Chapter 11, Case 1

Goal:To analyze and apply critical thinking skills in the pharmacokinetics and pharmacodynamics of psychopharmacological agents for patient treatment and health promotion while applying evidence-based research.

Chapter 11, Case 1Lotus is a 36-year-old Asian American female who recently started a new executive position with an advertising firm. While she loves her new job and the field of advertising, she admits that the new schedule is grueling and that she often doesn’t get home until quite late. She has noticed that it is difficult for her to relax before getting to bed and her mind often wanders to the many tasks she needs to complete when she returns to work in the morning. These “racing thoughts” result in significant initial insomnia, causing her to be alert for nearly an hour or more before she is able to fall asleep. When questioned about these symptoms, she claims that she has never seen a therapist before, doesn’t consider herself to be anxious or depressed, and has never had a problem with sleeping in the past. There are no worries of money or health-related issues, and she claims to enjoy her job and the people with whom she works. She even does not find these thoughts unpleasant, as she uses the time to plan her next day. She admits that they are just a bit intrusive and that she really needs to wind down and get more rest.Questions:

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Remember to answer these questions from your textbooks and clinical guidelines to create your evidence-based treatment plan. At all times, explain your answers.

YOUR RESPONSE MAY BE DIFFERENT THAN THE DIAGNOSIS AND TREATMENT FOUND IN YOUR TEXTBOOK.

Summarize the clinical case.

What is the DSM5 diagnosis?  Identify the rationale for your diagnosis using the DSM5 diagnostic criteria.

According to the clinical guidelines, which one pharmacological treatment is most appropriate to prescribe? Include the medication name, dose, frequency and rationale for this treatment.

According to the clinical guidelines, which one non-pharmacological treatment would you prescribe? (exclude psychotherapy modalities)  Include the risk and benefits of the chosen rationale for this treatment.

Include an assessment of medication’s appropriateness, cost, effectiveness, safety, and potential for patient adherence.

Use a local pharmacy to research the cost of the medication. Use great detail when answering questions 3-5.

Treatment of Anxiety
NUR 520
Psychopharmacology
Types of Anxiety Disorders in DSM V
(Diagnostic and Statistical Manual of Mental Disorders [DSM], 2013)
Generalized
Anxiety
Disorder
Panic Disorder
Separation
Anxiety
Disorder
Social Anxiety
Disorder
Selective
Mutism
Specific
Phobia
Agoraphobia
Neuroanatomy of Anxiety
➢ Anxiety and fear are regulated by
amygdala-center circuit
➢ Worry is regulated by cortico-striatothalamo-cortical circuit (CSTC)
➢ Overactivation of orbitofrontal cortex and
anterior cingulate cortex leads to fear
➢ Overactivation of dorsolateral prefrontal
cortex (DLPCF) and CSTC may lead to worry
and obsessions
➢These circuits may be involved in all anxiety
disorders.
Amygdala
Neurochemistry of Anxiety
➢
➢
➢
➢
➢
➢
➢
Noradrenergic System
Corticotropin-Releasing Hormone
Cortisol
Dopamine
Serotonin
Glutamate
GABA and benzodiazepine receptors
Amygdala
Neurobiology of Anxiety-GABA
Produced from the amino acid
gluatamate
Neurotransmitter involved in anxiety
disorders and effects of anxiolytic drugs
Regulatory role
Reduces activity of neurons in amygdala
and CSTC
Three main types of GABA receptors, A,
B, and C
Benzodiazepines
➢
Modulate excessive amygdala activity
➢
Some theories explain mechanism of action:
➢ Enhance phasic inhibitory actions at
postsynaptic GABA A receptor (less anxiety and
fear)
➢ Binding of alpha 2 subunits blocking excessive
release of glutamate (less anxiety)
➢ Binds to benzodiazepine receptors to enhance GABA
effects
➢ Schedule IV drugs (Controlled substance)
Uses for Benzodiazepines
Insomnia, anxiety, alcohol withdrawal states, muscle spasms due
to a variety of causes, including tetanus and cerebral spasticity,
epilepsy (clonazepam), anesthesia and sedation for endoscopies
and cardioversion.
The choice of drug as hypnotic and anxiolytic is determined by
pharmacokinetic properties.
Diazepam (Valium)
Formulation: tab 2mg, 5mg, 10mg
BenzodiazepineHypnotic
Long Acting
➢ FDA approved: Anxiety, sedation, muscle spasms,
alcohol withdrawal, seizure disorder, status epilepticus
➢ Off label use: sleep walking, serotonin syndrome
➢ Half-life: 30-100 hours
➢ Anxiety dosing: 2 – 4 mg po 2 times daily to 4 times daily
➢ Alcohol withdrawal dosing: 5mg po 3 times daily or 4
times daily prn
Black box warning: Avoid concomitant use with
opioids. Monitor patients for sedation. Avoid in
pregnancy and lactation
Beers Criteria: Avoid benzodiazepines (any type) for
treatment of insomnia, agitation, or delirium
Clonazepam (Klonopin)
Formulation: tab 0.5mg, 1mg, 2mg
• FDA approved: seizure disorder and panic disorder
BenzodiazepineHypnotic
Long Acting
• Off label use: anxiety disorders restless leg syndrome,
confusional arousals, sleep terrors
• Half life: 20-50 hours
• Starting dose: 0.25mg po bid, Max dose 4mg/daily
Black box warning: Avoid concomitant use with
opioids. Monitor patients for sedation. Avoid in
pregnancy and lactation
Beers Criteria: Avoid benzodiazepines (any type) for
treatment of insomnia, agitation, or delirium
Chlordiazepoxide (Librium)
Formulation: cap 5mg, 10mg, 25mg
➢ FDA approved: Anxiety, sedation, alcohol
withdrawal
BenzodiazepineHypnotic
Long Acting
➢ Half- life: 5-30 hours
➢ Starting dose 10 mg TID, Therapeutic Dose 15 to
100 mg
Black box warning: Avoid concomitant use with
opioids. Monitor patients for sedation. Avoid in
pregnancy and lactation
Beers Criteria: Avoid benzodiazepines (any type) for
treatment of insomnia, agitation, or delirium
Lorazepam (Ativan)
Formulation: 0.5mg, 1mg, 2mg
BenzodiazepineHypnotic
Intermediate
Acting
➢ FDA approved: Anxiety, insomnia, status
epilepticus,
➢ Off label use: chemo related nausea/vomiting,
preop sedation, neuroleptic malignant syndrome
➢ Half- life: 5-30 hours
➢ Starting dose 1 – 2 mg
➢ Therapeutic dose 1 – 10 mg
Black box warning: Avoid concomitant use with opioids. Monitor patients for
sedation. Avoid in pregnancy and lactation
Beers Criteria: Avoid benzodiazepines (any type) for treatment of insomnia,
agitation, or delirium
Alprazolam (Xanax)
Formulation: tab 0.25mg, 0.5mg, 1mg, 2mg
➢ FDA approved: Anxiety, panic disorder
BenzodiazepineHypnotic
Short Acting
➢ Half- life: 6-12 hours
➢ Starting dose 0.25 mg po bid, Therapeutic dose
0.25 to 10 mg
Black box warning: Avoid concomitant use with
opioids. Monitor patients for sedation.
Beers List: Avoid in elderly patients with delirium
Benzodiazepines-Side Effects
MOST COMMON SIDE EFFECTS:
Sedation and drowsiness, ataxia and memory impairment
OTHER SIDE EFFECTS:
Headache, giddiness, GI upset, skin rashes, reduced libido
Extrapyramidal reactions are rare. Paradoxical behavior effects and
perceptual disorders, e.g. hallucinations can occur.
Flumazenil reverses the sedative effects of benzodiazepines.
Benzodiazepines cross the placenta and can cause fetal cardiac
Arrhythmia and muscular hypotonia, suckling hypothermia, and
Respiratory depression in the newborn.
PMHNPs should Prescribe Benzodiazepines with Caution
Long-term use may lead to:
• Dependence
• Increased tolerance
• Rebound anxiety
• Rebound insomnia
• Seizures and tremors
• Withdrawal
Serotonin Agents
Antidepressants are leading agents to manage
anxiety disorders:
➢
Serotonin 1A receptors modulate antianxiety
effects of SSRIs
➢
SSRIs effects believed to be associated with
changes in functional or expression of
5HT1A receptors
➢
Reduction of anxiety and fear
FDA approved SSRIs and SNRIs for GAD
➢
Paroxetine and Escitalopram
➢
Venlafaxine and Duloxetine
Buspirone (Buspar)
Formulation: 5mg, 7.5mg, 10mg, 15mg, 30mg
NonBenzodiazepine
➢ Considered a generalized anxiolytic agent
➢ Buspirone is believed to have partial agonist
actions at pre and post synaptic 5HT 1A
➢ FDA approved: Anxiety
➢ Starting dose 5-10 mg TID
Therapeutic dose 30-60 mg
Treating
Anxiety
Disorders
Generalized Anxiety Disorder
➢ First-line of treatment includes: SSRIs,
SNRIs, Benzodiazepines, Buspar,
Gabapentin, Pregabalin, Trintellix, and
Viibryd
➢ Benzodiazepines may be used
in conjunction with SSRIs or SNRIs
➢ Longer time needed to achieve
remission of symptoms with SSRIs and
SNRIs
➢ Second-line of treatment may include
Mirtazapine, Trazodone, TCAs, and
Vilazodone
➢ Adjunctive medication approaches
include hypnotics, and atypical
antipsychotics
Social Anxiety Disorder
Treating
Anxiety
Disorders
➢
First-line of treatment includes: SSRIs,
SNRIs, Gabapentin, and Pregabalin
➢
Second-line treatment include: Beta
blockers: Propranolol (Inderal) Starting
dose 10-20 BID/TID, Therapeutic dose 20
to 320 mg, Benzodiazepines, and MAOIs
➢
Limited evidence about the use of
TCAs, Mirtazapine, Trazodone
➢
Adjunctive medication approaches
include Naltrexone, and Acamprosate
Post-traumatic Stress Disorder
➢ First-line of treatment includes: SSRIs and
SPARIs
➢FDA Approved: fluoxetine and venlafaxine
Treating
Anxiety
Disorders
➢ Second-line treatments (with
caution) includes: TCAs, MAOIs
, Gabapentin, and Benzodiazepines
➢ Adjunctive medication approaches includes:
Naltrexone, Acamprosate, Mirtazapine and,
beta blockers
➢Prazosin for nightmares
➢Propranolol for hypervigilance
Tricyclic
Antidepressants
Imipramine
Formulation: cap 75mg, 100mg, 125mg, 150mg
Formulation: tab 10mg, 25mg, 50mg
Off label use: generalized anxiety disorder
Inhibits norepinephrine and serotonin reuptake
• Anxiety dosing: 75mg-200mg daily, divided in 3 doses
• Side effects: urinary retention, pruritis, insomnia, weight
gain, impotence, gynecomastia, urinary frequency, impaired
coordination Adverse effects: blood dyscrasias, hypotension,
AV block, myocardial infarction, stroke, tardive
dyskinesia, glaucoma, serotonin syndrome
Black box warning: Increased suicidality in children to young
adults with major depressive disorder and psychiatric
disorders
Beers List: Avoid in elderly patients with delirium
Prazosin (Minipress)
Formulation: cap 1mg, 2mg 5mg
Alpha 1
Adrenergic
Antagonist
Used off label for nightmares in PTSD
Possibly reduces the corticotropin-releasing hormone
Reduces non-rapid eye movement in stage 1 of sleep
• Start at 1mg qhs X 3 nights
• Increased by 1mg q 3 nights until nightmares
improve or patient develops postural hypotension
• Some patients can gain benefit a 1mg and some
need >10mg, Max dose 15 mg
• Side effects: dizziness, drowsiness,
headache, urinary frequency, impotence
• Adverse effects: tachycardia, orthostatic
hypotension, palpitations
Clonidine (Catapres)
Formulation: tab 0.1mg, 0.2mg, 0.3 mg
Alpha 2
Adrenergic
Receptor
Agonist
Off label use: nightmares in PTSD, Tourette
syndrome
Reduces non-rapid eye movement sleep and
increases REM sleep (dose dependent)
• Dosing: 0.1 mg to 0.3 mg in divided doses
• Side effects: dizziness, somnolence,
headache, sexual dysfunction
• Adverse effects: rebound hypertension,
bradycardia, severe hypotension, AV block
➢ There are different types of anxiety
disorders
➢ Several class of medications are used to
manage anxiety disorders
Summary
➢ PMHNPs should follow prescribing
guidelines and recommendations
➢ Benzodiazepines are prescribed with
caution
➢ There are various treatment modalities for
anxiety disorders
➢ First-line, second-line, and adjunctive
treatment modalities should be followed
by PMHNPS
References
• American Psychiatric Association. (2013). Diagnostic and statistical
manual of mental disorders (5th ed.). Washington, DC.
• Preston, J., O’Neal, J., & Talaga, M. (2017). Handbook of clinical
psychopharmacology for therapists (8th ed.). Oakland, CA: New
Harbinger Publications, Inc
• Stahl, S. M., & Muntner, N. (2017). Stahl’s essential
psychopharmacology: Neuroscientific basis and practical applications
(4th ed.). Cambridge: Cambridge University Press.