Treisman

					                  Treating Depression
                    in the HIV Clinic
                                (and when to get help)


            Glenn J. Treisman, MD, PhD
                Professor
 Johns Hopkins University School of Medicine


                                                               The International AIDS Society–USA
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                           Slide 2




        Disclosure                       of things that may have affected my views and this presentation



      I have accepted honoraria from Boehringer-Ingelheim and
       Abbott in the last 12 months for talks related to HIV and
       Psychiatry
      I have been kicked off all the other drug company speakers
       lists because I will not use their slides
      I still think this “Conflicts of Interest” thing is ridiculous,
       along with HIPAA and the insanity at the airports
      I regularly accept payments from Johns Hopkins
       University
      I think doctors are obligated to think critically
      (Updated 05/02/08)
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                               Slide 3




 The Four Perspectives                                                        McHugh and Slavney




         Disease
         Temperament
         Behavior
         Life             Story


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 4




             Major Depression                               Demoralization




                                           Dysthymia
                                 “Depressive Personality”
                                    “Minor Depression”
                               Sub-syndromal Major Depression



GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 5


                  “Minor Depression”

          Sub-syndromal Major Depression
             Major Depression                               Demoralization




                                           Dysthymia
                                   “Depressive Personality”




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 6




        Depression diminishes
          Mood-the sense of baseline state of
           happiness that is usually present
          Vital sense-the sense of being well, healthy,
           energetic, alert and able
          Self Attitude-the sense of being good, of
           doing well, of effectiveness and utility to
           others

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 7




        Anhedonia
    Loss of reward (pleasure, satiation or satisfaction)
     associated with behaviors
         Appetite Directed Behaviors
               Sleeping
               Eating
               Sex
         Function Directed Behaviors
               Work
               Hobbies
               Exercise

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 8


        Disturbance of Neurophysiology
            Sleep
               EARLY MORNING AWAKENING
               Difficulty falling asleep

               Disrupted sleep architecture

            Appetite
               Change in food taste
               Weight loss or gain

               Immune function

            G.I. function
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 9




          Depression vs Bipolar Disorder
          Major depression
            4-8 % of the population

            Cyclic mood episodes all depressive

          Bipolar disorder
            1 % of the population

            Cyclic mood episodes depressive or
             manic

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 10


        Not every patient who ever had a
        mood is bipolar
          If they are bipolar, get help
          Patients with intense personality traits are
           hard to diagnose and tend to get missed or
           misdiagnosed




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 11




        When to get help
          Bipolar disorder
          Psychosis (hallucinations/delusions)
          Suicidal ideas
          Prior poor responses to treatment
          History of suicidal behavior
          Complex co-morbidity



GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 12


        How sure are we about the
        diagnosis?
         We can help clarify the diagnosis (although
          we know the disease better, primary
          providers often know the patients better and
          may have better sensitivity and specificity
          than we do)




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 13


        Diagnosis is confounded by
        personality style
          Introverts and Extroverts
          “Neurotic styles” and instability




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 14




     Depression prognosis
      Depression is a waxing and waning
       condition, patients will usually cycle out of it
      Subsequent episodes are longer, worse, and
       harder to treat, and the intervening well
       periods get shorter




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                             Slide 15

                              Pharmacotherapy
     •   poor sleep                     Bupropion                    • hypersomnia
     •   weight loss                    Nefazodone
                                        MAOI's                       • weight gain
     •   anxiety                        Trazodone                    • suicide potential
     •   G.I. disturbance               Mirtazepine
                                        Selegiline Patch             • chronicity

                                   Failure from side effects
     Desipramine                                                              Citalopram
     Nortriptyline                                                            Escitalopram
     Doxepin                        Failure after adequate trial              Fluoxetine
                                                                              Paroxetine
     (other TCA’s)                   Lithium augmentation                     Sertraline
     (Maprotiline)              Combination Antidepressants                   Venlafaxine
                                    Antipsychotics, Thyroid,                  Duloxetine
                                     Pindolol, Lamotrigene
                                         Augmentation
                                       ECT, TCMs, VNS
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 16


        Try dose elevation every two
        weeks
            Stop when limited by toxicity or no
             improvement




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 17




        Reasons for treatment failure
            Inadequate dose
            Inadequate length of the trial
            Inadequate compliance
            Wrong diagnosis
            Medical complication sustaining the condition
             (medication, condition, inflammation,
             underweight, dieting occult drug use)
            HARD CASE (about one third of cases)

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                     Slide 18




        Dose is inadequate
          Fluoxetine                                  (20 mg)                40 mg
          Sertraline                                  (50 mg)                100-200 mg
          Paroxetine                                  (30 mg)                60-80 mg
          Venlafaxine                                 (150 mg)               300 mg
          Citalopram                                  (40 mg)                60 mg
          Escitalopram                                (10 mg)                20 mg
          Duloxetine                                  (30 mg)                60 mg
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 19




        Try other drugs
          TCA’s (nortrityline, desipramine, doxepin)
          Bupropion XL (no sedation/no sexual s.e.)
          Mirtazapine (prorectic)




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 20




        Add augmentation
          Atypical neuroleptics (or typical)
          Lithium
          Thyroid Hormone
          Two antidepressant drug therapy
          Buspirone
          Phototherapy



GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 21


        Try to get the patient all the way
        well
            Partially well patients inevitably relapse




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                                                              Slide 22
Risks of Not Achieving Remission if
Symptoms Are Well Established
         Greater (3 to 4X) risk of relapse/recurrence1-3
         Continued impairment in work and
          relationships4
         More chronic depressive episodes1
         Neurodegeneration (hippocampus)
         Increased all-cause mortality (SUICIDE)5
          and morbidity/mortality with stroke,6
          diabetes,7, 8 MI,9 CVD,10 CHF,11 HIV,12 etc.
1Judd LL, et al. Am J Psychiatry. 2000;157:1501-1504; 2Paykel ES, et al. Psychol Med. 1995;25:1171-1180; 3Thase ME, et al. Am J Psychiatry.
1992;149:1046-1052; 4Miller IW, et al. J Clin Psychiatry. 1998;59:608-619; 5Murphy JM, et al. Arch Gen Psychiatry. 1987;44:473-480; 6Everson SA, et
al. Arch Intern. 1998;158:1133-1138; 7Lustman PJ, et al. Diabetes Care. 2000;23:934-942; 8de Groot M, et al. Psychosom Med. 2001;63:619-630;
9Frasure-Smith N, et al. JAMA. 1993;270:1819-1825; 10Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221-227; 11Vaccarino V, et al. J Am Coll

       GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
Cardiol. 2001;38:199-205; 12Ickovics JR, et al. JAMA. 2001;285:1466-1474.
                                                                                                           Slide 23
     Early Intervention May Allow
     Greater Opportunity for Remission
                                                                                   Placebo
                                                         *†                       Venlafaxine/venlafaxine XR
                   Remitters at Week 8 (%)



                                                                                   *†




                                                                  *P  0.0001 venlafaxine/venlafaxine XR vs. placebo
Remission defined as                         HAM-D17<7         †P  = 0.014 venlafaxine/venlafaxine XR  12 weeks vs.
                                                                               venlafaxine/venlafaxine XR >12 weeks
     GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13,
Kelsey JE. J Clin Psychopharmacol. 1996;16(3 Suppl 2):21S-26S;discussion 26S-28S. 2008.
                                                                                         Slide 24

             Remission* at 3 Months Predicts
             Better Long-Term Outcomes
                                    100




                                     80
                Recurrence of MDD
                 Over 2 Years (%)




                                     60
                                             45


                                     40


                                                                         18
                                     20




                                      0
                                          Rem ission                 No Rem ission



      Patients not treated to remission* of symptoms by 3 months were more
      than twice as likely to have a relapse/recurrence at long-term follow-up.

*Remission defined as HAM-DRS17 ≤7.
MDD = major depressive disorder; HAM-DRS17 = 17-item Hamilton Depression Rating Scale.
    GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
Simon GE et al. WHO Bulletin. 2000;78:430-445.
                                                                                        Slide 25
    Remission and Residual Symptoms:
    Predictors in Major Depression
             Residual Symptoms Predict Subsequent Early Relapse2



                                                                                    *




*P<.001 at 15 months.
    GJ Treisman, MD, PhD. Presented at IAS–USA
Paykel ES et al. Psychol Med. 1996;25:1171-1180. Washington Course, May 13, 2008.
                                                                              Slide 26




        Have another look at those drugs
          Beta-blockers
          Steroids
          Metoclopramide
          Colchicine




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 27
  Drugs causing Depression:
            Estrogens (testosterone/androgens)
            Progesterone (depot medroxy progesterone)
             clomifene, luprolide, tamoxifen
            Benzodiazepines, barbiturates
            Interferon (10-40%)
            Ranitidine
            Ca2+-channel blockers
            Chemotherapy agents
            Ciprofloxacin
            Reserpine (15%)


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 28
  Substance induced Depression:
            Alcohol
            Sedative-hypnotic (GABA drugs)
            Cocaine
            Psychostimulants




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 29
  Medical Causes of Depression:
          any auto-immune disorder
          vasculitis
          anemia
          hyper/hypothyroidism
          Cushing's syndrome
          hypercalcemia
          hyponatremia
          diabetes mellitus
          chronic hypoxia

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 30
  Neurologic disorders:
           CVA (30-50%)
           subdural hematoma
           epilepsy (45-55%)
           brain tumors
           multiple sclerosis (10-50%)
           transverse myelitis (50-70 %)
           Parkinson's disease (40-50%)
           Huntington's disease(40%)
           syphilis
           Alzheimer's disease (15-50%)


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 31

  Medical Causes of Depression:

           Infections:
                HIV
                HCV (25%)
                Mononucleosis
                influenza
           Cancer (20-45%):
                especially pancreatic CA (40-50%)


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 32




        Be a therapeutic optimist
            Never, never, never, never, never, give up
                     –Winston Churchill




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 33

        Global Significance of MDD:
        (WHO report, 1996)


            4th greatest disease burden worldwide.
            2nd condition greatest disease burden
             worldwide by 2020 (CAD 1st).
            Depression is currently the 2nd leading
             cause of disability from chronic illnesses
             (CAD 1st).
            Disease burden was measured as years of life lost
             to premature death & years lived with disability of
             specified severity & duration.
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                               Slide 34

           The Economic Burden of
           Depression (Greenberg et al.,1990)
         Treatment                                              12,000,000,000
               inpatient                                                     8,300,000,000
               outpatient                                                    2,900,000,000
               medications                                                   1,100,000,000
         Mortality                                              7,500,000,000
         Morbidity                                              23,800,000,000
               Absenteeism                                                   11,700,000,000
               decreased productivity                                        12,100,000,000
         Total Burden         43,700,000,000
         (Yes, that is billions)

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 35


       Impact of Depression on Medically Ill
                                         Patients
  Decreased quality of life
  Decreased function
  Poorer response to treatment
  Increased morbidity and mortality
  Increased cost of care
  Increased resource consumption
  Poorer compliance
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                    Slide 36
                                      Depression
                                      Dementia
                                      Delirium
                                      Demoralization
                                      Inactivity
                                      Physical Deconditioning
                                      Social Isolation
                                      Loss of Function
                                      Toxicity
Mental Illness                                                         Physical Illness
                                       Hopelessness
                                       Inactivity
                                       Physical Deconditioning
                                       Social Isolation
                                       Loss of Function
                                       Poor Compliance
                                       Impulsivity
                                       Toxicity

GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                                Slide 37


        Impact of Depression on
        Function
                               Complaint     Physical                   Bed days      (last mo nth)


                                             funct.
                               Depressive Sx 77.6                       1.40
                               HTN           86.4                       0.36
                               DM            81.5                       1.02
                               ACAD          65.8                       2.08
                               ANGINA        71.2                       0.30
                               Arthritis     80.6                       0.53
                               GI            82.8                       0.93
                               COPD          75.5                       1.14
                               Back Pain     79.0                       0.76


                                              Well, 1989 (11,242 pts in 3 cities screened for complaints and function


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                         Slide 38




        Impairment from Depression

                         Psych Dx Sheehan Missed                               Marital
                                  Disability Work %                            Distress
                                  Score           (out of 30)                  %
                         NONE     4.6        13.9                              7.7

                         Major      13.0                        40.0           42.1
                         depression
                         Major      17.6                        56.3           28.6
                         depression
                         + 2nd Dx

                                                                       Olfson 1997 1001 Kaiser HMO pts


GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                           Slide 39


        Psychiatric Disorders in Primary
        Care Patients
          All disorders                    26.7 %            Hoeper 1978 Arch RDC


          All disorders                    25 %        Schulberg 1987 Gen Hosp Psych 9 study meta


          All disorders                    26 %        Spitzer 1994 Jama Prime MD 1000


          All disorders                    19 %        Philbrick 1996 Gen int med rural office prime md


          All disorders                    22 %       Broadhead 1995 Arch Fam SDDS


          All disorders                    26 %       Leon 1995 Arch Fam SDDS




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                     Slide 40




        Depression in Primary Care
          5.8 %                                                   Hoeper 1978 Arch RDC


          12 % (6 % in remission)                                 Spitzer 1994 Jama Prime MD 1000


          5-10 % (review)                                         Katon 1992 gen hosp psych


          (community background 2-4 %)




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 41


        Recognition of Depression in
        Primary Care
            34 studies of primary care (most) 30-40 %
             Docherty1997 j clin psych


            1/3 of all patients with depression
               27 % of mild-moderate

               73 % of severe Schwenk 1996 gen hosp psych




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                  Slide 42


        Detecting Depression in Primary
        Care

                                           Mild       Moderate Severe                     All

                   % of SCID
                   Dx                      18 % 38 %                     73 %             4.9 %
                   Depression
                   Detected


                                              Coyne 1995 1580 Family Practice cases in Michigan




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                                                                             Slide 43


           Treatment of Medically
           Hospitalized Patients
            None                Benzo Imipramine Equivalents/day
                                only
                                                     < 75                 75-125 126-                              >200
                                                                                 200
            34 %                26 %                 11 %                 12 %                13 %                 4%


   Koenig, 1997 153 elderly medically ill inpatients treated at Duke by non-psychiatrist with major (91) or minor (62) depression
   (25 % were on antidepressants at admission)
   41 % of pts rec’d antidepressant Tx 22 % TCA, 21 % SSRI, only 11 % of pt’s not treated rec’d treatment after DC
GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.
                                                                              Slide 44


        Validity of Major Depression in
        Medically Ill Patients
          Specificity of symptoms
          Reliability of differing diagnostic methods
          Predictable response to treatment
          Association with specific disorders




GJ Treisman, MD, PhD. Presented at IAS–USA Washington Course, May 13, 2008.

				
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