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Presentation on theme: "CHARLES P. SAMENOW, MD, MPH INTRODUCTION TO PSYCHOPHARMACOLOGY."— Presentation transcript:


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


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


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 (Tricyclics, SSRIs) 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)


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) 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


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


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


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 Nigrostriatal pathway (part of EP system) Mesocortical pathway Hypoactivity: negative, cognitive, and mood symptoms Tuberoinfundibular pathway (inhibits prolactin release [D2]) Hyperactivity: positive symptoms (hallucinations,delusions) Mesolimbic pathway DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA

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

22 SCHIZOPHRENIA (TREATMENT) HIGHMEDIUMLOW Fluphenazine (D) TrifluoperazineThiothixine Haloperidol (D) PerphenazineProchlorperazineLoxapineAcetophenazineTriflupromazineChlorprothixineMesoridazineThioridazineChlorpromazine 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 EPS, HPL 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.


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



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 DisorderTreatment DepressionSSRI, SNRI, Buproprion, Mirtazepine Atypical DepressionMAOI Anxiety DisordersShort-Term: Benzodiazepine Long-Term: SSRI, SNRI OCDHigh Dose SSRI, Tricyclics PTSDSSRI Performance AnxietyBeta-Blocker PsychosisAtypical Antipsychotic Acute ManiaAtypical Antipsychotic, Lithium, Carbamazepine Bipolar MaintenanceAtypical Antipsychotics, Lithium Carbamazepine Bipolar DepressionLamotrigine, Some Atypicals Rapid Cyclling/Mixed EpisodesValproic Acid


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