Download Mental Health Medications CE for Pharmacy Technicians

2/12/2015
Disclosure
Mental Health Medications
CE for Pharmacy Technicians
• I have no financial interests to disclose
• I have no conflicts of interest to disclose
Brittany L. Keener, PharmD, BCPS
LCDR, United States Public Health Service
Alaska Native Medical Center
Mediset Pharmacy
Objectives
Objectives
• Review the definition and diagnostic criteria
for:
• Review the classes of drugs used to treat
depression, schizophrenia, bipolar, anxiety
• Review the general mechanism of action of
antidepressants (SSRI, SNRI, TCA, etc.),
benzodiazepines, antipsychotics, mood
stabilizers, etc.
• Review doses for drugs for each disease
state
–
–
–
–
Depression
Schizophrenia
Bipolar disorders
Anxiety
Objectives
• Review of main side effects and any
required monitoring for each drug
Mental Health Disorders
• In 2012, there were an estimated 43.7 million
adults aged 18 or older in the U.S. with any
mental illness (AMI)
– 18.6% of all adults1
• In 2012, there were an estimated 9.6 million
adults aged 18 or older in the U.S. with serious
mental illness (SMI)
– 4.1% of all adults1
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Mental Health Disorders
• The prevalence of AMI in American
Indian/Alaska Native adults in 2012 was
reported at 28.3%1
• The prevalence of SMI in American
Indian/Alaska Native adults in 2012 was
reported at 8.5%1
Depression
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•
•
•
•
•
•
•
•
Depressed mood most of the day
Diminished interest or pleasure in all or most activities
Significant unintentional weight loss or gain
Insomnia or sleeping too much
Agitation or psychomotor retardation noticed by others
Fatigue or loss of energy
Feeling of worthlessness or excessive guilt
Diminished ability to think or concentrate or indecisiveness
Recurrent thoughts of death
Bipolar
• Characterized by more than one bipolar
episode
• 3 types of bipolar disorder
– Bipolar 1
– Bipolar 2
– Cyclothymic Disorder
Depression
• Major Depressive Disorder requires two or
more major depressive episodes
– Depressed mood and/or loss of interest or
pleasure in life activities for at least 2 weeks
– At least five of the following symptoms that
cause clinically significant impairments in
social, work, or other important areas of
functioning almost every day
Schizophrenia
• Characterized by delusions, hallucinations,
disorganized speech and behavior, and other
symptoms that cause social or occupational
dysfunction
• Symptoms must have been present for six
months and include at least one month of
active symptoms
Bipolar
• Bipolar 1: manic, or rapid (daily) cycling
episodes of mania and depression
• Bipolar 2: recurrent depression
accompanied by hypomanic episodes
• Cyclothymic Disorder: a chronic state of
cycling between hypomanic and depressive
episodes that do not reach diagnostic
standard for bipolar
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Anxiety
• Characterized by excessive fear or anxiety that
is difficult to control and negatively and
substantially impacts daily functioning
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Phobias
Generalized Anxiety Disorder (GAD)
Panic disorder
Separation anxiety
Social anxiety (social phobia)
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder (PTSD)
Anxiety
• Panic disorder: Sudden
and repeated attacks of
fear that last for several
minutes
• Social anxiety: strong fear
of being judged by others
and of being embarrassed
for doing common things
in front of others
• OCD: the need to check
things repeatedly, frequent
thoughts, or perform
routines and rituals over
and over
• PTSD: develops after a
terrifying ordeal that
involves physical harm or
the threat of physical harm
Anxiety
• Phobias: Overwhelming
and unreasonable fear of
an object or situation that
poses little real danger but
provokes anxiety and
avoidance
• GAD: excessive worry
about a variety of
everyday problems for at
least 6 months
• Separation anxiety:
inappropriate and
excessive display of fear
and distress when faced
with situations of
separation from the home
or a specific attachment
figure
Insomnia
• Difficulty initiating or
maintaining sleep, or
nonrestorative sleep for at least
1 month
• Sleep disturbance (or daytime
fatigue) which causes clinically
significant distress or
impairment in social,
occupational, or other important
areas of functioning
• Does not occur exclusively
during the course of narcolepsy,
breathing-related sleep disorder,
circadian rhythm sleep disorder,
or a parasomnia
• The disturbance does not occur
exclusively during the course of
another mental disorder
• Not due to the direct
physiological effects of a
substance or a general medical
condition
Antidepressants
• SSRI
• SNRI
• TCA
•
•
•
•
NDRI
SARI
NaSSA
MAOI
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Antidepressants
SSRI
• SSRI: Selective Serotonin Reuptake
Inhibitor
•
•
•
•
•
•
– These drugs inhibit the reuptake of serotonin
into brain nerve cells
– This results in increasing the available
serotonin to stimulate the serotonin receptors
– Serotonin is believed to contribute to feelings
of well-being and happiness
Drug
FDA-Approved
Indication
Citalopram (Celexa)
SSRI
•
•
•
•
•
•
•
•
Weight gain
Suicidal ideation
Withdrawal symptoms
Sexual dysfunction
Anxiety
Tremor
Nausea
Headache
• 4 to 6 weeks to see full
effect, some suggest
even longer
• Metabolized by the
liver
• Drug interactions are
very common
• Serotonin Syndrome
Depression
– Increase the levels of both serotonin and
norepinephrine
– Norepinephrine in the brain helps to increase
concentration
Usual Adult Dose
Comments
Initial: 20 mg
Contraindicated with pimozide.
Max: 40 mg
Maximum dose 20 mg daily if >60 years old, hepatic impairment, CYP2C19 poor
metabolizer, or taking a CYP2C19 inhibitor.
SSRI
Escitalopram (Lexapro)
Depression (adults,
adolescents), GAD
(adults)
Initial: 10 mg
Usual: 10 mg
Max: 20 mg
Fluoxetine
(Prozac,Sarafem,Prozac
Weekly)
Depression, OCD,
bulimia, panic disorder,
PMDD (Sarafem)
Pediatrics: Depression,
OCD
Initial: 20 mg (10 mg for panic
disorder or in pediatrics; can use 20
mg for depression in heavier kids)
Usual: 20 mg
Max: 80 mg (minimal experience with
doses >20 mg in pediatrics)
Bulimia: 60 mg (can start lower to
improve tolerability)
Fluvoxamine (Luvox no
longer sold under brand
name)
OCD
Maximum dose 10 mg/day in elderly or hepatic impairment.
Contraindicated with pimozide, thioridazine.
Start Prozac Weekly 7 days after last fluoxetine dose.
Prozac Weekly: 90 mg once weekly
(depression)
Initial: 50 mg (25 mg pediatrics)
Usual: 100 mg to 300 mg; divide
doses >100 mg (50 mg to 200 mg
pediatrics; divide doses >50 mg)
Contraindicated with aldosterone (Lotronex), tizanidine (Zanaflex), thioridazine,
pimozide.
Bedtime dosing recommended.
Max: 300 mg; divide doses >100
mg (200 mg child <12 years; divide
doses >50 mg)
Fluvoxamine extendedrelease (Luvox CR)
OCD
Initial: 100 mg
Usual: 100 mg to 300 mg
Max: 300 mg
Paroxetine (Paxil, Paxil
CR,Brisdelle)
Paxil: Depression, panic
disorder, social anxiety
disorder, OCD, GAD,
PTSD
Paxil CR: Depression,
panic disorder, social
anxiety disorder, PMDD
Brisdelle: hot flashes
Paxil CR, initial: 12.5 mg; 25 mg for
depression
Max: 75 mg
Contraindicated with aldosterone (Lotronex), tizanidine (Zanaflex), thioridazine,
ramelteon, pimozide.
Sertraline (Zoloft)
Depression, OCD, panic
disorder, PTSD, PMDD,
social anxiety disorder
Pediatrics: OCD
Initial: 50 mg (25 mg for panic, PTSD, Contraindicated with pimozide.
children ages six to 12, and social
anxiety)
Max: 200 mg (children/adults)
Bedtime dosing recommended.
Antidepressants
• SNRI: Serotonin Norepinephrine Reuptake
Inhibitors
Fluoxetine (Prozac, Sarafem)
Citalopram (Celexa)
Escitalopram (Lexapro)
Paroxetine (Paxil, Pexeva)
Sertraline (Zoloft)
Fluvoxamine (Luvox)
Start with 10 mg daily
(12.5 mg Paxil CR) and do not exceed 40 mg daily (50 mg Paxil CR) in the elderly,
debilitated, or patients with hepatic or renal impairment.
Contraindicated with pimozide or thioridazine.
Paxil, initial: 20 mg; 10 mg for panic
disorder
Max: 60 mg
Brisdelle: 7.5 mg at bedtime
SNRI
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•
•
•
Venlafaxine (Effexor)
Desvenlafaxine (Pristiq)
Duloxetine (Cymbalta)
Levomilnacipran (Fetzima)
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Drug
FDA-Approved
Indication
Desvenlafaxine
succinate extendedrelease tablet (Pristiq)
Depression
Usual Adult Dose
Comments
Initial: 50 mg
Usual: 50 mg
Monitor blood pressure.
Max: 400 mg (no additional benefit of doses >50 mg)
SNRI
Desvenlafaxine
extended-release
tablet (Khedezla)
Depression
Initial: 50 mg
Usual: 50 mg
Max dose 50 mg daily in moderate renal impairment, and 50 mg every other
day in severe renal impairment.
Max dose 100 mg daily in moderate to severe hepatic impairment.
SNRI
As above.
Max: 400 mg (no additional benefit of doses >50 mg)
• Similar side effects to
SSRIs
• Nausea
• Dry Mouth
• Dizziness
• Excessive sweating
• Withdrawal problems
seem to be greater
• Other novel uses
(chronic pain)
Duloxetine (Cymbalta) Depression, GAD, Initial: 30 mg for pain or fibromyalgia. May start with 60
diabetic peripheral mg for other indications.
neuropathy,
Usual: 60 mg
fibromyalgia,
Max: 120 mg (no evidence of benefit vs 60 mg)
chronic
musculoskeletal
pain
Monitor blood pressure.
Avoid with potent CYP1A2 and CYP2D6 inhibitors.
Levomilnacipran
extended-release
capsules (Fetzima)
Monitor blood pressure and pulse.
Max dose 80 mg daily in moderate renal impairment, and 40 mg daily in
severe renal impairment.
Stronger inhibitor of norepinephrine reuptake than serotonin reuptake.
Depression
Initial: 20 mg
Usual: 40 mg to 120 mg
Max: 120 mg
Limit dose to 80 mg in patients on a strong CYP3A4
inhibitor such as ketoconazole.
Venlafaxine extended- Depression, GAD, Initial: 75 mg (37.5 mg for panic; option for depression
release capsule
social anxiety
and GAD)
(Effexor XR)
disorder, panic
disorder
Usual: 75 mg to 225 mg (75 mg for social anxiety)
Max: 225 mg (375 mg for severely depressed inpatients)
Monitor blood pressure.
Reduce dose by 25% to 50% in renal impairment. Reduce dose by 50% in
hemodialysis patients.
Reduce dose by at least 50% in hepatic impairment.
Venlafaxine extended- Depression, social Initial: 75 mg (37.5 mg option for depression)
release tablet
anxiety disorder
Usual: 75 to 225 mg (75 mg for social anxiety)
Max: 225 mg (375 mg for severely depressed inpatients)
As above.
Antidepressants
TCA
• TCA: Tricyclic and tetracyclic
Antidepressants
– Increase levels of norepinephrine and/or
serotonin but less selective than SSRI and
SNRI
•
•
•
•
•
Drug
Amitriptyline
Amitriptyline (Elavil)
Imipramine (Tofranil)
Nortriptyline (Pamelor, Norpress)
Doxepin (Sinequan)
Desipramine (Norpramin)
FDA-Approved
Indication
Depression
Usual Adult Dose
Contraindicated in acute post-MI period.
Usual: 100 mg to 200 mg (elderly and adolescents, 25 mg to 100
mg)
Max: 300 mg (150 mg elderly and adolescents)
Contraindicated in acute post-MI period.
TCA
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•
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•
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•
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Dry mouth
Blurred vision
Constipation
Urinary retention
Drowsiness
Increased appetite
Weight gain
• Drop in blood pressure
when moving from
sitting to standing
(lightheadedness)
• Increased sweating
Comments
Initial: 50 mg to 100 mg
Usual: 75 mg to 150 mg
Max: 150 mg (300 mg inpatients)
Desipramine
(Norpramin)
Depression
Doxepin
Depression, sleep Initial: 75 mg
maintenance
(Silenor)
Usual: 75 mg to 150 mg
Some patients may only need 40 mg or 50 mg daily (e.g., elderly
or adolescent).
Give once-daily doses at bedtime.
Some patients may only need 25 mg or 50 mg daily.
If given once daily, bedtime dosing preferred.
Take Silenor within 30 min. of bedtime, and not within three
hours of a meal.
Max: 300 mg (divide doses >150 mg)
Silenor: 3 to 6 mg (start with 3 mg if >65 years)
Imipramine pamoate
(Tofranil-PM)
Depression
Initial: 75 mg (100 mg to 150 mg, inpatient)
Contraindicated in acute post-MI period.
Usual: 75 mg to 150 mg (doses >100 mg usually not needed for
elderly and adolescents)
If given once daily, bedtime dosing is preferred.
Not for initial dosing in adolescents or elderly.
Max: 200 mg (300 mg inpatients)
Imipramine
hydrochloride (Tofranil)
Nortriptyline
Depression,
childhood
enuresis
Depression
Contraindicated in acute post-MI period.
Initial: 75 mg (100 mg divided, inpatient; 25 mg to 50 mg
adolescents and elderly)
Usual: 50 mg to 150 mg* (doses >100 mg usually not needed for
elderly and adolescents)
Max: 200 mg* (300 mg* inpatients)
*Divide doses>100 mg
If given once daily, bedtime dosing preferred.
Enuresis, initial, 25 mg at bedtime; max, lesser of 50 mg (75 mg
if over 12 years old) or 2.5 mg/kg. Consider dividing dose (midafternoon and bedtime) for early evening bedwetters.
Depression
Usual: 75 mg (30 mg to 50 mg elderly and adolescent)
Contraindicated in acute post-MI period.
Max: 150 mg
For daily doses >100 mg , monitor plasma levels (target 50
ng/mL to 150 ng/mL).
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Antidepressants
NDRI
• NDRI: Norepinephrine Dopamine Reuptake
Inhibitor
• Bupropion (Wellbutrin, Zyban)
– Increase levels of norepinephrine and dopamine
– Dopamine plays a major role in reward-motivated
behavior
Drug
FDA-Approved
Indication
Anxiety
Dry mouth
Irritability
Restlessness
Shortness of breath
Difficulty sleeping
Headache
Decreased appetite
Constipation
• Increased risk of
seizures
• Zyban is used for
tobacco cessation
Antidepressants
• SARI: Serotonin-2 antagonist/serotonin
reuptake inhibitor
– Block serotonin receptors and inhibit the
reuptake
– Results in increased levels of serotonin
Comments
Depression
Initial: 100 mg twice daily
Contraindicated in patients with seizure
Usual: 100 mg three times daily
risk. Heed dosing instructions to minimize
Max: 150 mg three times daily (75 mg risk of seizures.
once daily, severe cirrhosis)
Allow at least six hours between doses.
Bupropion hydrochloride
sustained release and
extended-release
(Wellbutrin SR, Wellbutrin
XL, Zyban, Forfivo XL)
Depression (Wellbutrin
XL, Wellbutrin SR,
Forfivo XL), seasonal
affective disorder
(Wellbutrin XL),
smoking cessation
(Zyban)
Wellbutrin XL:
Initial: 150 mg
Usual: 300 mg
Max: 450 mg
NDRI
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•
Usual Adult Dose
Bupropion (Wellbutrin)
Bupropion hydrobromide
extended-release tablet
(Aplenzin)
Wellbutrin SR:
Initial: 150 mg
Usual: 150 mg twice daily
Max: 200 mg twice daily
Zyban:
Initial: 150 mg
Usual: 150 mg twice daily
Max: 150 mg twice daily
Depression, seasonal Initial: 174 mg
affective disorder
Usual: 348 mg
Max: 522 mg
Contraindicated in patients with seizure
risk. Heed dosing instructions to minimize
risk of seizures.
Allow >8 hours between successive
doses of Zyban or Wellbutrin SR, and at
least 24 hours between successive doses
of Wellbutrin XL.
Max dose 150 mg every other day in
severe cirrhosis (or 100 mg once
daily, Wellbutrin SR).
Forfivo XL only for up-titration from
bupropion 300 mg/day.
Contraindicated in patients with seizure
risk.
Dose in severe hepatic impairment: 174
mg every other day.
SARI
• Trazodone (Desyrel)
• Nefazodone (Serzone)
• Vilazodone (Viibryd) – similar, but only a
partial agonist
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Drug
SARI
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FDA-Approved Indication
Trazodone (generics,
Oleptro)
Depression
Initial: 150 mg in divided doses
Vilazodone (Viibryd)
Depression
Initial: 10 mg
Usual: 40 mg
Max: 40 mg
• Nefazodone has
limited use due to risk
of liver failure and
death
Sedation
Headache
Dizziness
Weight changes
Tremor
Diarrhea
Nausea
Vomiting
Usual Adult Dose
Nefazodone
(Serzone)
Depression
Comments
Has been associated with
priapism.
Max: 400 mg (600 mg inpatient) Oleptro: Bedtime dosing
in divided doses
preferred.
Oleptro:
Initial: 150 mg
Max: 375 mg
Relatively high rate of
gastrointestinal side effects.
Use patient starter kit to aid
titration.
Initial: 100mg twice a day;
increase by 100-200mg a day
once a week
Max: 600mg
Antidepressants
Start at 50mg twice a day in
elderly patients.
Taper to discontinue
Contraindicated in hepatic
disease
NaSSA
• Mirtazapine (Remeron)
• NaSSA: Noradrenergic/Specific
Serotonergic Agent
– By blocking adrenergic receptors, these
drugs enhance the adrenergic and
serotonergic neurotransmission involved
in mood regulation
NaSSA
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•
•
•
•
•
•
Sedation
Dry mouth
Increased appetite
Weight gain
Dizziness
Increased triglycerides
Abnormal dreams
• Confusion
• Increased liver
enzymes
Drug
FDA-Approved Usual Adult
Indication
Dose
Comments
Mirtazapine
(Remeron,
Remeron
SolTab)
Depression
Best taken at bedtime due to
sedation
Initial: 15 mg
Max: 45 mg
Also available as oral
disintegrating tablets – do not
crush or chew
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Antidepressants
MAOI
•
•
•
•
• MAOI: Monoamine Oxidase
Inhibitors
– Monoamine oxidase is involved in
removing norepinephrine, serotonin, and
dopamine from the brain
– MAOIs prevent this removal, increasing
the levels available in the brain
MAOI
Tranylcypromine (Parnate)
Phenelzine (Nardil)
Selegiline (Emsam)
Isocarboxazid (Marplan)
Drug
FDA-Approved
Indication
Usual Adult Dose
Comments
Phenelzine (Nardil)
Depression
Initial: 15mg TID
Start at 7.5mg TID in elderly patients
Usual: 60-90mg TID or QID
Taper gradually to stop
Max: 90mg per day
• Typically reserved for
last line use due to drugfood interactions
resulting in dangerously
high blood pressure
• Significant drug
interactions
• Dry mouth
• Nausea
•
•
•
•
•
•
•
Diarrhea
Constipation
Headache
Drowsiness
Insomnia
Dizziness
Contraindicated in
hepatic disease
Tranylcypromine (Parnate)
Depression
Initial: 10mg TID for 2 weeks
Increase by 10mg per day every 1 to 3
weeks
Max: 60mg per day
Taper gradually to stop
Isocarboxazid (Marplan)
Depression
Initial: 10mg BID
Increase by 10mg per day every 2 to 4
days
Usual: 20-60mg BID to QID
Taper gradually to stop
Max: 60mg per day
Contraindicated in severe renal disease
Selegiline transdermal
(Emsam)
Depression
Initial: 6mg/24 hour patch daily
Skin irritation possible
Max: 12mg/24 hour patch daily
May increase by 3mg/24 hour patch every
2 weeks
Do not cut patches
Taper gradually to stop
Antipsychotics
Antipsychotics
• Used to treat both
schizophrenia and
bipolar disorder
• Aripiprazole,
olanzapine, quetiapine
approved for add-on
therapy for depression
• Others are used for
several different offlabel use
• Exact mechanism of
action is unknown
• Dopamine antagonists
– reduce dopaminergic
neurotransmission
First Generation (Typical)
Second & Third Generation
(Atypical)
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Prochlorperazine (Compazine)
Haloperidol (Haldol)
Thiothixene (Navane)
Pimozide (Orap)
Fluphenazine (Prolixin)
Loxapine (Loxitane)
Thioridazine (Mellaril)
Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Trifluoperazine (Stelazine)
Aripiprazole (Abilify)
Clozapine (Clozaril)
Iloperidone (Fanapt)
Ziprasidone (Geodon)
Paliperidone (Invega)
Risperidone (Riperdal)
Asenapine (Saphris)
Quetiapine (Seroquel)
Olanzapine (Zyprexa)
Lurasidone (Latuda)
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First Generation (Typical)
Antipsychotics
First Generation (Typical)
Antipsychotics
• Increased risk of extrapyramidal symptoms
(EPS)
–
–
–
–
•
•
•
•
•
•
Dystonia
Akathisia
Parkinsonism
Tardive dyskinesia
Drug
FDAApproved
Indication
Prochlorperazine
(Compazine)
Schizophrenia
Usual Adult Dose
Haloperidol
(Haldol)
Psychosis
Comments
First Generation (Typical)
Antipsychotics
Usual: 5 to 10mg every 6 to 8 hours
May increase by 5 to 10mg every 2 to 3 days
Max: 150mg per day
Discontinue if unexplained decrease in WBC
Oral
Initial: 0.5 to 2mg BID to TID for moderate symptoms; 3 to
5mg BID to TID for severe symptoms
Use lowest effective dose
Taper dose gradually to stop
Max: 100mg per day
If converting from oral greater than 100mg to IM injection,
give balance in 3 to 7 days
Dry mouth
Muscle stiffness
Muscle cramping
Tremors
Weight gain
Neuroleptic malignant syndrome (NMS)
Drug
FDAApproved
Indication
Usual Adult Dose
Comments
Thioridazine
(Mellaril)
Refractory
schizophrenia
Initial: 50 to 100mg TID
Discontinue if ANC <1000;
consider discontinuation if
unexplained decreases in WBC
Usual: 200 to 800mg per day divided BID to QID
Max: 800mg per day
Chlorpromazine
(Thorazine)
Psychosis
Mild to moderate symptoms
Initial: 10 to 25mg TID; increase by 20 to 50mg per day after 1 to 2 days, then every
3 to 4 days
Usual: 200 to 400mg divided TID to QID
Max: 1000mg per day
IM Injection - monthly
Initial: 10 to 20x the oral dose
Psychosis
Initial: 2mg TID for mild to moderate symptoms; 5mg BID
for severe symptoms
Discontinue if ANC <1000; consider discontinuation if
unexplained decrease in WBC
Usual: 2 to 5mg BID to TID
Severe symptoms (hospitalized)
Initial: 25mg IM x1 dose, may repeat with 25 to 50mg in 1 hour; increase IM dose
gradually over several days until symptoms controlled then switch to oral
Usual: 200 to 800mg per day divided TID to QID
Max: 400mg IM every 4 hours; 2000mg oral per day
Max: 60mg in 24 hours
Fluphenazine
(Prolixin)
Psychosis
Oral
Initial: 1 to 2.5mg daily divided every 6 to 8 hours
Usual: 2.5 to 10mg daily divided every 6 to 8 hours
Start low and titrate slowly in elderly
Discontinue if ANC <1000; consider discontinuation if
unexplained decreases in WBC
Perphenazine
(Trilafon)
Schizophrenia
Max: 40mg per day
IM Injection every 3 to 6 weeks
Initial: 1.25x oral daily dose or 12.5 to 25mg
Usual: 12.5 to 100mg IM every 3 to 6 weeks
Trifluoperazine
(Stelazine)
Max: 100mg per dose
Loxapine
(Loxitane)
Psychosis
Initial: 10mg BID, titrate over 7 to 10 days
Usual: 60 to 100mg daily divided BID to QID
Psychosis
Anxiety
Severely disturbed patients may require starting doses of
50mg per day in divided doses
Discontinue if ANC <1000; consider discontinuation if
unexplained decreases in WBC
Initial: 4 to 8mg TID
Use lower start doses in elderly
Usual: 8 to 16mg BID to QID
Use lowest, effective dose
Max: 64mg per day
Discontinue if ANC <1000;
consider discontinuation if
unexplained decreases in WBC
Psychosis
Initial: 1 to 2mg BID
Usual: 2 to 5mg BID
Max: 40mg per day
Discontinue if ANC <1000;
consider discontinuation if
unexplained decreases in WBC
Anxiety
Usual: 1 to 2mg BID
Max: 6mg per day for 12 weeks
Max: 250mg daily
Second & Third Generation
(Atypical)
• Less likely to cause EPS
• Clozapine may be the most effective
atypical antipsychotic, but its use is limited
due to risk of agranulocytosis and extensive
monitoring
• Black box warnings for increased mortality
risk in dementia-related psychosis
Discontinue if ANC <1000;
consider discontinuation if
unexplained decreases in WBC
Severe symptoms (non-hospitalized)
Initial: 25mg IM x1 dose, may repeat in 1 hour, then 25 to 50mg oral TID; may
increase by 25 to 50mg per day after 1 to 2 days then every 3 to 4 days
Usual: 200 to 600mg divided TID to QID
Max: 1000mg per day
Max: 450mg per month
Thiothixene
(Navane)
Start lower/titrate slower in
elderly patients
Second & Third Generation
(Atypical)
•
•
•
•
•
•
•
Sedation
Orthostatic hypotension
Weight gain
Hyperglycemia/ risk of developing diabetes
Lipid abnormalities
Cardiac effects (QT prolongation)
Drug interactions
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Drug
FDA-Approved
Indication
Usual Adult Dose
Comments
Aripiprazole
(Abilify)
Schizophrenia
Periodically reassess need for treatment
Bipolar
S (Oral): 10 to 15mg daily; Max 30mg daily
(IM): 400mg IM every 4 weeks; 300mg in poor
metabolizers
Depression (adjunct)
B (Oral): 15mg daily; Max 30mg daily
Clozapine
Also available as orally disintegrating
tablets
D (Oral): 2 to 5mg daily; Max 15mg daily
• Patient, prescriber, and pharmacy all must
be registered with a clozapine registry prior to
dispensing
• Requires monitoring of labs and reporting to
the registry (WBC and ANC)
–
–
–
–
Baseline
Weekly for 6 months
Every 2 weeks for 6 months
Every 4 weeks thereafter IF results are normal
Drug
FDA-Approved
Indication
Usual Adult Dose
Comments
Risperidone
(Riperdal)
Schizophrenia
S: Oral: 1 to 4mg daily divided up to BID; Max 16mg per
day
B: Oral: 2 to 3mg daily; Max 6mg per day
Renal and hepatic impairment adjustment
necessary
Periodically reassess need for treatment
Bipolar
S: IM: 25mg IM every 2 weeks: Max 50mg IM every 2
weeks
B: IM: 25mg IM every 2 weeks; Max 50mg IM every 2
weeks
Asenapine
(Saphris)
Quetiapine
(Seroquel)
See previous monitoring requirements
Re-titrate from 12.5mg daily if treatment is
interrupted for more than 2 days, taper over 1
to 2 weeks to discontinue
Iloperidone (Fanapt)
Schizophrenia
Initial: 1mg BID x1 day, then 2mg BID x1 day,
then increase by 2mg BID until target dose
Usual: 6 to 12mg BID
Max: 24mg daily
Periodically reassess need for treatment
Ziprasidone
(Geodon)
Schizophrenia
S: 20mg BID; Max 80mg BID
Periodically reassess need for treatment
Bipolar
B: 40 to 80mg BID: Max 80mg BID
Take with food
No supplementation needed with
hemodialysis
Paliperidone
(Invega)
Schizophrenia
Schizoaffective
disorder (SAD)
S: Oral: 6mg daily; Max 12mg daily
SAD: Oral: 6mg daily; Max 12mg daily
Titrate oral doses no more than 3md/day
every 4 to 5 days
S: IM: 234mg IM on day 1, 156mg on day 8,
117mg every 4 weeks; Max: 234mg every
month
SAD: IM: 234mg IM on day 1, 156mh on day 8,
78 to 234mg every 4 weeks
Adjust IM dose monthly as needed
See package insert for oral to IM or other
agent conversion and for missed injections
Drug
FDA-Approved
Indication
Usual Adult Dose
Comments
Olanzapine
(Zyprexa)
Schizophrenia
S:Oral: Initial: 5 to 10mg daily, may increase by 5mg per day weekly
Usual: 10mg daily
Max: 20mg daily
IM: Initial: Based on conversion from oral dose
Usual: Based on conversion from oral dose
Max: 300mg every 2 weeks or 405mg every 4 weeks
Start at 2.5 to 5mg daily in nonsmokers, elderly, debilitated, or
female patients or if at risk for low
blood pressure
Bipolar
Depression
(adjunct with
fluoxetine)
Periodically reassess need for
treatment
Available in combination with
fluoxetine (Symbyax)
B (acute depressive – with fluoxetine): Initial: 5mg daily
Usual: 5 to 12.5mg daily
Max: 20mg daily
Also available as oral
disintegrating tablets – do not
cut/crush/chew
D (with fluoxetine): Initial: 5mg daily
Usual: 5 to 20mg daily
Max: 20mg daily
No supplementation needed in
hemodialysis
Avoid use in severe hepatic dysfunction
Start with 25mg daily in elderly or debilitated
patients
A: 10mg IM x 1 dose; Max 30mg per day
May repeat dose 2 hours after initial dose x1, then 4 hours after 2nd
dose x1 as needed. May also give lower doses of 2.5 to 7.5mg, change
to oral version ASAP
Sublingual tablets – do not cut/crush/chew
Bipolar
B: 5 to 10mg BID
Periodically reassess need for treatment
Bipolar
Initial: 12.5mg daily/BID; increase by 25-50mg
daily
Usual: 150 to 300mg divided BID
Max: 900mg per day
B (manic/mixed): Initial: 10 to 15mg daily
Usual: 5 to 20mg daily
Max: 20mg daily
S: 5 to 10mg BID
S: Initial: 25mg BID up to 300-400mg daily
Usual: 150 to 750mg daily divided BID to TID
Max: 800mg per day
Treatment resistant
schizophrenia
When starting IM injection overlap with oral x3
weeks
Use 12.5mg IM injection if clinically warranted
Also available as sublingual tablets
Schizophrenia
Schizophrenia
Clozapine (Clozaril)
Agitation
(schizophrenia
or bipolar
associated)
Caution advised in hepatic
impairment
Dose adjustment necessary for hepatic impairment
Major
depressive
disorder
(adjunct)
B (manic): Initial: 50mg BID
Usual: 200 to 400mg BID
Max: 800mg per day
Periodically reassess need for treatment
Also available in XR tablets
B (acute depressive): Initial: 50mg QHS x1, 100mg
QHS x1, 200mg QHS x1, 300mg QHS
Usual: 300mg QHS
Max: 600mg per day(dose over 300mg rarely effective)
Bipolar
• Mood stabilizers are the cornerstone of
medication therapy
• Antipsychotics (alone or in combination
with mood stabilizers) are commonly used
• Several medications have limited use due to
side effects
• Consider required lab monitoring
Lurasidone
(Latuda)
Schizophrenia
Bipolar
S: Initial: 40mg daily
Usual: 40 to 160mg daily
Max: 160mg daily
Take with food
Requires both renal and hepatic
impairment dose adjustments
B (acute depressive): Initial: 20mg daily
Usual: 20 to 120mg daily
Max: 120mg daily
Can be used as monotherapy or as adjunct; doses over 80mg daily
rarely effective as monotherapy
Bipolar
• Lithium (Eskalith,
Lithobid)
• Lamotrigine (Lamictal,
Lamictal XR)
• Valproate (Depakene,
Depakote, Depakote ER,
Depakote DR, Depakote
Sprinkles, divalproex
sodium)
• Carbamazepine*
(Carbatrol, Equetro,
Tegretol, Tegretol XR)
• Oxcarbazepine*
(Trileptal)
• Gabapentin*
(Neurontin)
• Topiramate* (Topamax)
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Drug
Usual Adult Dose
Comments
Lithium
Bipolar/acute manic
IR: 1800mg daily, divided TID
Max: 2400mg daily
Available in immediate release and extended release forms – do not
crush/cut/chew ER form
Adjust dose every 4 to 7 days based on response and serum levels
Requires dose adjustment for renal impairment
Drug interactions: NSAIDs may increase lithium levels/risk of toxicity
Bipolar
• Lithium: exact mechanism unknown – alters
neuronal sodium transport
• Lamotrigine: also used for seizure
disorders; exact mechanism unknown –
inhibits voltage-dependent sodium channels
• Valproate: also used for seizure disorders;
exact mechanism unknown – increases
GABA effects
Drug
Usual Adult Dose
Comments
Valproate
Bipolar/acute manic
DR form
Initial: 250mg TID – may increase rapidly to lowest effective dose
Usual: 250 to 500mg TID
Max: 60mg/kg/day
Several products – they are NOT bioequivalent
ER form
Initial: 25mg/kg daily – may increase rapidly to lowest effective
dose
Usual: 25 to 60mg/kg daily
Max: 60mg/kg/day
Quetiapine
Bipolar I/manic
Initial: 50mg BID then increase by 100mg per day up to 200mg BID
by day 4, then increase by 200mg daily as needed
Usual: 200 to 400mg BID
Max: 800mg daily
Bipolar/acute depressive
Initial: 50mg QHS x1, 100mg QHS x1, 200mg QHS x1, 300mg
QHS
Usual: 300mg QHS
Max: 600mg per day – doses >300mg rarely more effective
ER: 1800mg daily, divided BID to TID
Max: 1800mg daily
IR: start with 600 to 900mg daily divided BID to TID, may increase by
300mg per day once a week until 1200mg per day, then may increase by
150 to 300mg per day once a week
Bipolar/maintenance
IR: 900 to 1200mg daily divided TID to QID
Max: 2400mg per day
ER: start with 900mg daily divided BID to TID, may increase by 300mg
per day once a week
ER: 900 to 1200mg daily divide BID to TID
Max: 1800mg per day
Lamotrigine
Bipolar I/maintenance
Monotherapy:
Initial: 25mg daily for 2 weeks, 50mg daily for 2
weeks, 100mg daily for 1 week
Usual: 200mg daily
Max: 200mg daily
Available in regular release and ER form
Rare, but serious rashes can occur
Taper doses to start and when discontinuing the drug
Requires dose adjustment for both renal and hepatic impairment
Valproate adjunct:
Initial: 25mg every other day for 2 weeks, 25mg daily
for 2 weeks, 50mg daily for 1 week
Usual: 100mg daily
Max: 100mg daily
Combo with carbamazepine/ phenytoin/
phenobarbital/ primidone:
Initial: 50mg daily for 2 weeks, 50mg BID for 2 weeks,
100mg BID for 1 week, 150mg BID for 1 week
Usual: 200mg BID
Max: 400mg per day
Combo with other agents:
Initial: 25mg daily for 2 weeks, 50mg daily for 2
weeks, 100mg daily for 1 week
Usual: 200mg daily
Max: 200mg daily
Drug
Usual Adult Dose
Comments
Olanzapine
Bipolar I/manic or mixed
Monotherapy
Initial: 10 to 15mg daily, adjust by 5mg per day as
needed
Usual: 5 to 20mg daily
Max: 20mg per day
For acute and maintenance: Start 5mg daily in non-smoker, elderly,
debilitated or female patients, or if hypotension risk
Periodically reassess need for treatment
Discontinue if ANC <1000; consider stopping if unexplained
decrease in WBC
Increase total daily dose by 8 to 20% if switching from DR
tablets to ER tablets
ER form: Do not cut/crush/chew
Contraindicated with significant hepatic impairment
Decrease start dose and titrate slowly in elderly patients
Adjust dose based on treatment response and serum levels
Take with food
Taper dose gradually to discontinue
IM injection available for acute agitation
Valproate or lithium adjunct
Initial: 10mg daily, adjust by 5mg per day as needed
Usual: 5 to 20mg daily
Max: 20mg per day
For acute depressive – use with fluoxetine
Bipolar I/acute depressive
Initial: 5mg QPM
Usual:5 to 12.5mg QPM
Max: 20mg per day
Adjust dose for hepatic impairment
For acute monotherapy or acute or maintenance lithium or
valproate adjunct: start 25mg QPM in elderly or debilitated
then increase by 25 to 50mg per day
Periodically reassess need for treatment
Discontinue if ANC <1000; consider stopping if unexplained
decrease in WBC
Lurasidone
Bipolar I/acute depressive
Initial: 20mg daily
Usual: 20 to 120mg daily
Max: 120mg daily
Give with food
Adjust dose for both renal and hepatic impairment
For monotherapy or valproate or lithium adjunct: doses >80mg per
day are rarely more effective as monotherapy
Aripiprazole
Bipolar I/manic, mixed
Monotherapy
Initial: 15mg daily
Usual: 15mg daily
Max: 30mg daily
Periodically reassess need for treatment
Discontinue if ANC <1000; consider stopping if unexplained
decrease in WBC
Anxiety
• Treatment includes both pharmacotherapy
and psychological therapy either alone or in
combination
• Treatment depends on several factors
• Start low and go slow no matter what agent
is being used in order to minimize side
effects
IM injection available for acute agitation
Valproate or lithium adjunct
Initial: 10 to 15mg daily
Usual: 15mg daily
Max: 30mg daily
Anxiety
•
•
•
•
•
•
•
SSRI
SNRI
Benzodiazepines
Buspirone
Antihistamines
Antipsychotics
Mood stabilizers
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Anxiety
Anxiety Disorder
First-Line Agents
Second-Line Agents
Generalized Anxiety
Disorder
SSRI or SNRI
Buspirone (Buspar; monotherapy or adjunct)
Slower onset and considered less effective than benzodiazepines, but no abuse
potential.
Bupropion XL 150 mg once daily, increased to 300 mg once daily
Hydroxyzine
• Benzodiazepines: enhance GABA effects
• Buspirone: exact mechanism unknown;
binds to serotonin and dopamine receptors
• Antihistamines: hydroxyzine has some
serotonergic activity
Imipramine10 to 25 mg once daily, titrated to 50 to 100 mg total daily dose
Avoid in patients at risk of suicide.
Pregabalin (Lyrica; monotherapy or adjunct)
Good evidence of efficacy compared to other second-line agents but side effects may
limit use (e.g., drowsiness, dizziness, weight gain, sexual dysfunction, abuse potential)
Efficacy may plateau at 300 to 450 mg total daily dose. Renal dose adjustment needed.
Onset as early as one week.
Quetiapine SR 150 mg once daily
Vortioxetine (Brintellix) (5 to 10 mg once daily effective in some studies)
Benzodiazepine
Panic Disorder
SSRI or venlafaxine
XR
Mirtazapine (Remeron) 7.5 mg once daily, increased to 15 to 30 mg after seven days.
Max dose 45 mg once daily.
TCAs
Benzodiazepine
Anxiety Disorder
First-Line Agents
Obsessive-Compulsive SSRI
Disorder
Second-Line Agents
Aripiprazole (adjunct) 10 mg once daily
Clomipramine
Insomnia
Mirtazapine
Quetiapine (adjunct) up to a total daily dose of 600 mg
• Difficulty falling asleep (sleep latency)
• Difficulty staying asleep (sleep
maintenance)
• May not feel rested (sleep quality)
• Transient (lasts days to weeks)
• Chronic (occurring nightly for greater than
six months)
Risperidone (adjunct) 2 to 4 mg total daily dose
Topiramate (adjunct)
May be more effective for compulsions than obsessions
Titrate over eight weeks from 25 mg daily to 400 mg max total daily dose.
Venlafaxine XR
Social Anxiety Disorder SSRI or venlafaxine
XR
Gabapentin 300 mg twice daily, titrated to 900 to 3600 mg total daily dose. Renal dose
adjustment needed.
Buspirone (adjunct)
Pregabalin
Efficacy may require 600 mg total daily dose. Renal dose adjustment needed.
Side effects may limit use (e.g., drowsiness, dizziness, weight gain, sexual dysfunction,
abuse potential).
Benzodiazepine
Post-Traumatic Stress
Disorder
SSRI or venlafaxine
XR
Mirtazapine
Eszopiclone (Lunesta; adjunct for sleep)
Olanzapine (adjunct; consider for hyperarousal and re-experiencing)
Risperidone (adjunct; consider for hyperarousal and re-experiencing)
Drug
Usual Adult Dose
Comments
Diphenhydramine
Avoid use
25 to 50mg
Poor evidence of efficacy
Anticholinergic side effects can occur (dry mouth, confusion, double vision, urinary retention,
wandering thoughts, visual disturbances, orthostatic hypotension)
Can become tolerant
Doxylamine
Avoid use
25mg
Poor evidence of efficacy
Anticholinergic side effects can occur
Doxepin (Silenor)
3 to 6mg
Approved for insomnia, to improve sleep maintenance
Increases sleep time by about 30 minutes
Dose-dependent risk of cardiovascular and anticholinergic side effects
Mirtazapine
(Remeron)
15mg
Off-label use
Increased risk of restless leg syndrome and periodic limb movement in sleep
Some evidence on reducing insomnia in depression, especially early in treatment
Less anticholinergic activity compared to doxepin
Trazodone
25 to 150mg
Off-label use
Limited efficacy data, especially in primary insomnia
Less anticholinergic activity compared to doxepin
Can cause priapism, even at low doses
Estazolam
0.5 to 2mg
Approved for insomnia, to improve sleep onset and maintenance
Drug interactions (contraindicated with azole antifungals)
Duration of 6 to 10 hours
Flurazepam
(Dalmane)
15 to 30mg
Approved for insomnia, to improve sleep onset and maintenance
Avoid use in the elderly (active metabolite with a long half-life)
Duration of 10 to 20 hours (potential for daytime drowsiness)
Nonprescription drugs
Insomnia
• Non-pharmacologic interventions
– Sleep hygiene
•
•
•
•
•
Nonprescription options
Benzodiazepines
Antidepressants
Sedative hypnotics: enhance GABA effects
Ramelteon: binds to melatonin receptors
Antidepressants
Benzodiazepines
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Drug
Usual Adult Dose
Comments
Drug
Usual Adult Dose
Comments
Lorazepam
(Ativan)
0.25 to 4mg
Off-label use
Generally used for secondary insomnia (due to anxiety)
Useful to improve sleep maintenance but not onset
Zolpidem (Ambien)
5 to 10mg
Approved for short-term treatment of insomnia to improve sleep onset
Lower risk of dependence than benzodiazepines
Delayed onset if taken with or immediately after a meal
Duration about 8 hours
Oxazepam
(Serax)
10 to 30mg
Off-label use
May be effective for sleep onset
Zolpidem CR
(Ambien CR)
6.25 to 12.5mg
Quazepam
(Doral)
7.5 to 15mg
Approved for insomnia, to improve sleep onset and maintenance
Avoid use in elderly due to long half-life
Duration of 10 to 20 hours (potential for daytime drowsiness)
Approved for insomnia to improve sleep onset and maintenance
Not limited to short-term use
No clinical advantage compared to the regular release
Delayed onset if taken with or immediately after a meal
Duration about 8 hours
Temazepam
(Restoril)
7.5 to 30mg
Approved for short-term treatment of insomnia to improve sleep onset and maintenance
Better choice for use in the elderly
Duration of 6 to 10 hours
Zolpidem
sublingual (Edluar)
5 to 10mg
Triazolam
(Halcion)
0.125 to 0.5mg
Approved for short-term treatment of insomnia
Concurrent use with 3A4 inhibitors such as azole antifungals and HIV protease inhibitors contraindicated
Avoid use in elderly due to risk of cognitive and behavioral side effects
Duration 2 to 5 hours
Approved for short-term treatment to improve sleep onset
Do not swallow whole or take with water – let dissolve under the tongue
Delayed onset if taken with or immediately after a meal
Duration about 8 hours
Zolpidem
sublingual
(Intermezzo)
1.75 (women)/
3.5mg(men)
Approved for insomnia associated with middle-of-the-night awakening
Taken only if there are at least 4 hours remaining before planned wake time
Do not swallow whole – let dissolve under the tongue
Delayed onset if taken with or immediately after a meal
Duration about 4 hours
Zolpidem oral
spray (Zolpimist)
5 to 10mg
Approved for short-term treatment of insomnia to improve sleep onset
Delayed onset if taken with or immediately after a meal
Duration about 8 hours
Zaleplon (Sonata)
5 to 20mg
Approved for short-term treatment of insomnia to improve sleep onset
Low-weight patients may respond to 5mg
No apparent withdrawal symptoms, daytime anxiety, sedation, or psychomotor impairment
Rebound insomnia more likely with higher doses
Lower risk of dependency compared to benzodiazepines
Delayed onset if taken with or immediately after a meal
Duration about 4 hours
Non-benzodiazepine Sedative Hypnotics
Eszopiclone
(Lunesta)
1 to 3mg
Ramelteon
(Rozerem)
8mg
Approved for insomnia to improve sleep onset and maintenance
Not limited to short-term use
Dose should not exceed 2mg in those taking strong 3A4 inhibitors
Delayed onset if taken with or immediately after a meal
Can cause metallic aftertaste
Duration about 8 hours
Approved for insomnia to improve sleep onset
Not limited to short-term use
Melatonin receptor agonist
Not a controlled substance
Contraindicated with fluvoxamine
Delayed onset if taken with or immediately after a meal
Duration about 8 hours
Learning Assessment
• TRUE/FALSE: Major Depressive Disorder
requires three or more major depressive
episodes.
• To be diagnosed with schizophrenia, how
long must symptoms be present?
• What are the three types of bipolar
disorder?
Learning Assessment
• Symptoms of _______ cluster around
excessive, irrational fear and dread.
• List the classes of drugs used to treat
depression, schizophrenia, bipolar, and
anxiety.
• TRUE/FALSE: The classes of medications
covered today generally work on
neurotransmitters in the brain.
Learning Assessment
• TRUE/FALSE: Citalopram 80mg daily is a
typical dose used to treat depression.
• _________ requires the patient, prescriber,
and pharmacy to be registered prior to
dispensing.
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References
1.
Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Mental Health
Findings, NSDUH Series H-47, HHS Publication No. (SMA) 13-4805. Rockville, MD: Substance Abuse and Mental Health Services
Administration, 2013.
2. Center for Substance Abuse Treatment. Managing Depressive Symptoms in Substance Abuse Clients During Early Recovery. Rockville (MD):
Substance Abuse and Mental Health Services Administration (US); 2008. (Treatment Improvement Protocol (TIP) Series, No. 48.) Appendix
D—DSM-IV-TR Mood Disorders. Available from: http://www.ncbi.nlm.nih.gov/books/NBK64063/.
3. American Psychiatric Association. Schizophrenia Fact Sheet. DSM5.org.
http://www.dsm5.org/Documents/Schizophrenia%20fact%20Sheet.pdf. Accessed January 2, 2015.
4. Substance Abuse and Meatal Health Services Administration. Mental Disorders. SAMHSA.gov. http://www.samhsa.gov/disorders/mental. Last
updated October 10, 2014. Accessed January 2, 2015.
5. National Institute of Mental Health. Anxiety Disorders. National Institutes of Health. http://www.nimh.nih.gov/health/topics/anxietydisorders/index.shtml. Accessed January 2, 2015.
6. Pharmacist’s Letter. Comparison of Antidepressants. Pharmacist’s Letter 2013; 29(12): 291206.
http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?rn=2&cs=NONMP&s=PL&pt=2&fpt=31&dd=291206&pb=PL&cat=4424
&segment=6383. Accessed January 3, 2015.
7. Epocrates Essentials Version 14.11.1. Last Updated January 3, 2015. Accessed January 3, 2015.
8. Pharmacist’s Letter. Pharmacotherapy of Bipolar Disorder in Adults. Pharmacist’s Letter. 2011; 27(6): 270603.
http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?rn=2&cs=NONMP&s=PL&pt=2&fpt=31&dd=270603&pb=PL&cat=4477
&segment=3370. Updated December 2014. Accessed January 3, 2015.
9. Pharmacist’s Letter. Pharmacotherapy of Anxiety Disorders. Pharmacist’s Letter. 2014: 30(10): 301006.
http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?nidchk=1&rn=2&cs=NONMP&s=PL&pt=2&fpt=56&dd=301006&pb=PL
&segment=7553. Accessed January 3, 2015.
10. Pharmacist’s Letter. Comparison of Insomnia Treatments. Pharmacist’s Letter 2014; 30(7): 300709.
http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?nidchk=1&rn=2&cs=NONMP&s=PL&pt=2&fpt=31&dd=300709&pb=PL
&cat=4477&segment=7197. Accessed January 3, 2014.
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