Antianxiety Agents, Sedative-Hypnotics and Antidepressants: Pharmacokinetics Adverse Effects Drug InteractionsGoalsAntianxiety/Sedative-Hypnotics: Diagnostic IndicationsAntianxiety AgentsSlide 5Sedative-HypnoticsPharmacokinetics: BenzodiazepinesSlide 8Pharmacokinetics: BuspironePharmacokinetics: Nonbenzodiazepine HypnoticsAdverse Effects: BenzodiazepinesSlide 12Adverse Effects: BuspironeDrug Interactions: BenzodiazepinesDrug Interactions: Anxiolytic/HypnoticsAntidepressants: Diagnostic IndicationsSlide 17Antidepressant AgentsSlide 19Pharmacokinetics: ADsPharmacokinetics: SSRIsAdverse Effects: AntidepressantsAdverse Effects: SSRIsAdverse Effects of AntidepressantsSlide 25Antidepressants: Drug InteractionsCYP 450 InhibitorsMinimizing the Risk of Drug Interactions Associated with AntidepressantsIndications for Therapeutic Drug MonitoringSlide 30Antianxiety Agents, Antianxiety Agents, Sedative-Hypnotics and Sedative-Hypnotics and Antidepressants:Antidepressants:PharmacokineticsPharmacokineticsAdverse EffectsAdverse EffectsDrug InteractionsDrug InteractionsPhilip G. Janicak, MDPhilip G. Janicak, MDProfessor of PsychiatryProfessor of PsychiatryRush University Medical CenterRush University Medical Center2GoalsGoalsAnxiolytic-Sedative-Hypnotics (ASHs)Anxiolytic-Sedative-Hypnotics (ASHs)Diagnostic indicationsDiagnostic indicationsClassification of ASHsClassification of ASHsRelevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug InteractionsAntidepressants (ADs)Antidepressants (ADs)Diagnostic indicationsDiagnostic indicationsClassification of ADsClassification of ADsRelevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug Interactions3Antianxiety/Sedative-Hypnotics:Antianxiety/Sedative-Hypnotics:Diagnostic IndicationsDiagnostic IndicationsGeneralized anxiety disorder (GAD)Generalized anxiety disorder (GAD)Phobic disordersPhobic disordersAnxiety disorder due to general medical conditionAnxiety disorder due to general medical conditionPanic disorderPanic disorderObsessive-compulsive disorder (OCD)Obsessive-compulsive disorder (OCD)Posttraumatic stress disorder (PTSD)Posttraumatic stress disorder (PTSD)Sleep disorders (dyssomnias; parasomnias)Sleep disorders (dyssomnias; parasomnias)4Antianxiety AgentsAntianxiety AgentsClass/Trade NameClass/Trade NameGeneric NameGeneric NameUsual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)BZDsBZDs Librium, othersLibrium, othersChlordiazepoxideChlordiazepoxide10-10010-100 Valium, othersValium, othersDiazepamDiazepam2-402-40 Serax, othersSerax, othersOxazepamOxazepam30-12030-120 Tranxene, othersTranxene, othersChlorazepateChlorazepate15-6015-60 AtivanAtivanLorazepamLorazepam1-101-10 CentraxCentraxPrazepamPrazepam20-6020-60 PaxipamPaxipamHalazepamHalazepam60-16060-160 XanaxXanaxAlprazolamAlprazolam0.75-40.75-4Serotonergic agentsSerotonergic agents Sertraline, othersSertraline, othersSSRIsSSRIs25-25025-250 BusparBusparBuspironeBuspirone15-6015-60 DesyrelDesyrelTrazodone*Trazodone*50-10050-100Noradrenergic agentsNoradrenergic agents InderalInderalPropranolol*Propranolol*30-12030-120 Catapres Catapres Clonidine*Clonidine*0.1-0.50.1-0.5*Not approved by the FDA.5Antianxiety AgentsAntianxiety AgentsClass/Trade NameClass/Trade NameGeneric NameGeneric NameUsual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)Serotonergic/noradrenergic agentsSerotonergic/noradrenergic agents Effexor XREffexor XRVenlafaxine XRVenlafaxine XR75-37575-375 CymbaltaCymbaltaDuloxetineDuloxetine20-6020-60AntihistaminesAntihistamines BenedrylBenedrylDiphenhydramine*Diphenhydramine*25-5025-50 AtaraxAtaraxHydroxyzine*Hydroxyzine*25-5025-50AnticonvulsantsAnticonvulsants NeurontinNeurontinGabapentin*Gabapentin*300-5,000300-5,000 LyricaLyricaPregabalin*Pregabalin*150-600150-600 GabitrilGabitrilTiagabine*Tiagabine*4-164-16 Depakote, othersDepakote, othersValproate*Valproate*250-2,000250-2,000Natural RemediesNatural Remedies KavatrolKavatrolKavaKava210-240 mg/kL210-240 mg/kLInvestigational TreatmentsInvestigational TreatmentsPartial BZD agonists (e.g., abecarnil)*, Neurosteroids*, Partial BZD agonists (e.g., abecarnil)*, Neurosteroids*, CRF antagonists*, Substance P antagonists*, NMDA CRF antagonists*, Substance P antagonists*, NMDA receptor antagonists*receptor antagonists**Not approved by the FDA.6Sedative-HypnoticsSedative-HypnoticsClass/Trade NameClass/Trade NameGeneric NameGeneric NameDaily Dosage (mg/d)Daily Dosage (mg/d)Benzodiazepines Long acting: Dalmane Flurazepam 15-45 Doral Quazepam 7.5-15 Intermediate acting: Prosom Estazolam 0.5-2 Restoril Temazepam 15-45 Short acting: Halcion Triazolam 0.125-0.25Nonbenzodiazepines Ambien Zolpidem 5-20 Sonata Zaleplon 5-20 Lunesta Eszopiclone 2-3 - Indiplon* 10-20Melatonin Receptor Agonists Rozerem Ramelteon 8-16Sedating antidepressants Desyrel Trazodone 25-100Barbituate like agents Notec Choral hydrate 500-1,500Natural Remedies - Melatonin* 0.3-2 - Valerian* 400-900*Not approved by the FDA.7Pharmacokinetics: BenzodiazepinesPharmacokinetics: BenzodiazepinesAbsorption:Absorption:Variable speedVariable speedOnset of action:Onset of action:Lipid solubility Lipid solubility →→ faster onset faster onsetDuration of action:Duration of action:Single dose:Single dose: the greater the lipid solubility the greater the lipid solubility →→ faster redistribution to fat tissues faster redistribution to fat tissues →→ shorter shorter duration of actionduration of actionChronic use:Chronic use: in equilibrium with fat tissues in equilibrium with fat tissuesProtein binding:Protein binding:HIGH for all agentsHIGH for all agentsMetabolism:Metabolism:Elimination half life:Elimination half life:Lorazepam, oxazepam, temazepam not Lorazepam, oxazepam, temazepam not metabolized by liver CYP 450metabolized by liver CYP 450In part, determines duration of actionIn part, determines duration of action8Pharmacokinetics: BenzodiazepinesPharmacokinetics: BenzodiazepinesDosing adjustmentsDosing adjustmentsElderlyElderlyHepatic impairmentHepatic impairmentCytochrome P450 isoenzymesCytochrome P450 isoenzymesRoute of AdministrationRoute of Administration Oral routeOral routeFaster absorption = greater “rush”Faster absorption = greater “rush”Acute
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