Dr. Dr. Ahmed El Missiry Ahmed El Missiry DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law A Professor of Psychiatry – ASUIP – WHO A Professor of Psychiatry – ASUIP – WHO Consultant Psychiatrist – Kent & Medway NHS Consultant Psychiatrist – Kent & Medway NHS Researcher, Neuropsychopharmacology Department Researcher, Neuropsychopharmacology Department Zurich Institute of Technology, Switzerland Zurich Institute of Technology, Switzerland Regional Representative – Royal College of Psychiatrists Regional Representative – Royal College of Psychiatrists (Addiction – KSS) (Addiction – KSS)
Transcript
Dr.Dr. Ahmed El MissiryAhmed El MissiryDPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law
A Professor of Psychiatry – ASUIP – WHO A Professor of Psychiatry – ASUIP – WHO Consultant Psychiatrist – Kent & Medway NHSConsultant Psychiatrist – Kent & Medway NHS
Researcher, Neuropsychopharmacology DepartmentResearcher, Neuropsychopharmacology DepartmentZurich Institute of Technology, SwitzerlandZurich Institute of Technology, Switzerland
Regional Representative – Royal College of Psychiatrists Regional Representative – Royal College of Psychiatrists (Addiction – KSS) (Addiction – KSS)
DisclosureDisclosure
In the past three years I received In the past three years I received
Honorariums from ApexPharma, Astra Zeneca, Honorariums from ApexPharma, Astra Zeneca,
The aches of the psycheThe aches of the psyche ……I do not like my state of mind I do not like my state of mind
I'm bitter, querulous, unkind.I'm bitter, querulous, unkind.I am always anxious and tense I am always anxious and tense
my thoughts make no sense my thoughts make no sense I dread the dawn's recurrent light; I dread the dawn's recurrent light;
I hate to go to bed at night.I hate to go to bed at night.I find no peace in paint or typeI find no peace in paint or type My world is but a lot of tripe. My world is but a lot of tripe. I'm disillusioned, empty-breastedI'm disillusioned, empty-breasted
ForFor what I think, I'd be arrested.what I think, I'd be arrested.I am not sick, I am not wellI am not sick, I am not well
My quondam dreams are shot to hell.My quondam dreams are shot to hell.My soul is crushed, my spirit sore; My soul is crushed, my spirit sore;
I do not like me any more.I do not like me any more.I want to stop this pain I want to stop this pain …… before I turn insane before I turn insane
Adapted poems
Not knowing where he was, his wife Not knowing where he was, his wife inserted her hands under his clothing inserted her hands under his clothing and said:and said:
““My brother, no fever in your My brother, no fever in your chest and limbs, chest and limbs, butbut sadness of sadness of
the heart…the heart…””
Ebbs Papyrus
Greek MythologyGreek Mythology
THE ALGEATHE ALGEA were the were the spirits of pain spirits of pain and suffering of both and suffering of both bodybody and and mind mind and are related to and are related to OizysOizys, the , the goddess goddess of miseryof misery and and sadnesssadness, and , and PenthosPenthos the god of the god of mourning and lamentationmourning and lamentation. .
Mens Sana en Corpora Sana Decimus Iuvenalis
Why Pain, psychological distress Why Pain, psychological distress (Anxiety and Depression)(Anxiety and Depression)??
Anxiety, Depression and Pain Symptoms Anxiety, Depression and Pain Symptoms are highly prevalent conditionsare highly prevalent conditions– Lifetime prevalence of Pain = 24-37%Lifetime prevalence of Pain = 24-37%11
– Lifetime prevalence of Depression = 5-10%Lifetime prevalence of Depression = 5-10%22
– Lifetime prevalence of Anxiety= 20%Lifetime prevalence of Anxiety= 20%22
Anxiety, Depression and Pain complicate Anxiety, Depression and Pain complicate each other, affect outcomes, cause more each other, affect outcomes, cause more morbidity and disability and increase costs. 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;41:934-941. 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, 1997. 45(1-2): p. 19-30.
Lifetime comorbidity of Lifetime comorbidity of mood and anxiety disordersmood and anxiety disorders
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 2001
DEPRESSION
48% of patients with PTSD1 Up to 65% of patients with Panic Disorder2
67% of patients with Obsessive-Compulsive Disorder4
42% of patients with Generalised Anxiety Disorder3
Up to 70% of patients with Social Anxiety Disorder5
Panic Disorder
GAD
Social Anxiety Disorder
Post-Traumatic Stress Disorder
OCD
“Comorbidity is the rule, not the exception”
Pain
Pain comorbidity= Av 65%
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?
Can pain be distressing ?!!Can pain be distressing ?!!The prevalence of depression in pain disordersThe prevalence of depression in pain disorders [1] [1]
– In general population pain = In general population pain = 18% 18% (4.7%-22%)(4.7%-22%)– In Primary Care clinics = In Primary Care clinics = 27% 27% (5.9%-46%)(5.9%-46%)– In pain clinics = In pain clinics = 52% 52% (1.5%-100%)(1.5%-100%)– In orthopedic clinics = In orthopedic clinics = 56% 56% (21%-89%)(21%-89%)– In dental/facial pain clinics = In dental/facial pain clinics = 85% 85% (35%-100%)(35%-100%)– In gynecology pelvic pain clinics = In gynecology pelvic pain clinics = 13% 13% (12%-17%)(12%-17%)
Prevalence of anxiety disorders in patients with chronic painPrevalence of anxiety disorders in patients with chronic pain– In general population= In general population= 35 % 35 % [2][2]
– back pain clinic = back pain clinic = 20% - 57% 20% - 57% [3,4][3,4]
1- Matthew et al Arch Intern Med. ;163:2433-2445, 20032- Manchikanti et al Pain Physician, Volume 5, Number 2, pp 149-15, 2002 3- Sommer 18th European Congress of Psychiatry. February 27, March 2, 20104- Moya et al Aten Primaria. 2000 Sep 15;26(4):239-44.
The likelihood of anxiety and depression The likelihood of anxiety and depression increase with the number of painful increase with the number of painful
symptomssymptoms
Kroenke K, Spitzer RL, Williams JB, et al. Physical symptoms in primary care: predictors of psychiatric disorders and functional impairment. Arch Fam Med.1994;3:774-779.
Blozik et al BMC Musculoskelet Disord. 2009 Jan 26;10:13.
N=448
Requited from Primary care
Does Depression Hurt?!Does Depression Hurt?!The prevalence of pain in depressed ranged from The prevalence of pain in depressed ranged from 15% 15% toto 100% 100% ( (mean prevalence, 65%mean prevalence, 65%). ).
SourceNo. of PatientsStudy SettingPatients With Pain, %
Bair et al573Primary care69
Delaplaine et al29Psychiatric inpatients51
Diamond432Neurology clinic85
Hollifield et al29Outpatient clinic59
Lindsay and Wyckoff196Private practice59
Mathew et al51Research institution77 Headache37 chest pain
Merskey and Spear85Psychiatric patients56
Pelz et al22Psychiatric patients41
Singhl150Depressed outpatients65
Vaeroy and Merskey28General practice43
von Knorring40Psychiatric inpatients60
von Knorring et al161Psychiatric inpatients57
Ward et al16Respondents to newspaper advertisement
100
Watts 100Psychiatric patients15
Chronic Pain in DepressionChronic Pain in Depression
18 980 subjects representative of the general populations of the United Kingdom, Germany, Italy, Portugal, and Spain.
Ohayon & Schatzberg Arch Gen Psychiatry. 2003;60:39-47
Does Depression Hurt?!Does Depression Hurt?!
Pain was 4 times more likely in subjects with major depressive disorder (OR 4.0; 95% CI, 3.5-4.7)
Does Depression Hurt?!Does Depression Hurt?!Results from the FINDER study
Demyttenaere et al (2010) Journal of Affective Disorders 125 53–60
FINDER was a 6-month prospective, observational study of 3468 outpatients with depression initiating antidepressant treatment.
•56.3% experienced mod/severe pain
•53.6% had mod/severe pain-related interference with functioning.
Graph adapted from Ohayon MM, Schatzberg AF. Arch Gen Psychiatry 2003;60: 39–47.
43% of depressed patients experienced chronic painful symptoms1
Pat
ient
s (%
)
Normal mood (n=18,232)
Participants with at least 1 depressivesymptom (n=3140)Depression – 5 DSM-IV criteria met (n=748)
0
10
20
30
40
50
Backache GI disease Joint/articular
Headache Limb ache 1 Chronicpainful
symptom
*††
* †*
*††
††
††
††
More Depressive Symptoms … More Depressive Symptoms … more painmore pain
Are Pain symptoms a marker for depression?
61 60
4339 39 39 37
0
10
20
30
40
50
60
70
sleepdisturbance
fatigue multiple complaints
(3+)
back pain shortness ofbreath
amplifiedcomplaints
vaguecomplaintsP
osi
tive
Pre
dic
tive
Val
ue
for
Dep
ress
ion
Gerber et al J Gen Intern Med. 1992 Mar-Apr;7(2):170-3
1,042 consecutive outpatients screened for depression
Does Anxiety Hurt?!Does Anxiety Hurt?!
0
10
20
30
40
50
60
Chronic pain (all) Neuropathic pain only
Condition
% o
f sub
ject
s
GAD population (n=13,386) Controls (n=89,971)
Brandenburg et al. Poster presented at The 25th Annual Conference of the Anxiety Disorders Association of America (ADAA) , March 2005, Seattle, WA, USA
***
***
Are Pain symptoms a marker for Anxiety?
n=1000
Kroenke K et al. Arch Fam Med 1994;3:774–779
Pre
va
len
ce
in
an
xie
ty d
iso
rde
rs (
%)
Chest pain Abdominal Headache Fatigue
40
30
20
10
0
33%31%
28% 26%
pain
77%
52%
38%
23%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Psychological Initial Somatic FacultativeSomatic
Persistent Somatic
Rec
og
nis
ed b
y C
lin
icia
n (
%) Rates of Recognition of Depression and Anxiety
by Style of Clinical Presentation
Kirmayer LJ et al. Am J Psychiatry 1993; 150: 734-741
Initial presented with 1 psychological
symptom
Initial presented with only 1 somatic
presented with only somatic symptoms
Persistent presented with only somatic & did not believe any
psychological cause
Does Pain affect the recognition of Anxiety & Depressive disorders? More than 50% of depressed or anxious
patients presenting with pain are not recognized
The Central effect
Stahl, 2008
Why we can not see the depression and anxiety in Why we can not see the depression and anxiety in pain?pain?
The Central effect
Stahl, 2008
Why we can not see the pain in depression?Why we can not see the pain in depression?
Why we can not see the pain?Why we can not see the pain?Diagnostic Criterion Bias
*Symptoms of GAD and SAD.DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
Symptom OverlapSymptom OverlapAnxiety*
Depressed mood
Loss of interest or pleasure
Appetite disturbance
Worthlessness
Suicidal ideation
Low self-esteem
AgitationIrritabilityFatigue
Difficulty concentrating
Sleep disturbanceMuscle tensionGI complaints
Pain
Anxiety
Worry
Dry mouth
Palpitations
Sweating
Trembling
Blushing
Stuttering
Depression
The Spectrum of Symptoms
Emotional SymptomPhysical SymptomsSadness & TearfulnessBody Aches and Pains
Loss of InterestHeadaches
Anxiety / IrritabilityTiredness and Fatigue
HopelessnessSexual dysfunction
Concentration DifficultiesGI Changes
Negative cognitions & GuiltVasomotor changes
Suicidal Ideations
Sleep Disturbances
Appetite \wt changes
Psychomotor problemsAdapted from DSM-IV APA 1994
Why we can not see the depression?Why we can not see the depression?2- Diagnostic Criterion Bias
Affective Spectrum DisordersAffective Spectrum Disordersassociated with painassociated with pain
Mood disorders
Major depressive disorderMajor depressive disorder
PolypharmacyPolypharmacy– Increase risk of side effects /drug interactions Increase risk of side effects /drug interactions – Increase risk of substance misuseIncrease risk of substance misuse
The effect of poor recognition on The effect of poor recognition on the treatment outcomesthe treatment outcomes
Increase depression Increase depression Increase PainIncrease PainIncrease functional disability Increase functional disability Decrease quality of LifeDecrease quality of LifeIncreased Relapse Rates Increased Relapse Rates Decreased Remission RatesDecreased Remission RatesIncrease health care utilizationIncrease health care utilizationIncrease suicide ratesIncrease suicide rates
Pain is an independent risk factor Pain is an independent risk factor for suicide for suicide [8][8]
Chronic pain associated with increased risk of Chronic pain associated with increased risk of suicidesuicide [1, 2, 3][1, 2, 3] Rates of suicidal ideation & attemptsRates of suicidal ideation & attempts [4, 5][4, 5] Over 30% of chronic pain patients reported suicidal Over 30% of chronic pain patients reported suicidal ideationideation [6][6]
37% of patients receiving opioid therapy reported 37% of patients receiving opioid therapy reported suicidal thoughtssuicidal thoughts & & 20% an attempt20% an attempt [7][7]..Mental pain in is associated with Mental pain in is associated with risk of risk of suicidesuicide [9][9]..
[1] Fishbain et al Clin J Pain. 1991;7:29–36[2] Penttinen et al Am J Public Health. 1995;85:1452–1453. [3] Tang et al Psychol Med. 2006;36:575–586[4] Breslau et al Neurology. 1992;42:392–395.[5] Hinkley et al 1994;9:175–185.[6] Edwards et al Pain. 2006;126:272–279.[7] Saffier et al. K Journal of Substance Abuse Treatment. 2007;33:303–311[8] Ilgen et al Gen Hosp Psychiatry. 2008; 30(6): 521–527. [9] Van Heeringen et al Psychiatry Res. 2010 Feb 28;181(2):141-4.
““For several years I have been aware of my For several years I have been aware of my own mortalityown mortality, , for some strange reason it for some strange reason it had been on my mind…had been on my mind…Since I have had Since I have had this deteriorating back problem which this deteriorating back problem which causes constant pain and …… a barrier of causes constant pain and …… a barrier of intimacy …intimacy … . I had two spinal interventions . I had two spinal interventions to cure the pain, I had great to cure the pain, I had great disappointment when the first failed, and disappointment when the first failed, and was devastated when the second failed, was devastated when the second failed, ….….I was told nothingI was told nothing… … I have had one I have had one hope and now it is gone …. this feels like hope and now it is gone …. this feels like the sword of Damocles ….the sword of Damocles …. How long it will How long it will be another day, month, several months? be another day, month, several months? Before I…..”Before I…..”
– Descending inhibitionsDescending inhibitionsOpioid system Opioid system 5HT system 5HT system NE system NE system OthersOthers
– Descending facilitationDescending facilitation
Sensory- Discriminatory
pathway
Motivational Affective pathway
Stahl, 2008
Ascending pathways
Descending Inhibitory System
Opiate
(endorphins)
Serotonin
Norepenephrine
Sub P (NK1,2,3)
VIP (VIPR)
Somatostatin
Calcitonin
GABA
Glutamate
Glycine
NMDA
NO
CCK
Sympathetic
Stahl, 2008
Descending Tracts
PAIN:
Depletion of monoamines
Increase CRF
IL2 – TNF –IL6
DEPRESSION & ANXIETY:
Endogenous OpiatesEndogenous Opiates
NE - NE - 5HT 5HT
CCK
Sub-P
Possible Explanation: Descending Pathways
Distress and pain disorders share the same anatomical sites
Process information from sensory to emotional
(mood & pain)
executive functions & perceived control
over pain
Rational cognitive functions & pain
processing
memory of emotional reactions
Associative and episodic
memories
Reward increases in negative
affects
Induction of Negative Mood Disrupts EmotionInduction of Negative Mood Disrupts EmotionRegulation Neurocircuitry and Enhances PainRegulation Neurocircuitry and Enhances Pain
UnpleasantnessUnpleasantness
Berna C et al. Biol Psychiatry 2010;67:1083-1090
Negative or neutral moods were induced in healthy volunteers who underwent heat pain whilst in an fMRI scanner .
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
Pain was rated more unpleasant after the sad mood induction. Depressed mood was associated with increases in negative pain-related cognitions (catastrophizing)
Increase Awareness Increase Awareness Better identification Better identification Proper & early treatment for Neuropathic Pain Proper & early treatment for Neuropathic Pain Proper & early treatment for Depression/anxiety Proper & early treatment for Depression/anxiety
Treatment for Neuropathic PainTreatment for Neuropathic PainTreatment / control of cause Treatment / control of cause Alternative treatments Alternative treatments (TENS, Acupuncture)(TENS, Acupuncture)Pharmacotherapy: Pharmacotherapy: – NSAID / Pain KillersNSAID / Pain Killers– SNRIs / TCA SNRIs / TCA – Anti-epileptics Anti-epileptics – Alpha 2 Delta agonists Alpha 2 Delta agonists – Opiate Based preparation !!Opiate Based preparation !!
TMSTMSEpidural blocksEpidural blocks Implantable drug pumpsImplantable drug pumpsNeurostimulationNeurostimulationsurgical interventionssurgical interventionsPsychological: Psychological: CBT for Pain CBT for Pain
Risk of iatrogenic addiction in patients treated with opioids
A systematic review 41 A systematic review 41 studies with conflicting studies with conflicting findings findings Risk can be Risk can be relatively high relatively high (<10%)(<10%) or low or low (<0.1%).(<0.1%). [1][1]
A systematic review noted the A systematic review noted the prevalence of prevalence of [2][2]
– Lifetime SUD 36% to 56%Lifetime SUD 36% to 56%– Current SUD 43%Current SUD 43%– Aberrant medication-taking Aberrant medication-taking
behaviours 5% to 24%behaviours 5% to 24%
[1] Wasan et al. 2006 [2] Martell et al 2007
Risk factors for opioid abuse in patients with chronic pain are [3]: •young age, •male gender,•past alcohol or cocaine abuse, •previous drug conviction, •mental health disorders,•pain in multiple regions,•pain after MVA
[3] Højsted & Sjøgren
Opioid treatment; Opioid treatment; may need a revisitmay 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, and more subjects living aloneimpaired neuropsychological performance reaction times, psychomotor speed, and working memory
Psychosocial: Psychosocial: CBT for Depression, social inclusion & re-habitation CBT for Depression, social inclusion & re-habitation
How to achieve recovery?How to achieve recovery?
Pooled data from Thase et al & Nemerrof et al
What Antidepressant to Use?What Antidepressant to Use?
What Antidepressant to Use in What Antidepressant to Use in painful depression?painful depression?
What SNRI to use in Painful Anxiety & What SNRI to use in Painful Anxiety & Depression?Depression?
Duloxetine & Venlafaxine are both effective….Duloxetine & Venlafaxine are both effective….Duloxetine & Venlafaxine are both effective….Duloxetine & Venlafaxine are both effective….
Perahia D et al. Comparing Duloxetine and Venlafaxine in the Treatment of Major Depressive Disorder Using a Global Benefit-Risk Approach. New Clinical Drug Evaluation Unit (NCDEU) Florida 2005
No significant difference at 6 or 12 weeks
-16
-14
-12
-10
-8
-6
-4
-2
0
0 1 2 3 4 6 8 10 12
Leas
t Squ
ares
Mea
n C
hang
e
Duloxetine (n=318)
Venlafaxine XL (n=330)
Weeks
Duloxetine 60mg OD Duloxetine 60-120mg
Ven 75mg OD Ven 150mg OD Ven 150-225mg
Imp
rove
me
nt
What Antiepileptic to use?What Antiepileptic to use?
Telephone 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
What other interventions to use?What other interventions to use?
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.
Conclusion:Conclusion:
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
Dr.Dr. Ahmed El MissiryAhmed El MissiryDPP Msc (neuro-psych) MD MRCPsych MISAM, LLB LawDPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law
A A Professor of Psychiatry – ASUIP – WHOProfessor of Psychiatry – ASUIP – WHO
Consultant Psychiatrist – Kent & Medway NHSConsultant Psychiatrist – Kent & Medway NHSResearcher, Neuropsychopharmacology DepartmentResearcher, Neuropsychopharmacology Department
Zurich Institute of Technology, SwitzerlandZurich Institute of Technology, Switzerland Royal College of Psychiatrists Regional Representative KSS – Royal College of Psychiatrists Regional Representative KSS –
