Presentation on theme: "Pain, Anxiety & Depression:"— Presentation transcript:
1Pain, Anxiety & Depression: the aches of the psycheDr. Ahmed El MissiryDPP Msc (neuro-psych) MD MRCPsych MISAM, LLB LawA Professor of Psychiatry – ASUIP – WHOConsultant Psychiatrist – Kent & Medway NHSResearcher, Neuropsychopharmacology DepartmentZurich Institute of Technology, SwitzerlandRegional Representative – Royal College of Psychiatrists (Addiction – KSS)
2Disclosure In the past three years I received Honorariums from ApexPharma, Astra Zeneca, BMS, Delta, Janssen Cilag, Lily, Lundbeck, Pfizer, WyethResearch grants from ApexPharmaAdvisory ApexPharma, Janssen Cilag, Pharmed International
3The aches of the psyche … I do not like my state of mindI'm bitter, querulous, unkind.I am always anxious and tensemy thoughts make no senseI dread the dawn's recurrent light;I hate to go to bed at night.I find no peace in paint or typeMy world is but a lot of tripe.I'm disillusioned, empty-breastedFor what I think, I'd be arrested.I am not sick, I am not wellMy quondam dreams are shot to hell.My soul is crushed, my spirit sore;I do not like me any more.I want to stop this pain … before I turn insaneAdapted poems
4Not knowing where he was, his wife inserted her hands under his clothing and said: “My brother, no fever in your chest and limbs, but sadness of the heart…”Ebbs Papyrus
5Greek MythologyTHE ALGEA were the spirits of pain and suffering of both body and mind and are related to Oizys, the goddess of misery and sadness, and Penthos the god of mourning and lamentation.Mens Sana en Corpora SanaDecimus Iuvenalis
6Why Pain, psychological distress (Anxiety and Depression)? Anxiety, Depression and Pain Symptoms are highly prevalent conditionsLifetime prevalence of Pain = 24-37%1Lifetime prevalence of Depression = 5-10%2Lifetime prevalence of Anxiety= 20%2Anxiety, Depression and Pain complicate each other, affect outcomes, cause more morbidity and disability and increase costs.Regier DA, Myers JK, Kramer M, et al. The NIMH Epidemiologic Catchment Area program: historical context, major objectives, and study population characteristics. Arch Gen Psychiatry.1984;41:Kessler, R.C., S. Zhao, D.G. Blazer, and M. Swartz, Prevalence, correlates, and course of minor depression and major depression in the National Comorbidity Survey. J Affect Disord, (1-2): p
7“Comorbidity is the rule, not the exception” Lifetime comorbidity of mood and anxiety disorders“Comorbidity is the rule, not the exception”1 Kessler et al, Arch Gen Psychiatry 1995; 2 DSM-IV-TR™ 2000; 3 Brawman-Mintzer et al, Am J Psychiatry 1993;4 Rasmussen et al, J Clin Psychiatry 1992 ; 5Dunner, Depression and Anxiety 2001DEPRESSION48% of patients with PTSD1Up to 65% of patients with Panic Disorder267% of patients with Obsessive-Compulsive Disorder442% of patients with Generalised Anxiety Disorder3Up to 70% of patients with Social Anxiety Disorder5Panic DisorderGADSocial Anxiety DisorderPost-Traumatic Stress DisorderOCDPain comorbidity= Av 65%Pain
8topics today Strength of association (D/R – Predictive) Can Pain be distressing? What is the prevalence of Anxiety & depression in painful disorders?Do depression & anxiety hurt? What is the prevalence of pain symptoms in Anxiety & depression?Does the presence of pain affect recognition and treatment of anxiety / depression?What is the common neurobiological basis of pain/anxiety/ depression?What are the treatments available?
9Can pain be distressing ?!! The prevalence of depression in pain disorders In general population pain = 18% (4.7%-22%)In Primary Care clinics = 27% (5.9%-46%)In pain clinics = 52% (1.5%-100%)In orthopedic clinics = 56% (21%-89%)In dental/facial pain clinics = 85% (35%-100%)In gynecology pelvic pain clinics = 13% (12%-17%)Prevalence of anxiety disorders in patients with chronic painIn general population= 35 % back pain clinic = 20% - 57% [3,4]1- Matthew et al Arch Intern Med. ;163: , 20032- Manchikanti et al Pain Physician, Volume 5, Number 2, pp , 20023- Sommer 18th European Congress of Psychiatry. February 27, March 2, 20104- Moya et al Aten Primaria Sep 15;26(4):
10The likelihood of anxiety and depression increase with the number of painful symptoms One thousand adult patientsAny SymptomDepressionAnxietyNPain16 (7)5 (2)2 (1)2150-150 (22)27 (12)17 (7)2252-367 (35)44 (23)25 (13)1914-5140 (61)100 (44)68 (30)2306-8113 (81)84 (80)68 (48)1309+Kroenke K, Spitzer RL, Williams JB, et al. Physical symptoms in primary care: predictors of psychiatric disorders and functional impairment. Arch Fam Med.1994;3:
11Increasing pain predicts increased Anxiety & Depression <0.001N=448Requited from Primary care<0.001Blozik et al BMC Musculoskelet Disord Jan 26;10:13.
13Does Depression Hurt?!The prevalence of pain in depressed ranged from 15% to 100% (mean prevalence, 65%).Patients With Pain, %Study SettingNo. of PatientsSource69Primary care573Bair et al51Psychiatric inpatients29Delaplaine et al85Neurology clinic432Diamond59Outpatient clinicHollifield et alPrivate practice196Lindsay and Wyckoff77 Headache37 chest painResearch institutionMathew et al56Psychiatric patientsMerskey and Spear4122Pelz et al65Depressed outpatients150Singhl43General practice28Vaeroy and Merskey6040von Knorring57161von Knorring et al100Respondents to newspaper advertisement16Ward et al15Watts
14Chronic Pain in Depression Does Depression Hurt?!Chronic Pain in Depressionsubjects representative of the general populations of the United Kingdom, Germany, Italy, Portugal, and Spain.Pain was 4 times more likely in subjects with major depressive disorder (OR 4.0; 95% CI, )Ohayon & Schatzberg Arch Gen Psychiatry. 2003;60:39-47
15Does Depression Hurt?! Results from the FINDER study FINDER was a 6-month prospective, observational study of 3468 outpatients with depression initiating antidepressant treatment.56.3% experienced mod/severe pain53.6% had mod/severe pain-related interference with functioning.Demyttenaere et al (2010) Journal of Affective Disorders –60
1643% of depressed patients experienced chronic painful symptoms1 More Depressive Symptoms … more pain43% of depressed patients experiencedchronic painful symptoms1Normal mood (n=18,232)50Participants with at least 1 depressivesymptom (n=3140)††40Depression – 5 DSM-IV criteria met (n=748)30Patients (%)††20††††*10*††**†BackacheGI diseaseJoint/articularHeadacheLimb ache 1 ChronicpainfulsymptomGraph adapted from Ohayon MM, Schatzberg AF. Arch Gen Psychiatry 2003;60: 39–47.
17Are Pain symptoms a marker for depression? 1,042 consecutive outpatients screened for depressionGerber et al J Gen Intern Med Mar-Apr;7(2):170-3
18Does Anxiety Hurt?! *** *** Brandenburg et al. Poster presented at The 25th Annual Conference of the Anxiety Disorders Association of America (ADAA) , March 2005, Seattle, WA, USA
19Are Pain symptoms a marker for Anxiety? 4030201033%31%28%26%anxiety disorders (%)Prevalence inChest pain Abdominal Headache FatiguepainKroenke K et al. Arch Fam Med 1994;3:774–779
20Does Pain affect the recognition of Anxiety & Depressive disorders? More than 50% of depressed or anxious patients presenting with pain are not recognizedRates of Recognition of Depression and Anxietyby Style of Clinical PresentationRecognised by Clinician (%)Persistent presented with only somatic & did not believe any psychological causepresented with only somatic symptomsInitial presented with only 1 somaticInitial presented with 1 psychological symptomKirmayer LJ et al. Am J Psychiatry 1993; 150:
21Why we can not see the depression and anxiety in pain? The Central effectStahl, 2008
22Why we can not see the pain in depression? The Central effectStahl, 2008
23Difficulty concentrating Why we can not see the pain?Diagnostic Criterion BiasSymptom OverlapAnxiety*DepressionAnxietyWorryDry mouthPalpitationsSweatingTremblingBlushingStutteringDepressed moodLoss of interest or pleasureAppetite disturbanceWorthlessnessSuicidal ideationLow self-esteemAgitationIrritabilityFatigueDifficulty concentratingSleep disturbanceMuscle tensionGI complaintsPain*Symptoms of GAD and SAD.DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
24The Spectrum of Symptoms Why we can not see the depression?2- Diagnostic Criterion BiasThe Spectrum of SymptomsPhysical SymptomsEmotional SymptomBody Aches and PainsSadness & TearfulnessHeadachesLoss of InterestTiredness and FatigueAnxiety / IrritabilitySexual dysfunctionHopelessnessGI ChangesConcentration DifficultiesVasomotor changesNegative cognitions & GuiltSuicidal IdeationsSleep DisturbancesAppetite \wt changesPsychomotor problemsAdapted from DSM-IV APA 1994
27Somatization Vs Psycholization: Why we can not see the depression?3- Presentation BiasSomatization Vs Psycholization:Cheung (1987) described 3 explanatory models for illness;psychological,somatic, ormixedIn depression:45-95% Report Somatic symptoms only50% Report unexplained symptoms11% Denies depression
28Depression and anxiety are Often Missed when The Presentation is Physical Adapted from Kirmayer et al AJP1993
29The effect of poor recognition on the patient’s treatment MistreatmentUnder treatmentDecreased treatment efficacyPolypharmacyIncrease risk of side effects /drug interactionsIncrease risk of substance misuse
30The effect of poor recognition on the treatment outcomes Increase depressionIncrease PainIncrease functional disabilityDecrease quality of LifeIncreased Relapse RatesDecreased Remission RatesIncrease health care utilizationIncrease suicide rates
31Pain is an independent risk factor for suicide  Chronic pain associated with increased risk of suicide [1, 2, 3] Rates of suicidal ideation & attempts [4, 5]Over 30% of chronic pain patients reported suicidal ideation 37% of patients receiving opioid therapy reported suicidal thoughts & 20% an attempt .Mental pain in is associated with risk of suicide . Fishbain et al Clin J Pain. 1991;7:29–36 Penttinen et al Am J Public Health. 1995;85:1452–1453. Tang et al Psychol Med. 2006;36:575–586 Breslau et al Neurology. 1992;42:392–395. Hinkley et al 1994;9:175–185. Edwards et al Pain. 2006;126:272–279. Saffier et al. K Journal of Substance Abuse Treatment. 2007;33:303–311 Ilgen et al Gen Hosp Psychiatry. 2008; 30(6): 521–527. Van Heeringen et al Psychiatry Res Feb 28;181(2):141-4.
32“For several years I have been aware of my own mortality, for some strange reason it had been on my mind…Since I have had this deteriorating back problem which causes constant pain and …… a barrier of intimacy … . I had two spinal interventions to cure the pain, I had great disappointment when the first failed, and was devastated when the second failed, ….I was told nothing… I have had one hope and now it is gone …. this feels like the sword of Damocles …. How long it will be another day, month, several months? Before I…..”Jan 2008
35Descending Inhibitory System Opiate(endorphins)SerotoninNorepenephrineSympatheticDescending Inhibitory System++Sub P (NK1,2,3)VIP (VIPR)SomatostatinCalcitoninGABAGlutamateGlycineNMDANOCCKStahl, 2008
38Distress and pain disorders share the same anatomical sites executive functions & perceived control over painProcess information from sensory to emotional (mood & pain)Rational cognitive functions & pain processingAssociative and episodic memoriesmemory of emotional reactionsRewardincreases in negative affects
39Induction of Negative Mood Disrupts Emotion Regulation Neurocircuitry and Enhances Pain UnpleasantnessNegative or neutral moods were induced in healthy volunteers who underwent heat pain whilst in an fMRI scanner.Pain was rated more unpleasant after the sad mood induction. Depressed mood was associated with increases in negative pain-related cognitions (catastrophizing)Background: Depressed mood alters the pain experience. Yet, despite its clear clinical relevance, little is known about the cognitive and neural mechanisms underlying this phenomenon. We tested an experimental manipulation to unravel the interaction between depressedmood and pain. We hypothesized that dysregulation of the neural circuitry underlying emotion regulation is the mechanism whereby painprocessing is affected during depressed mood.Methods: Using functional magnetic resonance imaging, we compared the effects of sad and neutral cognitive mood inductions on affective pain ratings, pain-specific cognitions, and central pain processing of a tonic noxious heat stimulus in 20 healthy volunteers.Results: The increase in negative pain-specific cognitions during depressed mood predicted the perceived increase in pain unpleasantness. Following depressed mood induction, brain responses to noxious thermal stimuli were characterized by increased activity in a broad network including prefrontal areas, subgenual anterior cingulate cortex, and hippocampus, as well as significantly less deactivation whencompared with pain responses in a neutral mood. The participants who reported the largest increase in pain unpleasantness after the sadmood induction showed greater inferior frontal gyrus and amygdala activation, linking changes in emotion regulation mechanisms withenhancement of pain affect.Conclusions: Our results informhowdepressedmoodand chronic pain co-occur clinically and may serve to develop and translate effectiveinterventions using pharmacological or psychological treatment.Areas that showed increased activity during pain in the depressed mood state - left insula, thalamus, hippocampus, IFG, dlPFC, OFC, and the sACC. The thalamus and the insular cortex are part of the afferent nociceptive network.dlPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; OFC, orbitofrontal cortex sACC – subgenual anteria cingulate cortexBerna C et al. Biol Psychiatry 2010;67:
40Proposed cognitive models increased negative mood → increased catastrophizing → increased pain unpleasantnessPain related cognitionsIncreased catastrophizing (rumination)More activity in IFG and amygdalaeinduced Negative moodexplains 34% variabilityStrong effectMechanisitic hypothesis: Dysfunction of emotion regulationIncreased cognitive loadPainIncreased Pain Unpleasantnessexplains 58% variabilityNo effectIncreased activity in the left IFG, dlPFC and OFCChange in neural processing in prefrontal areasLess activity in IFG and amygdalaeBerna C et al. Biol Psychiatry 2010;67:dlPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; OFC, orbitofrontal cortex
41Depressed patients seen in primary care How we can help ?Increase Awareness Better identification Proper & early treatment for Neuropathic Pain Proper & early treatment for Depression/anxietyDepressed patients seen in primary care
42Treatment for Neuropathic Pain Treatment / control of causeAlternative treatments (TENS, Acupuncture)Pharmacotherapy:NSAID / Pain KillersSNRIs / TCAAnti-epilepticsAlpha 2 Delta agonistsOpiate Based preparation !!TMSEpidural blocksImplantable drug pumpsNeurostimulationsurgical interventionsPsychological: CBT for Pain
43Risk of iatrogenic addiction in patients treated with opioids A systematic review 41 studies with conflicting findings Risk can be relatively high (>10%) or low (<0.1%). A systematic review noted the prevalence of Lifetime SUD 36% to 56%Current SUD 43%Aberrant medication-taking behaviours 5% to 24%Risk factors for opioid abuse in patients with chronic pain are :young age,male gender,past alcohol or cocaine abuse,previous drug conviction,mental health disorders,pain in multiple regions,pain after MVA Wasan et al  Martell et al 2007 Højsted & Sjøgren
44Opioid treatment; may need a revisit A large population-based study found that opioid usage was significantly associated with:more severe pain,poorer self-rated health,lower quality of life,less physical activity,lower employment,higher levels of health careutilization, andmore subjects living aloneimpaired neuropsychological performance reaction times, psychomotor speed, and working memoryHøjsted & Sjøgren Curr Opin Anaesthesiol Oct;20(5):451-5.
4520-30% partial response (Residual symptom). Treatment of anxiety and depression(4)Psychosocial andoccupationalfunctioningrestoredAim at Recovery(3)Sustainedabsence ofsymptoms(2)Remission ofsymptomsQuality of RecoverySymptomatic recoverySyndromal recoveryFunctional recovery.(1)ResponseTo treatment20-30% partial response (Residual symptom).Road To Recovery
46Residual Symptoms Predicts Higher Relapse Rates 20406080100120124681012Months of Follow-upProbability of Remaining Well (%)Remission (n=41)Residual Symptoms(n=19)Rush AJ, et al Psychiatry Ann. 1995; 25: 704
47What is the impact of pain on treatment? The challenge in treatmentWhat is the impact of pain on treatment?Painful Somatic symptoms may be less responsive to treatment relative to other symptomsDepressive symptomsPositive well beingNon painfulSomatic symptomsPainful SomaticsymptomsGreco T et al. J Gen Intern Med 2004; 19:
48Painful symptoms are associated with worse depression outcome What is the impact of pain on treatment?the ARTIST TrialDepression outcome at 6 month for n=573 Treated in primary carePainful symptoms are associated with worse depression outcome458 (80%) have pain190 (33%) mild pain165 (29%) moderate pain103 (18%) severe painDepressive symptomsAround 60% adequate treatment was givenDeVeaugh-Geiss ey al Pain Medicine 2010; 11: 732–741
49How to achieve recovery? Proper identification & early treatment for DepressionPharmacotherapy:SNRIs / TCAMood stabilizers (CBZ)Alpha 2 Delta agonists (pregabalin / Gabalin)BZDPipe Lines: NMDA AntagonistsSomatic Treatment: TMSPsychosocial:CBT for Depression, social inclusion & re-habitation
50What Antidepressant to Use? Pooled data from Thase et al & Nemerrof et al
51What Antidepressant to Use in painful depression?
52What SNRI to use in Painful Anxiety & Depression? Duloxetine & Venlafaxine are both effective….-16-14-12-10-8-6-4-21234681012Least Squares Mean ChangeDuloxetine (n=318)Venlafaxine XL (n=330)WeeksDuloxetine 60mg ODDuloxetine 60-120mgVen 75mg ODVen 150mg ODVen 150225mgImprovementNo significant difference at 6 or 12 weeksPerahia D et al. Comparing Duloxetine and Venlafaxine in the Treatment of Major Depressive DisorderUsing a Global Benefit-Risk Approach. New Clinical Drug Evaluation Unit (NCDEU) Florida 2005
53What Antiepileptic to use? NNTAnticonvulsant mechanisms of actionReduction of excitatory amino acid activityModulation ofCa++ChannelsIncrease in CNS GABA activityDecrease in sodium channel activityDrug3.3 (2–9.4)+Carbamazepine3.7 (2.4–8.3)+ (?)GabapentinLamotrigine3.0 (2.3–4.5)Topiramate3.3 (2.3–5.9)PregabalinVinik J Clin Endocrinol Metab Aug;90(8):
54PregabalinSibilia Quilici et al BMC Neurology 2009
55Pregabalin HAM-A score 20 HAM-D score <15 *** *** *** *** *** * ** †***†***†***†***†****//D4EP*P<0.05, **P<0.01, ***P0.001 vs. placebo†P<0.05 vs. venlafaxineTelephone assessment on Day 4. Mean baseline HAM-A ~27.5.Change over time based on MMRM analysis. Endpoint: 8 weeks (LOCF, ANCOVA)Herman et al. CINP 2008
57What other interventions to use? PsychologicalUsesBehaviouralIncrease exercise/activity levels; overcome fear–avoidanceCognitive-behaviouralReduce depression and anxiety associated with pain; develop effective coping strategies; reduce problematic cognitive styles.InterpersonalAddress role transitions due to pain; relationship difficulties/conflictsAdjunctive techniquesBiofeedbackMuscle relaxation; control of physiological parameters contributing to pain (e.g., headache)Guided imageryRelaxation; distraction from painHypnosisRelaxation; pain severity reduction; distractionProgressive muscle relaxationMuscle relaxation; distraction from pain
58Conclusion:Despite the frequent coexistence of depression , anxiety and pain the magnitude and implications of that relationship are still unclear.Neglecting the treatment of fatigue, low energy , and painful physical symptoms in depressed patients can lead to unsatisfactory outcomes, characterized by a failure of depressed patients to return to normal social and occupational functioning.Keller MB et al 1992 , Judd LL et all 1998, Angst J 1992and Kupfer DJ 1991; Sheline YI et al 1996; Blier P et al. 2001
60THANKS Dr. Ahmed El Missiry A Professor of Psychiatry – ASUIP – WHO DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB LawA Professor of Psychiatry – ASUIP – WHOConsultant Psychiatrist – Kent & Medway NHSResearcher, Neuropsychopharmacology DepartmentZurich Institute of Technology, SwitzerlandRoyal College of Psychiatrists Regional Representative KSS – AddictionOffice:Pagoda CMHC Hermitage Lane, Barming Maidstone.Kent ME16 9PDTel:Mobile: