysisThree studies (n=269) showed that comprehensive PR significantly more effective vs standard care in reducing anxiety (SMD = -0.33, CI: -0.57 to -0.09, p=.008)Education alone and exercise alone did not significantly reduce anxiety

Coventry PA, Hind D. Comprehensive pulmonary rehabilitation for anxiety and depression in adults with chronic obstructive pulmonary disease: Systematic review and meta-analysis. J Psychosom Res. 63(5):551-565. 2007

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Treatment of anxiety in COPD- Pulmonary Rehab

Emery et al. (2003)Supervised 10 week programExerciseEducation Stress management techniquesSignificant reduction in anxiety and improved enduranceAttendance at education and stress management sessions alone did not help

Emery CF, et al. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease. Health Psychol. 17:232-240. 1998

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Depression in COPD

Around 40% of those with COPD have significant depressionMore common in COPD than some other chronic illnessesQuality of life more correlated to depression than FEV1

1) Norwood R. A review of etiologies of depression in COPD. International Journal of COPD. 2(4):495-491. 2007 2) Stage K et al. Depression in COPD-management and quality of life considerations. International Journal of COPD. 1(3):315-320. 2006.

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Depression in COPD

Bidirectional relationship likely between COPD and depressionCOPD may increase risk of developing depression Highest within first year following diagnosisDepression may increase risk of exacerbations requiring admission and mortality

1)Tsai TY et al. Increased risk and related factors of depression among patients with COPD: a population based cohort study. BMC Public Health. Oct 19.13:976. 2013 2)

Laurin C et al. Impact of Anxiety and Depression on Chronic Obstructive Pulmonary Disease Exacerbation Risk. Am J

Respir

Crit

Care Med. 185(9):918-923. 2012.

3) Fan V et al. Sex, depression, and Risk of Hospitalization and Mortality in Chronic Obstructive Pulmonary Disease. Arch Intern Med. 167(21):2345-2353. 2007.

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Effect of COPD on depression

InflammationAnxiety and depressed mood induced by endotoxin exposurePositively correlated with cytokine secretionMDD occurs in about a quarter of pts given interferon for Hep CCOPD associated with increased inflammatory markersCRP, WBC, IL-6,IL-8, and fibrinogenRemission of depression accompanied by normalization of inflammatory markersInconsistent associations found between inflammatory markers in COPD and depression

1) Su B et al. Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. .

PLoS

ONE 11

(4): e0150586.

doi:10.1371/journal.pone.0150586. 2016 2)

Reichenburg

A et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 58(5):445-52. 2001.3)

Nguyen H et al. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulmonary Medicine. 16:173. 2016

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Effect of COPD on depression

Loss of functionality Decreased mobilityInability to continue work or recreational activitiesShifted roles in family or workSocial isolation

Norwood R. A review of etiologies of depression in COPD. International Journal of COPD. 2(4):495-491. 2007

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Effect of Depression on COPD

Depression associated with chronic low-grade inflammatory responseStress may play role in release of pro-inflammatory cytokinesReduced availability of tryptophan possible mechanismHyperactivity of HPA axis and hypercortisolemia associated with stress and depressionRelationship and causality not clearPossible worsening of COPD symptoms secondary to weakened immunity and increased inflammation?

1)

Berk

M et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Medicine, 11:200. 2013. 2) Laurin C, et al. Impact of Anxiety and Depression on Chronic Obstructive Pulmonary Disease Exacerbation Risk. Am J

respir

Crit

Care Med. 85(9):918-923. 2012.

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Effect of Depression on COPD

Depressed pts more likely toStart smoking and continue smokingHave poor adherence to medications and pulmonary rehabilitationHave decreased physical activityFail to report symptom deterioration and seek help

Laurin C, et al. Impact of Anxiety and Depression on Chronic Obstructive Pulmonary Disease Exacerbation Risk. Am J respire

Crit

Care Med. 85(9):918-923. 2012.

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Usmani

Z, et al. Systematic meta-analysis of pharmacological interventions for the treatment of anxiety in patients with chronic obstructive pulmonary disease. 2(7);2018

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Safety of Antidepressants in COPD

Vozoris et al. 2018Retrospective studySmall but significant increases inHospitalization or pneumonia (HR 1.15, 95% CI 1.05-1.25)ER visits for COPD or pneumonia (HR 1.13 95% CI 1.03-1.24)All-cause mortality (HR 1.20 95% CI 1.11-1.29)Qian et al. 2013Retrospective studyLower mortality with antidepressant treatmentHR=0.43 95% CI 0.36-0.51

1)

Vozoris

Nt

, et al. Serotonergic antidepressant use and morbidity and mortality among older adults with COPD.

Eur

Respir

J. 52(1). 2018 2

)

Qian

J et al. Effects of Depression Diagnosis and Antidepressant Treatment on Mortality in Medicare Beneficiaries with COPD. J Am

Geriatr

Soc. 61(5):754-761. 2013.

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Treatment of Depression in COPD- Pulmonary Rehab

Pulmonary rehabilitationRetrospective study105 pts completing >6 sessions73% with significant improvement in depression19% with no change8% with worsening depressionHigher depression at baseline more likely to respond

Alsaraireh F, Aloush S. Does pulmonary rehabilitation alleviate depression in older patients with chronic obstructive pulmonary disease. Saudi Med J. 38(5):491-496. 2017

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Treatment of Depression in COPD- Pulmonary Rehab

Small RCT (n=24) 8 weeks of PR in treatment groupSignificant improvementDepressionOverall symptoms, activity, impact of illnessDyspneaImprovement in depression not correlated with improvement in dyspnea

Paz-Diaz H et al. Pulmonary Rehabilitation Improves Depression, Anxiety, Dyspnea and Health Status in Patients with COPD. Am J Phys Med Rehabil. 86(1):30-36. 2005

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Smoking cessation in COPD

Most effective measure for controlling progression Improves responses to bronchodilator drugs and inhaled CSReduces incidence of acute exacerbations and bronchial infectionsAbout 40% of COPD patients are active smokersSome studies show no difference in motivation to quit versus non-COPD smokers

Jimenez-Ruiz C et al. Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Eur

Respir J 46:61-79. 2015.

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Smoking cessation in COPD

Education of importance of stoppingSlowing progressionDecreased dyspnea, cough, exacerbations, infectionsAssessment of motivation and self-efficacyLow self efficacy- treatment and support criticalLow motivation- effective health education and motivational interviewingRCT using spirometry to show lung ageSignificant difference in success compared to controlNNT=14

Jimenez-Ruiz C et al. Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Eur

Respir J 46:61-79. 2015. Parkes G, et al. Effect on smoking quit rate of telling patients their lung age: the Step2quit randomized controlled trial. BMJ. 336(7644):598-600. 2008

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Smoking cessation in COPD

Assessment of nicotine dependenceMay still be high despite low total number of cigarettes/dSmoking within 30 minutes of awakening sign of high dependenceDiscussion of previous attempts at quittingMost take 4-7 times to successfully quitCounselling EducationSetting quit date Non-judgmental stanceMotivational interviewing techniquesGroup interventions equally effective as individual support

Jimenez-Ruiz C et al. Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Eur

Respir J 46:61-79. 2015.

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Smoking Cessation in COPD

Nicotine replacement therapySeveral formsIncrease risk of quitting 50-70%No clear differences between formsCombining patch with oral form more effective than either alone

1)Stead LF,

Perera

R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database of

Syst

Rev. 2012, Issue 11. Art. No.: CD000146.

doi

: 10.1002/14651858.CD000146.pub4.

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Smoking cessation in COPD

Varenicline RCT of 504 smokers with COPDContinuous abstinence rate weeks 9-52 18.6% versus 5.6% (OR, 4.04; 95% CI, 2.13-7.67; P<.0001)Bupropion 150mg bidRCT of 404 smokers with mild-mod COPDAbstinence rate of 16% versus 9% for placebo at 6 months (p=<0.05)Somewhat less effective than combination NRT or vareniclineCombined varenicline and buproprion more effective than varenicline alone71% abstinence rate versus 43.8% (CI, 1.11-8.92; p=0.16)Only in heavily dependent smokers

1)Tashkin DP, et al. Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled,

randomised

trial. Lancet 2001; 357: 1571–1575. 2)Tashkin DP, et al Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest. 139(3):591-599.

2011 3) Rose JE,

Behm

FM. Combination

Varenicline

/

Buproprion

Treatment Benefits Highly Dependent Smokers in an Adaptive Smoking Cessation Program. Nicotine

Tob

Res. 19(8):999-1002. 2017.

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Summary

Anxiety and depression are common problems in COPD

Bidirectional relationships between COPD and anxiety and depression likely

Approach to treatment multifaceted

Medications

Psychotherapy

Pulmonary rehabilitation

Smoking cessation critical in COPD and more difficult with untreated anxiety and depression