Ahmed El Missiry Aches of the Psyche by Q1Diqd

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									              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 am always anxious and tense
              my thoughts make no sense
I dread the dawn's recurrent light;
               I hate to go to bed at night.
I find no peace in paint or type
        My world is but a lot of tripe.
I'm disillusioned, empty-breasted
               For what I think, I'd be arrested.
I am not sick, I am not well
             My 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 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;41:934-941.
 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
     mood and anxiety disorders
 “Comorbidity is the rule, not the exception”

48% of patients with PTSD1                                      Up to 65% of patients with Panic Disorder2


                       Post-Traumatic
                                                               Panic                            Pain comorbidity=
                       Stress Disorder                                                          Av 65%
                                                              Disorder

                                                                                                     Pain
                                            DEPRESSION
                 Social
                Anxiety                                                     GAD
                Disorder                          OCD

 Up to 70% of patients with                   67% of patients with                    42% of patients with
 Social Anxiety Disorder5                     Obsessive-Compulsive                    Generalised Anxiety
                                              Disorder4                               Disorder3
        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
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 [1]
       –   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 % [2]
       – back pain clinic = 20% - 57% [3,4]


1- Matthew et al Arch Intern Med. ;163:2433-2445, 2003
2- Manchikanti et al Pain Physician, Volume 5, Number 2, pp 149-15, 2002
3- Sommer 18th European Congress of Psychiatry. February 27, March 2, 2010
4- Moya et al Aten Primaria. 2000 Sep 15;26(4):239-44.
          The likelihood of anxiety and depression
            increase with the number of painful
                         symptoms

                          One thousand adult patients




                                Pain             N          Anxiety           Depression           Any Symptom
                                  1-0          215             )1( 2               )2( 5                  )7( 16
                                  3-2          225            )7( 17             )12( 27                 )22( 50
                                  5-4          191           )13( 25             )23( 44                 )35( 67
                                  8-6          230           )30( 68            )44( 100                )61( 140
                                  +9           130           )48( 68             )80( 84                )81( 113
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.
           Increasing pain predicts increased
                 Anxiety & Depression
                   12
                             Depression <0.001
  N=448            10        Anxiety <0.001
  Requited           8
  from Primary
  care               6
                     4
                     2
                     0
                          NPAD-d in NPAD-d in NPAD-d in
                           lowest     middle   highest
                           quartile  quartiles quartile

Blozik et al BMC Musculoskelet Disord. 2009 Jan 26;10:13.
Does Depression Hurt?!
      The prevalence of pain in depressed ranged from
      15% to 100% (mean prevalence, 65%).
Source                No. of Patients   Study Setting              Patients With Pain% ,
Bair et al            573               Primary care               69
Delaplaine et al      29                Psychiatric inpatients     51
Diamond               432               Neurology clinic           85
Hollifield et al      29                Outpatient clinic          59
Lindsay and Wyckoff   196               Private practice           59
Mathew et al          51                Research institution       77 Headache
                                                                   37 chest pain
Merskey and Spear     85                Psychiatric patients       56
Pelz et al            22                Psychiatric patients       41
Singhl                150               Depressed outpatients      65
Vaeroy and Merskey    28                General practice           43
von Knorring          40                Psychiatric inpatients     60
von Knorring et al    161               Psychiatric inpatients     57
Ward et al            16                Respondents to newspaper   100
                                            advertisement
Watts                 100               Psychiatric patients       15
Does Depression Hurt?!
                              Chronic Pain in Depression

       18 980 subjects 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, 3.5-4.7)
Ohayon & Schatzberg Arch Gen Psychiatry 47-60:39;2003 .
Does 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
  pain

  •53.6% had
  mod/severe
  pain-related
  interference with
  functioning.


Demyttenaere et al (2010) Journal of Affective Disorders 125 53–60
More Depressive Symptoms … more pain
                         43% of depressed patients experienced
                              chronic painful symptoms1

                                Normal mood (n=18,232)
                   50
                                Participants with at least 1 depressive                                     ††

                   40           symptom (n=3140)
                                Depression – 5 DSM-IV criteria met (n=748)
    Patients (%)




                   30
                                                                           ††

                   20                                                                        ††
                               ††
                   10                                       ††                           *
                           *                †           *
                                        *
                    0
                        Backache    GI disease      Joint/        Headache         Limb ache  1 Chronic
                                                   articular                                   painful
                                                                                              symptom




                                            Graph adapted from Ohayon MM, Schatzberg AF. Arch Gen Psychiatry 2003;60: 39–47.
                                                     Are Pain symptoms a marker for
                                                               depression?
1,042 consecutive outpatients screened for depression
    Positive Predictive Value for Depression




                                               70     61          60
                                               60
                                               50                            43
                                                                                        39        39        39        37
                                               40
                                               30
                                               20
                                               10
                                               0
                                                       sleep      fatigue    multiple back pain shortness of amplified vague
                                                    disturbance             complaints            breath complaints complaints
                                                                               (3+)


Gerber et al J Gen Intern Med. 1992 Mar-Apr;7(2):170-3
Does Anxiety Hurt?!
                              60
                                             GAD population (n=13,386)                  Controls (n=89,971)

                              50
                                       ***
                              40
              % of subjects




                              30


                              20


                              10                                                            ***

                               0

                                      Chronic pain (all)                               Neuropathic pain only
                                                                        Condition


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
                        40     33%
                                            31%
                                                       28%
anxiety disorders (%)




                        30                                                26%
   Prevalence in




                        20

                        10

                        0
                             Chest pain   Abdominal   Headache            Fatigue
                                             pain




                                                      Kroenke K et al. Arch Fam Med 1994;3:774–779
 Does Pain affect the recognition of Anxiety & Depressive
 disorders?        More than 50% of depressed or anxious
                                                                    patients presenting with pain are not
                              90%                                                recognized
                              80%
                                               77%
                                                                Rates of Recognition of Depression and Anxiety
Recognised by Clinician (%)




                              70%                                       by Style of Clinical Presentation
                              60%                                          52%
                              50%
                                                                                                    38%
                              40%

                              30%                                                                                                        23%
                              20%

                              10%

                              0%
                                        Psychological                Initial Somatic           Facultative                 Persistent Somatic
                                                                                                Somatic
                                    Initial presented with 1   Initial presented with only   presented with only              Persistent presented
                                    psychological symptom                 1 somatic           somatic symptoms                 with only somatic &
                                                                                                                                did not believe any
                                                                                                                               psychological cause


                                                                                                   Kirmayer LJ et al. Am J Psychiatry 1993; 150: 734-741
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?
   The Central effect




                                             Stahl, 2008
Why we can not see the pain?
   Diagnostic Criterion Bias

                              Symptom Overlap
         Anxiety*                                                      Depression
                 Anxiety                           Depressed mood
                                     Agitation
            Worry                    Irritability    Loss of interest
         Dry mouth                     Fatigue           or pleasure
       Palpitations                   Difficulty             Appetite
       Sweating                    concentrating             disturbance
                                 Sleep disturbance
        Trembling                                         Worthlessness
                                  Muscle tension
          Blushing                 GI complaints      Suicidal ideation
              Stuttering
                                         Pain          Low self-esteem




  *Symptoms of GAD and SAD.
  DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
Why we can not see the depression?
   2- Diagnostic Criterion Bias
                    The Spectrum of Symptoms
    Emotional Symptom              Physical Symptoms
     Sadness & Tearfulness          Body Aches and Pains
       Loss of Interest                  Headaches
      Anxiety / Irritability        Tiredness and Fatigue
        Hopelessness                 Sexual dysfunction
    Concentration Difficulties           GI Changes
   Negative cognitions & Guilt       Vasomotor changes
       Suicidal Ideations
      Sleep Disturbances
      Appetite \wt changes

     Psychomotor problems
                                          Adapted from DSM-IV APA 1994
2- Diagnostic Criterion Bias

            Affective Spectrum Disorders
                associated with pain
  Mood disorders
     Major depressive disorder
     Dysthymic disorder
     Premenstrual dysphoric disorder
    Bipolar disorder (especially bipolar depression or mixed)
  Anxiety / neurotic disorders
    Generalized anxiety disorder
    Panic disorder
    Posttraumatic stress disorder
    Somatization / somatoform pain disorders
  Painful Functional somatic disorders
    Fibromyalgia
    Irritable bowel syndrome
    Migraine
Stahl, 2008
Why we can not see the depression?
   3- Presentation 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
Depression and anxiety are Often
Missed when The Presentation is
           Physical
 % of Correct Diagnosis of MDD/AD



                                    90
                                             77
                                    80
                                                        N=685
                                    70
                                    60
                                    50
                                    40
                                    30                          22
                                    20
                                    10
                                     0
                                         Psychosocial   Somatic Complains
                                          Complains
                                                                 Adapted from Kirmayer et al AJP1993
The effect of poor recognition on
    the patient’s 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                                    [8]


            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 [6]
            37% of patients receiving opioid therapy reported
            suicidal thoughts & 20% an attempt [7].
            Mental pain in is associated with   risk of
            suicide [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
  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
                 Ascending
                 pathways




                                Motivational
                             Affective pathway
   Sensory-
Discriminatory
   pathway                                  Stahl, 2008
Opiate                         Sympathetic

  (endorphins)
                 Descending
                  Inhibitory
Serotonin          System
Norepenephrine




                                            Sub P (NK1,2,3)
                                             VIP (VIPR)
                                             Somatostatin
                                             Calcitonin
                                             GABA
                                             Glutamate
                                             Glycine
                                             NMDA
                                             NO
                                             CCK
                                                               Stahl, 2008
Descending Tracts
Possible Explanation: Descending Pathways
PAIN:
  Depletion of monoamines
  Increase CRF
  IL2 – TNF –IL6



DEPRESSION & ANXIETY:
   Endogenous Opiates
   NE -  5HT
   CCK
   Sub-P
   Distress and pain disorders share the same anatomical
                            sites

                                              executive functions
                                              & perceived control
                                                   over pain


Process information from
  sensory to emotional                            Rational cognitive
     (mood & pain)                                 functions & pain
                                                        processing




 Associative
                                 memory of             Reward
and episodic
                                 emotional      increases in negative
  memories
                                  reactions            affects
              Induction of Negative Mood Disrupts Emotion
              Regulation Neurocircuitry and Enhances Pain
                             Unpleasantness
    Negative 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)

     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

Berna C et al. Biol Psychiatry 2010;67:1083-1090
            Proposed cognitive models
      increased negative mood → increased catastrophizing → increased pain unpleasantness

                               Pain related                                                           More activity in IFG
                                                     Increased
                                cognitions                                                               and amygdalae
                                                   catastrophizing                           explains
                                                    (rumination)                                34%
             induced                                                                       variability
             Negative                                                                                            Strong effect
               mood                             Mechanisitic hypothesis:
                                           Dysfunction of emotion regulation
                                                Increased cognitive load                                        Increased Pain
                Pain                                                                                            Unpleasantness


                                                                                          explains                  No effect
                                                      Increased                               58%
                  Change in neural
                                                    activity in the                      variability
                      processing in
                                                   left IFG, dlPFC                                          Less activity in IFG and
                   prefrontal areas
                                                       and OFC                                                           amygdalae

Berna C et al. Biol Psychiatry 2010;67:1083-1090   dlPFC, dorsolateral prefrontal cortex; IFG, inferior frontal gyrus; OFC, orbitofrontal cortex
How we can help ?
Increase Awareness
Better identification
Proper & early treatment for Neuropathic Pain
Proper & early treatment for Depression/anxiety


                                Depressed
                              patients seen in
                               primary care
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        Risk factors for opioid
   studies with conflicting      abuse in patients with
   findings Risk can be         chronic pain are [3]:
   relatively high (>10%) or low •young age,
   (<0.1%). [1]                  •male gender,
                                 •past alcohol or cocaine
   A systematic review noted the abuse,
   prevalence of [2]             •previous drug conviction,
    – Lifetime SUD 36% to 56%    •mental health disorders,
    – Current SUD 43%            •pain in multiple regions,
                                 •pain after MVA
    – Aberrant medication-taking
      behaviours 5% to 24%
[1] Wasan et al. 2006   [2] Martell et al 2007   [3] 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. 2007 Oct;20(5):451-5.
                                                (4)
Treatment of anxiety                     Psychosocial and
and depression                             occupational
                                           functioning
                                             restored
Aim at
                                                               (3)
Recovery                             (2)
                                 Remission of
                                                            Sustained
                                                            absence of
Quality of Recovery               symptoms                  symptoms
   Symptomatic recovery
   Syndromal recovery
   Functional recovery.
                               (1)
                           Response
                          To treatment
   20-30%
    partial
  response
 (Residual
 symptom).
                                     Road To Recovery
                                   Residual Symptoms Predicts
                                      Higher Relapse Rates
                                   120
Probability of Remaining Well (%




                                   100

                                    80
                                                                                              Remission (n=41)

                                    60
                 )




                                                                                              Residual Symptoms
                                                                                              (n=19)
                                    40

                                    20

                                     0
                                         1   2      4     6       8      10      12
                                                 Months of Follow-up

                                                              Rush AJ, et al Psychiatry Ann. 1995; 25: 704
The challenge in treatment


   Painful Somatic symptoms may be less responsive
        to treatment relative to other symptoms

                                           Depressive symptoms

                                           Positive well being



                                           Non painful
                                           Somatic symptoms

                                            Painful Somatic
                                            symptoms




                                     Greco T et al. J Gen Intern Med 2004; 19: 813-818
                                                    the ARTIST Trial
   Depression outcome at 6 month for n=573 Treated in primary care

          Painful symptoms are associated with worse
                     depression outcome
458 (80%) have pain                                              Depressive symptoms
190 (33%) mild pain        0.8                                             0.72
                                 Remission                    0.65                0.67
165 (29%) moderate pain    0.7
103 (18%) severe pain            Partial response
                           0.6
                           0.5
 Around 60%                0.4
 adequate treatment
                           0.3            0.24         0.25
 was given
                           0.2     0.11
                           0.1
                            0
                                  Severe pain        Moderate pain          Mild pain
  DeVeaugh-Geiss ey al Pain Medicine 2010; 11: 732–741
How to achieve recovery?

   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
     What Antidepressant to Use?




Pooled data from Thase et al & Nemerrof et al
What Antidepressant to Use in
painful depression?
What SNRI to use in Painful Anxiety &
Depression?
  Duloxetine & Venlafaxine are both effective….
                                                                                             Weeks
                                                      0        1           2            3           4           6           8          10           12
                                                 0
                    Least Squares Mean Change




                                                 -2
                                                                                                                            Duloxetine (n=318)
      Improvement




                                                 -4                                                                         Venlafaxine XL (n=330)

                                                 -6

                                                 -8

                                                -10

                                                -12

                                                -14

                                                -16           Duloxetine 60mg OD                                                        -
                                                                                                                            Duloxetine 60120mg

                                                          Ven 75mg OD                   Ven 150mg OD                                   -
                                                                                                                                Ven 150 225mg

                                  No significant difference at 6 or 12 weeks



                                                            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
    What Antiepileptic to use?
  Anticonvulsant mechanisms
  of action
                          Decrease in   Increase    Modulation   Reduction
                            sodium       in CNS         of          of
                                                                                 NNT
  Drug                     channel        GABA        Ca++       excitatory
                            activity     activity    Channels    amino acid
                                                                  activity

  Carbamazepine               +                                               3.3 (2–9.4)

  Gabapentin                  +            +          )?( +                   3.7 (2.4–8.3)

  Lamotrigine                 +                         +
  Topiramate                  +            +                        +         3.0 (2.3–4.5)

  Pregabalin                               +            +                     3.3 (2.3–5.9)




Vinik J Clin Endocrinol Metab. 2005 Aug;90(8):4936-45.
   Pregabalin




Sibilia Quilici et al BMC Neurology 2009
 Pregabalin
                                                                                                                 HAM-A score 20
                                                                                                                 HAM-D score <15

                                       0                                   Placebo (n=127)
                                       -2
                                                                           Venlafaxine XR 75-225 mg/day (n=122)
          Mean change from baseline




                                       -4
                                                                           Pregabalin 300-600 mg/day (n=121)
                                       -6
                                                ***
                                                 †
                                       -8          ***
                                                    †
                                      -10                ***
                                                          †
                                      -12                      ***
                                                                †
                                      -14                            ***
                                                                      †
                                      -16                                                                        *
                                      -18
                                                                                    **
                                      -20                                                           *       //
                                            0   D4 1     2     3     4       5      6         7         8        EP
                                                                                                                 9
                                                                      Weeks
                                                                                        *P<0.05, **P<0.01, ***P0.001 vs. placebo
                                                                                          †P<0.05 vs. venlafaxine

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
Treatment
What other interventions to use?
Psychological        Uses
Behavioural          Increase exercise/activity levels; overcome fear–
                     avoidance
Cognitive-           Reduce depression and anxiety associated with
behavioural          pain ;develop effective coping strategies; reduce
                     problematic cognitive styles.
Interpersonal        Address role transitions due to pain; relationship
                     difficulties/conflicts
Adjunctive
techniques
Biofeedback          Muscle relaxation; control of physiological
                     parameters contributing to pain (e.g., headache)
Guided imagery       Relaxation; distraction from pain
Hypnosis             Relaxation; pain severity reduction; distraction
Progressive muscle   Muscle relaxation; distraction from pain
relaxation
Conclusion:
     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
               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: 01622-724200
Mobile: 07876284356
Email: missiry@yahoo.com

								
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