Psychopharmacology of Antidepressants Mood Stabilizers and Anxiolytic Sedative Hypnotics Philip G Janicak M D Professor of Psychiatry Rush University Medical Center 01 14 19 1 Pharmacology of Antidepressants and Mood Stabilizers Objectives 01 14 19 Characterize the different classes of antidepressants and mood stabilizers based on their mechanism of action Review adverse effects of these agents Provide a summary of the pharmacokinetics and potential for drug interactions Review treatment strategies for the drug management of depression and bipolar mania based on the existing data clinical experience and risk benefit ratio 2 Psychopharmacology of Antidepressants and Mood Stabilizers Psychopharmacology of Antidepressants and Mood Stabilizers Schematic diagram of Monoamine Neuron Electron microscope Fluorescence microscope Cell body Amine granules Axon Varicosities Pharmacology of Antidepressants and Mood Stabilizers Components of a Synapse 01 14 19 5 Pharmacology of Antidepressants and Mood Stabilizers Major Classes of Antidepressants Defined by Putative Mechanism of Action SE and NE uptake inhibition SE uptake inhibition Bupropion aminoketone Monoamine oxidase inhibitors MAOIs 01 14 19 Atomoxetine DA and NE uptake inhibition Nefazodone phenylpiperazine NE uptake inhibition Serotonin selective reuptake inhibitors SSRIs 5 HT2 receptor blockers and SE uptake inhibition Tricyclic antidepressants TCAs Venlafaxine Duloxetine Nonselective and irreversible Selective and or reversible RIMAs Not available 6 Pharmacology of Antidepressants and Mood Stabilizers Pharmacodynamics of Antidepressants Norepinephrine receptors Postsynaptic alpha1 and alpha2 beta1 and beta2 Presynaptic alpha2 Serotonin receptors Postsynaptic 5 HT1A and 5 HT2 Presynaptic 5 HT1A Others 01 14 19 Dopamine Acetylcholine CRH 7 Pharmacology of Antidepressants and Mood Stabilizers Pharmacology of Mirtazapine 01 14 19 de Boer J Clin Psychiatry 1996 8 Pharmacology of Antidepressants and Mood Stabilizers Cascade of Intraneuronal Events 01 14 19 9 Pharmacology of Antidepressants and Mood Stabilizers Potential Adverse Effects of Antidepressant Therapy Central Nervous System Cardiac Orthostasis hypertension heart block tachycardia Dizziness cognitive impairment sedation light headedness somnolence nervousness insomnia headache tremor changes in satiety and appetite Gastrointestinal Urogenital Erectile dysfunction ejaculation disorder anorgasmia priapism Nausea constipation vomiting dyspepsia diarrhea Autonomic Nervous System Dry mouth urinary retention blurred vision sweating 01 14 19 10 Pharmacology of Antidepressants and Mood Stabilizers Antidepressants Drug Interactions The pharmacologic action of a drug may be altered with the coadministration of a second drug by 01 14 19 Increasing or decreasing a known effect Creating an adverse effect Creating a new effect not seen with either drug alone Interaction may be pharmacodynamic pharmacokinetic or idiosyncratic 11 Pharmacology of Antidepressants and Mood Stabilizers Antidepressants and the Cytochrome P450 System 01 14 19 Antidepressants and mood stabilizers may be inhibitors inducers or substrates of one or more cytochrome P450 isoenzymes Knowledge of their P450 profile is useful in predicting drug drug interactions When some isoenzymes are absent of inhibited others may offer a secondary metabolic pathway P450 1A2 2C subfamily 2D6 and 3A4 are especially important to antidepressant metabolism and drug drug interactions 12 Pharmacology of Antidepressants and Mood Stabilizers Minimizing the Risk of Drug Interactions Associated with Antidepressants When adding an antidepressant with a potential for pharmacokinetic interaction to another drug clinicians could 01 14 19 Reduce the dose of the current drug Begin with a low dose of the antidepressant Use therapeutic drug monitoring where appropriate Monitor therapeutic and adverse effects Choose an antidepressant with a favorable profile for that interaction 13 Psychopharmacology of Antidepressants and Mood Stabilizers Treatment of an Acute Major Depressive Episode Clinical Presentation Major depressive episode mild to moderate single or recurrent nonpsychotic Treatment Strategy start SSRI VENLAFAXINE NEFAZODONE OR MIRTAZAPINE if expense not an issue or USE PREVIOUSLY EFFECTIVE AD at least 6 weeks with adequate dose and or plasma level or HCA if side effects are tolerated preferably a secondary amine TCA Adapted from Janicak PG Davis JM Preskorn SH Ayd FJ Jr Principles and Practice of Psychopharmacotherapy 3rd ed Philadelphia PA Lippincott Williams Wilkins 2001 14 Psychopharmacology of Antidepressants and Mood Stabilizers Treatment of an Acute Major Depressive Episode Clinical Presentation Atypical depression start Treatment Strategy MONOAMINE OXIDASE INHIBITOR MAOI N B Must wait at least 5 weeks after fluoxetine 2 3 weeks after other SSRIs venlafaxine nefazodone mirtazapine insufficient response Adapted from Janicak PG Davis JM Preskorn SH Ayd FJ Jr Principles and Practice of Psychopharmacotherapy 3rd ed Philadelphia PA Lippincott Williams Wilkins 2001 15 Psychopharmacology of Antidepressants and Mood Stabilizers Treatment of an Acute Major Depressive Episode Clinical Presentation Psychotic depression Treatment Strategy start or may start Serious suicidal risk Rapid physical deterioration Prior history of nonresponse to medication and or good response to ECT SECOND GENERATION ANTIPSYCHOTIC SGA plus AD insufficient response ELECTROCONVULSIVE THERAPY SGA Possibly TMS or VNS Adapted from Janicak PG Davis JM Preskorn SH Ayd FJ Jr Principles and Practice of Psychopharmacotherapy 3rd ed Philadelphia PA Lippincott Williams Wilkins 2001 16 Pharmacology of Antidepressants and Mood Stabilizers Bipolar Disorder Major Points 01 14 19 Bipolar and related disorders are some of the most challenging conditions to diagnose and manage Pharmacotherapy is the primary treatment Lithium is often insufficient Anticonvulsants and second generation antipsychotics may be effective alternatives or supplements 17 Pharmacology of Antidepressants and Mood Stabilizers Bipolar Disorder General Considerations 01 14 19 Afflicts 1 of the population Psychosocial environmental stressors influence occurrence Birth cohort effect genetic risk High morbidity and mortality Overall 11 suicide rate Untreated 20 25 will commit suicide 18 Pharmacology of Antidepressants and Mood Stabilizers Mood Disorders Therapeutic Options Lithium Anticonvulsants Valproate Lamotrigine
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