Presentation on theme: "Dr. Ahmed El Missiry DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law A Professor of Psychiatry – ASUIP – WHO Consultant Psychiatrist – Kent & Medway NHS."— Presentation transcript:
Dr. Ahmed El Missiry DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law A Professor of Psychiatry – ASUIP – WHO Consultant Psychiatrist – Kent & Medway NHS Researcher, Neuropsychopharmacology Department Zurich Institute of Technology, Switzerland Regional Representative – Royal College of Psychiatrists (Addiction – KSS)
Disclosure In the past three years I received Honorariums from ApexPharma, Astra Zeneca, BMS, Delta, Janssen Cilag, Lily, Lundbeck, Pfizer, Wyeth Research grants from ApexPharma Advisory ApexPharma, Janssen Cilag, Pharmed International
The aches of the psyche … I do not like my state of mind I'm bitter, querulous, unkind. I'm bitter, querulous, unkind. I am always anxious and tense my thoughts make no sense my thoughts make no sense 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 type My world is but a lot of tripe. My world is but a lot of tripe. I'm disillusioned, empty-breasted For what I think, I'd be arrested. For what I think, I'd be arrested. I 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; I do not like me any more. I do not like me any more. I want to stop this pain … before I turn insane Adapted poems
Not 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
Greek Mythology THE 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 Sana Decimus Iuvenalis
Why Pain, psychological distress (Anxiety and Depression)? Anxiety, Depression and Pain Symptoms are highly prevalent conditions –Lifetime prevalence of Pain = 24-37% 1 –Lifetime prevalence of Depression = 5-10% 2 –Lifetime prevalence of Anxiety= 20% 2 Anxiety, 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
Lifetime comorbidity of mood 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 ; 5 Dunner, Depression and Anxiety 2001 DEPRESSION 48% of patients with PTSD 1 Up to 65% of patients with Panic Disorder 2 67% of patients with Obsessive-Compulsive Disorder 4 42% of patients with Generalised Anxiety Disorder 3 Up to 70% of patients with Social Anxiety Disorder 5 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 ?!! 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 pain –In general population= 35 %  –back pain clinic = 20% - 57% [3,4] 1- Matthew et al Arch Intern Med. ;163: , Manchikanti et al Pain Physician, Volume 5, Number 2, pp , Sommer 18th European Congress of Psychiatry. February 27, March 2, Moya et al Aten Primaria Sep 15;26(4):
The likelihood of anxiety and depression increase with the number of painful symptoms 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: One thousand adult patients Any SymptomDepressionAnxietyNPain 16 (7)5 (2)2 (1) (22)27 (12)17 (7) (35)44 (23)25 (13) (61)100 (44)68 (30) (81)84 (80)68 (48)1309+
Increasing pain predicts increased Anxiety & Depression <0.001 Blozik et al BMC Musculoskelet Disord Jan 26;10:13. N=448 Requited from Primary care
Does Depression Hurt?! The prevalence of pain in depressed ranged from 15% to 100% (mean prevalence, 65%). Patients With Pain, %Study SettingNo. of PatientsSource 69 Primary care573Bair et al 51 Psychiatric inpatients29Delaplaine et al 85 Neurology clinic432Diamond 59 Outpatient clinic29Hollifield et al 59 Private practice196Lindsay and Wyckoff 77 Headache 37 chest pain Research institution51Mathew et al 56 Psychiatric patients85Merskey and Spear 41 Psychiatric patients22Pelz et al 65 Depressed outpatients150Singhl 43 General practice28Vaeroy and Merskey 60 Psychiatric inpatients40von Knorring 57 Psychiatric inpatients161von Knorring et al 100 Respondents to newspaper advertisement 16Ward et al 15 Psychiatric patients100Watts
Chronic Pain in Depression 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?! Pain was 4 times more likely in subjects with major depressive disorder (OR 4.0; 95% CI, )
Does Depression Hurt?! Results from the FINDER study Demyttenaere et al (2010) Journal of Affective Disorders –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 symptoms 1 Patients (%) Normal mood (n=18,232) Participants with at least 1 depressive symptom (n=3140) Depression – 5 DSM-IV criteria met (n=748) BackacheGI diseaseJoint/ articular HeadacheLimb ache 1 Chronic painful symptom * * * * More Depressive Symptoms … more pain
Are Pain symptoms a marker for depression? Gerber et al J Gen Intern Med Mar-Apr;7(2): ,042 consecutive outpatients screened for depression
Does 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 ***
Are Pain symptoms a marker for Anxiety? n=1000 Kroenke K et al. Arch Fam Med 1994;3:774 – 779 Prevalence in anxiety disorders (%) Chest pain Abdominal Headache Fatigue % 31% 28% 26% pain
Recognised by Clinician (%) Rates of Recognition of Depression and Anxiety by Style of Clinical Presentation Kirmayer LJ et al. Am J Psychiatry 1993; 150: Persistent presented with only somatic & did not believe any psychological cause presented with only somatic symptoms Initial presented with only 1 somatic Initial presented with 1 psychological symptom 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 pain?
The Central effect Stahl, 2008 Why we can not see the pain in depression?
Why we can not see the pain? Diagnostic Criterion Bias *Symptoms of GAD and SAD. DSM-IV-TR. Washington, DC: American Psychiatric Association; Symptom Overlap Anxiety* Depressed mood Loss of interest or pleasure Appetite disturbance Worthlessness Suicidal ideation Low self-esteem Agitation Irritability Fatigue Difficulty concentrating Sleep disturbance Muscle tension GI complaints Pain Anxiety Worry Dry mouth Palpitations Sweating Trembling Blushing Stuttering Depression
The Spectrum of Symptoms Physical SymptomsEmotional Symptom Body Aches and PainsSadness & Tearfulness HeadachesLoss of Interest Tiredness and FatigueAnxiety / Irritability Sexual dysfunctionHopelessness GI ChangesConcentration Difficulties Vasomotor changesNegative cognitions & Guilt Suicidal Ideations Sleep Disturbances Appetite \wt changes Psychomotor problems Adapted from DSM-IV APA 1994 Why we can not see the depression? 2- Diagnostic Criterion Bias
Somatization Vs Psycholization: Cheung (1987) described 3 explanatory models for illness; psychological, somatic, or mixed In depression: 45-95% Report Somatic symptoms only 50% Report unexplained symptoms 11% Denies depression Why we can not see the depression? 3- Presentation Bias
Depression and anxiety are Often Missed when The Presentation is Physical Adapted from Kirmayer et al AJP1993 N=685
The effect of poor recognition on the patients treatment Mistreatment Under treatment Decreased treatment efficacy Polypharmacy –Increase risk of side effects /drug interactions –Increase risk of substance misuse
The effect of poor recognition on the treatment outcomes Increase depression Increase Pain Increase functional disability Decrease quality of Life Increased Relapse Rates Decreased Remission Rates Increase health care utilization Increase suicide rates
Pain 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] 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.
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…..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
The biology of Pain Sensory channels: –Sensory discriminative component –Motivational affective component Pain Modulation –Spinal Modulation (Gate Theory) Melzack and Wall 1965 –Descending inhibitions Opioid system 5HT system NE system Others –Descending facilitation
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
PAIN: Depletion of monoamines Increase CRF IL2 – TNF –IL6 DEPRESSION & ANXIETY: Endogenous Opiates Endogenous Opiates NE - 5HT NE - 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 Emotion Regulation Neurocircuitry and Enhances Pain Unpleasantness Berna C et al. Biol Psychiatry 2010;67: 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 are part of the afferent nociceptive network. dlPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; OFC, orbitofrontal cortex sACC – subgenual anteria cingulate cortex Pain was rated more unpleasant after the sad mood induction. Depressed mood was associated with increases in negative pain-related cognitions (catastrophizing)
Pain Proposed cognitive models Berna C et al. Biol Psychiatry 2010;67: increased negative mood increased catastrophizing increased pain unpleasantness induced Negative mood Pain related cognitions Increased catastrophizing (rumination) Mechanisitic hypothesis: Dysfunction of emotion regulation Increased cognitive load Change in neural processing in prefrontal areas Increased activity in the left IFG, dlPFC and OFC Increased Pain Unpleasantness More activity in IFG and amygdalae Strong effect Less activity in IFG and amygdalae No effect explains 58% variability explains 34% variability dlPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; OFC, orbitofrontal cortex
How we can help ? Depressed patients seen in primary care Increase Awareness Better identification Proper & early treatment for Neuropathic Pain Proper & early treatment for Depression/anxiety Increase Awareness Better identification Proper & early treatment for Neuropathic Pain Proper & early treatment for Depression/anxiety
Treatment for Neuropathic Pain Treatment / control of cause Alternative treatments (TENS, Acupuncture) Pharmacotherapy: –NSAID / Pain Killers –SNRIs / TCA –Anti-epileptics –Alpha 2 Delta agonists –Opiate Based preparation !! TMS Epidural blocks Implantable drug pumps Neurostimulation surgical interventions Psychological: CBT for Pain
Risk of iatrogenic addiction in patients treated with opioids A systematic review 41 studies with conflicting findings Risk can be relatively high (>10%) or low ( 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%  Wasan et al  Martell et al 2007 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  Højsted & Sjøgren
Opioid 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 care utilization, and more subjects living alone impaired neuropsychological performance reaction times, psychomotor speed, and working memory Højsted & Sjøgren Curr Opin Anaesthesiol Oct;20(5):451-5.
(3) Sustained absence of symptoms (3) Sustained absence of symptoms (4) Psychosocial and occupational functioning restored (4) Psychosocial and occupational functioning restored Road To Recovery (1) Response To treatment (1) Response To treatment (2) Remission of symptoms (2) Remission of symptoms Aim at Recovery 20-30% partial response (Residual symptom). Quality of Recovery Symptomatic recovery Syndromal recovery Functional recovery. Treatment of anxiety and depression
Residual Symptoms Predicts Higher Relapse Rates Months of Follow-up Probability of Remaining Well (% ) Remission (n=41) Residual Symptoms (n=19) Rush AJ, et al Psychiatry Ann. 1995; 25: 704
Greco T et al. J Gen Intern Med 2004; 19: Depressive symptoms Positive well being Non painful Somatic symptoms Painful Somatic symptoms Painful Somatic symptoms may be less responsive to treatment relative to other symptoms The challenge in treatment
Depressive symptoms Painful symptoms are associated with worse depression outcome the ARTIST Trial Depression outcome at 6 month for n=573 Treated in primary care DeVeaugh-Geiss ey al Pain Medicine 2010; 11: 732– (80%) have pain 190 (33%) mild pain 165 (29%) moderate pain 103 (18%) severe pain Around 60% adequate treatment was given
Proper identification & early treatment for Depression Pharmacotherapy: –SNRIs / TCA –Mood stabilizers (CBZ) –Alpha 2 Delta agonists (pregabalin / Gabalin) –BZD –Pipe Lines: NMDA Antagonists Somatic Treatment: TMS Psychosocial: CBT for Depression, social inclusion & re-habitation How to achieve recovery?
Pooled data from Thase et al & Nemerrof et al What Antidepressant to Use?
What Antidepressant to Use in painful depression?
What SNRI to use in Painful Anxiety & Depression? 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 Least Squares Mean Change Duloxetine (n=318) Venlafaxine XL (n=330) Weeks Duloxetine 60mg OD Duloxetine mg Ven 75mg ODVen 150mg ODVen mg Improvement
What Antiepileptic to use? NNT Anticonvulsant mechanisms of action Reduction of excitatory amino acid activity Modulation of Ca++ Channels Increase in CNS GABA activity Decrease in sodium channel activity Drug 3.3 (2–9.4) + Carbamazepine 3.7 (2.4–8.3) + (?)++ Gabapentin ++ Lamotrigine 3.0 (2.3–4.5) +++ Topiramate 3.3 (2.3–5.9) ++ Pregabalin Vinik J Clin Endocrinol Metab Aug;90(8):
Pregabalin Sibilia Quilici et al BMC Neurology 2009
Pregabalin 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 EP // *** * ** * D4 *** *** *** *** * P<0.05, ** P<0.01, *** P vs. placebo P<0.05 vs. venlafaxine HAM-A score 20 HAM-D score <15
PsychologicalUses BehaviouralIncrease exercise/activity levels; overcome fear– avoidance Cognitive- behavioural Reduce depression and anxiety associated with pain; develop effective coping strategies; reduce problematic cognitive styles. InterpersonalAddress role transitions due to pain; relationship difficulties/conflicts Adjunctive techniques BiofeedbackMuscle relaxation; control of physiological parameters contributing to pain (e.g., headache) Guided imageryRelaxation; distraction from pain HypnosisRelaxation; pain severity reduction; distraction Progressive muscle relaxation Muscle relaxation; distraction from pain 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: 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. Ahmed El Missiry DPP Msc (neuro-psych) MD MRCPsych MISAM, LLB Law A Professor of Psychiatry – ASUIP – WHO Consultant Psychiatrist – Kent & Medway NHS Researcher, Neuropsychopharmacology Department Zurich Institute of Technology, Switzerland Royal College of Psychiatrists Regional Representative KSS – Addiction Office: Pagoda CMHC Hermitage Lane, Barming Maidstone. Kent ME16 9PD Tel: Mobile: