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Introduction to Psychopharmacology

Introduction to Psychopharmacology. Charles P. Samenow, MD, MPH. Objectives. Identify major classes of somatic treatments for the major DSM-IV-TR Diagnoses Describe basic mechanism of action of somatic treatments Explain how mechanism of action related to major side effect profiles.

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Introduction to Psychopharmacology

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  1. Introduction to Psychopharmacology Charles P. Samenow, MD, MPH

  2. Objectives • Identify major classes of somatic treatments for the major DSM-IV-TR Diagnoses • Describe basic mechanism of action of somatic treatments • Explain how mechanism of action related to major side effect profiles

  3. Antidepressants

  4. TricyCLIC ANTIDEPRESSANTS • Block the re-uptake of three neurotransmitter systems: • Serotonin • Norepinephrine • Dopamine • Utilized in: • Major Depressive Disorder • Dysthymia • Generalized Anxiety Disorder • Panic Disorder • Obsessive-Compulsive Disorder

  5. Tricyclic ANTIDEPESSANTS • Older “Dirtier” Medication: • 3-4 weeks for onset (sometimes even 4-6 weeks) • Can be lethal in overdose (cardiotoxic) • Have side effect profiles: • Anticholinergic: dry mouth, constipation, confusion, urinary retention • Histaminic blockade: sedation and weight gain • Alpha-adrengergic blockade: orthostatic hypotention • Serotinergic: sexual side effect

  6. MAOI • Block Monoamine Oxidase in the wall of the gut, CNS and platelets leading to build up of Dopamine and Norepinephrine • Utilized in: • Major Depressive Disorder • Atypical Depression • Anxiety Disorders

  7. MAOI • Inhibition of MAO in the gut leads to increased Tyramine absorption. Hence, patients must avoid Tyramine containing foods (fava beans, aged meats and cheeses, wines, sauerkraut, etc…) • Ingestion of Tyramine can lead to hypertensive crisis • Require 3-4 weeks (sometimes 6-8 weeks) • Fatal in overdose • Cannot be combined with other serotinergic acting drugs (Tricyclic’s, SSRI’s) due to risk of serotonin syndrome. • Overdose can be fatal

  8. SSRI • Blockade of serotonin reuptake from the synapse • Utilized in: • Major Depression • Dysthymia • OCD • Panic Disorder • PTSD • Social Phobia • Bulimia Nervosa • Depressed phase of Bipolar (only with a mood stabilizer)

  9. SSRI • Take 2-4 weeks for onset • Fewer side effects than older medications – “Cleaner” and more easily tolerated • First line agents in pregnancy (although Class C) • Major side effects: • Gastrointestinal (first few days) • Sexual Side Effects • Black Box Warning: Increased Suicidality in Adolescents • Treatment emergent mania in bipolar disorder • Discontinuation Syndrome

  10. SNRI • Blocks Re-uptake of Serotonin and Norepinephrine • Careful balance between two neurotransmitter systems • Utilized in Depression, Anxiety and Pain Syndromes • “Cleaner”/More Easily Tolerated • Major Side Effects: • Blood Pressure • Discontinuation Syndrome

  11. MISCELLANEOUS • Wellbutrin (Buproprion) • Inhibition of Norepinephrine Re-uptake • No sexual side effects • Also marketed as Zyban for smoking cessation • Contraindicated in eating disorders due to lowering seizure threshold • Main side effect is anxiety • Remeron (Mirtazapine) • Alpha-2 Antagonist (net effect -> increased norepinephrine) • May cause sedation or increased weight gain • Often used in the elderly

  12. SEDATIVES/ANXIOLYTICS

  13. BENZODIAZAPINES • Use is determined by ½ life: • Long (Diazepam, Chlorediazepoxide) • Medium (Alprazolam) • Short (Lorazepam) • Utilized for panic and insomnia • Potentiation of GABA receptors by binding to special binding site • Long-term use may lead to tolerance, withdrawal and physiologic dependence • Side effects are sedation and amnesia

  14. Others • Beta-Blockers – • Utilized for performance anxiety • Centrally acting/lipophilic  propranolol

  15. ANTIPSYCHOTICS

  16. TYPICAL ANTIPSYCHOTICS • High Potency (Haldol) • Primary action is blocking D2 receptors (antagonist) • High affinity for D2 = lower dose • Good control of positive symptoms • Major Side Effects: • EPS -dystonic reactions, prolactin, akasthesia, parkinsonism • Neuroleptic Malignant Syndrome – • Mid/Low Potency (Thorazine) • Lower affinity for D2 = higher dose • Less EPS • More anticholinergic, alpha-adreinergic, and histiminic side effects

  17. Dopamine Hypothesis of Schizophrenia Nigrostriatal pathway (part of EP system) Mesocortical pathway Hypoactivity:negative, cognitive, and mood symptoms Mesolimbic pathway Hyperactivity:positive symptoms (hallucinations, delusions) Tuberoinfundibular pathway (inhibits prolactin release [D2])

  18. Clinical profile: Dopamine (D2) blockade EFFICACY: (+) SSX Mesolimbic Mesocortical Nigrostriatal Tuberoinfundibular D2 D2 INEFFICACY: (-) SSX, cognition, mood SIDE EFFECTS: EPS D2 SIDE EFFECTS: HPL D2

  19. Schizophrenia (Treatment) HIGH MEDIUM LOW Perphenazine Prochlorperazine Loxapine Acetophenazine Triflupromazine Chlorprothixine Mesoridazine Thioridazine Chlorpromazine Fluphenazine (D) Trifluoperazine Thiothixine Haloperidol (D) EPS, HPL EPS, HPL Anti-H1: Sedation, wt gain Anti-α-1: Orthostasis, reflex tachycardia Anti-M1: Blurry vision, dry mouth, constipation, urinary retention, tachycardia, memory problems or delirium in susceptible patients Anti-H1 Anti-α-1 Anti-M1 Seizure, arrythmias, retinitis, skin discoloration, photosens

  20. EPS • Dystonia – acute, involuntary muscle spasms often seen in ocular muscles and neck • Parkinsonism – tremor, cogwheel rigidity, masked facies, and shuffling gait • Akasthesia – a subjective sense of restlessness. • Tardive Dyskinesia – long-term involuntary jerking of face, neck, trunk or extremities. May be permanent. http://www.youtube.com/watch?v=R0EbgpyztCA

  21. ATYPICAL (SECOND GENERATION) • Utilized in: • Acute Schizophrenia • Maintenance of Schizophrenia • Acute Mania • Maintenance of Bipolar • Treatment of Bipolar Depression • Mechanism of Action: Blockade of D2 and 5HT-2A. Serotonin modulate dopamine, particularly in the nigrostriatal pathways. Hence, more Dopamine blockade in the mesolimbic as opposed to nigrostriatal pathways.

  22. ATYPICALS • Often first line • Efficacy on positive and negative symptoms • NMS and EPS unlikely • Side Effects are based on receptor profile • Prolongation of QTc (Cardiovascular) • Metabolic Syndrome • Weight Gain • Glucose Intolerance • Increased Lipids and Triglycerides

  23. MOOD STABILIZERS

  24. LITHIUM • Indicated for acute mania and maintenance bipolar • Specific evidence to support use in preventing suicide • Blocks inositol-1-phosphatase • Narrow therapeutic range: dangerous in overdose • Side Effects: • Tremor • Renal Impairment • Thyroid Dysfunction • Cardiovascular

  25. ANTICONVULSANTS • Major Agents: Carbamazepine, Valproic Acid and Lamotrigene • May prevent kindling • Each agent has side effects that are outside scope of this lecture

  26. Summary

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