Pharmacology of Antidepressants and Mood StabilizersObjectivesDepression: DiagnosisDiagnostic Indications for Antidepressants (DSM-IV Categories)DSM-IV Diagnostic Criteria for a Major Depressive EpisodeTHERAPEUTIC OPTIONSMajor Classes of Antidepressants Defined by Putative Mechanism of ActionPharmacodynamics of AntidepressantsSlide 9Components of a SynapseCascade of Intraneuronal EventsPsychopharmacology of MirtazapineMonoamine Oxidase InhibitorsAntidepressants: Adverse Effects, Pharmacokinetics and Drug-InteractionsPotential Side Effects of Antidepressant TherapyPolypharmacy with a Single Drug: “Cocktail” of Effects of the Tricyclic Antidepressant AmitriptylineSelective Serotonin Reuptake InhibitorsComparison of Pharmacokinetic ParametersDrug-Drug InteractionsAntidepressants and the Cytochrome P450 SystemMinimizing the Risk of Drug-drug Interactions Associated With AntidepressantsTreatment of an Acute Major Depressive EpisodeSlide 23Slide 24Slide 25Slide 26Slide 27Bipolar Disorder: Major PointsBipolar Disorder: General ConsiderationsBipolar Disorder: Long-Term PrognosisBipolar Disorder: Symptom DomainsTreatment of Bipolar DisorderLithiumSlide 34Slide 35AnticonvulsantsValproateAnticonvulsantsSlide 39Second Generation AntipsychoticsOlanzapineSlide 42Mood Stabilizers: Adverse Effects, Pharmacokinetics and Drug-InteractionsLithium: Adverse EffectsAnticonvulsants: Adverse EffectsPharmacokinetic Properties of Primary Mood StabilizersDrug Interactions with Mood StabilizersStrategy for Treatment of Acute ManiaSlide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Slide 57ReferencesAbstractTABLE 1: ANTIDEPRESSANTSAdverse Effects of AntidepressantsSlide 62CYP450 Isoenzyme Inhibition by the SSRIs01/14/19 1Pharmacology of Antidepressants and Mood StabilizersPhilip G. Janicak, M.D.Professor of Psychiatry and PharmacologyUniversity of Illinois at Chicago01/14/19 2ObjectivesReview the signs and symptoms of major depression and bipolar disorderCharacterize the different classes of antidepressants and mood stabilizers based on their mechanism of actionReview the pharmacokinetics, adverse effects and potential for drug interactions of these agentsReview treatment strategies for the drug management of depression and bipolar mania based on the existing data, clinical experience, and risk-benefit ratiopharmacology of antidepressants and mood stabilizers01/14/19 3Depression: DiagnosisClinical depression is common, but often misdiagnosedAbout 50% of suicides are associated with depressionDepression can adversely impact other medical conditionsComorbid anxiety is frequent and can substantially increase suicide riskAlthough 70% of depressions can respond to appropriate medication, many patients never receive an adequate trialpharmacology of antidepressants and mood stabilizers01/14/19 4Diagnostic Indications forAntidepressants (DSM-IV Categories)Mood disordersMajor depressive disorderSingle of recurrentWith or without melancholiaSeasonal patternBipolar disorderDepressedMixedCyclothymic disorderDysthymic disorderOther psychotic disorders (e.g., schizoaffective disorder, depressive type)Mood disorder due to a general medical conditione.g., dementia with depression (e.g., Alzheimer’s type, vascular)Substance-induced mood disordere.g., amphetamine or similarly acting synpathomimetic intoxication or withdrawalpharmacology of antidepressants and mood stabilizers01/14/19 5DSM-IV Diagnostic Criteria for aMajor Depressive EpisodePresence of at least five of the following symptoms during the same 2-week period (nearly every day), representing a change from previous functioning; at least one symptom is either (a) depressed mood, or (b) loss of interest or pleasure.MoodDepressed mood (irritable mood in children and adolescents)Marked diminished interest or pleasure in almost all activitiesBehavioralSignificant weight loss or gain (failure to attain expected weight gain in children)Insomnia or hypersomniaObservable psychomotor agitation or retardationFatigue or loss of energyCognitiveFeelings of worthlessness, or of excessive or inappropriate guiltDiminished ability to think or concentrate, or indecisivenessRecurrent thoughts of death; recurrent suicidal ideation, plans, or attemptspharmacology of antidepressants and mood stabilizers01/14/19 6PharmacotherapyAntidepressantsAnxiolyticsMood stabilizersAntipsychoticsPsychotherapyCognitive behavioral therapyInterpersonal therapyMarital/family counselingGroup therapySomatic TherapyElectroconvulsive therapyBright light therapyPossibly:Transcranial magnetic stimulationVagal nerve stimulationSleep deprivationTHERAPEUTIC OPTIONSpharmacology of antidepressants and mood stabilizers01/14/19 7Preskorn SH. Outpatient Management of Depression. 1994.Major Classes of Antidepressants Defined by Putative Mechanism of ActionCombined NE and SE uptake inhibitionTricyclic antidepressants (TCAs)VenlafaxineSE uptake inhibitionSerotonin selective reuptake inhibitors (SSRIs)5-HT2 receptor blockers and SE uptake inhibitionNefazodone (phenylpiperazine)DA and NE uptake inhibitionBupropion (aminoketone)Monoamine oxidase inhibitors (MAOIs)Nonselective and irreversibleSelective and/or reversible (RIMAs)pharmacology of antidepressants and mood stabilizers01/14/19 8Pharmacodynamics of AntidepressantsNorepinephrine receptorsPostsynaptic (alpha1 and alpha2; beta1and beta2)Presynaptic (alpha2)Serotonin receptorsPostsynaptic (5-HT1A and 5-HT2)Presynaptic (5-HT1A)OthersDopamineAcetylcholinepharmacology of antidepressants and mood stabilizers01/14/19 9pharmacology of antidepressants and mood stabilizers01/14/19 10Components of a Synapsepharmacology of antidepressants and mood stabilizers01/14/19 11Cascade of Intraneuronal Eventspharmacology of antidepressants and mood stabilizers01/14/19 12Psychopharmacology of Mirtazapinepharmacology of antidepressants and mood stabilizers01/14/19 13pharmacology of antidepressants and mood stabilizers Nonselective/nonreversibleHydrazine (e.g., phenelzine)Nonhydrazine (e.g., tranylcypromine) Selective/nonreversibleMAO-B (e.g., deprenyl) Selective/reversibleMAO-A (e.g., moclobemide)Monoamine Oxidase Inhibitors01/14/19 14Antidepressants:Adverse Effects, Pharmacokineticsand Drug-Interactionspharmacology of antidepressants and mood stabilizers01/14/19