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UIC PCOL 425 - Pharmacology of Antidepressants Mood Stabilizers

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Psychopharmacology of Antidepressants, Mood Stabilizers and Anxiolytic/Sedative-HypnoticsObjectivesSlide 3Slide 4Components of a SynapseMajor Classes of Antidepressants Defined by Putative Mechanism of ActionPharmacodynamics of AntidepressantsPharmacology of MirtazapineCascade of Intraneuronal EventsPotential Adverse Effects of Antidepressant TherapyAntidepressants: Drug InteractionsAntidepressants and the Cytochrome P450 SystemMinimizing the Risk of Drug Interactions Associated with AntidepressantsTreatment of an Acute Major Depressive EpisodeSlide 15Slide 16Bipolar Disorder: Major PointsBipolar Disorder: General ConsiderationsMood Disorders: Therapeutic OptionsLithium (Monovalent cation)LithiumAnticonvulsantsValproate (Simple branched-chain carboxylic acids)LamotrigineAnticonvulsantsSecond Generation AntipsychoticsOlanzapineSlide 28Pharmacokinetic Properties of Primary Mood StabilizersMood Stabilizers: Drug InteractionsStrategy for Treatment of Acute ManiaSlide 32Slide 33Slide 34Slide 35ReferencesAbstractAntidepressantsAdverse Effects of AntidepressantsAdverse Effects of Antidepressants (con’t)Comparison of Pharmacokinetic Parameters01/14/19 1Psychopharmacology of Antidepressants, Mood Stabilizers and Anxiolytic/Sedative-HypnoticsPhilip G. Janicak, M.D.Professor of PsychiatryRush University Medical Center01/14/19 2Pharmacology of Antidepressants and Mood StabilizersObjectives•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 ratioPsychopharmacology of Antidepressants and Mood StabilizersSchematic diagram of Monoamine NeuronElectron microscope Fluorescence microscopeCell bodyAxonAminegranulesVaricositiesPsychopharmacology of Antidepressants and Mood Stabilizers01/14/19 5Pharmacology of Antidepressants and Mood StabilizersComponents of a Synapse01/14/19 6Pharmacology of Antidepressants and Mood StabilizersMajor Classes of Antidepressants Defined by Putative Mechanism of Action•SE and NE uptake inhibition•Tricyclic antidepressants (TCAs)•Venlafaxine•Duloxetine*•SE uptake inhibition•Serotonin selective reuptake inhibitors (SSRIs)•5-HT2 receptor blockers and SE uptake inhibition•Nefazodone (phenylpiperazine)•NE uptake inhibition•Atomoxetine•DA and NE uptake inhibition•Bupropion (aminoketone)•Monoamine oxidase inhibitors (MAOIs)•Nonselective and irreversible•Selective and/or reversible (RIMAs)*Not available01/14/19 7Pharmacology of Antidepressants and Mood StabilizersPharmacodynamics 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•Dopamine•Acetylcholine•CRH01/14/19 8Pharmacology of Antidepressants and Mood StabilizersPharmacology of Mirtazapinede Boer, J Clin Psychiatry, 199601/14/19 9Pharmacology of Antidepressants and Mood StabilizersCascade of Intraneuronal Events01/14/19 10Pharmacology of Antidepressants and Mood StabilizersCardiacOrthostasis,hypertension,heart block,tachycardiaUrogenitalErectile dysfunction,ejaculation disorder,anorgasmia, priapismCentral Nervous SystemDizziness, cognitive impairment,sedation, light-headedness,somnolence, nervousness,insomnia, headache, tremor,changes in satiety and appetiteGastrointestinalNausea, constipation,vomiting, dyspepsia,diarrheaAutonomic Nervous SystemDry mouth, urinary retention,blurred vision, sweatingPotential Adverse Effects ofAntidepressant Therapy01/14/19 11Pharmacology of Antidepressants and Mood StabilizersAntidepressants: Drug Interactions•The pharmacologic action of a drug may be altered with the coadministration of a second drug by:•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 idiosyncratic01/14/19 12Pharmacology of Antidepressants and Mood StabilizersAntidepressants and the Cytochrome P450 System•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 interactions01/14/19 13Pharmacology of Antidepressants and Mood StabilizersMinimizing the Risk of Drug Interactions Associated with Antidepressants•When adding an antidepressant with a potential for pharmacokinetic interaction to another drug, clinicians could:•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 interactionMajor depressive episode• mild to moderate • single or recurrent• nonpsychoticSSRI, 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)startClinical Presentation Treatment StrategyTreatment of an AcuteMajor Depressive EpisodeAdapted from Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.Psychopharmacology of Antidepressants and Mood Stabilizers14•Atypical depressionMONOAMINE OXIDASE INHIBITOR (MAOI)(N.B.: Must wait at least 5 weeks after fluoxetine; 2-3 weeks after other SSRIs, venlafaxine, nefazodone, mirtazapine)start(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.Clinical Presentation Treatment StrategyTreatment of an AcuteMajor Depressive EpisodePsychopharmacology of Antidepressants and Mood Stabilizers15SECOND GENERATION ANTIPSYCHOTIC (SGA)plus ADELECTROCONVULSIVE THERAPY (SGA)•Possibly TMS or


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UIC PCOL 425 - Pharmacology of Antidepressants Mood Stabilizers

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