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Update in Clinical Psychopharmacology

Update in Clinical Psychopharmacology. Peter A. DeMaria, Jr., M.D., FASAM Tuttleman Counseling Services Temple University Clinical Associate Professor of Psychiatry Temple University School of Medicine Philadelphia, PA. Disclosures.

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Update in Clinical Psychopharmacology

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  1. Update in Clinical Psychopharmacology Peter A. DeMaria, Jr., M.D., FASAM Tuttleman Counseling Services Temple University Clinical Associate Professor of Psychiatry Temple University School of Medicine Philadelphia, PA

  2. Disclosures • I have no actual or potential conflict of interest in relation to this educational activity or presentation. • Use of trade versus generic drug names • Off-label use of drugs.

  3. Treatment Planning 1. Medication 2. Psychotherapy 3. Combined medication and psychotherapy

  4. Referral for Psychopharmacologic Evaluation/Treatment 1. When to refer 2. Preparing the patient 3. What to expect 4. The challenge of split treatment • Communication • Dynamics • Ethics • Legal issues 5. What to expect

  5. Neurotransmission Taken from: Bloom FE, Neurotransmission in the Central Nervous System in Goodman & Gilman’s Pharmacological Basis of Therapeutics, 9th Ed, p. 270

  6. Pharmacokinetics Taken from: Julien, R. A Primer of Drug Action. WH Freeman Co., New York, 1998. p. 25.

  7. Drug Interactions • Synergism (e.g. alcohol + sedative) • Induction of enzymes and increased metabolism • Inhibition of enzymes and delayed metabolism • In vitro versus clinical significance FDA approval vs. clinical use (“Off-label use”)

  8. Selecting a Psychotropic Agent • Diagnosis/symptom complex • Patient’s prior response • Family member’s experience • FDA approved indication • Pharmacologic actions • Documented efficacy • Side effect profile • Insurance coverage/finances • Patient preference

  9. DSM-IV Classification of Depressive Disorders • Adjustment disorder with depressed mood • Dysthymia • Major depression (MDD) • Premenstrual Dysphoric disorder (PMDD)

  10. Pharmacotherapy options • Monoamine oxidase inhibitors (MAOI) • Tricyclic antidepressants (TCA) • Amitriptyline (Elavil) Imipramine (Tofranil) • Nortriptyline (Pamelor) Desipramine (Norpramin) • Selective Serotonin Reuptake Inhibitors (SSRI) • Serotonin and Norepinephrine Reuptake inhibitors (SNRI) • Atypical antidepressants • Bupropion (Wellbutrin) Nefazodone (Serzone) • On the horizon

  11. Selective Serotonin Reuptake Inhibitors (SSRI) 1. Examples Sertraline (Zoloft) Fluoxetine(Prozac) Citalopram (Celexa) Escitalopram (Lexapro) Paroxetine (Paxil) Fluvoxamine (Luvox) 2. Mechanism of Action Blocks re-uptake of serotonin thereby increasing serotonin in the synapse

  12. SSRI - FDA Approved Indications • Therapeutic Response • Can take between 2 and 8 weeks • Response is gradual • Others may notice the response before the • patient does

  13. SSRI/SNRI Side Effects • Gastrointestinal • Anxiety/insomnia • Flushing/night sweats • Vivid dreams • Weight change • Sexual dysfunction

  14. Antidepressant-Induced Sexual Dysfunction Desire Decreased libido Arousal Difficulties w/ erection/lubrication Orgasm Delayed orgasm/anorgasmia Management • Spontaneous resolution • Decrease dose • Change agent • Adjunctive medication Selective PDE5 Inhibitor Bupropion (Wellbutrin) Cyproheptadine (Periactin)

  15. “Poop-out” Effect 1. Definition 2. Explanation • Placebo response • Inadequate dose • Potential changes in receptors 3. Management • Drug holiday • Increase dose • Change antidepressant • Add agent with NE or DA properties

  16. Discontinuation Syndrome • Develops after abrupt cessation of SSRI/SNRI • Symptoms = washed-out, flu-like, lightheaded, H/A, emotional liability, diarrhea • Can occur with all SSRIs/SNRIs • May be related to half-life • Worse with paroxetine (Paxil) and venlafaxine (Effexor) • Abates with re-challenge of SSRI/SNRI • Slow taper of SSRI/SNRI or change to longer acting agent.

  17. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) • Mechanism of Action • Examples and Indications • Side Effects MDD = Major depressive disorder, GAD = Generalized anxiety disorder, PD = Panic disorder, SAD = Social anxiety disorder, FM = Fibromyalgia.

  18. Treatment Resistant Depression 1. Is the patient medication compliant? 2. Is the diagnosis correct? 3. Change agents-Within/between classes 4. Antidepressant combinations -Complementary mechanisms of action 5. Add psychotherapy 6. Augmentation strategies • Lithium Thyroid hormone • Antipsychotic Estrogen 7. ECT/Focal Brain Stimulation

  19. Focal Brain Stimulation • Vagal Nerve Stimulation (VNS) • Pulse generator implanted in the left chest wall • Electrode wrapped around the left vagus nerve • Pulse on for 30 seconds and off for 5 minutes • Efficacy = ? • Transcranial magnetic stimulation (TMS) • Uses an electromagnetic coil placed against the scalp to create a rapidly changing magnetic field that depolarizes neurons. • Outpatient procedure • Safe and well tolerated • Efficacy =?

  20. How long to Treat? • 6-12 months • Longer if, • Return of symptoms on discontinuation of AD • Recurrent episodes of depression • Severe depression (suicide attempt, psychosis) Taken from: Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd Ed., Cambridge University Press. 2000, p. 150.)

  21. FDA Suicide Warning • Black Box Warning • All antidepressants • Increased risk of suicidal thinking and behaviors • Affects 18-24 y/o

  22. On the Horizon • Corticotropin releasing factor-1 (CRF1) antagonists • Glucocorticoid receptor antagonists • Substance P receptor antagonists • NMDA receptor antagonists • Melanocyte inhibiting factor (nemifitide) • Omega -3 fatty acids • Melatonin receptor antagonists • Focal and deep brain stimulation therapies

  23. STAR*D • Largest (n=4041, age 18-75 y/o) study of treatment of non-psychotic MDD • Multiple real-world psychiatric and primary care settings • Conducted between July 2001 and April 2004 • Funded by National Institute of Mental Health (NIMH) • Goal was remission (< 5 on the QIDS-C16) • Treatment involved 6 levels with patient ability to choose options • Available at www.star-d.org

  24. (Rush AJ et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psych 163:1905-1917, 2006.)

  25. STAR*D • MDD is a chronic and recurrent illness. • Using objective measurements of symptoms and side effects a can help with treatment decisions. • Remission can take time (at least 8, but up to 14 weeks). • Many steps may be needed to reach remission. • Remission rate of 50% was reached after 2 steps. • Remission rate of 70% was reached after 4 steps • Remission results in better log-term outcomes. • Participant attrition is high. (Warden D et al. The STAR*D project results: a comprehensive review of findings. Current Psychiatry Reports 9:449-459, 2007.)

  26. Break Time

  27. DSM-IV Anxiety Disorders 1. Adjustment disorder 2. Generalized anxiety disorder (GAD) 3. Panic disorder 4. Obsessive-compulsive disorder (OCD) 5. Social anxiety disorder (social phobia) 6. Acute stress disorder 7. Post traumatic stress disorder (PTSD) 8. Specific phobia

  28. Benzodiazepines Taken from: Kaplan SI, Sadock BJ. Kaplan & Sadock’s Synopsis of Psychiatry, 8th ed., Lippincott, Williams & Wilkins, Philadelphia, 1998, p. 996. AdvantagesDisadvantages -Rapid onset of action -Physiologic dependence -Highly effective -Addicting -Impaired cognition Anterograde amnesia

  29. J of Clin. Psychiatry, 60(5), 252, May 1999

  30. MDD=major depressive disorder, PMDD=peri-menstrual dysphoric disorder, PD = panic disorder, PTSD=post-traumatic stress disorder, GAD=generalized anxiety disorder, OCD=obsessive-compulsive disorder, SP=social phobia, BN = bulimia nervosa, ND = nicotine dependence, FM = fibromyalgia

  31. Advantages High efficacy Non-addicting Effective for a number of conditions Disadvantages Can take 2-8 weeks or longer to be effective Side effects Drug interactions Discontinuation syndrome SSRI/SNRIs in Anxiety Disorders

  32. Other Options for Anxiety Disorders • Buspirone (BuSpar) • Beta blockers • Combinations • SSRI/SNRI + Benzodiazepine • Antipsychotics • Trifluoperazine (Stelazine) • Quetiapine (?) • Pregabalin (?)

  33. Psychotropic Choices for Specific Conditions

  34. DSM-IV Psychotic Disorders 1. Schizophreniform disorder 2. Schizophrenia 3. Schizoaffective disorder 4. Brief psychotic disorder

  35. Positive Symptoms Hallucinations Delusions Disorganization Agitation Negative symptoms Blunted affect Emotional withdrawal Social withdrawal Anhedonia The Disease Process

  36. FDA Approved Indications for Atypical Antipsychotics OLA = Olanzapine, RIS = Risperidone, ILO = Iloperidone, QUE = Quetiapine, ZIP = Ziprasidone, ARI = Aripiprazole, ASEN = Asenapine

  37. Atypical (2nd Generation) Antipsychotics • HL=haloperidol (Haldol), CPZ=chlorpromazine (Thorazine), CLZ=clozapine (Clozaril), • RIS=risperidone (Risperdal), OLZ=olanzapine (Zyprexa), QTP=quetiapine (Seroquel), • ZIP=ziprasidone (Geodon) • (Taken from: Jam, MW. Advances in the treatment of psychosis: • a multidisciplinary continuing education program. Power-Pak CE, New York, NY 2001, p. 8.)

  38. Metabolic Syndrome & Atypical Antipsychotics Risk of adverse effects at therapeutic doses: 0 = None, ++ = Sometimes, +++ = Frequently J. Clin. Psych 2004: 66; 267-272

  39. CATIE • 1460 “real-world” schizophrenics (no first-break schizophrenics) • NIMH funded • Comparison of second generation antipsychotics to a representative first generation antipsychotic (perphenazine).

  40. CATIE • Overall findings: • Discontinuation rates for all agents were high. • Olanzapine was the most efficacious medication, however, it was associated with the greatest weight gain, and the worst metabolic profiles. • For those patients changing drugs due to tolerability, olanzapine and risperidone were more efficacious second choice drugs. • Ziprasidone had a better metabolic profile.

  41. DSM-IV Mood Disorders Bipolar disorder (manic-depressive disorder) • Bipolar I (recurrent major depression and mania) • Bipolar II (recurrent major depression with hypomania) • Specifiers • Rapid cycling (more than 4 episodes in a 12 month period) • Seasonal pattern Cyclothymia

  42. The Heterogeneity of Bipolar Disorder Taken from: http://www.psychosis-bipolar.com/information-about-psychoses-57.htmlTaken

  43. Pharmacotherapy for Mood Disorders 1. Mood stabilizers Lithium 2. Anticonvulsant Mood Stabilizers Valproic acid (Depakote) Carbamazepine (Tegretol) Oxcarbazepine (Trileptal) Lamotrigine (Lamictal) Topiramate (Topamax)-? 3. Atypical Antipsychotics Olanzapine (Zyprexa) Risperidone (Risperdal) Quetiapine (Seroquel) Aripiprazole (Abilify) Ziprasidone (Geodon) 4. Combination Olanzapine/fluoxetine (Symbyax)

  44. Treating Bipolar Disorder • Use mood charting. • Combination pharmacotherapy is the rule rather than the exception. • Mood stabilizers are the cornerstone of therapy. • Optimize therapeutic effect and tolerability while minimizing side effects. • Antidepressants mat worsen the disease course. • Anticonvulsants & FDA suicide warning

  45. Pharmacotherapy for Bipolar Disorder

  46. Insomnia • A symptom, not a diagnosis • Evaluate for underlying cause • Promote good sleep hygiene • Use a sleep log • Pharmacotherapy • 10 days or less • Options • Non-benzodiazepine hypnotics • Benzodiazepine hypnotics • Sedating antihistamines • Sedating antidepressants • Sedating antipsychotics

  47. Attention Deficit Hyperactivity Disorder 1. Stimulants • Amphetamine salts (Adderall) • Methylphenidate (Ritalin, Concerta, Focalin) • Dextroamphetamine (Dexedrine) • Pemoline (Cylert) 2. Non-stimulants • Atomoxetine (Strattera) • Guanfacine extended release (Intuniv) • Others • Bupropion(Wellbutrin) • Tricyclic antidepressants • Venlafaxine (Effexor) 3. New Delivery Systems • Methylphenidate patch (Daytrana) • Pro-drug: lisdexamfetamine (Vyvanse)

  48. Pharmacotherapy for Eating Disorders 1. Classification Anorexia nervosa Bulimia nervosa Eating disorder NOS 2. Pharmacotherapy options SSRIs for bingeing/purging Topiramate for binging/purging - ? Treatment for co-morbid disorders

  49. Pharmacotherapy for Personality DisordersSymptom targeted

  50. Pharmacotherapy in Severe Personality DisordersMeta-analysis of 21 retrieved studies-Borderline & Schizotypal P.D. NS = Not significant, S = Significant, HS = Highly significant (+) = Small, (++) = Moderate, (+++) = Large, (++++) = Very large Ingehoven T et al. J. Clinical Psychiatry 71(1):14-25, 2010

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