I Got The Blues - Alaska ...

1/14/2019

I Got The Blues
HEIDI BRAINERD, RPH, MS. BCPP, BCPS
JENNIFER PANGALANGAN, PHARM D

Disclosure Statement

I do not have (nor does any immediate family member have) a vested interest in or affiliation
with any corporate organization offering financial support or grant monies for this continuing
education activity, or any affiliation with an organization whose philosophy could potentially bias
my presentation.

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Objectives – Pharmacy Technicians
1. Describe the expected length of SSRI therapy for an adult experiencing a second episode of
Major Depression

2. Define REMS

3. Lis three psychiatric medications that have an FDA mandated REMS

Objectives - Pharmacists
1. Describe the expected length of SSRI therapy for an adult experiencing a second episode of
Major Depression

2. List three medications that are pharmacologically classified as a monoamine oxidase inhibitor

3. Discuss approaches for evaluating pediatric prescriptions for antidepressants which are not
FDA approved for this population

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Pre Test
1. True or False? Pharmacy Personal do not need to provide patients on Vivitrol with the REMS
information about severe injection site reactions.
2. RJ is a 24 year old male taking Levetiracetam for seizures. He presents with a 21 day history
of feeling sad most of the time, missing work 4 times because he slept through his alarm and
continued to sleep all day, feeling tired, sluggish, not able to concentrate and gaining 10 pounds
without trying to. RJs boss gave him a written reprimand which is the first step in documenting a
reason to terminate his employment at his company. Which is the best option given the above
information:
 a) Do nothing, RJ does not meet criteria for major depression.
 b) Start Bupropion – it’s activating and will pep him up.
 c) Start Sertraline for a major depressive episode, give RJ a 12 week prescription so he doesn’t miss any
    more work for appointments.
 d) Refer to PCP for medical evaluation.

Pre Test, continued
3. How long should pharmacotherapy be continued after a third episode of major depression?
 a)    4-9 months after symptoms stabilize.
 b)    12 months after symptoms stabilize.
 c)    Discontinue as soon as symptoms are reduced 75%
 d)    Indefinitely, possibly life-long.

4. Which of the following best represents an acceptable starting dose of SSRI in an 80 year old
patient with normal renal and hepatic function and no drug interactions?
  a)     Sertraline 12.5 mg daily
  b)     Citalopram 40mg daily
  c)     Fluoxetine 20mg daily
  d)     Paroxetine 20mg daily

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Board Certification in Psychiatric
Pharmacy (BCPP)
 Board of Pharmacy Specialties
   Certifies and recertifies 11 different specialties, including psychiatric pharmacy
     Currently, there are more than 1,000 Board Certified Psychiatric Pharmacists
   https://www.bpsweb.org/bps-specialties/psychiatric-pharmacy/

 College of Psychiatric and Neurologic Pharmacists (cpnp)
   Provides both the board certification and recertification study materials
   Annual meeting April 7-10, 2019 Salt Lake City, Utah
   https://cpnp.org/

Major Depressive Disorder (MDD)
Statistics in Alaska
 Alaska has one of the highest rates of suicide per capita in the country

 The rate of suicide in the United States was 12.57 suicides per 100,000 people in 2013
  By comparison, in 2014, Alaska’s rate was 22.3 suicides per 100,000 people

 More than 90% of people who die by suicide have depression or another diagnosable, treatable
 mental or substance abuse disorder, according to the American Association of Suicidology

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Diagnostic Criteria MDD
DSM-5
 Five of more of the following symptoms have been present during the same 2-week period and
 represent a change from previous functioning; at least one of the symptoms is (1) depressed
 mood or (2) loss of interest or pleasure  Excludes symptoms clearly attributable to another
 medical condition.
     1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (feels sad,
        empty, hopeless) or observation made by others (appears tearful). (In children and adolescents can
        be irritable mood).
     2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every
        day (as indicated by either subjective account or observation).
     3. Significant weight loss when not dieting or weight gain (change of more than 5% of body weight in
        one month), or decrease or increase in appetite nearly every day (In children, consider failure to make
        expected weight gain).

Diagnostic Criteria MDD
DSM-5, continued
4.     Insomnia, or hypersomnia nearly every day.
5.     Psychomotor agitation or retardation nearly every day (observable by others, not merely
       subjective feelings or restlessness or being slowed down).
6.     Fatigue or loss of energy nearly every day.
7.     Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional)
       nearly every day (not merely self-reproach or guilt about being sick.)
8.     Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by
       subjective account or as observed by others).
9.     Recurrent thoughts of death (not fear of dying), recurrent suicidal ideation without a specific
       plan, or a suicide attempt or a specific plan for committing suicide.

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Diagnostic Criteria MDD
DSM-5, continued
 The symptoms cause clinically significant distress or impairment in social, occupational or other
 important areas of functioning.
 The episode is not attributable to the physiological effects of a substance or another medical
 condition.
 The occurrence of the major depressive episode is not better explained by schizoaffective
 disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and
 unspecified schizophrenia spectrum and other psychotic disorders.
 There has never been a manic episode of hypomanic episode.

Classifications of Major Depressive
Disorder
 Severity of Episode – determined by the number and severity of diagnostic criteria met and the
 degree of functional impairment
   Mild episodes- 5-6 depressive symptoms and minimal functional impairment
   Severe episodes – nearly all symptoms present and significant functional impairment
 Presence of Psychotic Features
   Episode characterized by delusions or hallucinations (usually auditory)
   Psychotic features are either mood-congruent or mood incongruent
   Mood incongruent features indicate worse prognosis
 In Remission
   Absence of significant symptoms for at least 2 months
   Partial remission defined as either continued presence of some symptoms but either full criteria not met OR
    duration is less than 2 months
 Chronic - full criteria for a major depressive episode met for a minimum of 2 years

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Descriptive Specifiers for MDD
With Anxious Features                                             With Mood-Incongruent Psychotic
                                                                    Features
With Mixed Features
                                                                   With Catatonia
With Melancholic Features
                                                                   With Peripartum onset
With Atypical Features
                                                                   With Seasonal Pattern (recurrent
With Mood- Congruent Psychotic                                     episode only)
 Features

Recording the Diagnosis
Terms are listed in the following order
   Major Depressive Disorder
    Single or recurrent episode
    Severity/psychotic/remission specifiers
    As many of the specifiers that apply to the current episode

   Why is this important to know?
    Helps guide treatment and length of therapy

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Signs and Symptoms of Depression
SIGECAPS
    Sleep disturbances
    Interest (loss of)
    Guilt (excessive)
    Energy (changes in)
    Concentration(impaired)
    Appetite changes
    Psychomotor agitation or retardation
    Suicidal ideations or actions

 Vague complaints with no identifiable medical cause

Rating Scales for MDD
Practice Pearl – The rater should pick one and use it consistently. The pharmacist does not need
to be the rater, does need to be able to interpret and clinically correlate data
 Hamilton Depression Rating Scale (HAM-D) – Gold Standard for clinical research
 Montgomery-Asberg Depression Rating Scale (MADRS)
 Geriatric Depression Scale (GDS)
 Children’s Depression Rating Scale-Revised (CDRS-R)
 Guidelines for Adolescent Preventive Services (GAPS) questionnaire
 Pediatric Symptom Checklist (PSC)

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Reporting personal MDD diagnosis to the
Alaska Board of Pharmacy
 All pharmacists and pharmacy techs must answer the following professional fitness question at
 time of initial licensure and all subsequent renewal:
                              “Have you experienced or been treated for
                        bipolar disorder, schizophrenia, paranoia, depression,
                            (except for situational or reactive depression),
                       psychotic disorder, or other mental or physical disability?

  A “yes” answer to this question requires a fit to practice letter from the licensee/applicant’s primary
   care physician. The fit to practice does not have to disclose specific medications; only the status of the
   condition and how it affects the ability to safely provide services

Clinical Course of Major Depressive
Disorder
 First episode may occur at any age (average onset late 20s)
 No one size fits all description, symptoms may develop suddenly or over time
 Median time to recover with adequate treatment is 20 weeks
 Untreated episodes can last over 6 months
 Risk of Recurrence
  1 prior episode, 50 % will experience another episode
  2 prior episodes, 70 % will experience another episode
  3 or more prior episodes- at least 90% of people will experience another episode

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Suicide Risk
 The possibility of suicidal behavior exists at all times during major depressive episodes
 The most consistently described risk factor is a past history of suicide attempts or threats but
 most completed suicides are NOT preceded by unsuccessful attempts.
   Risk factors for completed suicide: male, single or living along, prominent feelings of hopelessness.
   Presence of borderline personality disorder markedly increases risk for future suicide attempts.

Suicide Risk Factors: IS PATH WARM?
 Ideation
 Substance Abuse
 Purposelessness
 Anxiety
 Trapped (feelings of no way out)
 Hopelessness
 Withdrawal
 Anger
 Recklessness
 Mood changes (dramatic)

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Resources for Mental Health Crisis
Intervention
 Pharmacy staff are NOT expected to provide crisis intervention counseling unless specially
 training- stay within your scope of training.
 Pharmacy staff ARE advised to have the contact information for emergency health recourses
 available to provide people.
http://www.muni.org/departments/health/phip/documents/community%20resource%20list%2
 05%2023%2018.pdf
http://www.suicide.org/hotlines/alaska-suicide-hotlines.html
http://www.alaska211.org/Search.aspx

Treatment Guidelines for Major
Depressive Disorder
https://cpnp.org/guideline/external/depression (lists the major guidelines with links)

Baseline evaluation:
Obtain the baseline info needed to make a plan which includes but is not limited to: family,
medical, social, psychiatric history, previous hospitalizations, previous suicide attempts, previous
treatments and response to each, PE and labs to r/o medical causes of depression, interview to
identify detailed list of target symptoms and goals of therapy and make a safety plan for
appropriate interventions if the patient develops suicidal ideation or behaviors.

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Non-Pharmacologic Treatment
Options available in Alaska
 Psychotherapy including Cognitive Behavior Therapy and Interpersonal Therapy.
 Transcranial Magnetic Stimulation – magnetic coils stimulate regions of the brain involved in
 mood.
 Electroconvulsive Therapy
 Bright Light Therapy (first-line treatment for MDD with seasonal pattern)
  Expose to 30 minutes of artificial light (2500-10000lux) when waking up each morning, activates retinal
   cells that connect to the hypothalamus.

Phases of MDD Pharmacologic
Treatment
 Acute Phase (antidepressant therapy is started and response is monitored)
 Continuation Phase (significant improvement in symptoms or full remission)
  Antidepressant treatment should continue at the same dose as the acute phase for additional 4-9
   months.
  Relapse risk without treatment 20-85%

 Maintenance Phase (recommended for chronic depressive symptoms or with history of three
 of more MDD episodes)
  Duration is indefinite, may be lifelong

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General Approach:
No one size fits all answer!
 Baseline eval, medical, family, psychiatric history. Review complete med list including OTC,
 herbal and illicit substances. Perform baseline labs to r/o other causes of depression, r/o other
 psychiatric disorders (bipolar disorder), make a plan to address target symptoms, goals of
 therapy and a safety plan for development of suicidal thoughts.
 Initial treatment can be with medications, psychotherapy or a combination of both.
 First line therapy SSRI, SNRI, Bupropion or Mirtazapine

Assessment of Antidepressant Pharmacotherapy
During Acute Phase: Weeks 1-4

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Assessment of Antidepressant Pharmacotherapy
During Acute Phase: Weeks 4-8

Choosing pharmacologic agent for acute
phase of MDD treatment
 Factors to Consider:
    Prior response (prior family response if applicable)
    Patient preference (tolerability and side effect profile)
    Dosing parameters
    Co-morbidities/organ system function
    Potential drug/drug and drug/disease interactions
    Cost (insurance coverage)

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Pharmacologic Treatment of MDD
 Selective Serotonin Reuptake Inhibitors (SSRIS) - first line work horse
 Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) - alternative first line
 Bupropion
 Mirtazapine
 Monoamine Oxidase Inhibitors
 Nefazodone/Trazodone
 Vilazodone
 Vortioxetine

Selective Serotonin Reuptake Inhibitors
(SSRI)
 Fluoxetine
   Starting 20mg/day, Usual 20-60mg/day
   Very long half-life (50 hours), caution in elderly
   Drug interactions: moderate inhibitor 2C19 (increased bleeding risk with warfarin), potent inhibitor 2D6
 Citalopram
   Starting 20mg/day, Usual 20-60mg/day
   Dose dependent QT prolongation (don’t exceed 40mg daily)
   Drug Interactions: 2D6 weak- moderate inhibitor, caution with concomitant medications solely metabolized by
    2D6 (metoprolol, desipramine) **azithromycin QT prolongation**
   Contraindications: Use with Pimozide or other agents that may prolong QT interval
 Escitalopram
   Starting 10mg/day, Usual 10-20mg/day
   Drug Interactions: 2D6 weak-moderate inhibitor

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Selective Serotonin Reuptake Inhibitors
(SSRI)
 Sertraline
   Starting 25-50mg/day, Usual 50-200mg/day
   Drug interactions: weak-moderate inhibitor of 2D6
   Increased absorption with food

Paroxetine
   Starting 12.5-20mg/day, Usual 20-75mg/day
   Drug interactions: potent inhibitor of 2D6
   Clinically significant risk of withdrawal syndrome with abrupt withdrawal – concern in rural areas with
    delays in mail delivery, pregnancy caution in first trimester for septal wall defects)

Selective Serotonin Norepinephrine
Reuptake Inhibitors (SNRI)
 Venlafaxine
   Starting 37.5mg/day, Usual 75-375 mg/day
   Drug interactions: weak inhibitor 2D6, substrate 2D6 (increased concentrations with paroxetine, fluoxetine, bupropion)
   Causes sedation (take at night) , diaphoresis (dose reduction), GI upset take with food, sexual dysfunction (switch to non-
    serotonergic agent (bupropion), switch to agent with serotonin 2A receptor antagonism (mirtazapine) or use PDE5 inhibitor.
 Desvenlafaxine
   Starting & Usual 50mg/day
   Drug interactions: minor substrate of CYP3A4, induces 3A4 (weak)
   Causes dizziness, insomnia, diaphoresis, nausea, dry mouth
 Duloxetine
   Starting 60mg/day, Usual 60-120mg/day
   Weak-moderate inhibitor of CYP2D6 (increases TCA and other 2D6 substrates), Substrate of 2D6, increased concentrations
    with 2D6 inhibitors (paroxetine, fluoxetine, bupropion), increased risk of bleeding with NSAIDS, antiplatelet and
    anticoagulants
   Causes dizziness (take at night) or insomnia(take in the morning), GI NV (take with food & at night), sexual disfunction (may
    switch or augment or use PDE5 inhibitor)

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Dopamine Norepinephrine Reuptake
Inhibitor
 Bupropion
    Starting 150mg/day, Usual 300-450mg/day
    Causes Dry mouth, sweating, nervousness, tremor, and a dose dependent increased risk for seizures
    Drug interactions: metabolized by CYP2B6
    Lower risk of sexual dysfunction than other antidepressants
    Contraindications: seizure disorder, bulimia or anorexia, abrupt discontinuation of alcohol or sedatives,
     use of MAOI therapy, including linezolid, within 14 days

Serotonin Modulators
 Trazodone
  Starting 150mg/day, Usual 150-600mg/day
  MOA: weak inhibition of 5-HT and NE reuptake, weak alpha-1 antagonist, serotonin 5HT2 antagonist,
   histamine antagonist
  Causes orthostatic hypotension (move slowly when changing position), Nausea (take with food),
   headache, dizziness and somnolence (dose at night), risk of priapism
  Contraindicated with use of MAOI, including Linezolid, within 14 days

Nefazodone
  Starting 50mg/day, Usual 150-300mg/day

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Norepinephrine-Serotonin Modulator
 Mirtazapine
  Starting 15mg/day, Usual 15-45mg/day
  MOA: Increases the synaptic concentration of serotonin and norepinephrine through presynaptic alpha-
   2 antagonism. Serotonin 5 HT2 and 5 HT3 receptor antagonist
  Causes sedation (take at bedtime), increased appetite and weight gain, hypertriglyceridemia, dry mouth
  Contraindicated use of a monoamine oxidase inhibitor (MAOI), including Linezolid, within 14 days

Tricyclic Antidepressants (TCA)
 MOA: inhibit presynaptic 5-HT and NE reuptake by inhibition of the 5-HT and NE transporters in
 the neurons of the CNS, increases 5-HT and NE in the respective synaptic clefts
Major Side Effects: weight gain, sedation (take at bedtime), mania (rare, stop and evaluate for
 bipolar disorder), anticholinergic supportively manage blurred vision, drug mouth, constipation,
 stop and change agent for cognitive impairment, delirium, cardiotoxicity (V tach, heart block is
 primary manifestation of OD), orthostatic hypotension (slowly change positions), tachycardia
 (change agent)
Contraindications: use of MAOI therapy, including Linezolid, within 14 days, recent myocardial
 infarction
MANY drug interactions!

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TCAs, continued.
 Amitriptyline
   Starting 25-50mg/day, Usual 100-300mg/day

 Nortriptyline
   Starting 25mg/day, Usual 50-200mg/day
   Active metabolite of amitriptyline

         T : tonic-clonic seizures upon withdrawal
         C : cardiac problems such as QT interval prolongation
         A : anti-cholinergic effects

Monoamine Oxidase Inhibitors (MAOI)
 MOA: potent, irreversible inhibitor of monoamine oxidase (MAO). Through blockade of this
 enzyme levels of norepinephrine, serotonin, and dopamine are increased in the synapse
   This enzyme lives in the brain, but also in the liver and the gut. In these other areas, MAO catalyzes
    oxidative deamination of drugs and potentially toxic substances such as tyramine. This leads to many
    drug and food interactions
   Tyramine rich foods in combo with a MAOI can cause Hypertensive Crisis
   Very high risk for drug interactions

 Linezolid is an oxazolidinone antibiotic that causes mild reversible nonselective inhibition of
 monoamine oxidase

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Augmentation Agents for Major
Depression
 Lithium
 Second Generation Antipsychotics

Response to Treatment
 Definition of response: 50% reduction in symptoms
  Nearly 2/3 of people don’t achieve remission with initial pharmacotherapy.

 Possible reasons for non-response:
 Comorbid disorders including substance abuse
 Inadequate dose or duration of medication
 Incorrect diagnosis
 Non-adherence to treatment (potentially from adverse effects)
 Unaddressed psychosocial stressors or psychologic issues.
 After these are addressed can consider options on next slide.

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Options for Partial Response or Non-
Response to treatment
 Switching
  Often considered if little or no symptoms improvement despite adequate dose for 4-8 weeks.
  No studies have demonstrated clear benefit of switching to an antidepressant within the same class or
   to an agent with a different mechanism of action.
  Tapering may be required to minimize withdrawal symptoms
    Cross Taper
      Dose of current antidepressant is gradually reduced while the new medication is initiated and dose titrated , usually over 1-2
       weeks
    Direct Switch
      Current antidepressant is stopped, new antidepressant started

Options for Partial Response or Non-
Response to Treatment, continued
 Augmentation
  Addition of second antidepressant or other medication with a different mechanism of action to existing
   antidepressant treatment regime (don’t augment an SSRI with an SNRI or vise versa)
  Considered if there is a partial response to treatment after 4-8 weeks.

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Length of Therapy
 No one size fits all; as a general guideline:

 Treatment should continue at the same dosage as required in the acute phase of an additional
 4 to nine months for first and second episodes of Major Depression then individual plan for
 continuation/discontinuation reassessed.

 Maintenance therapy is recommended with a history of 3 or more episodes of major
 depression indefinitely and may be life long.

Rural Alaska Treatment Considerations
 Rapid drug discontinuation can both unmask symptoms and lead to antidepressant
 discontinuation syndrome.
 People residing in rural areas should request refills of medications 14 days in advance
 (pharmacy can keep request until date insurance will reimburse)
 Paroxetine in particular is associated with significant withdrawal syndrome and should not be
 abruptly stopped.
 One strategy to manage delays is to cut appropriate tablets (not SR) into ½ or ¼ and take an
 increment of the dose to avoid abruptly running out. Fluoxetine capsules can be mixed with
 water and ½ or ¼ of the mixture taken (refrigerate remainder).
 Pharmacies consider keeping back up supplies of SSRIs in clinics both for initiation of treatment
 and as emergency medication supplies if replacement is delayed.

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FDA Risk Evaluation and Mitigation
Strategies (REMS)
In 2007, a new law that gave FDA many new authorities and responsibilities to enhance drug safety was
enacted. It's called the Food and Drug Administration Amendments Act- sometimes called "FDAAA"- and
one of its provisions gave FDA the authority to require a Risk Evaluation and Mitigation Strategy-(REMS)
from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks.
A REMs may be required by the FDA as part of the approval of a new product, or for an approved product
when new safety information arises. Essentially, a REMS is a safety strategy to manage a known or potential
serious risk associated with a medicine and to enable patients to have continued access to such medicines
by managing their safe use.
Since medicines are very different from each other, each REMS for each medicine is also different.
This presentation discussed REMS and how they are used to help ensure that the benefits of certain
medicines continue to outweigh their risks.

Why do pharmacy personal need to know about
REMS?
A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the U.S. Food and Drug
Administration (FDA) can require for certain medications with serious safety concerns to help ensure
the benefits of the medication outweigh its risks. REMS are designed to reinforce medication use
behaviors and actions that support the safe use of that medication. While all medications have
labeling that informs health care stakeholders about medication risks, only a few medications require
a REMS.
    REMS are designed to help reduce the occurrence and/or severity of certain serious risks, by
informing and/or supporting the execution of the safe use conditions described in the medication's
                             FDA-approved prescribing information.
REMS are not designed to mitigate all the adverse events of a medication, these are communicated to
health care providers in the medication’s prescribing information. Rather, REMS focus on preventing,
monitoring and/or managing a specific serious risk by informing, educating and/or reinforcing actions
to reduce the frequency and/or severity of the event.

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REMS for Pharmacy Staff - not business as usual!
Extra required steps for medications with REMS
https://www.fda.gov/Drugs/DrugSafety/REMS/ucm592662.htm
Requirements vary for individual REMS and practice settings but may include:
  Certification process for the pharmacy or healthcare setting (identify authorized representative)
  Staff training
  Verify safe use conditions (verifying required lab monitoring is done or patient or prescriber is enrolled
   in REMS)
  Counsel patients and or provide educational materials or a medication guide
  Medication guides are part of labeling, only a small number of medication guides are included as part or
   REMS
  The medication may have special ordering requirements such as obtained through a specific supplier

Current REMS – 76 entries
https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

Examples (not inclusive)
Buprenorphine Transmucosal Products for Opioid Dependence (BTOD)
Clozapine
Naltrexone
Opioid Analgesic REMS
Sodium Oxybate
Suboxone/Subutex

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Pregnancy
Patient Resources with links to other resources:
 Pregnancy exposure registries:
https://www.fda.gov/scienceresearch/specialtopics/womenshealthresearch/ucm134848.htm
CDC Pregnancy Resources: https://www.cdc.gov/pregnancy/index.html
https://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html
https://mothertobaby.org/fact-sheets/paroxetine-paxil-pregnancy/

Randomized, double blinded, placebo controlled trials are not conducted on pregnant women so
pregnancy registries are an important source of safety information. Pregnancy data is primarily
obtained from retrospective database studies or prospective cohort studies.

Antidepressants in Pregnancy
Risks are no clearly defined. Generally accepted principles:
 Persistent neonatal pulmonary hypertension of the newborn has been associated with SSRI use,
 especially during the third trimester, though data is inconclusive.
 Paroxetine is associated with septal wall defects and as the heart is being formed in the first
 trimester, paroxetine is NOT recommended for women trying to conceive or in the first trimester
 of pregnancy.
 Monoamine Oxidase Inhibitors demonstrated teratogenicity in animal studies
 St. John’s Work not recommended in pregnancy, conflicting evidence about increased uterine
 tonicity in animal studies.

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Antidepressants in pregnancy
 Antidepressant therapy is generally recommended for pregnancy patients with moderate to
 severe symptoms or if h/o recurrent, severe depression.
 Psychotherapy (CBT or IPT) is recommended for mild to moderate depression.
 Single medication at a higher dose if favored over polypharmacy, the lowest effective dose
 should be used.
 Medication selection is based on history of efficacy, prior antidepressant exposure during
 pregnancy and available safety information.
 Sertraline is generally considered the first-line agent in pregnancy, reassuring data for
 citalopram,, escitalopram, early exposure to paroxetine or fluoxetine may increase risk of some
 birth defects
 Consider tapering SSRI near delivery to minimize neonatal withdrawal and restart after birth to
 decrease postpartum depression.

Antidepressants in Lactation
Breastfeeding Resources:
https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm (contains link to other breastfeeding
resources)

 Risk of untreated post-partum depression/risk of infant exposure to breast milk.
 Based on small studies, Sertraline and Paroxetine at the lowest effective dose preferred
 because of non-detectable serum levels in infants.
 Newer antidepressants lack data, use only if demonstrated efficacy in past episodes is clear and
 no contraindications exist.
 Clinical utility of discarding breast milk obtained at Tmax has NOT BEEN ESTABLISHED

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Pediatrics
CDC Resources https://www.cdc.gov/childrensmentalhealth/depression.html

http://pediatrics.aappublications.org/content/pediatrics/141/3/e20174081.full.pdf

Research by the American Academy of Pediatrics shows that only 50% of adolescents with
depression are diagnosed before reaching adulthood. In primary care (PC), as many as 2 in 3
youth with depression are not identified by their PC providers and fail to receive any kind of
care.‍Even when diagnosed by PC providers, only half of these patients are treated appropriately.‍

Pharmacotherapy in Pediatrics
 Pharmacotherapy should be reserved for children and adolescents who meet criteria for
 moderate to severe major depression, persistent depressive disorder (dysthymia), or depressive
 symptoms with functional impairment, as well as nonresponse to psychotherapy.
 Same diagnostic criteria as adult patients, however, may use different rating scale
 Prior to starting antidepressants, clinicians should educate patients and families about
 depression, including its symptoms and available treatments. Clinicians should also discuss the
 benefits and side effects of pharmacotherapy, the United States Food and Drug Administration
 boxed warning about suicidal ideation and behavior, and risks of untreated depression.
 For children and adolescents, medications are generally started at approximately one-half the
 usual adult dose

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 Antidepressants in Pediatrics
 First line generally Fluoxetine
   Has the most consistent, high quality evidence
   FDA approved for MDD 8-18 years old
 Second line
   Sertraline, Escitalopram, or Citalopram
     Escitalopram FDA approved for MDD 12-17 years old
   Venlafaxine
     Comparable results to SSRIs

 Third Line
   Bupropion or Duloxetine
     Typically after failure of Fluoxetine, another SSRI, and venlafaxine

Mirtazapine found no advantage over placebo
Tricyclics are rarely used to treat pediatric depression due to side effects and lack of evidence. If used, obtain BP, pulse,
and EKG: at baseline, when therapeutic dose reached, when dose is changed

 Antidepressants in Pediatrics
 An adequate antidepressant trial in children and adolescents lasts 6 to 12 weeks, which
 includes the time to titrate from the starting dose to the minimum therapeutic dose, as well as 4
 to 6 weeks at the minimum therapeutic dose
 For depressed patients who improve but do not remit at the minimum therapeutic dose, a dose
 increase within the therapeutic range is indicated, provided the drug is tolerated. If
 improvement is insufficient after 4 weeks at the maximum therapeutic dose, switching
 medications is indicated
 Clinicians and families should monitor patients who are treated with pharmacotherapy by
 assessing symptoms, including suicidal and homicidal ideation and behavior, anxiety and panic
 attacks, agitation, irritability or hostility, impulsivity, akathisia (ie, restlessness and inability to sit
 down), and insomnia

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Antidepressants in Advanced Age
https://www.cdc.gov/aging/depression/index.html (contains link to other resources)

 Initiate at lower dose and titrate more slowly than young, healthy adults.
 Choice of antidepressant includes consideration of organ system function, minimizing drug
 interactions and side effects.
 Monotherapy preferred over polypharmacy , switching preferred to augmentation.
 SSRIs are treatment of choice with careful monitoring for DIADH and hyponatremia.

Post Test
1. True or False? Pharmacy Personal do not need to provide patients on Vivitrol with the REMS
information about severe injection site reactions.
2. RJ is a 24 year old male taking Levetiracetam for seizures. He presents with a 21 day history
of feeling sad most of the time, missing work 4 times because he slept through his alarm and
continued to sleep all day, feeling tired, sluggish, not able to concentrate and gaining 10 pounds
without trying to. RJs boss gave him a written reprimand which is the first step in documenting a
reason to terminate his employment at his company. Which is the best option given the above
information:
 a) Do nothing, RJ does not meet criteria for major depression.
 b) Start Bupropion – it’s activating and will pep him up.
 c) Start Sertraline for a major depressive episode, give RJ a 12 week prescription so he doesn’t miss any
    more work for appointments.
 d) Refer to PCP for medical evaluation.

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Post Test, continued
3. How long should pharmacotherapy be continued after a third episode of major depression?
 a)    4-9 months after symptoms stabilize.
 b)    12 months after symptoms stabilize.
 c)    Discontinue as soon as symptoms are reduced 75%
 d)    Indefinitely, possibly life-long.

4. Which of the following best represents an acceptable starting dose of SSRI in an 80 year old
patient with normal renal and hepatic function and no drug interactions?
  a)     Sertraline 12.5 mg daily
  b)     Citalopram 40mg daily
  c)     Fluoxetine 20mg daily
  d)     Paroxetine 20mg daily

References
American Psychiatric Association. (2013). Depressive Disorders. In Diagnostic and statistical manual of mental disorders (5th ed.).
Washington, DC: Author. https://doi.org/10.1176/appi.books.9780890425596.dsm04
https://cpnp.org/guideline/external/depression
https://www.fda.gov/aboutfda/transparency/basics/ucm325201.htm ACCESSED 1-8-2019
https://www.fda.gov/Drugs/DrugSafety/REMS/default.htm accessed 1-8-2019
https://www.fda.gov/Drugs/DrugSafety/REMS/ucm592662.htm accessed 1-8-2019
https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm accessed 1-8-2019
https://www.fda.gov/scienceresearch/specialtopics/womenshealthresearch/ucm134848.htm accessed 1-10-2019
https://www.cdc.gov/pregnancy/index.html accessed 1-10-2019
https://mothertobaby.org/fact-sheets/paroxetine-paxil-pregnancy/ accessed 1-10-2019
CPNP, summary , BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h3190 (Published 08 July 2015)Cite this as: BMJ 2015;351:h3190
https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm accessed 1-12-2019
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556848/

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References, cont.
https://www.cdc.gov/aging/depression/index.html accessed 1-12-2019
Zuckerbrot RA, Cheung A, Jensen PS, et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation,
Identification, Assessment, and Initial Management. Pediatrics. 2018;141(3):e20174081 accessed 1-10-19
http://pediatrics.aappublications.org/content/pediatrics/141/3/e20174081.full.pdf accessed 1-10-19
http://pediatrics.aappublications.org/content/pediatrics/141/3/e20174082.full.pdf accessed 1-10-19
Hetrick SE, McKenzie JE, Cox GR, et al. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane
Database Syst Rev 2012; 11:CD004851 accessed 1-10-19
http://pediatrics.aappublications.org/content/pediatrics/141/3/e20174082.full.pdf accessed 1-10-19
https://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-
Materials/Downloads/ad-pediatric-dosingchart11-14.pdf accessed 1-10-19
Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents
with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA 2008; 299:901. accessed 1-10-19
https://www.cdc.gov/aging/depression/index.html accessed 1-12-2019

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