J. David Kinzie, M.D., FAC Psych Professor of Psychiatry

Transcription

1 J. David Kinzie, M.D., FAC Psych Professor of Psychiatry

2 I. The Evidence Against Evidence- Based Practice II. The Personal Side of Personal Medicine III. Why Epistemology is Important

3 Example is 42-year-old male with history of Trauma, placed on Paxil by PCP

4 Evidence based practice is a treatment approach, but correct treatment depends on correct diagnosis Ex. 42-year-old male w/history of Trauma, placed on Paxil by PCP Patient had long history of severe torture in Ethiopia, with head injury, ongoing threat to his life, depression, hypertension, asylum seeker, no income Diagnosis: Complex PTSD, Major Depression, hypertension, probable TBI, with severe medical & social problems, without resources

5 Evidence based practice relies on doubleblinded placebo controlled studies and discounts experience 42-year-old male with history of Trauma, placed on Paxil by PCP I placed Patient on doxepin up to 150 mgs hs clonidine.4 hs lisinopril 20 mgs am In 1 week, Patient s BP controlled In 1 month, he slept all night w/o nightmares

6 My colleagues and I have treated over 2,000 torture victims, and the experience provides effective treatment.

7 Kim et al: 52 weeks open label clinical experience of paroxetine, % complete Tasker et al: paroxetine in chronic PTSD, placebo controlled, flexible dosage, % complete Marshall et al: paroxetine for chronic PTSD, placebo controlled, % complete

8 Smajkec et al: sertraline, paroxetine, & vexlafaxine in Bosnian refugees, 2001 Stein et al: Pooled analysis of placebo controlled studies, 2003 All used CAP for diagnoses > 50 Some used Sheehan Disability & GCI Compared to placebo, all showed statistical improvement

9 Bipolar disorder Dissociative disorder Patient involved in litigation or receiving disability Patient who received formal psychotherapy or ECT within 12 weeks prior to study Alcohol or drug dependence within 6 months

10 Pregnancy or lactating On St. John s Wart Being a homicide or suicidal risk Serious medical condition Psychotropic medicines were discontinued, usually 1 2 weeks Psychiatric disorders axis I, except anxiety and depression, eligible if focus of attention was PTSD

11 The studies, although statistically positive, have huge drop out rates and exclusions criteria would disqualify most patients coming for treatment.

12 22 Torture Survivors treated for 1 year Scale: CES-D SPRINT Sheehan Soc Dis Intake: year: Sig: <.000 <.000 <.000 Like other studies, ours shows a large group improvement in symptoms and in disability

13 2 patients (9%) showed no improvement Evidence-based practice under ideal conditions can show what might work but not what drug won t work with what patients

14 The use of genomics DNA, & other genetic information to inform ideal drug therapy based on the individuals personal gene expression, especially in psychopharmacology

15 I looked up test for DNA on the internet Anybody can put anything on the internet and attribute it to anybody Issac Newton

16 23 & Me Company: $300 Results: 100% European Father s Family Northern European Mother s Family Western European Straight brown hair

17 Increased Risk Prostate Cancer Venous Thromboembolism Chronic Kidney Disease Slow metabolism of coumadin

18 Decreased Risk Alzheimer's Macular Degeneration Parkinson Disease Rheumatoid Arthritis Typical reaction to all antidepressants (doesn t help to know what to use)

19 2D6 at least 16 variants All tricylics imipramine Most SSRIs fluoxetine paroxetine Venlafaxine Opiods codeine, morphine, oxycodone

20 Antipsychotic haloperidol, risperadal, perphenazine, apriprozale, chlorpromazine Beta Blockers Amphetamine Duloxetine Promethazine Inhibition of 2D6, most antidepressants and antipsychotics, some can cause 80% decrease in clearance

21 TCAs SSRIs Diazepam phenobarbital Omerprazole Propanolol Inhibitors Strong = 80% decrease in clearance - fluoxamine

22 Poor metabolizers of 2C19 3 5% of Caucasians % of Asians Poor metabolizers of 2D6 6 10% of Caucasians 15 20% of Asians Ultra rapid metabolizers Greater in Middle Easterners and North Africans

23 Can show potential problems with psychotropic medicine slow metabolizers or rapid metabolizers (increased or decreased blood level) Can also show about drug interactions, particularly inhibitions

24 Patient is 71 year-old Vietnamese female Long history of psychosis On 32 mgs. perphenazine and 30 mgs. aripiprazole, lisinopril and hydrochlorthiazide Still having hallucinations No side effects Questions: Is she a rapid metabolizer? Can we go higher on the antipsychotic medicine?

25 Affected Drug Clinical Impact Causative Agent Perphenazine % Abilify, 2D6 Intermediate metabolizer, hydrochlorothiazide Abilify Some increase lisinopril, perphenazine, 2D6 Intermediate metabolizer lisinopril Some increase Abilify, hydrochlorothiazide, lovastatin dehydro-aripiprazole (Abilify's active metabolite lovastatin acid (lovastatin's active metabolite) alendronate None None None hydrochlorothiazide None lisinopril, lovastatin, perphenazine lovastatin None hydrochlorothiazide, lisinopril 2C19 Normal metabolizer No impact

26 Effects: Increase in perphenazine levels possible due to CYP2D6 intermediate metabolizer. Management: Consider monitoring for extrapyramidal effects, sedation or other adverse effects. Patient may need a lower dose than average and if needed trifluoperazine may be an alternative. Effects: Aripraprazole levels tend to be elevated in CYP2D6 intermediate metabolizers. Management: Consider monitoring for akithesia or other adverse effects and reducing dose when necessary. Olanzapine may be an option for this patient if it were necessary to change agents.

27 Personalized Medicine Genomic can indicate what medicine may be a problem, but is complicated by drug interactions and unknown factors Can not indicate (at this time) what is best to use.

28 Paraphrasing Rev. Johnson in Blazing Saddles Are we doing the magnificent work of medical science or are we just jerking off?

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30 Branch of philosophy concerned with the nature and scope of knowledge What is knowledge? How is it acquired? To what extent is it possible for a given subject to be known?

31 1. Patient s narrative (History) 2. Observation of Patient (Mental Status Exam) 3. Psychiatrist experience with previous similar patients 4. Patient medicine history and others medicine acceptance or rejection of medicine side effects 5. Psychiatrist feelings nonverbal interaction feelings of opposition or easy relationships

32 6. Psychiatrist s familiarity with specific medicine 7. Opinions of experts and teachers 8. Results of evidence based studies what may work? 9. Genomic information What is the metabolism activity and potential drug interaction? 10. Drug company information medical journals and direct advertisement to the public

33 If we want to understand nature, if we want to master our physical surroundings, then we must use all ideas, all methods and not just a small section of them. Paul Feyerabend ( ) Philosopher of Science