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Antianxiety Agents, Antianxiety Agents, Sedative-Hypnotics and Sedative-Hypnotics and
Antidepressants:Antidepressants:PharmacokineticsPharmacokineticsAdverse EffectsAdverse Effects
Drug InteractionsDrug Interactions
Philip G. Janicak, MDPhilip G. Janicak, MD
Professor of PsychiatryProfessor of Psychiatry
Rush University Medical CenterRush University Medical Center
2
GoalsGoals
Anxiolytic-Sedative-Hypnotics (ASHs)Anxiolytic-Sedative-Hypnotics (ASHs) Diagnostic indicationsDiagnostic indications Classification of ASHsClassification of ASHs Relevant PharmacokineticsRelevant Pharmacokinetics Serious Adverse EffectsSerious Adverse Effects Drug InteractionsDrug Interactions
Antidepressants (ADs)Antidepressants (ADs) Diagnostic indicationsDiagnostic indications Classification of ADsClassification of ADs Relevant PharmacokineticsRelevant Pharmacokinetics Serious Adverse EffectsSerious Adverse Effects Drug InteractionsDrug Interactions
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Antianxiety/Sedative-Hypnotics:Antianxiety/Sedative-Hypnotics:Diagnostic IndicationsDiagnostic Indications
Generalized anxiety disorder (GAD)Generalized anxiety disorder (GAD) Phobic disordersPhobic disorders Anxiety disorder due to general medical conditionAnxiety disorder due to general medical condition
Panic disorderPanic disorder Obsessive-compulsive disorder (OCD)Obsessive-compulsive disorder (OCD) Posttraumatic stress disorder (PTSD)Posttraumatic stress disorder (PTSD)
Sleep disorders (dyssomnias; parasomnias)Sleep disorders (dyssomnias; parasomnias)
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Antianxiety AgentsAntianxiety AgentsClass/Trade NameClass/Trade Name Generic NameGeneric Name Usual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)
BZDsBZDs
Librium, othersLibrium, others ChlordiazepoxideChlordiazepoxide 10-10010-100
Valium, othersValium, others DiazepamDiazepam 2-402-40
Serax, othersSerax, others OxazepamOxazepam 30-12030-120
Tranxene, othersTranxene, others ChlorazepateChlorazepate 15-6015-60
AtivanAtivan LorazepamLorazepam 1-101-10
CentraxCentrax PrazepamPrazepam 20-6020-60
PaxipamPaxipam HalazepamHalazepam 60-16060-160
XanaxXanax AlprazolamAlprazolam 0.75-40.75-4
Serotonergic agentsSerotonergic agents
Sertraline, othersSertraline, others SSRIsSSRIs 25-25025-250
BusparBuspar BuspironeBuspirone 15-6015-60
DesyrelDesyrel Trazodone*Trazodone* 50-10050-100
Noradrenergic agentsNoradrenergic agents
InderalInderal Propranolol*Propranolol* 30-12030-120
Catapres Catapres Clonidine*Clonidine* 0.1-0.50.1-0.5*Not approved by the FDA.
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Antianxiety AgentsAntianxiety AgentsClass/Trade NameClass/Trade Name Generic NameGeneric Name Usual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)
Serotonergic/noradrenergic agentsSerotonergic/noradrenergic agents
Effexor XREffexor XR Venlafaxine XRVenlafaxine XR 75-37575-375
CymbaltaCymbalta DuloxetineDuloxetine 20-6020-60
AntihistaminesAntihistamines
BenedrylBenedryl Diphenhydramine*Diphenhydramine* 25-5025-50
AtaraxAtarax Hydroxyzine*Hydroxyzine* 25-5025-50
AnticonvulsantsAnticonvulsants
NeurontinNeurontin Gabapentin*Gabapentin* 300-5,000300-5,000
LyricaLyrica Pregabalin*Pregabalin* 150-600150-600
GabitrilGabitril Tiagabine*Tiagabine* 4-164-16
Depakote, othersDepakote, others Valproate*Valproate* 250-2,000250-2,000
Natural RemediesNatural Remedies
KavatrolKavatrol KavaKava 210-240 mg/kL210-240 mg/kL
Investigational TreatmentsInvestigational Treatments Partial 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.
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Sedative-HypnoticsSedative-HypnoticsClass/Trade NameClass/Trade Name Generic NameGeneric Name Daily 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 0.125-0.25
Nonbenzodiazepines
Ambien Zolpidem 5-20
Sonata Zaleplon 5-20
Lunesta Eszopiclone 2-3
- Indiplon* 10-20
Melatonin Receptor Agonists
Rozerem Ramelteon 8-16
Sedating antidepressants
Desyrel Trazodone 25-100
Barbituate like agents
Notec Choral hydrate 500-1,500
Natural Remedies
- Melatonin* 0.3-2
- Valerian* 400-900*Not approved by the FDA.
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Pharmacokinetics: BenzodiazepinesPharmacokinetics: Benzodiazepines
Absorption:Absorption: Variable speedVariable speed
Onset of action:Onset of action: Lipid solubility Lipid solubility →→ faster onset faster onset
Duration 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 action
Chronic use:Chronic use: in equilibrium with fat tissues in equilibrium with fat tissues
Protein binding:Protein binding: HIGH for all agentsHIGH for all agents
Metabolism:Metabolism:
Elimination half life:Elimination half life:
Lorazepam, oxazepam, temazepam not Lorazepam, oxazepam, temazepam not metabolized by liver CYP 450metabolized by liver CYP 450
In part, determines duration of actionIn part, determines duration of action
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Pharmacokinetics: BenzodiazepinesPharmacokinetics: Benzodiazepines
Dosing adjustmentsDosing adjustments ElderlyElderly Hepatic impairmentHepatic impairment Cytochrome P450 isoenzymesCytochrome P450 isoenzymes
Route of AdministrationRoute of Administration Oral routeOral route
Faster absorption = greater “rush”Faster absorption = greater “rush”
Acute parenteral (IM)Acute parenteral (IM) Lorazepam – Lorazepam – drug of choicedrug of choice, rapid and reliable absorption, rapid and reliable absorption Chlordiazepoxide and diazepam – may precipitate locally Chlordiazepoxide and diazepam – may precipitate locally
and are poorly absorbed, painfuland are poorly absorbed, painful
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Pharmacokinetics: BuspironePharmacokinetics: Buspirone
TT½½ – 2-3 hrs – 2-3 hrs
Slow onset of actionSlow onset of action Weeks vs. daysWeeks vs. days
CYP 3A4 substrateCYP 3A4 substrate Inducers Inducers → ? Loss of efficacy→ ? Loss of efficacy Inhibitors → ? Toxicity or increased side effectsInhibitors → ? Toxicity or increased side effects
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Pharmacokinetics:Pharmacokinetics:Nonbenzodiazepine HypnoticsNonbenzodiazepine Hypnotics
(Selectively bind to the BZD(Selectively bind to the BZD11 receptors) receptors)
ZaleplonZaleplon ZolpidemZolpidem EszopicloneEszopiclone
MetabolismMetabolism Aldehyde Aldehyde oxidase,oxidase,
CYP 3A4CYP 3A4
Various CYP Various CYP isoenzymesisoenzymes
CYP 3A4, CYP 3A4, 2E12E1
Tmax (Hr)Tmax (Hr) 1.41.4 1.41.4 11
T1/2 (Hr)T1/2 (Hr) 1.041.04†† 2.1*2.1*†† 6*6*††
* Prolonged in elderly; * Prolonged in elderly; †† prolonged in severe hepatic impairment prolonged in severe hepatic impairment
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Adverse Effects: Adverse Effects: BenzodiazepinesBenzodiazepines
SedationSedation and impairment of performance and impairment of performance Psychomotor skillsPsychomotor skills
Driving; engaging in dangerous physical activities; using Driving; engaging in dangerous physical activities; using hazardous machineryhazardous machinery
Especially during initial phase of treatmentEspecially during initial phase of treatment MemoryMemory impairment impairment
Anterograde amnesia (desired before surgery, Anterograde amnesia (desired before surgery, other procedures)other procedures)
Dose-related, and tolerance may not developDose-related, and tolerance may not develop Most likely with triazolamMost likely with triazolam
DisinhibitionDisinhibition Possible risk factors: History of aggression, Possible risk factors: History of aggression,
impulsivity, borderline or antisocial personalityimpulsivity, borderline or antisocial personality
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Adverse Effects:Adverse Effects:BenzodiazepinesBenzodiazepines
Abuse potentialAbuse potential decreases when properly prescribed and decreases when properly prescribed and supervised.supervised.
DependenceDependence may occur at usual doses taken beyond several may occur at usual doses taken beyond several weeks.weeks.
Withdrawal Withdrawal may occur even when discontinuation is not abrupt may occur even when discontinuation is not abrupt (e.g., by 10% every 3 days). Symptoms include: tachycardia, (e.g., by 10% every 3 days). Symptoms include: tachycardia, increased blood pressure, muscle cramps, anxiety, insomnia, increased blood pressure, muscle cramps, anxiety, insomnia, panic attacks, impairment of memory and concentration, panic attacks, impairment of memory and concentration, perceptual disturbances, derealization, hallucinations, perceptual disturbances, derealization, hallucinations, hyperpyrexia, seizures. May continue for months.hyperpyrexia, seizures. May continue for months.
Rebound anxietyRebound anxiety: : return of target symptoms, with increased return of target symptoms, with increased intensity.intensity.
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Adverse Effects: BuspironeAdverse Effects: Buspirone
AdvantagesAdvantages No sedation or impairment of performanceNo sedation or impairment of performance No cross-tolerance with BZDsNo cross-tolerance with BZDs No tolerance or withdrawalNo tolerance or withdrawal No abuse potentialNo abuse potential
DisadvantagesDisadvantages NauseaNausea HeadacheHeadache Insomnia, nervousnessInsomnia, nervousness RestlessnessRestlessness Dizziness, lightheadednessDizziness, lightheadedness
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Drug Interactions: Drug Interactions: BenzodiazepinesBenzodiazepines
Additive Additive pharmacodynamicpharmacodynamic effects effects(e.g., alcohol) (e.g., alcohol)
BZD BZD withdrawalwithdrawal when other drugs that when other drugs that increase seizure risk are also takenincrease seizure risk are also taken
Diazepam may increase levels of Diazepam may increase levels of digoxin digoxin and phenytoinand phenytoin
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Drug Interactions: Drug Interactions: Anxiolytic/HypnoticsAnxiolytic/Hypnotics
Drugs that affect CYP 3A4Drugs that affect CYP 3A4 Inhibit BZD metabolismInhibit BZD metabolism
(e.g., fluoxetine/norfluoxetine via P450 3A3/4 (e.g., fluoxetine/norfluoxetine via P450 3A3/4 inhibits metabolism of triazolam)inhibits metabolism of triazolam)
Effect on zolpidem > zaleplonEffect on zolpidem > zaleplon May be clinically nonsignificantMay be clinically nonsignificant
Clinically relevant increased exposure for Clinically relevant increased exposure for eszopiclone and inhibitorseszopiclone and inhibitors
Additive CNS depressionAdditive CNS depression Alcohol, antipsychotics, mood stabilizersAlcohol, antipsychotics, mood stabilizers
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Antidepressants: Antidepressants: Diagnostic Indications Diagnostic Indications
Mood disordersMood disorders Major depressive disorderMajor depressive disorder
Single or recurrentSingle or recurrent With or without melancholiaWith or without melancholia Seasonal patternSeasonal pattern
Bipolar disorderBipolar disorder DepressedDepressed MixedMixed
Cyclothymic disorderCyclothymic disorder Dysthymic disorderDysthymic disorder
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Other psychiatric Other psychiatric disorders (e.g., disorders (e.g., schizoaffective disorder, depressive type)schizoaffective disorder, depressive type)
Mood disorder Mood disorder due to a general medical due to a general medical condition condition (e.g., dementia with depression; (e.g., dementia with depression; Alzheimer’s type)Alzheimer’s type)
Substance-induced Substance-induced mood disorder (e.g., mood disorder (e.g., amphetamine or similarly acting amphetamine or similarly acting sympathomimetic intoxication or withdrawal)sympathomimetic intoxication or withdrawal)
Antidepressants: Antidepressants: Diagnostic Indications Diagnostic Indications
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Antidepressant AgentsAntidepressant AgentsClass/Generic NameClass/Generic Name Trade NameTrade Name Usual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)
SSRISSRI
CitalopramCitalopram CelexaCelexa 20-4020-40
EscitalopramEscitalopram LexaproLexapro 1-201-20
FluoxetineFluoxetine ProzacProzac 10-6010-60
FluvoxamineFluvoxamineaa LuvoxLuvox 100-300100-300
ParoxetineParoxetine PaxilPaxil 10-5010-50
SertralineSertraline ZoloftZoloft 50-20050-200
SNRISNRI
AtomoxetineAtomoxetineaa StratteraStrattera 60-12060-120
DSNRIDSNRI
DuloxetineDuloxetine CymbaltaCymbalta 30-6030-60
MilnacipranMilnacipranbb 100-200100-200
VenlafaxineVenlafaxine EffexorEffexor 75-37575-375
AminoketoneAminoketone
BupropionBupropion WellbutrinWellbutrin 150-450150-450
TriazolopyridineTriazolopyridine
NefazodoneNefazodone SerzoneSerzonecc 100-600100-600
TrazodoneTrazodone DesyrelDesyrel 150-600150-600
SSRI, Selective serotonin reputake inhibitor; SSRI, selective norepinephrine, DSNI, dual norepinphrine reputae inhibitor; TCA, Tricyclic antidepressant; MAOI, monoamine oxidase inhibitor.
aNot approved by the FDA for depression. bNot available in the United States. cSerzone no longer available. dTransdermal system approved for depression.
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Antidepressant AgentsAntidepressant AgentsClass/Generic NameClass/Generic Name Trade NameTrade Name Usual Daily Dosage (mg/d)Usual Daily Dosage (mg/d)
TetracyclicTetracyclic
AmoxapineAmoxapine AscendinAscendin 200-600200-600
MaprotilineMaprotiline LudiomilLudiomil 75-22575-225
MirtazapineMirtazapine RemeronRemeron 15-4515-45
TCATCA
AmitriptylineAmitriptyline ElavilElavil 75-30075-300
ClomipramineClomipramine AnafranilAnafranil 100-250100-250
DesipramineDesipramine Norpramine Norpramine 75-30075-300
Doxepin Doxepin SinequanSinequan 75-30075-300
ImipramineImipramine TofranilTofranil 75-30075-300
NortriptylineNortriptyline PamelorPamelor 75-30075-300
ProtriptylineProtriptyline VivactilVivactil 20-6020-60
TrimipramineTrimipramine SurmontilSurmontil 75-30075-300
MAOIMAOI
IsocarboxazidIsocarboxazid MarplanMarplan 40-6040-60
PhenelzinePhenelzine NardilNardil 30-9030-90
TranylcypromineTranylcypromine ParnateParnate 30-6030-60
SelegilineSelegilinedd EmsamEmsam 20mg/20 cm20mg/20 cm22 patch patch
SSRI, Selective serotonin reputake inhibitor; SSRI, selective norepinephrine, DSNI, dual norepinphrine reputae inhibitor; TCA, Tricyclic antidepressant; MAOI, monoamine oxidase inhibitor.
aNot approved by the FDA for depression. bNot available in the United States. cSerzone no longer available. dTransdermal system approved for depression.
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Pharmacokinetics: ADsPharmacokinetics: ADsDrugDrug AbsorptionAbsorption DistributionDistribution MetabolismMetabolism Elimin tElimin t
1/21/2
SSRIsSSRIs complete High PB hepaticfluoxetineactive met.
24 hoursfluox. days
VenlafaxineVenlafaxine complete widelyLow PB
hepaticactive metabolites
5 hours
NefazodoneNefazodone complete1st pass effect
loose PB hepatic active metabolites
2-4 hours
MirtazapineMirtazapine complete high PB hepatic active metabolites
20-40 hours> in women
TCAsTCAs complete1st pass effect
High PB hepaticCYP 2D6
24 hours
21
Pharmacokinetics: SSRIsPharmacokinetics: SSRIs
CitalopramCitalopram FluoxetineFluoxetine SertralineSertraline ParoxetineParoxetine FluvoxamineFluvoxamine
% protein-bound% protein-bound 8080 9494 9999 9595 7777
Peak plasma level Peak plasma level (hour)(hour)
3-43-4 6-86-8 6-86-8 2-82-8 2-82-8
Half-life (hours)Half-life (hours) 3535 24-7224-72 2525 2020 1515
Dose range (mg/d)Dose range (mg/d) 20-6020-60 20-8020-80 50-20050-200 10-5010-50 50-30050-300
Absorption altered Absorption altered by fast or fed statusby fast or fed status
NoNo NoNo YesYes NoNo NoNo
Linear Linear pharmacokineticspharmacokinetics
YesYes NoNo YesYes NoNo NoNo
GI absorption (%)GI absorption (%) ~100~100 8080 4444 6464 9494
Van Harten. Van Harten. Clin PharmacokinetClin Pharmacokinet, 1993. Preskorn. , 1993. Preskorn. Clin PharmacokinetClin Pharmacokinet. 1997. Data on file. Forest Laboratories, Inc. Preskorn. . 1997. Data on file. Forest Laboratories, Inc. Preskorn. J Clin PsychiatryJ Clin Psychiatry. 1993.. 1993.
22
CardiacCardiacOrthostasis,
hypertension,heart block,tachycardia
UrogenitalUrogenitalErectile dysfunction,ejaculation disorder,
anorgasmia, priapism
Central Nervous SystemCentral Nervous SystemDizziness, cognitive impairment,
sedation, light-headedness,somnolence, nervousness,
insomnia, headache, tremor,changes in satiety and appetite
GastrointestinalGastrointestinalNausea, constipation,vomiting, dyspepsia,
diarrhea
Autonomic Nervous SystemAutonomic Nervous SystemDry mouth, urinary retention,
blurred vision, sweating
Adverse Effects: AntidepressantsAdverse Effects: Antidepressants
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Adverse Effects: SSRIsAdverse Effects: SSRIs
AdvantagesAdvantages Improved safety and tolerability (e.g., cardiac Improved safety and tolerability (e.g., cardiac
toxicity)toxicity) Better long-term compliance (?)Better long-term compliance (?)
DisadvantagesDisadvantages Sexual dysfunctionSexual dysfunction Increased risk of suicide (?)Increased risk of suicide (?) Drug interactionsDrug interactions
Pharmacodynamic (serotonin syndrome)Pharmacodynamic (serotonin syndrome) Pharmacokinetic (CYP 450 inhibition)Pharmacokinetic (CYP 450 inhibition)
24
Adverse Effects of AntidepressantsAdverse Effects of AntidepressantsDrugsDrugs SedationSedation AnticholinergicsAnticholinergics Orthostatic HypotensionOrthostatic Hypotension Cardiac EffectsCardiac Effects
SSRIsSSRIs
CitalopramCitalopram LowLow NoneNone NoneNone NoneNone
EscitalopramEscitalopram LowLow NoneNone NoneNone NoneNone
FluoxetineFluoxetine LowLow NoneNone NoneNone NoneNone
FluvoxamineFluvoxamine LowLow NoneNone NoneNone NoneNone
ParoxetineParoxetine LowLow LowLow NoneNone NoneNone
SertralineSertraline LowLow NoneNone NoneNone NoneNone
SNRIsSNRIs
Atomoxetine*Atomoxetine* LowLow LowLow LowLow LowLow
DSNRIsDSNRIs
DuloxetineDuloxetine LowLow LowLow LowLow LowLow
MilnacipranMilnacipran LowLow LowLow LowLow LowLow
VenlafaxineVenlafaxine LowLow LowLow LowLow LowLow
AminoketonesAminoketones
BupropionBupropion LowLow Very lowVery low Very low - noneVery low - none LowLow
TriazolopyridinesTriazolopyridines
NefazodoneNefazodone LowLow LowLow LowLow LowLow
TrazodoneTrazodone HighHigh LowLow ModerateModerate LowLow
SSRI, Selective serotonin reputake inhibitor; SSRI, selective norepinephrine, DSNI, dual norepinphrine reputae inhibitor; TCA, Tricyclic antidepressant; MAOI, monoamine oxidase inhibitor. Adapted from Ward M. Appendix B. In: Flaherty J, Davis JM, Janicak PG, eds. Psychiatry: Diagnosis and Therapy. 2nd ed. Norwalk, Conn: Appleton & Lange, 1995:493-494. aAmoxapine is the only antidepressant with a clinically meaningful potency for blocking D2 receptors with the potential to cause acute and tardive extrapyramidal effects. * Not FDA approved for depression.
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DrugsDrugs SedationSedation AnticholinergicsAnticholinergics Orthostatic HypotensionOrthostatic Hypotension Cardiac EffectsCardiac Effects
TetracyclicsTetracyclics
AmoxapineAmoxapineaa LowLow ModerateModerate LowLow NoneNone
MaprotilineMaprotiline ModerateModerate ModerateModerate LowLow ModerateModerate
MirtazapineMirtazapine ModerateModerate LowLow LowLow LowLow
TCAsTCAs
AmitriptylineAmitriptyline HighHigh HighHigh ModerateModerate HighHigh
ClomipramineClomipramine HighHigh HighHigh LowLow ModerateModerate
DesipramineDesipramine LowLow LowLow LowLow ModerateModerate
Doxepin Doxepin HighHigh ModerateModerate ModerateModerate ModerateModerate
ImipramineImipramine ModerateModerate ModerateModerate HighHigh HighHigh
NortriptylineNortriptyline ModerateModerate ModerateModerate LowLow ModerateModerate
ProtriptylineProtriptyline LowLow ModerateModerate LowLow ModerateModerate
TrimipramineTrimipramine HighHigh HighHigh ModerateModerate HighHigh
MAOIsMAOIs
IsocarboxazidIsocarboxazid LowLow NoneNone HighHigh NoneNone
PhenelzinePhenelzine LowLow LowLow HighHigh NoneNone
TranylcypromineTranylcypromine HighHigh Very lowVery low Very lowVery low NoneNone
Selegiline TSSelegiline TS LowLow LowLow HighHigh High (high doses)High (high doses)
Adverse Effects of AntidepressantsAdverse Effects of Antidepressants
SSRI, Selective serotonin reputake inhibitor; SSRI, selective norepinephrine, DSNI, dual norepinphrine reputae inhibitor; TCA, Tricyclic antidepressant; MAOI, monoamine oxidase inhibitor. Adapted from Ward M. Appendix B. In: Flaherty J, Davis JM, Janicak PG, eds. Psychiatry: Diagnosis and Therapy. 2nd ed. Norwalk, Conn: Appleton & Lange, 1995:493-494. aAmoxapine is the only antidepressant with a clinically meaningful potency for blocking D2 receptors with the potential to cause acute and tardive extrapyramidal effects.
26
Antidepressants: Antidepressants: Drug Interactions Drug Interactions
Antidepressants and mood stabilizers may be Antidepressants and mood stabilizers may be inhibitors, inducers, or substratesinhibitors, inducers, or substrates of one or more of one or more cytochrome P450 isoenzymescytochrome P450 isoenzymes
Knowledge of their Knowledge of their P450 profileP450 profile is useful in is useful in predicting drug-drug interactionspredicting drug-drug interactions
When some isoenzymes are absent or inhibited, When some isoenzymes are absent or inhibited, others may offer a others may offer a secondary metabolic pathwaysecondary metabolic pathway
P450 P450 1A2, 2C (subfamily), 2D6, and 3A41A2, 2C (subfamily), 2D6, and 3A4 are are especially important to antidepressant metabolism especially important to antidepressant metabolism and drug-drug interactionsand drug-drug interactions
27
CYP 450 InhibitorsCYP 450 Inhibitors
Rank 1A2 2D6 3A4
High Fluvoxamine FluoxetineParoxetine
NefazodoneFluvoxamineFluoxetine
Mod Fluoxetine Sertraline
Min ParoxetineNefazodoneVenlafaxine
NefazodoneVenlafaxineFluvoxamine
Venlafaxine
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Minimizing the Risk of Drug Minimizing the Risk of Drug Interactions Associated with Interactions Associated with
AntidepressantsAntidepressants When adding an antidepressant with a potential
for pharmacokinetic interaction to another drug, clinicians could: Reduce the dose Reduce the dose of the current drug Begin with a low dose Begin with a low dose of the antidepressant Use therapeutic drug monitoring therapeutic drug monitoring where
appropriate MonitorMonitor therapeutic and adverse effects Choose an antidepressantChoose an antidepressant with a favorable profile
for that interaction
29
Indications forIndications forTherapeutic Drug MonitoringTherapeutic Drug Monitoring
Nonresponders Nonresponders for dosage adjustmentfor dosage adjustment
Suspicion of Suspicion of noncompliancenoncompliance
To avoid To avoid toxicitytoxicity (especially in the elderly) (especially in the elderly)
OverdoseOverdose
If If adverse effects adverse effects limit further dosage increaseslimit further dosage increases
Patients with Patients with absorption abnormalitiesabsorption abnormalities
DocumentDocument response response
30
GoalsGoals
Anxiolytic-Sedative-Hypnotics (ASHs)Anxiolytic-Sedative-Hypnotics (ASHs) Diagnostic indicationsDiagnostic indications Classification of ASHsClassification of ASHs Relevant PharmacokineticsRelevant Pharmacokinetics Serious Adverse EffectsSerious Adverse Effects Drug InteractionsDrug Interactions
Antidepressants (ADs)Antidepressants (ADs) Diagnostic indicationsDiagnostic indications Classification of ADsClassification of ADs Relevant PharmacokineticsRelevant Pharmacokinetics Serious Adverse EffectsSerious Adverse Effects Drug InteractionsDrug Interactions