cns depressants and antidepressants - cal tox€¦ · cns depressants and antidepressants pamela e....

CNS Depressants and CNS Depressants and AntidepressantsAntidepressants

Pamela E. Potter, Ph.D.Pamela E. Potter, Ph.D.Dept. PharmacologyDept. Pharmacology

Midwestern UniversityMidwestern UniversityArizona College of Osteopathic Arizona College of Osteopathic

MedicineMedicine

CNS Depressants CNS Depressants

AlcoholAlcoholOpiumOpiumBromidesBromides-- 1800s1800sChloral hydrateChloral hydrate-- 1800s1800sBarbituratesBarbiturates-- 19121912-- 1950s1950sBenzodiazepinesBenzodiazepines-- 19611961Zolpidem (Ambien), zalpelon Zolpidem (Ambien), zalpelon (Sonata)(Sonata)-- 1990s1990s-- 2000s2000s

Drugs and the GABAAReceptor

Drugs and the GABADrugs and the GABAAAReceptorReceptor

BarbituratesBarbiturates

Increase Increase durationduration of action of GABA of action of GABA Independently opens ClIndependently opens Cl-- channelchannelInhibits other excitatory receptorsInhibits other excitatory receptorsVery low margin of safety Very low margin of safety Low therapeutic index (LDLow therapeutic index (LD5050 vsvs TDTD5050))

EffectsEffects

Diminish awarenessDiminish awarenessDecrease response to stimulationDecrease response to stimulationDecrease cognitionDecrease cognitionDecrease activityDecrease activityDrowsiness, lethargyDrowsiness, lethargyAmnesiaAmnesiaHypnosisHypnosis

Side EffectsSide EffectsCNS depressionCNS depressionrespiratory depression!respiratory depression!dangerous when combined with dangerous when combined with alcoholalcoholphysical dependencephysical dependencesevere withdrawalsevere withdrawal

Overdose Overdose can be can be Fatal!Fatal!

BenzodiazepinesBenzodiazepines

Very commonly prescribed in 1960s Very commonly prescribed in 1960s (housewife’s friend)(housewife’s friend)anxiolyticanxiolytic-- immediate, effectiveimmediate, effectivesedativesedative--hypnotic hypnotic anticonvulsantanticonvulsantintensifyintensify the action of GABAthe action of GABA-- very very safe, even in overdosesafe, even in overdose

Benzodiazepines Facilitate Benzodiazepines Facilitate GABAGABA

Barbiturates Potentiate GABABarbiturates Potentiate GABA

Dose- Effect Relationships

.1 1 10 100 1000

HalfHalf--lives (hrs)lives (hrs)

DiazepamDiazepam 43 (3043 (30--60)60)ChlordiazepoxideChlordiazepoxide 1515--4040NordiazepamNordiazepam 4040--100100Lorazepam (Ativan)Lorazepam (Ativan) 1414Oxazepam (Oxazepam (SeraxSerax)) 88AlprozolamAlprozolam (Xanax)(Xanax) 1212

The sedative/anticonvulsant action of The sedative/anticonvulsant action of diazepam is shorter than its other effectsdiazepam is shorter than its other effectsTime to peak effect of lorazepam ranges Time to peak effect of lorazepam ranges from 1from 1--6 hrs6 hrs

Cimetidine Inhibition of Cimetidine Inhibition of Benzodiazepine MetabolismBenzodiazepine Metabolism

MidazolamMidazolam +Cimetidine

Erythromycin Decreases Erythromycin Decreases Metabolism of MidazolamMetabolism of Midazolam

MidazolamMidazolam +Erythromycin

CNS DepressantsCNS DepressantsThe effects areThe effects are suprasupra--additiveadditive--i.e., the effects of two together are i.e., the effects of two together are greater than the sum of the two greater than the sum of the two alonealoneBenzodiazepines can produce physical Benzodiazepines can produce physical and psychological dependenceand psychological dependence

Zolpidem (Ambien)Zolpidem (Ambien)

Binds to benzodiazepine receptor Binds to benzodiazepine receptor subtype subtype BZ1BZ1VERY rapid actionVERY rapid action; “blackouts”; “blackouts”Little effect on REM sleepLittle effect on REM sleepApproved for shortApproved for short--term treatment term treatment of insomniaof insomniaZalpelon (Sonata) similarZalpelon (Sonata) similar

AntihistaminesAntihistamines

Diphenhydramine (Benadryl)Diphenhydramine (Benadryl)ChlorpheneramineChlorpheneramine ((ChlorChlor--TrimetonTrimeton))DimenhydrinateDimenhydrinate (Dramamine)(Dramamine)Block H1 receptorBlock H1 receptorVery sedating until tolerance develops Very sedating until tolerance develops

ToleranceTolerance-- AntihistaminesAntihistamines

MSLT SSS

Benzodiazepine Benzodiazepine ToleranceTolerance

Khanna et al, Pharm. Biochem. Behav. 59, 511-519 (1998)

Chlordiazepoxide

Diazepam

Tolerance to PentobarbitalTolerance to Pentobarbital


Benzodiazepines cause Benzodiazepines cause tolerance to tolerance to EtOHEtOH


ToleranceTolerance-- AlcoholAlcohol

CarisoprodolCarisoprodol (Soma)(Soma)

SedatingSedating muscle relaxant, in a group that muscle relaxant, in a group that also includes also includes

cyclobenzaprinecyclobenzaprine ((FlexerilFlexeril), ), metaxolonemetaxolone((SkelaxinSkelaxin), ), methocarbamolmethocarbamol ((RobaxinRobaxin))

These act as sedatives in the brain stemThese act as sedatives in the brain stemCarisprodolCarisprodol is converted to is converted to meprobamatemeprobamate(Milltown),(Milltown), which acts like a barbituratewhich acts like a barbiturateNow a very popular drug of abuseNow a very popular drug of abuse

2

Meprobamate (C9H18N2O4)

Conversion of Conversion of CariosprodolCariosprodol to to MeprobamateMeprobamate

/CarisoprodolMeprobamate

CNS Depressants and CNS Depressants and DrivingDriving

At any time, about 5% of people are At any time, about 5% of people are taking prescribed benzodiazepinestaking prescribed benzodiazepinesIn drivers apprehended for impaired In drivers apprehended for impaired driving, 10driving, 10--15% will have 15% will have benzodiazepines in their bloodbenzodiazepines in their bloodThe effect of benzodiazepines on The effect of benzodiazepines on driving performance is variable and not driving performance is variable and not always easy to predictalways easy to predict

CNS Depressants/DrivingCNS Depressants/Driving

Diazepam, Diazepam, flunitrazepamflunitrazepam and and clonazepamclonazepam seem to be the most seem to be the most common drugs reported in drivers common drugs reported in drivers suspected to be impairedsuspected to be impaired

Drug Alcohol Depend. 47, 125Drug Alcohol Depend. 47, 125--136 (1997)136 (1997)

CNS Depressants & Car CNS Depressants & Car AccidentsAccidents

Australian study showed that drivers with Australian study showed that drivers with benzodiazepines in their blood were benzodiazepines in their blood were somewhat more likely (O.R. 4.5 somewhat more likely (O.R. 4.5 vsvs 3.2) to 3.2) to cause a car accidentcause a car accidentThose with BAC > 0.5% had an O.R. of Those with BAC > 0.5% had an O.R. of 34.134.1The odds of having an accident if The odds of having an accident if psychotropic drugs were combined with psychotropic drugs were combined with alcohol was increased 1.7 timesalcohol was increased 1.7 times


Austrian study of drivers injured in car Austrian study of drivers injured in car accidents found:accidents found:36.9% had BAC = .149 36.9% had BAC = .149 ± .054± .0548.1 % of drivers had benzodiazepines, 8.1 % of drivers had benzodiazepines, average drug level 68.7± 62.6 mcg/laverage drug level 68.7± 62.6 mcg/lAnother study found Another study found vigiliancevigiliance impaired impaired after single dose of 5 and 10 mg after single dose of 5 and 10 mg diazepam, 0.5 mg alprazolam, but not diazepam, 0.5 mg alprazolam, but not 10 mg oxazepam10 mg oxazepam


55-- year study showed elderly people year study showed elderly people taking benzodiazepines (Medicaid records) taking benzodiazepines (Medicaid records) 22--4 times more likely to cause an 4 times more likely to cause an automobile accident at higher doses of automobile accident at higher doses of diazepam (diazepam (≥ 20 mg/day)≥ 20 mg/day)

At low doses, likelihood of accident no At low doses, likelihood of accident no higher than nonhigher than non--drug controldrug controlTCAs (e.g. TCAs (e.g. 125 mg 125 mg amitriptylineamitriptyline) increased ) increased likelihood 5likelihood 5--6 times6 times

Alprazolam ImpairmentAlprazolam Impairment

1 mg alprozolam (Zanax) given 1 hour before the driving test, compared with placebo Neuropsychopharmacology 27, 260-269 (2002)

Zolpidem Impairs DrivingZolpidem Impairs Driving

*

**

EtOH was administered to produce BAC 0.05% on Day 1. Zolpidem or Zapelon were administered during the night, and driving was measured 6 hours later (in the morning)

Triazolam compares to Triazolam compares to EtOHEtOH at at producing impairmentproducing impairment

Alcohol breath measure was 0.13% at time of testing

BenzodiazepinesBenzodiazepinesDrugDrug Driving Impaired TherapeuticDriving Impaired TherapeuticFlurazepamFlurazepam 15 mg15 mg 15 mg, bedtime15 mg, bedtimeFlunitrazepamFlunitrazepam 1 mg1 mg ----------TemazepamTemazepam > 20 mg> 20 mg 15 mg15 mgTriazolamTriazolam 0.5 mg0.5 mg 0.25 mg0.25 mgOxazepamOxazepam 1010--50 mg50 mg 1010--15 mg15 mgDiazepamDiazepam 5 mg t.i.d.5 mg t.i.d. 22--10 mg10 mgLorazepamLorazepam 0.5 mg0.5 mg 22--3 mg3 mg

Hum. Psychopharmacol. Clin. Exp. 13, S49-S63 (1998)

Concentrations Producing Concentrations Producing ImpairmentImpairment

Other DrugsOther DrugsDrugDrug Dose: Driving ImpairedDose: Driving Impaired TherapeuticTherapeuticSecobarbitalSecobarbital 200 mg200 mg 100100--200 mg200 mgBuspironeBuspirone 10 mg, t.i.d.10 mg, t.i.d. 10 mg10 mgZolpidemZolpidem > 10 mg> 10 mg 55--10 mg10 mgZalpelonZalpelon > 20 mg> 20 mg 55--10 mg10 mgDiphenhydramineDiphenhydramine 50 mg50 mg 50 mg50 mgLoratadineLoratadine (Claritin)(Claritin) 20 mg20 mg 10 mg10 mgCarisoprodolCarisoprodol -------- 400 mg, t.i.d.400 mg, t.i.d.

Hum. Psychopharmacol. Clin. Exp. 13, S49-S63 (1998)

AntidepressantsAntidepressantsAntidepressants

DepressionDepressionOne of most common mental illnesses One of most common mental illnesses (10(10--25%)25%)Symptoms: Symptoms:

Depressed moodDepressed moodDiminished interest Diminished interest Weight/appetite changeWeight/appetite changeInsomnia/Insomnia/hypersomniahypersomnia, Fatigue, FatigueWorthlessness, IndecisivenessWorthlessness, IndecisivenessSuicidal thoughtsSuicidal thoughts

Noradrenergic PathwaysNoradrenergic Pathways

NorepinephrineNorepinephrine

MoodMood-- antidepressants affect NEantidepressants affect NEMay be involved in anxietyMay be involved in anxietyPain regulationPain regulationLearning and memory Learning and memory Stress depletes NEStress depletes NEAlpha and beta receptorsAlpha and beta receptorsDrugs act on synthesis, uptake Drugs act on synthesis, uptake and breakdownand breakdown

Serotonin PathwaysSerotonin Pathways

Serotonin Serotonin

MoodMooddepression treated with 5HT redepression treated with 5HT re--uptake uptake inhibitorsinhibitors

May promote sleep (May promote sleep (tryptophantryptophan))AnxietyAnxietyObsessive compulsive disorderObsessive compulsive disorderHunger or appetiteHunger or appetitePerception (LSD)Perception (LSD)Many receptor subtypes, targeted by Many receptor subtypes, targeted by newer drugs newer drugs

The Amine HypothesisThe Amine HypothesisThe Amine Hypothesis

PET ScansPET Scans

Treatments for Treatments for DepressionDepression

Tricyclic AntidepressantsTricyclic AntidepressantsMonoamine Oxidase InhibitorsMonoamine Oxidase InhibitorsSelective Serotonin Reuptake Selective Serotonin Reuptake Inhibitors (SSRIs)Inhibitors (SSRIs)“Newer” antidepressants“Newer” antidepressantsElectroconvulsive therapyElectroconvulsive therapy

Tricyclic Tricyclic AntidepressantsAntidepressants

Tricyclic AntidepressantsTricyclic Antidepressants

Inhibit reInhibit re--uptake of NE and 5HTuptake of NE and 5HTAnticholinergic/AntihistamineAnticholinergic/AntihistamineSedation, often significantSedation, often significantNo euphoria/ low abuse potentialNo euphoria/ low abuse potential22--3 weeks to have effect3 weeks to have effect

TCA MetabolismTCA Metabolism

More sedating/ anticholinergic

Less sedating/ anticholinergic

EffectsEffectsCNSCNS

SedationSedationMemory/cognitionMemory/cognitionAnalgesiaAnalgesia

Periphery Periphery Cardiac depression/irritabilityCardiac depression/irritabilityTorsadesTorsades de pointesde pointesalpha1 blockade, postural hypotensionalpha1 blockade, postural hypotension

TCA UsesTCA UsesDepressionDepression

22--3 weeks for effect3 weeks for effectSide effects and potential toxicity limits useSide effects and potential toxicity limits use

Panic disorderPanic disorderChronic painChronic pain, headache, headache

Very low dosesVery low dosesFibromyalgiaFibromyalgiaEnuresisEnuresis

Side EffectsSide Effects

Blurred vision, Dry mouthBlurred vision, Dry mouthTachycardiaTachycardiaConstipation, Urinary retentionConstipation, Urinary retentionOrthostatic hypotensionOrthostatic hypotensionSinus tachycardiaSinus tachycardiaWeight gainWeight gainSedationSedation

Monoamine Oxidase Monoamine Oxidase InhibitorsInhibitors

Irreversibly inhibit MAOIrreversibly inhibit MAO--A, which breaks A, which breaks down NE & 5HT, and MAOdown NE & 5HT, and MAO--B, which B, which breaks down DAbreaks down DA

Used for depression which doesn’t Used for depression which doesn’t respond to other drugs, atypical respond to other drugs, atypical depression, etc...depression, etc...

Phenelzine (Nardil)Phenelzine (Nardil)Tranylcypromine (Parnate)Tranylcypromine (Parnate)

Side EffectsSide EffectsSevere hypertensive crisis! Severe hypertensive crisis!

MAO in the gut breaks down certain MAO in the gut breaks down certain amines as we eat them, such as amines as we eat them, such as tyraminetyramineTyramineTyramine causes release of NEcauses release of NETyramineTyramine in foods: red wine, beer, aged in foods: red wine, beer, aged cheese, etc…cheese, etc…

SympathomimeticsSympathomimetics (cold medicines) also (cold medicines) also cause cause HTxHTx with MAOIswith MAOIs

Side EffectsSide EffectsTremorsTremorsSedation, excitation, insomniaSedation, excitation, insomniaOrthostatic hypotensionOrthostatic hypotensionDelayed ejaculationDelayed ejaculationFatigueFatigueWeight gain, skin rashWeight gain, skin rashDizziness, blurred vision, constipationDizziness, blurred vision, constipation

SSRIsSSRIsInhibit reInhibit re--uptake of 5uptake of 5--HTHT

Fluoxetine (Prozac) Fluoxetine (Prozac) Sertraline (Zoloft)Sertraline (Zoloft)Fluvoxamine (Luvox)Fluvoxamine (Luvox)Paroxetine (Paxil)Paroxetine (Paxil)Citalopram (Celexa)Citalopram (Celexa)EscitalopramEscitalopram (Lexapro)(Lexapro)

Inhibit NE & 5Inhibit NE & 5--HT reHT re--uptakeuptakeVenlafaxine (Effexor)Venlafaxine (Effexor)

SSRIsSSRIs

FluoxetineFluoxetineProzac, Prozac Weekly, genericProzac, Prozac Weekly, genericSerafemSerafem (14 days before menses)(14 days before menses)Antidepressant effect usually takes 3Antidepressant effect usually takes 3--4 4 weeks to developweeks to develop

Antidepressants are NOT mood altering Antidepressants are NOT mood altering drugs, they do NOT cause euphoriadrugs, they do NOT cause euphoria

Fluoxetine MetabolismFluoxetine Metabolism

NorfluoxetineFluoxetine

PharmacokineticsPharmacokinetics--FluoxetineFluoxetine

Slow onset of effectSlow onset of effectLate side effectsLate side effectsLong duration after drug discontinuedLong duration after drug discontinuedHalfHalf--life of 4.7 and 16.7 for fluoxetine life of 4.7 and 16.7 for fluoxetine and and norfluoxetinenorfluoxetine after 3after 3--6 6 mosmosadministrationadministration

Brunswick et al, J. Brunswick et al, J. ClinClin. . PsychopharmPsychopharm. 21: 616. 21: 616--618 (2001)618 (2001)

Drug InteractionsDrug Interactions

Fluoxetine inhibits CYP2D6Fluoxetine inhibits CYP2D6Increases levels of tricyclic antidepressants Increases levels of tricyclic antidepressants (clearance (clearance decdec. 70% or more). 70% or more)Toxicity may occur with TCAs if combined Toxicity may occur with TCAs if combined with fluoxetinewith fluoxetineCYP2D6 inhibition interferes with CYP2D6 inhibition interferes with conversion of some conversion of some opioidsopioids to active to active compounds compounds

Paroxetine (Paxil)Paroxetine (Paxil)

Shorter halfShorter half--life and shorter duration of life and shorter duration of action than fluoxetineaction than fluoxetineLess effect on most hepatic enzymes Less effect on most hepatic enzymes (except CYP2D6), fewer drug (except CYP2D6), fewer drug interactionsinteractionsMore selective than fluoxetine for 5More selective than fluoxetine for 5--HT HT uptakeuptakeMore likely to cause sedationMore likely to cause sedation

PharmacokineticsPharmacokinetics

DRUGDRUG

ParoxetineParoxetineSertralineSertralineCitalopramCitalopramEscitalopramEscitalopramFluvoxamine Fluvoxamine

Usual Dose Usual Dose (mg/day)(mg/day)

2020--40 40 100100--1501502020--40401010--2020

100100--200200

PharmacokineticsPharmacokineticsDRUGDRUG

ParoxetineParoxetineSertralineSertralineCitalopramCitalopramEscitalopramEscitalopramFluvoxamineFluvoxamine

tt1/21/2 Conc.Conc.hr (hr (ngng/ml)/ml)

2222 3030--10010024 (65)24 (65) 2525--50503636 7575--15015030 (59)30 (59) ----1515--2020 100100--200200

Heterocyclic Heterocyclic AntidepressantsAntidepressants

Venlafaxine (Effexor)Venlafaxine (Effexor)Blocks both 5Blocks both 5--HT and NE reHT and NE re--uptakeuptakeLong duration of actionLong duration of actionSide effects commonSide effects commonIncreases blood pressure in some Increases blood pressure in some patientspatients

Antidepressant TrendsAntidepressant Trends

Pirraglia et al, Prim. Care Com. J. Clin. Psychiat. 5:153-157 (2003)

Uses of SSRIsUses of SSRIsDepression Depression -- very effectivevery effectivePanic disorderPanic disorderObsessiveObsessive--compulsive disordercompulsive disorderBulimiaBulimiaPMDDPMDDAlcoholismAlcoholism-- recoveryrecoveryPremature ejaculationPremature ejaculation

Side EffectsSide EffectsMild: no cardiac toxicityMild: no cardiac toxicityGI: nausea, loss of appetiteGI: nausea, loss of appetiteWeight loss or gainWeight loss or gainCNS: anxiety, insomnia, or sedationCNS: anxiety, insomnia, or sedationSexual disinterest/dysfunctionSexual disinterest/dysfunctionPhotosensitivityPhotosensitivity

Serotonin SyndromeSerotonin SyndromeWith MAOIsWith MAOIsAgitation, confusion, deliriumAgitation, confusion, deliriumHyperpyrexia, shiveringHyperpyrexia, shiveringDiaphoresis, diarrhea, hyperreflexia, Diaphoresis, diarrhea, hyperreflexia, tremortremorMay progress to convulsions and comaMay progress to convulsions and coma

Discontinuation Discontinuation SymptomsSymptoms

Rare, may last 5Rare, may last 5--8 days 8 days dizziness, ataxia, dizziness, ataxia, parasthesiasparasthesiasfluflu--like symptoms, sleep like symptoms, sleep disturbances disturbances anxiety, agitation, crying spells, anxiety, agitation, crying spells, irritability. irritability. most common with short acting most common with short acting drugs, e.g. drugs, e.g. paroxetineparoxetine

Mirtazapine (Remeron)Mirtazapine (Remeron)

NOT an uptake inhibitorNOT an uptake inhibitorblocks presynaptic blocks presynaptic αα22 receptorsreceptors

blocks 5blocks 5--HTHT2A2A and 5and 5--HTHT33 receptorsreceptorsReduces anxiety, insomnia, nausea, sexual Reduces anxiety, insomnia, nausea, sexual problemsproblems

Antihistamine Antihistamine –– significant significant sedationsedationEffects similar to TCAs, without cardiac Effects similar to TCAs, without cardiac toxicitytoxicity

Ridout et al, Hum. Psychopharm. 18: 261-269 (2003)

Mirtazapine Sedation Mirtazapine Sedation Paroxetine, 20 mg

Mirtazapine, noct.

Mirtazapine, morn

Placebo

LARS sedation, mean maximum change from baseline ± SEM on Day 2, *p>0.05

Bupropion (Wellbutrin) Bupropion (Wellbutrin)

Inhibits DA reInhibits DA re--uptakeuptake((ZybanZyban))-- extended release, smoking extended release, smoking cessationcessation

Side EffectsSide EffectsCNS stimulation, anxiety, but not sedatingCNS stimulation, anxiety, but not sedating

May cause May cause seizuresseizures ((espesp with TCAs)with TCAs)

May work where others haven’t May work where others haven’t Few sexual side effects Few sexual side effects

Antidepressant TrendsAntidepressant Trends

Pirraglia et al, Prim. Care Com. J. Clin. Psychiat. 5:153-157 (2003)

Driving ImpairmentDriving ImpairmentElderly drivers taking TCAs about 2x more Elderly drivers taking TCAs about 2x more likely to be involved in an accidentlikely to be involved in an accident**

Studies using standard driving tests Studies using standard driving tests designed to investigate antidepressant designed to investigate antidepressant effectseffectsDriving 62 mi on a highway at 59 mph and Driving 62 mi on a highway at 59 mph and a steady lateral position a steady lateral position SDLP measuredSDLP measured

**LeveilleLeveille et al, et al, EpidemiolEpidemiol. 5: 591. 5: 591--598 (1994)598 (1994)**Ray et al, Am. J. Ray et al, Am. J. EpidemiolEpidemiol. 136: 873. 136: 873--883 (1992)883 (1992)

SDLPSDLP

SDLP rises SDLP rises exponetiallyexponetially as BAC risesas BAC risesBAC over 0.5 mg/ml correlates with BAC over 0.5 mg/ml correlates with increased fatal accidentsincreased fatal accidentsBAC of 0.5 mg/ml causes a 2.4 cm. BAC of 0.5 mg/ml causes a 2.4 cm. change in SDLPchange in SDLPTest other drugs against this criteriaTest other drugs against this criteria

TCAs and drivingTCAs and driving

Meta analysis of 10 studiesMeta analysis of 10 studiesAcute doses of Acute doses of

Amitriptyline, 75 mgAmitriptyline, 75 mgDoxepinDoxepin, 75 mg, 75 mgImipramine, 50 mgImipramine, 50 mg

Caused changes in SDLP equivalent to BAC Caused changes in SDLP equivalent to BAC 0.8 mg/ml0.8 mg/mlBUT after 1 week treatment tolerance had BUT after 1 week treatment tolerance had developed to the effectdeveloped to the effect

RamaekersRamaekers, JG, J. , JG, J. ClinClin. . PsychiatPsychiat. 64:20. 64:20--29 (2003)29 (2003)

TCAs and DrivingTCAs and Driving

BAC 0.8 mg/ml

Ramaekers, J, J. Clin. Psychiat. 64:20-29 (2003)

SSRIs and DrivingSSRIs and DrivingFluoxetine and Fluoxetine and paroxetineparoxetine (SSRIs) (SSRIs) considered nonconsidered non--sedating, have never sedating, have never been shown to affect drivingbeen shown to affect drivingVenlafaxine also does not affect drivingVenlafaxine also does not affect drivingNefazodone has some effect, but Nefazodone has some effect, but tolerance develops rapidlytolerance develops rapidly

SSRIs and DrivingSSRIs and Driving


Ridout et al, Hum. Psychopharm. 18: 261-269 (2003)

Mirtazapine increases Mirtazapine increases reaction timereaction time

Fluoxetine/Fluoxetine/BDZsBDZs


BAC 0.8 mg/ml

Somnolence/DrivingSomnolence/Driving


SummarySummary

TCAs can significantly impair driving, TCAs can significantly impair driving, especially if combined with alcoholespecially if combined with alcoholSSRIs in general do not affect driving SSRIs in general do not affect driving abilityability-- but might increase the effects of but might increase the effects of BDZsBDZs or alcoholor alcoholMirtazapine causes somnolence, but Mirtazapine causes somnolence, but driving studies have not been donedriving studies have not been doneThere are no studies for There are no studies for bupropionbupropion, , although impairment is highly unlikelyalthough impairment is highly unlikely

cns depressants and antidepressants - cal tox€¦ · cns depressants and antidepressants pamela e....

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