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Introduction to Psychopharmacology

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Presentation on theme: "Introduction to Psychopharmacology"— Presentation transcript:

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

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8 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

9 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)

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11 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

12 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

13 MISCELLANEOUS Wellbutrin (Buproprion) Remeron (Mirtazapine)
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

14 SEDATIVES/ANXIOLYTICS

15 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

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17 Others Beta-Blockers – Utilized for performance anxiety
Centrally acting/lipophilic  propranolol

18 ANTIPSYCHOTICS

19 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

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

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

22 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

23 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.

24 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.

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26 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

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28 MOOD STABILIZERS

29 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

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

31 Summary Disorder Treatment Depression
SSRI, SNRI, Buproprion, Mirtazepine Atypical Depression MAOI Anxiety Disorders Short-Term: Benzodiazepine Long-Term: SSRI, SNRI OCD High Dose SSRI, Tricyclics PTSD SSRI Performance Anxiety Beta-Blocker Psychosis Atypical Antipsychotic Acute Mania Atypical Antipsychotic, Lithium, Carbamazepine Bipolar Maintenance Atypical Antipsychotics, Lithium Carbamazepine Bipolar Depression Lamotrigine, Some Atypicals Rapid Cyclling/Mixed Episodes Valproic Acid


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