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SSRI: Pharmacology Update for ADPH Nurse PractitionersSSRI: Pharmacology Update for ADPH Nurse Practitioners

Produced by the Alabama Department of Public HealthVideo Communications and Distance Learning DivisionProduced by the Alabama Department of Public HealthVideo Communications and Distance Learning Division

Satellite Conference and Live WebcastFriday, November 7, 2014

8:30 – 10:30 a.m. Central Time

Satellite Conference and Live WebcastFriday, November 7, 2014

8:30 – 10:30 a.m. Central Time

FacultyFaculty

Charles Thomas, PD, RPh, FAPhAState Pharmacy DirectorBureau of Professional and Support Services

Charles Thomas, PD, RPh, FAPhAState Pharmacy DirectorBureau of Professional and Support Servicesand Support Services

Alabama Department of Public Healthand Support Services

Alabama Department of Public Health

SerotoninSerotonin• Serotonin (pronounced /ˌsɛrəˈtoʊnɨn/)

or 5 - Hydroxytryptamine (5 - HT) is a

monoamine neurotransmitter

• Biochemically derived from

• Serotonin (pronounced /ˌsɛrəˈtoʊnɨn/)

or 5 - Hydroxytryptamine (5 - HT) is a

monoamine neurotransmitter

• Biochemically derived from y

tryptophan, serotonin is primarily

found in the gastrointestinal (GI) tract,

platelets, and in the central nervous

system (CNS) of humans and animals

y

tryptophan, serotonin is primarily

found in the gastrointestinal (GI) tract,

platelets, and in the central nervous

system (CNS) of humans and animals

SerotoninSerotonin• Modulation of serotonin at synapses

is thought to be a major action of

several classes of pharmacological

antidepressants

• Modulation of serotonin at synapses

is thought to be a major action of

several classes of pharmacological

antidepressants

SerotoninSerotonin• It is a well - known contributor to

feelings of well - being; therefore it is

also known as a happiness hormone

• 20 % is synthesized in serotonergic

• It is a well - known contributor to

feelings of well - being; therefore it is

also known as a happiness hormone

• 20 % is synthesized in serotonergic

neurons in the CNS where it has

various functions

– These include the regulation of

mood, appetite, sleep, as well as

muscle contraction

neurons in the CNS where it has

various functions

– These include the regulation of

mood, appetite, sleep, as well as

muscle contraction

Action of SerotoninAction of Serotonin• It plays an important role in

postprandial satiety, anxiety, sleep,

mood, obsessive - compulsive, and

impulse control disorders

• It plays an important role in

postprandial satiety, anxiety, sleep,

mood, obsessive - compulsive, and

impulse control disorders

• Decreased serotonin activity (either

by tryptophan depletion or serotonin

antagonists) can contribute to an

increased food intake

• Decreased serotonin activity (either

by tryptophan depletion or serotonin

antagonists) can contribute to an

increased food intake

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PharmacologyPharmacology• Increase serotonin available

in the brain

• Depression results when certain

brain chemicals (neurotransmitters)

• Increase serotonin available

in the brain

• Depression results when certain

brain chemicals (neurotransmitters) ( )

get out of balance (low)

( )

get out of balance (low)

Mechanism of ActionMechanism of Action• Not fully understood but it involves

selective serotonin reuptake

blockade at the neuronal membrane,

thus enhancing serotonin (5 - HT)

• Not fully understood but it involves

selective serotonin reuptake

blockade at the neuronal membrane,

thus enhancing serotonin (5 - HT)

effectseffects

Mechanism of ActionMechanism of Action• Initially the availability of serotonin is

increased in the somatodendritic

area; however, during chronic use of

SSRIs, serotonin auto receptors are

• Initially the availability of serotonin is

increased in the somatodendritic

area; however, during chronic use of

SSRIs, serotonin auto receptors are

down regulated and desensitized

– This allows for an increase in

serotonin release in the axon

terminal synapses

down regulated and desensitized

– This allows for an increase in

serotonin release in the axon

terminal synapses

Mechanism of ActionMechanism of Action• Due to the increase of serotonin in

the synapses, there is an increase in

its neuronal impulses

• Due to the increase of serotonin in

the synapses, there is an increase in

its neuronal impulses

PharmacologyPharmacology• Target Serotonin in Brain

– SSRIs prevent reabsorption or

reuptake back into the sending

neuron

• Target Serotonin in Brain

– SSRIs prevent reabsorption or

reuptake back into the sending

neuron

– Therefore more serotonin between

neurons in the brain

– Therefore more serotonin between

neurons in the brain

PharmacologyPharmacology– Equals greater reduction in

depression

– Differ from each other by degree of

selectivity for the serotonin

– Equals greater reduction in

depression

– Differ from each other by degree of

selectivity for the serotonin y

transporter

• Share most indications

y

transporter

• Share most indications

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PharmacologyPharmacology• Inhibit reuptake of serotonin by

serotonin transporters located on

pre - synaptic neurons

– Increases available serotonin in

• Inhibit reuptake of serotonin by

serotonin transporters located on

pre - synaptic neurons

– Increases available serotonin in

brain

– Exact mechanism not known

brain

– Exact mechanism not known

PharmacologyPharmacology– Members of class differ in degree

of selectivity for binding to the

serotonin transporter

– Limited to activity in other

– Members of class differ in degree

of selectivity for binding to the

serotonin transporter

– Limited to activity in other y

receptors provides a more

favorable adverse event profile

compared with tricyclics

y

receptors provides a more

favorable adverse event profile

compared with tricyclics

PharmacologyPharmacology• Which to use?

– Drug interactions

• Citalopram - QT prolongation -

Not with drugs that do the same

• Which to use?


• Citalopram - QT prolongation -

Not with drugs that do the sameNot with drugs that do the same

– Patient previous response

– Patient specific characteristics

– Metabolize or inhibit

CYP450 isoenzyme

Not with drugs that do the same

– Patient previous response

– Patient specific characteristics

– Metabolize or inhibit

CYP450 isoenzyme

Advantages of SSRIsAdvantages of SSRIs• Newer (second generation)

antidepressants

– Fewer side effects than

first generation

• Newer (second generation)

antidepressants

– Fewer side effects than

first generationg

• First Generation Includes

– Tricyclic antidepressants

and MAOIs

g

• First Generation Includes

– Tricyclic antidepressants

and MAOIs

Advantages of SSRIsAdvantages of SSRIs• Other second generation

antidepressants include:

– Buproprion (Wellbutrin and

duloxetine(Cymbalta)

• Other second generation

antidepressants include:

– Buproprion (Wellbutrin and

duloxetine(Cymbalta)( y )( y )

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Advantages of SSRIsAdvantages of SSRIs• SSRIs are generally chosen as

first - line antidepressants due to

their safety in overdose and

improved tolerability

• SSRIs are generally chosen as

first - line antidepressants due to

their safety in overdose and

improved tolerability

• Work Well in most people

• Starter drug of choice in most people

• Work Well in most people

• Starter drug of choice in most people

Advantages of SSRIsAdvantages of SSRIs• Other first - line agents include

SNRIs, bupropion and mirtazapine

• Treatment selection is based on

individual patient characteristics

• Other first - line agents include

SNRIs, bupropion and mirtazapine

• Treatment selection is based on

individual patient characteristics p

• Co morbidities

• Concomitant medication

p

• Co morbidities

• Concomitant medication

Advantages of SSRIsAdvantages of SSRIs• Individual or strong family

history of response to a

particular medication

• Patient preference

• Individual or strong family

history of response to a

particular medication

• Patient preferencepp

Advantages of SSRIsAdvantages of SSRIs• Recommendations SSRIs as

monotherapy for patients who are at

Stage 1 depression

• Citalopram and fluoxetine should be

• Recommendations SSRIs as

monotherapy for patients who are at

Stage 1 depression

• Citalopram and fluoxetine should be

avoided in patients with QT interval

prolongation or in patients who are

taking other drugs that increase the

QT interval

• Not recommended with MAOI therapy

avoided in patients with QT interval

prolongation or in patients who are

taking other drugs that increase the

QT interval

• Not recommended with MAOI therapy

Advantages of SSRIsAdvantages of SSRIs• I would not use SSRIs as

monotherapy in patients who have

bipolar disorder, due to the

increased likelihood of precipitation

• I would not use SSRIs as

monotherapy in patients who have

bipolar disorder, due to the

increased likelihood of precipitation

of a mixed / manic episode

• Avoid SSRI therapy in patients who

have closed - angle glaucoma,

because SSRIs may result in

increased intraocular pressure

of a mixed / manic episode

• Avoid SSRI therapy in patients who

have closed - angle glaucoma,

because SSRIs may result in

increased intraocular pressure

Antidepressants vs PlaceboAntidepressants vs Placebo• Most studies that evaluate

antidepressants have done so in the

secondary setting rather than the

primary setting

• Most studies that evaluate

antidepressants have done so in the

secondary setting rather than the

primary setting

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Antidepressants vs PlaceboAntidepressants vs Placebo– In primary care, there is a 12 -

month depression prevalence of

18.1%

– Patients with depression in the

– In primary care, there is a 12 -

month depression prevalence of

18.1%

– Patients with depression in the p

primary care setting often present

with somatic symptoms, including

gastrointestinal, skeletal muscle,

and cardiovascular complaints

p

primary care setting often present

with somatic symptoms, including

gastrointestinal, skeletal muscle,

and cardiovascular complaints

SSRIHalf-Life

(h)MetaboliteHalf-Life

Peak Plasma Level

(h)

% Protein Bound

Bioavailability

(%)Initial Dose

Citalopram(CeleXA)

35S-desmethyl-citalopram:

59 hours4 80 80 20 mg qAM

Escitalopram(Lexapro)

27-32S-desmethyl-citalopram:

59 hours5 56 80 10 mg qAM

FLUoxetine(PROzac, Initial: 24-72

N fl ti(PROzac, PROzac Weekly, Sarafem, Selfemra)

Initial: 24 72Chronic: 96-

144

Norfluoxetine:4-16 days

6-8 95 72 10-20 mg qAM

FluvoxaMINE(Luvox CR)

16 N/A 3 80 53 50 mg qhs

PARoxetine(Paxil, Paxil CR, Pexeva)

21 N/A 5 95 >90 10-20 mg qAM

Sertraline(Zoloft)

26N-desmethyl-

sertraline:62-104 hours

5-8 98 88 25-50 qAM

Indications Citalopram Hydrobromide

Escitalopram Fluoxetine HCL

Fluvoxamine Maleate

Paroxetine HCL

Paroxetine Mesylate

Sertraline HCL

Impairment Dosing Adjustment

Yes Yes Yes Yes

Hepatic Impairment Dosing Adjustment

Yes Yes Yes Yes Yes

social phobia (social anxiety disorder)

Yes† Yes† Yes† Yes Yes Yes Yes

premenstrual dysphoric disorder (PMDD)

Yes† Yes Yes† Yes Yes Yes

premature ejaculation

Yes† Yes† Yes† Yes†

posttraumatic stress

Yes† Yes† Yes† Yes Yes Yes

disorder (PTSD)

panic disorder Yes† Yes† Yes Yes† Yes Yes Yes

obsessive-compulsive disorder (OCD)

Yes† Yes Yes Yes Yes Yes

hot flashes Yes† Yes† Yes Yes Yes†

generalized anxiety disorder (GAD)

Yes Yes† Yes Yes Yes†

depression Yes Yes Yes Yes† Yes Yes Yes

Yes – Labeled

Yes+ ‐ Off‐label, Recommended

NR – Off‐label, Not Recommended

List SSRIsList SSRIs

Generic Name Brand Name

citalopram Celexa

escitalopram Lexapro

fluoxetine Prozacfluoxetine Prozac

fluvoxamine Luvox

paroxetine Paxil

sertraline Zoloft

vilazodone Viibryd

List SSRIs / SNRIList SSRIs / SNRI

Generic Brand

Desvenlafaxine Pristiq

Duloxetine Cymbaltau o et e Cy ba ta

Levomilnacipran Fetzima

Milnacipran Savella

Venlafaxine Effexor

Other UsesOther Uses• Anxiety disorders - Panic, OCD,

General anxiety disorder, PTSD,

social anxiety disorder

– None are superior to another

• Anxiety disorders - Panic, OCD,

General anxiety disorder, PTSD,

social anxiety disorder

– None are superior to anotherp

– May be used continuously or

during luteal phase

– Premature ejaculation

– Hot flashes

p

– May be used continuously or

during luteal phase

– Premature ejaculation

– Hot flashes

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Uses DiscussionUses Discussion• SSRIs not preferentially recommended

over SNRIs or other second

generation antidepressants

• Choice based on

• SSRIs not preferentially recommended

over SNRIs or other second

generation antidepressants

• Choice based on

– Adverse event profile


– Prior Hx of response

– Cost

– Adverse event profile


– Prior Hx of response

– Cost

Daily Dose ChartDaily Dose ChartDosage Chart

SSRIDosage Chart SSRI

Drug DosageCitalopram 20 - 40 mg / dayEscitalopram 10 - 20 mg / dayEscitalopram 10 20 mg / dayFluoxetine 20 - 80 mg / dayFluvoxamine 50 - 300 mg / dayParoxetine 20 - 60 mg / daySertraline 50 - 200 mg / dayVilazodone 10 mg / day; increase to

target of 40 mg / day

Drugs to AvoidDrugs to Avoid• These are General Guidelines

• Have to be evaluated based on drug

information and individual Hx

• Some interactions may not be severe

• These are General Guidelines

• Have to be evaluated based on drug

information and individual Hx

• Some interactions may not be severe• Some interactions may not be severe

– adjust each accordingly

• Check with Physician or Pharmacist

– Many Pharmacists provide

MTM Consultations

• Some interactions may not be severe

– adjust each accordingly

• Check with Physician or Pharmacist

– Many Pharmacists provide

MTM Consultations

Drugs To AvoidDrugs To Avoid• Ideally MTM consultation prior to taking

• Can contribute to Serotonin Syndrome

• Patient should let MD know all meds

patient is taking

• Ideally MTM consultation prior to taking

• Can contribute to Serotonin Syndrome

• Patient should let MD know all meds

patient is takingpatient is taking

– Include OTC, herbs, all other

possible interactors

• Not all drugs in each category interact

patient is taking

– Include OTC, herbs, all other

possible interactors

• Not all drugs in each category interact

Drugs To AvoidDrugs To AvoidAlcohol Allergy / Cold Meds

Antidepressants –other

Antidiabetic meds

Antipsycoticmedications

Asthma medications

Blood pressure meds Detoxification meds

Heart medications L – tryptophan

Migraine medications Seizure medications

Theophylline Tranquilizers

Tremor medications Warfarin

Increase Serotonin ActivityIncrease Serotonin Activity• Nefazodone (Serzone)

• Trazodone(Desyrel)

• Venlafaxine (Effexor)

• Nefazodone (Serzone)

• Trazodone(Desyrel)

• Venlafaxine (Effexor)

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Increase Serotonin ActivityIncrease Serotonin Activity• Natural Products - Possible Interaction

– 5 - hydroxytryptophan (5 - HTP) -

Migraine - Risk SS

– S - adenosylmethionine (SAMe) -

• Natural Products - Possible Interaction

– 5 - hydroxytryptophan (5 - HTP) -

Migraine - Risk SS

– S - adenosylmethionine (SAMe) -– S - adenosylmethionine (SAMe) -

Osteoarthritis and depression -

Risk SS

– St John’s Wort - Depression

– Folate - May be beneficial

– S - adenosylmethionine (SAMe) -

Osteoarthritis and depression -

Risk SS

– St John’s Wort - Depression

– Folate - May be beneficial

Side EffectsSide Effects• Note: Not all SSRIs produce all of the

listed side effects

• Not every one who takes the SSRIs

have Side Effects - some do not

• Note: Not all SSRIs produce all of the

listed side effects

• Not every one who takes the SSRIs

have Side Effects - some do not

have any

• Some side effects dissipate or

disappear quickly

• Some side effects continue

throughout Tx

have any

• Some side effects dissipate or

disappear quickly

• Some side effects continue

throughout Tx

General Side EffectsGeneral Side Effects• Elderly may be more sensitive to them

• If severe or not tolerable -

contact physician

• If not sure side effects are from meds

• Elderly may be more sensitive to them

• If severe or not tolerable -

contact physician

• If not sure side effects are from meds• If not sure side effects are from meds

- contact Physician

• MTM Consultation

• If not sure side effects are from meds

- contact Physician

• MTM Consultation

Bothersome Side EffectsBothersome Side EffectsApathy Appetite Loss

Body aches Constipation

Diarrhea Dizziness

Dry mouth Headache

Insomnia NauseaInsomnia Nausea

Nervousness Rash

Sexual dysfunction Stomach upset

Sweating Tingling

Tiredness Tremors

Weakness

SSRI Top 20 Adverse Reactions / Side Effects Table

Adverse

reaction/side

effect

Citalopram

HBr

Escitalopram Fluoxetine

HCl

Fluvoxamine

Maleate

Paroxetine

HCl

Paroxetine

Mesylate

Sertraline

HCl

nausea 21% 15 - 18% 12 - 29% 34 - 40% 4.3 - 26% 4.3 - 26% 25%insomnia 15% 9 - 12% 10 - 33% 21 - 35% 8 - 24% 8 - 24% 21%ejaculation dysfunction

6.1% 12% 2 - 7% 8 - 11% 13 - 28% 13 - 28% >14%

drowsiness 18% 6 - 13% 5 - 17% 22 - 27% 9 - 24% 9 - 24% 13%asthenia Reported Reported 7 - 21% 14 - 26% 12 - 22% 12 - 22% >1%diarrhea 8% 8% 8 - 18% 11 - 18% 6 - 18% 6 - 18% 20%anxiety 4% Reported 6 - 15% 5 - 8% 2 - 5% 2 - 5% 4%dizziness 2% 5% 9% 11 - 15% 6 - 14% 6 - 14% 12%tremor 8% Reported 3 - 13% 5 - 8% 4 - 11% 4 - 11% 8%libido 1.3 - 3 - 6% 1 - 11% 4 - 6% 3 - 12% 3 - 12% 6%decrease 3.8%hyperhidrosis 11% 4 - 5% 2 - 8% 6 - 7% 6 - 11% 6 - 11% 7%

yawning 2% 2% 1 - 11% 2 - 5% 4 - 5% 4 - 5% >1%dyspepsia 5% 3% 6 - 10% 8 - 10% 2 - 5% 2 - 5% 8%impotence (erectile dysfunction)

2.8% 2% 1 - 7% 2% 4 - 10% 4 - 10% >1%

headache 24% 21% 22 - 35% 6.3 - 27% 6.3 - 27% 25%xerostomia 20% 6 - 9% 4 - 12% 10 - 14% 3 - 18% 3 - 18%anorexia 4% 4 - 17% 6 - 14% 1 - 9% 1 - 9% 6%constipation 3 - 5% 5% 4 - 10% 5 - 16% 5 - 16% 6%fatigue 5% 5 - 8% Reported <4.9% <4.9% 12%pharyngitis 3 - 10% 6% 1 - 4% 1 - 4% pharyngitis

Serotonin Syndrome All SSRIs

Prolonged QT interval Citalopram, fluoxetine

Stroke CitalopramWorsening depression, suicidal thoughts, suicide

All SSRIs

Mania Fluoxetine, sertraline

Erythema multiforme Fluoxetine

SJS, Toxic Epidermal Necrolysis (TEN) Fluvoxamine, paroxetine, sertraline(S S )

Rare But Serious ADRsRare But Serious ADRs

(SJS only)

Hyponatremia Fluoxetine, fluvoxamine, sertraline

Abnormal bleeding Fluoxetine, fluvoxamine

Agranulocytosis Fluvoxamine

Acute hepatitis Paroxetine

Seizure Fluoxetine, fluvoxamine, paroxetine, sertraline

Anaphylaxis Sertraline

Rhabdomyolysis Sertraline

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Serious Side EffectsSerious Side Effects• Chest pain

• Palpitations or irregular heartbeat

• Vision disturbances

• Confusion

• Chest pain

• Palpitations or irregular heartbeat

• Vision disturbances

• ConfusionConfusion

• Tremor

• Muscle Spasm

• Fever

• Serotonin Syndrome

Confusion

• Tremor

• Muscle Spasm

• Fever

• Serotonin Syndrome

Side Effects DiscussionSide Effects Discussion• QT interval prolongation

– Citalopram associated with dose -

related QT interval prolongation

Torsade de pointes has

• QT interval prolongation

– Citalopram associated with dose -

related QT interval prolongation

Torsade de pointes has– Torsade de pointes has

been reported

– Torsade de pointes has

been reported

Side Effects DiscussionSide Effects Discussion• GI – most common first two weeks

– Nausea - transient and mild

– Diarrhea, dry mouth, constipation,

vomiting also

• GI – most common first two weeks

– Nausea - transient and mild

– Diarrhea, dry mouth, constipation,

vomiting alsovomiting also

– Sertraline - higher incidence

vomiting also

– Sertraline - higher incidence

Side Effects DiscussionSide Effects Discussion• Sexual dysfunction

– Men - ejaculatory delay, decreased

libido and ED

Women decreased libido and

• Sexual dysfunction

– Men - ejaculatory delay, decreased

libido and ED

Women decreased libido and– Women - decreased libido and

orgasm dysfunction

– Paroxetine – highest rate

– Women - decreased libido and

orgasm dysfunction

– Paroxetine – highest rate

Side Effects DiscussionSide Effects Discussion• Bleeding - Impaired platelet

aggregation due to serotonin

depletion - may increase bleeding risk

– Epistaxis most common

• Bleeding - Impaired platelet

aggregation due to serotonin

depletion - may increase bleeding risk

– Epistaxis most commonp

– GI bleeding - Combo with other

antiplatelet drugs i.e. aspirin

p

– GI bleeding - Combo with other

antiplatelet drugs i.e. aspirin

Side Effects DiscussionSide Effects Discussion• Hyponatremia - from inappropriate

antidiuretic hormone secretion

– serum sodium levels less than

110 mmol / L

• Hyponatremia - from inappropriate

antidiuretic hormone secretion

– serum sodium levels less than

110 mmol / L

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Side Effects DiscussionSide Effects Discussion• Dermatologic – Rare

– Severe cutaneous, Stevens -

Johnson syndrome, toxic

epidermal necrolysis and erythema

• Dermatologic – Rare

– Severe cutaneous, Stevens -

Johnson syndrome, toxic

epidermal necrolysis and erythemap y y

multiforme reported

p y y

multiforme reported

Side Effects DiscussionSide Effects Discussion• Neonatal abstinence syndrome

– Poor feeding, hypoglycemia,

hypothermia, lethargy or irritability,

vomiting, etc.) have been reported

• Neonatal abstinence syndrome

– Poor feeding, hypoglycemia,

hypothermia, lethargy or irritability,

vomiting, etc.) have been reported g, ) p

in infants exposed to SSRIs in utero

g, ) p

in infants exposed to SSRIs in utero

Side Effects DiscussionSide Effects Discussion• When treating a pregnant woman with

an SSRI during the third trimester, the

physician should carefully consider the

potential risks and benefits of treatment

• When treating a pregnant woman with

an SSRI during the third trimester, the

physician should carefully consider the

potential risks and benefits of treatment

– If clinically feasible, and taking the

drug half - life into consideration,

tapering of the serotonergic agent

prior to delivery may be considered

as an alternative. [50547]

– If clinically feasible, and taking the

drug half - life into consideration,

tapering of the serotonergic agent

prior to delivery may be considered

as an alternative. [50547]

Drug InteractionsDrug Interactions• All agents interact with MAOIs,

triptans, linezolid and tramadol

which can increase the risk of

serotonin syndrome

• All agents interact with MAOIs,

triptans, linezolid and tramadol

which can increase the risk of

serotonin syndrome

• Fluoxetine and fluvoxamine interact

with alprazolam - there is an increase

in plasma concentrations and half -

life of alprazolam

• Fluoxetine and fluvoxamine interact

with alprazolam - there is an increase

in plasma concentrations and half -

life of alprazolam

Drug InteractionsDrug Interactions• Fluoxetine, fluvoxamine, and

paroxetine interact with beta -

blockers, which results in increased

BB concentration

• Fluoxetine, fluvoxamine, and

paroxetine interact with beta -

blockers, which results in increased

BB concentration

(heart block, bradycardia)

• Fluoxetine and fluvoxamine

interact with carbamazepine,

causing an increase in

carbamazepine concentrations

(heart block, bradycardia)

• Fluoxetine and fluvoxamine

interact with carbamazepine,

causing an increase in

carbamazepine concentrations

Drug InteractionsDrug Interactions• MAO inhibitors - SSRIs are

contraindicated in patients receiving

MAO inhibitors or within two weeks

of their discontinuation

• MAO inhibitors - SSRIs are

contraindicated in patients receiving

MAO inhibitors or within two weeks

of their discontinuation

• SSRIs, SNRIs, and other

serotonergic drugs

• SSRIs, SNRIs, and other

serotonergic drugs

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Drug InteractionsDrug Interactions– Meperidine, triptans, most

antidepressants, amphetamines, ergot

alkaloids, dopamine antagonists, St.

John’s wort, and others

– Meperidine, triptans, most

antidepressants, amphetamines, ergot

alkaloids, dopamine antagonists, St.

John’s wort, and others

– Do not co - administer SSRIs with an

SNRI or another SSRI as the risk for

serotonin syndrome or neuroleptic

malignant syndrome is greatly increased

– Monitor Close for SS

– Do not co - administer SSRIs with an

SNRI or another SSRI as the risk for

serotonin syndrome or neuroleptic

malignant syndrome is greatly increased

– Monitor Close for SS

Drug InteractionsDrug Interactions• Antithrombotic drugs

– Anticoagulants, antiplatelet drugs,

nonsteroidal anti - inflammatory

drugs, and aspirin should be

• Antithrombotic drugs

– Anticoagulants, antiplatelet drugs,

nonsteroidal anti - inflammatory

drugs, and aspirin should be g , p

administered with caution

– Especially with elderly

g , p

administered with caution

– Especially with elderly

Drug InteractionsDrug Interactions– Monitor for signs and symptoms of

bleeding while taking an SSRI with

an anticoagulant medication and to

promptly report any bleeding

– Monitor for signs and symptoms of

bleeding while taking an SSRI with

an anticoagulant medication and to

promptly report any bleeding

events to the practitionerevents to the practitioner

Drug InteractionsDrug Interactions• CYP 450 isozymes

• Fluoxetine and Paroxetine inhibit

CYP2D6 - increasing drug levels

• Fluvoxamine inhibit CYP2C19

• CYP 450 isozymes

• Fluoxetine and Paroxetine inhibit

CYP2D6 - increasing drug levels

• Fluvoxamine inhibit CYP2C19• Fluvoxamine - inhibit CYP2C19,

CYP1A2, CYP3A4 interact - tricyclic

antidepressants, antipsychotics,

propranolol and warfarin

• Fluvoxamine - inhibit CYP2C19,

CYP1A2, CYP3A4 interact - tricyclic

antidepressants, antipsychotics,

propranolol and warfarin

Drug InteractionsDrug Interactions• QT Interval Prolongation

– Citalopram - Fluoxetine - Current

use with drugs that prolong QT

interval not recommended

• QT Interval Prolongation

– Citalopram - Fluoxetine - Current

use with drugs that prolong QT

interval not recommended

• CYP2C19 inhibitors, the

maximum recommended daily

dose is 20 mg due to the risk

of QT interval prolongation

• CYP2C19 inhibitors, the

maximum recommended daily

dose is 20 mg due to the risk

of QT interval prolongation

X – Contraindicated

X-BBW – Contraindicated and Black Box Warning

BBW – Black Box Warning, Not Contraindicated

Yes – REMS or MedGuide is available

Safety Issue

Citalopram Hbr

Escitalopram Fluoxetine Hcl

Fluvoxamine Maleate

Paroxetine HCl

Paroxetine Mesylate

Sertraline HCl

REMS

Safety IssuesSafety Issues

MedGuide Yes Yes Yes Yes Yes Yes Yes

citalopram hypersensitivity

X X

MAOI therapy X X X X X X

children BBW BBW BBW BBW BBW BBW BBW

suicidal ideation

BBW BBW BBW BBW BBW BBW BBW

pregnancy X X

11/4/2014

11

Safety IssuesSafety Issues• Increased Risk of suicide

– All antidepressants - Children and

young adults, especially the first

few months of therapy

• Increased Risk of suicide

– All antidepressants - Children and

young adults, especially the first

few months of therapypy

– AACP- Risk benefit ratio favorable

with close monitoring

– Careful monitoring for all patients

on initiation of therapy with SSRI

py

– AACP- Risk benefit ratio favorable

with close monitoring

– Careful monitoring for all patients

on initiation of therapy with SSRI

Safety IssuesSafety Issues• QT Prolongation - Citalopram

can prolong

– Not recommended in patients with

congenital long QT syndrome,

• QT Prolongation - Citalopram

can prolong

– Not recommended in patients with

congenital long QT syndrome, g g Q y ,

bradycardia, or uncorrected

electrolyte disturbances or using

other drugs that prolong QT

g g Q y ,

bradycardia, or uncorrected

electrolyte disturbances or using

other drugs that prolong QT

Safety IssuesSafety Issues– Poor metabolizers of CYP2C19 -

max dose 20mg / d

– Frequent monitoring indicated if

mandatory concurrent use

– Poor metabolizers of CYP2C19 -

max dose 20mg / d

– Frequent monitoring indicated if

mandatory concurrent useyy

Safety IssuesSafety Issues• Pregnancy

– Paroxetine Category D

– Most Category C

• Pregnancy

– Paroxetine Category D

– Most Category C

– Some studies show septal heart

defects when mothers taking

sertraline or citalopram in

early pregnancy

– Some studies show septal heart

defects when mothers taking

sertraline or citalopram in

early pregnancy

Safety IssuesSafety Issues– Persistent pulmonary hypertension

of newborn with maternal use after

20 weeks

– 3rd trimester use associated with

– Persistent pulmonary hypertension

of newborn with maternal use after

20 weeks

– 3rd trimester use associated with

neonatal abstinence syndrome

after delivery

neonatal abstinence syndrome

after delivery

Safety IssuesSafety Issues• Breast feeding - benefits weighed

against risk

– Sertraline, paroxetine and

nortriptyline may be preferred due

• Breast feeding - benefits weighed

against risk

– Sertraline, paroxetine and

nortriptyline may be preferred due p y y p

to low concentrations

p y y p

to low concentrations

11/4/2014

12

Safety IssuesSafety Issues• Abrupt discontinuation

– Avoid if possible

– Flu - like symptoms

• Abrupt discontinuation

– Avoid if possible

– Flu - like symptoms

– Gradual tapering recommended

– Paroxetine - withdraw 2 weeks

– Fluoxetine - lowest rate due to

slow metabolism

– Gradual tapering recommended

– Paroxetine - withdraw 2 weeks

– Fluoxetine - lowest rate due to

slow metabolism

Safety IssuesSafety Issues• Bipolar Disorder

• Precipitation of mania in patients

with bipolar disorder can occur and

should be considered when selecting

• Bipolar Disorder

• Precipitation of mania in patients

with bipolar disorder can occur and

should be considered when selecting g

drug therapy

g

drug therapy

Efficacy MonitoringEfficacy Monitoring• Patients will show substantial

improvement during the first 2 weeks

of treatment, but a maximum

improvement may not be evident for

• Patients will show substantial

improvement during the first 2 weeks

of treatment, but a maximum

improvement may not be evident for

4 or more weeks

• A similar delayed pattern

(4 to 6 weeks) of therapeutic

response is similar among all

antidepressant agents

4 or more weeks

• A similar delayed pattern

(4 to 6 weeks) of therapeutic

response is similar among all

antidepressant agents

Efficacy MonitoringEfficacy Monitoring• Baseline and periodic electrolyte

measurements in patients at risk for

significant electrolyte disturbances

• ECG for QT interval prolongation

• Baseline and periodic electrolyte

measurements in patients at risk for

significant electrolyte disturbances

• ECG for QT interval prolongationQ p gQ p g

Efficacy MonitoringEfficacy Monitoring• Monitor for serotonin syndrome

– Signs / symptoms include

mental status changes,

tachycardia, in coordination,

• Monitor for serotonin syndrome

– Signs / symptoms include

mental status changes,

tachycardia, in coordination, y , ,

nausea, vomiting and diarrhea

y , ,

nausea, vomiting and diarrhea

Major Counseling PointsMajor Counseling Points• Avoid activities requiring mental

alertness of coordination until drug

effects are realized

• Report use of a MAOI within the last

• Avoid activities requiring mental

alertness of coordination until drug

effects are realized

• Report use of a MAOI within the last p

14 days prior to initiation of drug

p

14 days prior to initiation of drug

11/4/2014

13

Major Counseling PointsMajor Counseling Points• Report worsening depression,

suicidal ideation, agitation,

irritability, or unusual changes in

behavior, especially at initiation of

• Report worsening depression,

suicidal ideation, agitation,

irritability, or unusual changes in

behavior, especially at initiation of

therapy or with dose changestherapy or with dose changes

Major Counseling PointsMajor Counseling Points• Immediately report any symptoms of

QT prolongation (CP, SOB, syncope,

palpitations, dizziness), especially

with citalopram and fluoxetine

• Immediately report any symptoms of

QT prolongation (CP, SOB, syncope,

palpitations, dizziness), especially

with citalopram and fluoxetine

• May cause sexual dysfunction

• Symptomatic improvement may not

be seen for a few weeks

• May cause sexual dysfunction

• Symptomatic improvement may not

be seen for a few weeks

Major Counseling PointsMajor Counseling Points• Report signs / symptoms of

serotonin syndrome (high fever,

agitation, confusion, hallucinations,

hyperreflexia, n / v / d)

• Report signs / symptoms of

serotonin syndrome (high fever,

agitation, confusion, hallucinations,

hyperreflexia, n / v / d)

– Concurrent use of serotonergic

agents (Triptans, tryptophan),

linezolid, lithium, tramadol, or St.

John’s wort may increase risk

– Concurrent use of serotonergic

agents (Triptans, tryptophan),

linezolid, lithium, tramadol, or St.

John’s wort may increase risk

Major Counseling PointsMajor Counseling Points• Report signs of hyponatremia (HA,

difficulty concentrating, confusion,

memory impairment, and weakness /

unsteadiness that may lead to falls),

• Report signs of hyponatremia (HA,

difficulty concentrating, confusion,

memory impairment, and weakness /

unsteadiness that may lead to falls),

especially with fluoxetine,

fluvoxamine and sertraline

• Report decreased appetite and

weight loss

especially with fluoxetine,

fluvoxamine and sertraline

• Report decreased appetite and

weight loss

Major Counseling PointsMajor Counseling Points• Report skin rash, with or without

systemic symptoms (fever, edema,

pulmonary effects)

• Consult healthcare professional prior

• Report skin rash, with or without

systemic symptoms (fever, edema,

pulmonary effects)

• Consult healthcare professional prior p p

to new drug use, including OTC and

herbal drugs

p p

to new drug use, including OTC and

herbal drugs

Major Counseling PointsMajor Counseling Points• Advise against sudden

discontinuation due to significant

withdrawal symptoms

• Avoid or minimize consumption of

• Advise against sudden

discontinuation due to significant

withdrawal symptoms

• Avoid or minimize consumption of p

alcohol while on this drug

• Concomitant use of ASA, NSAIDs,

warfarin, or other anticoagulants may

increase the risk of bleeding

p

alcohol while on this drug

• Concomitant use of ASA, NSAIDs,

warfarin, or other anticoagulants may

increase the risk of bleeding

11/4/2014

14

Instructions for AdministrationInstructions for Administration

• Citalopram, escitalopram, fluoxetine

– May be taken in the morning or

evening without regard to food

• Citalopram, escitalopram, fluoxetine

– May be taken in the morning or

evening without regard to foodg g

• Fluvoxamine

– Take at bedtime

– Do not crush or chew extended -

release capsules

g g

• Fluvoxamine

– Take at bedtime

– Do not crush or chew extended -

release capsules


– Divide total daily doses > 100 mg

of immediate - release tablets into

2 doses

– Divide total daily doses > 100 mg

of immediate - release tablets into

2 doses

• If 2 doses of unequal size are to

be taken daily, the larger dose

should be taken at bedtime

• If 2 doses of unequal size are to

be taken daily, the larger dose

should be taken at bedtime


• Paroxetine

– Administer as a single dose without

regard to food usually in the morning

• Paroxetine

– Administer as a single dose without

regard to food usually in the morning

– Suspension: Shake well before using

– Controlled - release tablets: Do not

crush or chew tablet; swallow whole

– Suspension: Shake well before using

– Controlled - release tablets: Do not

crush or chew tablet; swallow whole


• Sertraline

– Oral concentrate: Dilute in 4

ounces (one - half cup) using only

• Sertraline

– Oral concentrate: Dilute in 4

ounces (one - half cup) using only ( p) g y

water, ginger ale, lemon - lime

soda, lemonade or orange juice;

dilute immediately before use - do

not mix in advance

( p) g y

water, ginger ale, lemon - lime

soda, lemonade or orange juice;

dilute immediately before use - do

not mix in advance

Serotonin Syndrome (SS)Serotonin Syndrome (SS)• Neuromuscular effects

• Autonomic effects

• Mental status changes

• Neuromuscular effects

• Autonomic effects

• Mental status changes

Serotonin Syndrome (SS)Serotonin Syndrome (SS)• Occurrence - Central and peripheral

serotonin receptors are over

stimulated through action of

medications or drugs of abuse

• Occurrence - Central and peripheral

serotonin receptors are over

stimulated through action of

medications or drugs of abuse

• Incidence unknown but uncommon

• Symptoms non specific diagnostic

criteria vary

• Mild symptoms may be ignored

• Incidence unknown but uncommon

• Symptoms non specific diagnostic

criteria vary

• Mild symptoms may be ignored

11/4/2014

15

SS Signs and SymptomsSS Signs and Symptoms• Hallmark sign - clonus - involuntary

rapid muscle contraction and

relaxation or tremor

• Mental Status changes

• Hallmark sign - clonus - involuntary

rapid muscle contraction and

relaxation or tremor

• Mental Status changes g

– Pressured speech

– Hypomania

– Hypervigilance

g

– Pressured speech

– Hypomania

– Hypervigilance

SS Signs and SymptomsSS Signs and Symptoms– Hyperactivity

– Hallucinations

– Delirium

– Hyperactivity

– Hallucinations

– Delirium

– Confusion

– Agitation

– Confusion

– Agitation

SS Signs and SymptomsSS Signs and Symptoms• Automomic changes

– Diarrhea

– Mydriasis

– Fever

• Automomic changes

– Diarrhea

– Mydriasis

– FeverFever

– Flushing

– Increased bowel sounds

– Respiratory rate

– Tearing

Fever

– Flushing

– Increased bowel sounds

– Respiratory rate

– Tearing

SS Signs and SymptomsSS Signs and Symptoms• Neuromuscular

– Hyperreflexia

– Increased muscle tone

• Neuromuscular

– Hyperreflexia

– Increased muscle tone

– Restlessness

– Rhabdomyolysis

– Rigidity

– Restlessness

– Rhabdomyolysis

– Rigidity

SS Signs and SymptomsSS Signs and Symptoms– Shivering

– Spontaneous, inducible or

ocular clonus

Tremor

– Shivering

– Spontaneous, inducible or

ocular clonus

Tremor– Tremor– Tremor

SS Signs and SymptomsSS Signs and Symptoms• Occur typically after increase in dose

or overdose or addition of other

serotonergic drug

• 67 % symptoms within 6 hours

• Occur typically after increase in dose

or overdose or addition of other

serotonergic drug

• 67 % symptoms within 6 hoursy p


y p


11/4/2014

16

SS Signs and SymptomsSS Signs and Symptoms• Mild SS

– May not be recognized

– Patients with increased temperature

and muscle rigidity should be

• Mild SS

– May not be recognized

– Patients with increased temperature

and muscle rigidity should beand muscle rigidity should be

considered medical emergency

– Multiorgan failure within hours

and muscle rigidity should be

considered medical emergency

– Multiorgan failure within hours

SS Signs and SymptomsSS Signs and Symptoms• SS can occur after discontinuance of

long acting medications

– Prozac, Sarafem

MAOI Marplan Phenelzine etc

• SS can occur after discontinuance of

long acting medications

– Prozac, Sarafem

MAOI Marplan Phenelzine etc– MAOI - Marplan Phenelzine, etc. – MAOI - Marplan Phenelzine, etc.

SS Causative AgentsSS Causative Agents• Causes

– Increased serotonin production

– Inhibition of serotonin reuptake

• Causes


– Inhibition of serotonin reuptake

– Inhibition of serotonin metabolism

– Increased serotonin release

– Stimulation of serotonin receptors




SS Causative AgentsSS Causative Agents• Administration of two or more drugs

that affect the serotonin system

through different mechanisms


• Administration of two or more drugs

that affect the serotonin system

through different mechanisms





– Multiple mechanisms




– Multiple mechanisms

SS Causative AgentsSS Causative Agents• Increased serotonin production

– L- tryptophan - serotonin precursor

• Inhibition of serotonin reuptake

• Increased serotonin production

– L- tryptophan - serotonin precursor

• Inhibition of serotonin reuptake

– Chlorpheniramine (Chlortirmeton),

SSRIs, St. John’s wort, tramadol

(Ultram), Trazodone (Desyrel),

tricyclic antidepressants

(clomipramine imipramine)

– Chlorpheniramine (Chlortirmeton),

SSRIs, St. John’s wort, tramadol

(Ultram), Trazodone (Desyrel),

tricyclic antidepressants

(clomipramine imipramine)

SS Causative AgentsSS Causative Agents– Dextromethorphan

(Robitussin DM, etc.)

– Meperidine (Demerol)

Methadone

– Dextromethorphan

(Robitussin DM, etc.)

– Meperidine (Demerol)

Methadone– Methadone

– Pentazocine (Talwin)

– Venlaxafine (effexor)

– Methadone

– Pentazocine (Talwin)

– Venlaxafine (effexor)

11/4/2014

17

SS Causative AgentsSS Causative Agents• Inhibition of serotonin metabolism

– MAOI inhibitors - isocarboxazid

(Marplan), phenelzine (Nardil),

selegiline (eldepryl), and

• Inhibition of serotonin metabolism

– MAOI inhibitors - isocarboxazid

(Marplan), phenelzine (Nardil),

selegiline (eldepryl), and g ( p y ),

tranylcypromine (Parnate)

g ( p y ),

tranylcypromine (Parnate)

SS Causative AgentsSS Causative Agents• Increased serotonin release

– Dextromethorphan, meperidine,

methadone,

methylenedioxymethamphetamine

• Increased serotonin release

– Dextromethorphan, meperidine,

methadone,

methylenedioxymethamphetaminey y p

(MDMA, ecstasy), Mirtazapine

(Remeron)

y y p

(MDMA, ecstasy), Mirtazapine

(Remeron)

SS Causative AgentsSS Causative Agents• Stimulation of serotonin receptors

– Buspirone, lysergic acid

diethylamide (LSD), meperidine,

lithium, metoclopramide (reglan),

• Stimulation of serotonin receptors

– Buspirone, lysergic acid

diethylamide (LSD), meperidine,

lithium, metoclopramide (reglan), , p ( g ),

dihydroergotamine (DHE 45) and

triptans (sumatriptan etc. )

, p ( g ),

dihydroergotamine (DHE 45) and

triptans (sumatriptan etc. )

SS Causative AgentsSS Causative Agents• Alteration of the elimination of a

serotonergic drug - some SSRIs can

inhibit metabolism of tramadol by

CYP2D6 inhibition - increase

• Alteration of the elimination of a

serotonergic drug - some SSRIs can

inhibit metabolism of tramadol by

CYP2D6 inhibition - increase

serotonergic activityserotonergic activity

SS Causative AgentsSS Causative Agents• Occurrance - Elimination of a

serotonergic drug which is altered

– SSRIs can inhibit tramadol by

CYP2D6 inhibition - increasing

• Occurrance - Elimination of a

serotonergic drug which is altered

– SSRIs can inhibit tramadol by

CYP2D6 inhibition - increasing g

serotonergic activity

• See Interaction Chart

g

serotonergic activity

• See Interaction Chart

SS Causative AgentsSS Causative AgentsInhibition of Serotonin

Reuptake

Generic Name Brand

Chlorpheniramine Chlortrimeton

Dextromethorphan Robitussin

Hypericum perforatum St. John’s wort

Cyclobenzaprine Flexeril

Meperidine Demerol

Methadone Dolophine

11/4/2014

18

SS Causative AgentsSS Causative AgentsInhibition of Serotonin

Reuptake

Generic Name Brand

Sibutramine Meridia

Tramadol Ultram

Trazodone Desyrel

Tricyclics(clomipramine, imipramine)

numerous

Venlafaxine Effexor

SS Causative AgentsSS Causative Agents

Increased Serotonin Release:

Generic Brand

Dextromethorphan Robitussin,Delsym

Meperidine

Methadone

Methylenedioxymethamphetamine MDMA, ecstasy

Mirtazapine Remeron

SS Causative AgentsSS Causative AgentsStimulation of Serotonin

Receptors

Generic Brand

Buspirone Buspar

Lysergic acid diethylamide LSDLysergic acid diethylamide LSD

Meperidine

Lithium

Metoclopramide Reglan

Dihydroergotamine D.H.E. 45

Triptans Sumatriptan etc.

SS TreatmentSS Treatment• Treatment - Discontinue

offending drug

– Supportive care

Mild to moderate cases resolve in

• Treatment - Discontinue

offending drug

– Supportive care

Mild to moderate cases resolve in– Mild to moderate cases resolve in

24 - 72 hours

– Severe cases longer

– Mild to moderate cases resolve in

24 - 72 hours

– Severe cases longer

SS TreatmentSS Treatment• Mild cases - Benzodiazepines

(reduce hypertonicity and

neurologic excitability)

• Severe cases - Sedation,

• Mild cases - Benzodiazepines

(reduce hypertonicity and

neurologic excitability)

• Severe cases - Sedation, ,

paralyzation, intubation

,

paralyzation, intubation

SS TreatmentSS Treatment• Fever - Caused by excessive muscular

activity, not a change in hypothalamic

temperature set point - antipyretic

therapy not recommended

• Fever - Caused by excessive muscular

activity, not a change in hypothalamic

temperature set point - antipyretic

therapy not recommended

• Serotonin antagonists have

been recommended

– Cyproheptadine (periactin)

– Chlorpromazine (Thorazine)

• Serotonin antagonists have

been recommended

– Cyproheptadine (periactin)

– Chlorpromazine (Thorazine)

11/4/2014

19

SS CommentarySS Commentary• Relatively few patients get SS

• Fatalities rare

• Improvement seen with

supportive care

• Relatively few patients get SS

• Fatalities rare

• Improvement seen with

supportive caresupportive care

• No way to predict

supportive care

• No way to predict

SS CommentarySS Commentary• Some combinations

more problematic

– Tramadol and other

antidepressants

• Some combinations

more problematic

– Tramadol and other

antidepressantsp

• Avoid if possible, alter doses

p

• Avoid if possible, alter doses

SS CommentarySS Commentary– Linezolid - monitor- may reduce

antidepressant dose during Tx

– MAOI - 50 %

• Avoid adding up to 2 weeks

– Linezolid - monitor- may reduce

antidepressant dose during Tx

– MAOI - 50 %

• Avoid adding up to 2 weeks• Avoid adding up to 2 weeks

• 5 weeks for fluoxetine

• Avoid adding up to 2 weeks

• 5 weeks for fluoxetine

SS CommentarySS Commentary• Triptans - FDA alert

– Use with SSRS or SNRIs

– Incidence low

• Triptans - FDA alert

– Use with SSRS or SNRIs

– Incidence low

– Patients should be educated about

problem if unavoidable

– Patients should be educated about

problem if unavoidable

SS CommentarySS Commentary• Avoid unnecessary combinations

– Counsel patients on problems

– Contact prescriber for even

mild symptoms

• Avoid unnecessary combinations

– Counsel patients on problems

– Contact prescriber for even

mild symptomsmild symptoms

– DC and get help if severe

symptoms occur

mild symptoms

– DC and get help if severe

symptoms occur

SSRIs and PregnancySSRIs and Pregnancy• SSRIs most prescribed

• Risks weighed against benefits

• Preterm birth rates not

clearly defined

• SSRIs most prescribed

• Risks weighed against benefits

• Preterm birth rates not

clearly definedclearly definedclearly defined

11/4/2014

20

SSRIs and PregnancySSRIs and Pregnancy• Congenital malformations

– Paroxetine cardiac risk about 2 %

– 1 % in all infants

• Congenital malformations

– Paroxetine cardiac risk about 2 %

– 1 % in all infants

• Autism

– Not clearly defined by studies

• Autism

– Not clearly defined by studies

SSRIs and Breast MilkSSRIs and Breast Milk• Risks and benefits

– Need by mother

– Potential effects on milk production

– Amount of drug excreted into

• Risks and benefits

– Need by mother

– Potential effects on milk production

– Amount of drug excreted intoAmount of drug excreted into

human milk

– Extent of oral absorption by

breastfeeding infant

– Potential adverse effects on the


Amount of drug excreted into

human milk

– Extent of oral absorption by


– Potential adverse effects on the


SSRIs and Breast MilkSSRIs and Breast Milk• Risks and Benefits

– Most often in two months

and younger

Rare in six months or older

• Risks and Benefits

– Most often in two months

and younger

Rare in six months or older– Rare in six months or older

– Pharmacogenetics emerging

guidance may help

individualize decisions

– Rare in six months or older

– Pharmacogenetics emerging

guidance may help

individualize decisions

SSRIs and Breast MilkSSRIs and Breast Milk• Database Recommended

– LactMed - http://toxnet.nlm.nih.gov

– There’s an APP for that!

• Database Recommended

– LactMed - http://toxnet.nlm.nih.gov

– There’s an APP for that!

– Recommended reference for

up to date information

– Recommended reference for

up to date information

SSRIs and Breast MilkSSRIs and Breast Milk

SSRIs Exceeding 10% of Maternal Plasma Concentration

Reference

Citalopram Weissman 2004

Fluoxetine Weissman 2004 20Fluoxetine Weissman 2004, 20 product labeling

Fluvoxamine Weissman 2004

Sertraline Hendrick 2001, Stowe 2003

Venlafaxine Newport 2009

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Most common antidepressant in

children and adolescents

• Fluoxetine most used - Starting dose

10 to 20 mg once daily

• Most common antidepressant in

children and adolescents

• Fluoxetine most used - Starting dose

10 to 20 mg once dailyg y

– Graduating dose

• Citalopram and Sertraline – Not FDA

approved yet

• All available in liquid formulations

g y

– Graduating dose

• Citalopram and Sertraline – Not FDA

approved yet

• All available in liquid formulations

11/4/2014

21

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Escitalopram

– FDA approved for adolescents

– Starting dose 10 mg up to 20 mg

once daily

• Escitalopram

– FDA approved for adolescents

– Starting dose 10 mg up to 20 mg

once dailyonce dailyonce daily

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Citalopram and Sertraline

– Evidence of use

– Sertraline 25 mg once daily increased

to 50 mg once daily, increased every

• Citalopram and Sertraline

– Evidence of use

– Sertraline 25 mg once daily increased

to 50 mg once daily, increased everyto 50 mg once daily, increased every

two weeks up to 200 mg once daily

– Citalopram initial dose - 10 mg once

daily increased to 20 mg once daily

after a week, maximum dose 40 mg

once daily

to 50 mg once daily, increased every

two weeks up to 200 mg once daily

– Citalopram initial dose - 10 mg once

daily increased to 20 mg once daily

after a week, maximum dose 40 mg

once daily

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Follow up

– Weekly for 4 weeks

– Every 2 weeks for 4 weeks

• Follow up

– Weekly for 4 weeks

– Every 2 weeks for 4 weeks

– At week 12 then as indicated

– Continue for at least 6 - 12 months

– Taper when DC’d

– At week 12 then as indicated

– Continue for at least 6 - 12 months

– Taper when DC’d

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Side effects

– Dose dependent - resolve with time

– Rule out bi - polar disorder

M it f it ti di i hibiti

• Side effects

– Dose dependent - resolve with time

– Rule out bi - polar disorder

M it f it ti di i hibiti– Monitor for agitation, disinhibition

and suicidal thoughts

– Common side effects include

• Headache, sleepiness

or disturbance

– Monitor for agitation, disinhibition

and suicidal thoughts

– Common side effects include

• Headache, sleepiness

or disturbance

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Abrupt discontinuation - Avoid

– May cause worsening depression

and suicidality

Fluoxetine lowest risk due to

• Abrupt discontinuation - Avoid

– May cause worsening depression

and suicidality

Fluoxetine lowest risk due to– Fluoxetine lowest risk due to

long half - life

– Fluoxetine lowest risk due to

long half - life

SSRIs Pediatric DepressionSSRIs Pediatric Depression• QT prolongation

– Don’t use citalopram

– Use with caution in patients with

congenital heart disease liver

• QT prolongation

– Don’t use citalopram

– Use with caution in patients with

congenital heart disease livercongenital heart disease, liver

disease or arrhythmias

congenital heart disease, liver

disease or arrhythmias

11/4/2014

22

SSRIs Pediatric DepressionSSRIs Pediatric Depression• Suicidality

– Mentioned in MedGuide

– Dispensed with prescriptions

• Suicidality

– Mentioned in MedGuide

– Dispensed with prescriptions

– Weigh benefits vs. risks

– Monitor for

– Weigh benefits vs. risks

– Monitor for

SSRIs and the ElderlySSRIs and the Elderly• First line treatment in elderly

• Little evidence as opposed

to tricyclics

• First line treatment in elderly

• Little evidence as opposed

to tricyclics

SSRIs and the ElderlySSRIs and the Elderly• Weigh benefits vs. risk

• Advantages - Fewer anticholinergic

effects, benign cardiovascular

profile, ease of use and safety

• Weigh benefits vs. risk

• Advantages - Fewer anticholinergic

effects, benign cardiovascular

profile, ease of use and safety p , y

in overdose

• Few differences in different forms

p , y

in overdose

• Few differences in different forms

SSRIs and the ElderlySSRIs and the Elderly• Adverse effects in elderly

– Falls, hyponatremia, weight loss,

sexual dysfunction and

drug interactions

• Adverse effects in elderly

– Falls, hyponatremia, weight loss,

sexual dysfunction and

drug interactionsg

• Patient monitoring important

• Titrate slowly

• Use caution for interacting drugs

g

• Patient monitoring important

• Titrate slowly

• Use caution for interacting drugs

Dispensing Role of NursesDispensing Role of Nurses• Nurses in Health Department

Statutorily allowed to dispense

– Counseling Patient in Dispensing

• Uses of drug

• Nurses in Health Department

Statutorily allowed to dispense

– Counseling Patient in Dispensing

• Uses of drug• Uses of drug

• Dosage to take

• Side effects

• Uses of drug

• Dosage to take

• Side effects

Dispensing Role of NursesDispensing Role of Nurses• Interactions - Check for

and counsel

• Inform patient about their drug

• PILs

• Interactions - Check for

and counsel

• Inform patient about their drug

• PILs• PILs• PILs

11/4/2014

23

ReferencesReferences• http://health.howstuffworks.com/mental

-health/depression/facts/selective-

serotonin-reuptake-inhibitors-ssris.htm

• Clinical Pharmacology - Elsevier / Gold

• http://health.howstuffworks.com/mental

-health/depression/facts/selective-

serotonin-reuptake-inhibitors-ssris.htm

• Clinical Pharmacology - Elsevier / Gold

Standard Copyright 2014 edition

• http://www.mayoclinic.org/diseases-

conditions/depression/in-

depth/ssris/art-20044825

Standard Copyright 2014 edition

• http://www.mayoclinic.org/diseases-

conditions/depression/in-

depth/ssris/art-20044825

ReferencesReferences• Facts about serotonin syndrome

Pharmacist’s Letter / Prescriber’s

Letter 2009;25(10):251002.

• PL Detail - Document, SSRIs for

• Facts about serotonin syndrome

Pharmacist’s Letter / Prescriber’s

Letter 2009;25(10):251002.

• PL Detail - Document, SSRIs for

Pediatric Depression. Pharmacist’s

• Letter / Prescriber’s Letter.

January 2014

Pediatric Depression. Pharmacist’s

• Letter / Prescriber’s Letter.

January 2014

ReferencesReferences• LexiComp:

http://online.lexi.com/lco/action/home

• Clinical effects of pharmacological

variations in selective serotonin

• LexiComp:

http://online.lexi.com/lco/action/home

• Clinical effects of pharmacological

variations in selective serotonin

reuptake inhibitors: an overview-

©2005 Blackwell Publishing Ltd Int J

Clin Pract, December 2005, 59, 12,

1428–1434

reuptake inhibitors: an overview-

©2005 Blackwell Publishing Ltd Int J

Clin Pract, December 2005, 59, 12,

1428–1434

ReferencesReferences• Auburn University Drug

Information Center

• The Transfer of Drugs and

Therapeutics Into Human Breast Milk:

• Auburn University Drug

Information Center

• The Transfer of Drugs and

Therapeutics Into Human Breast Milk:

An Update on Selected Topics- Hari

Cheryl Sachs and COMMITTEE ON

DRUGS- Pediatrics; originally

published online August 26, 2013;DOI:

10.1542/peds.2013-1985

An Update on Selected Topics- Hari

Cheryl Sachs and COMMITTEE ON

DRUGS- Pediatrics; originally

published online August 26, 2013;DOI:

10.1542/peds.2013-1985

ReferencesReferences• Tolerability of selective serotonin

reuptake inhibitors: issues relevant to

the elderly

• Draper B1, Berman K.- PMID:

• Tolerability of selective serotonin

reuptake inhibitors: issues relevant to

the elderly

• Draper B1, Berman K.- PMID:

18540689 [PubMed - indexed for

MEDLINE]

18540689 [PubMed - indexed for

MEDLINE]

References References • See comment in PubMed Commons

below Can J Clin Pharmacol. 2000

Summer;7(2):91-5.Use of SSRIs in

the elderly: obvious benefits but

• See comment in PubMed Commons

below Can J Clin Pharmacol. 2000

Summer;7(2):91-5.Use of SSRIs in

the elderly: obvious benefits but

unappreciated risks. Herrmann N.

• www.princeton.edu/~achaney/tmve/...

/Serotonin.ht...Cached Similar

Princeton University

unappreciated risks. Herrmann N.

• www.princeton.edu/~achaney/tmve/...

/Serotonin.ht...Cached Similar

Princeton University

11/4/2014

24

Contact InformationContact Information

Charles Thomas, PD, RPh, FAPhAState Pharmacy DirectorBureau of Professional and Support Services

Charles Thomas, PD, RPh, FAPhAState Pharmacy DirectorBureau of Professional and Support Servicesand Support Services

Alabama Department of Public Health

[email protected]

and Support ServicesAlabama Department of Public Health

[email protected]

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