NR546 WEEK 7 TEST YOUR KNOWLEDGE: GERIATRIC & ADDICTION PSYCHOPHARMACOLOGY | 49 QUESTIONS & ANSWERS WITH EVIDENCE-BASED RATIONALES | FOCUSED REVIEW OF DELIRIUM, POLYPHARMACY, OPIOID USE DISORDER, & BENZODIAZEPINE TAPERING PROTOCOLS

Neurotransmitters involved in ADHD

Dopamine & norepinephrine

-affect symptoms of inattention & hyperactivity

Pharmacologic Treatment of Sleep Disorders:

Over-the-counter

Melatonin

Orexin receptor antagonists

Antidepressants

Z-drugs

Benzodiazepines

prevalence of ADHD in the United States population

6.1 million children are diagnosed with ADHD in the U.S.

-Boys more likely than girls (12.9% boys, 5.6% girls)

-1/3 have symptoms into adulthood

-6 in 10 children have at least one other mental, emotional, or behavioral disorder

-Comorbidities:

• Behavior/conduct problems

• Anxiety

• Depression

• Autism spectrum disorder

• Tourette syndrome

ADHD Symptoms:

Typically start before age 12, may begin to appear early as 3:

-Selective Attention

• lack of attention to detail

• careless mistakes

• not listening

• losing things

• diverting attention

• forgetfulness

-Lack of Sustained Attention

• poor problem solving

• difficulty completing tasks

• disorganization

• difficulty sustaining mental effort

-Impulsivity

• excessive talking

• blurting things out

• not waiting one's turn

• interrupting

-Hyperactivity

• fidgeting

• leaving one's seat

• running, climbing

• trouble playing quietly

*Symptoms related to attention usually develop 2-4 years after the emergence of hyperactive symptoms in childhood

ADHD lifespan considerations

-Symptoms change with age.

-Not only a childhood diagnosis

-Hyperactivity decreases markedly with age

-Primary Symptoms: inattention, restlessness, cognitive & emotional impulsivity, executive functioning deficits, and self-regulation

-Adults struggling with executive functioning difficulties and disorganization may experience occupational stress or anxiety.

neurobiological factors that contribute to ADHD: Genetics

Important role in development of ADHD.

-heritability of up to 88%

Other risk factors for ADHD include

-premature birth​

-low birth weight​

-maternal stress during pregnancy​

-prenatal substance exposure, including tobacco ​

-adverse childhood environmental ​

-psychosocial stress

-inconsistent parenting practices ​

neurobiological factors that contribute to ADHD: Neuroanatomy

Specific ADHD symptoms may arise from abnormalities within circuits in the prefrontal cortex (PFC)

-affect executive function

neurobiological factors that contribute to ADHD: Neural Networks

-symptoms often become noticeable at about 6-7 years of age, possibly due to abnormalities in the prefrontal cortex circuits or errors in the synaptic pruning process.

-Both selective and sustained attention are modulated by the corticostriatal-thalamocortical (CSTC) loop

• same loop that is associated with anxiety.

• ADHD is an alternative diagnosis to consider when clients present with anxiety symptoms. ​

neurobiological factors that contribute to ADHD: Neural Signaling

Norepinephrine (NE) and dopamine (DA) are associated with inefficient information processing in the prefrontal circuits.

-Rather than a deficiency, NE and DA are "out of tune."

• Agents that can increase the firing of both DA and NE may help increase prefrontal activity.

• ADHD medications commonly target both dopamine and norepinephrine.

• Stimulants, including stimulant medications, caffeine, and nicotine enhance DA release and arousal.

The PMHNP is considering treatment options for an 18-year-old man with ADHD who has a history of alcohol and marijuana abuse. Which of the following accurately explains the effects of different stimulant formulations on neuronal firing?

Pulsatile stimulation amplifies undesirable phasic DA and NE firing, which can lead to euphoria and abuse.

Rationale: Phasic firing is hypothetically associated with reward, feelings of euphoria, and abuse potential.​ Immediate-release stimulants rapidly increase DA and NE, especially increasing phasic firing, not tonic firing. Therefore, immediate-release stimulants have a higher risk of abuse. Extended-release formulations of stimulants lead to a gradual and sustained increase in NE and DA, enhancing tonic firing, which is hypothetically linked to the therapeutic effects of stimulants. They are amplifying tonic NE and DA signals, which are thought to be low in ADHD. The extended-release formulations occupy the NE transporter in the prefrontal cortex with slow enough onset and for long enough to enhance tonic NE and DA signaling; however, they do not block DA transporters fast or long enough in the nucleus accumbens to increase phasic signaling, thus reducing abuse potential.

A 27-year-old bartender was diagnosed with ADHD at age 10. She has been on and off medication since then, first on immediate-release methylphenidate, then on the methylphenidate patch. She experimented with illicit drugs during her late adolescence and is still a heavy drinker. After a few years of self-medication with alcohol and cigarettes, she is seeking medical attention again. You decide to put her on 80 mg/day of atomoxetine, one of the non-stimulant medications effective in ADHD.

Why does atomoxetine lack abuse potential?

It increases dopamine levels in the prefrontal cortex but not in the nucleus accumbens.

Rationale: The prefrontal cortex lacks high concentrations of dopamine transporters (DAT), so in this brain region, DA gets inactivated by norepinephrine transporters (NET). Therefore, inhibiting NET in the prefrontal cortex increases both DA and NE. As only a few NET exist in the nucleus accumbens, atomoxetine does not induce an increase in DA and NE in the nucleus accumbens, the reward center of the brain, thus atomoxetine does not have abuse potential.​

In the nucleus accumbens, there are only a few NE neurons and NE transporters. Inhibiting NET in the nucleus accumbens will not lead to an increase in NE or DA. Atomoxetine does not modulate serotonin levels. The striatum and the anterior cingulate cortex are not brain areas involved in reward.

Chris is a 44-year-old client presenting with comorbid alcohol abuse, generalized anxiety, and ADHD. Which disorder should be treated first?

Alcohol abuse

Rationale: It is important to treat identified diagnoses in terms of the highest degree of impairment. Alcohol abuse should be treated prior to any mood and anxiety disorders, then any remaining ADHD symptoms can be treated.

Pharmacologic agents used to treat ADHD:

stimulants

-stimulate the release of NE and DA or boost the firing of associated neurons

• may help improve information processing

-effective for 70-80% of clients with ADHD

-first choice of medications for children

-schedule II controlled substances​

-no refills permitted​

non-stimulant medications

-selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex and enhancement of norepinephrine neurotransmission

-can help lower distractibility and improve attention, working memory, and impulsivity

-commonly used in cases in which a client does not respond to stimulant medications or where stimulants are contraindicated

-low risk of abuse or diversion​

-often prescribed for adults with ADHD

combination of stimulant and non-stimulant medications is sometimes used when ADHD includes argumentative or oppositional symptoms

Stimulant Medications

Methylphenidate

dexmethylphenidate (Focalin)

amphetamine (Adzenys)

dextroamphetamine (Adderall)

lisdexamfetamine (Vyvanse)

Methylphenidate

Low risk of adverse effects​

Available formulations:​

-Ritalin​

• available in immediate-release (IR) and extended-release (XR)​

• available in beads that may be sprinkled on food for children who cannot swallow pills ​

-Concerta

​• biphasic - combined immediate and delayed release in one medication​

-Daytrana​ ​

​• patch applied in the morning and removed after 9 hours

dexmethylphenidate (Focalin)

-Available in immediate release and extended release​

-More potent than Ritalin​

-High risk of adverse effects

amphetamine (Adzenys)

-It is available in an orally-disintegrating extended-release formula for children who cannot swallow pills. ​

-Avoid prescribing when an MAOI has been used within 14 days.

dextroamphetamine (Adderall)

-Available in immediate and extended-release formulations​

-Often dosed in AM (IR or XR) with a PM or PM PRN (IR) dose if med effects diminish prior to the end of school, study, or the workday​

-Most abused and diverted prescription stimulants

lisdexamfetamine (Vyvanse)

-Biologically inactive until metabolized by the body (Prodrug)​

-Less abuse and diversion potential than other stimulants​

-Higher-cost medication

ADHD Prescribing Pearls

-Before initiation of any stimulant, obtain thorough health history.

-Assess for a personal or family history of cardiac disease

• EKG is required if cardiac history is present in a first-degree relative

-BP, height, & weight should be monitored regularly during tx

-CNS stimulants may cause psychotic or manic symptoms in clients with no prior hx or may exacerbate behavior disturbance symptoms and thought disorders in clients with pre-existing psychosis

-Assess all clients for bipolar disorder before tx

-CNS stimulants may exacerbate comorbid anxiety & substance use disorders.

-Tx efficacy will be noted within the first week of tx

-Increased irritability and insomnia can be treated with a low dose of non-stimulant medication which will allow the client to fall asleep.

-Abrupt withdrawal after prolonged use can result in irritability and rebound symptoms

-Stimulants can cause or worsen tics; stimulants may unmask the presence of tics

-When switching stimulants, D/C the current med & start the new med at a starting dose the next day

-Stimulant meds available to treat ADHD are available as immediate-release or sustained-release formulations

-Short-acting medications are at higher risk for diversion. Careful monitoring is required. Occasional urine drug screens should be obtained to verify the presence of amphetamines and the absence of other substances of abuse.

ADHD Patient Education

-Common side effects include restlessness, irritability, anxiety, insomnia, stomachache, headaches, tics, and worsening of aggression symptoms.​

-Clients may note a worsening of symptoms, or "crash" when the medication wears off, especially with immediate-release (IR) medications.​

-Medications may cause appetite changes and subsequent weight loss.

• Take medication with breakfast to decrease anorexia.

Non-Stimulant Medications

noradrenergic (NRI)

-atomoxetine (Strattera)

α 2 agonists

-clonidine

-guanfacine

Norepinephrine Dopamine Reuptake Inhibitor​

-bupropion (Wellbutrin)

noradrenergic (NRI)

atomoxetine (Strattera)​

-drug of choice for adults with ADHD​

-no abuse potential

-​tolerated well when prescribed in twice daily dosing​-appropriate choice for comorbid substance abuse​

-may augment the effects of antidepressants and antianxiety medications

-​can be dosed at bedtime if fatigue is noted

-​unlikely to worsen tics ​

α 2 agonists

May be taken as monotherapy or with stimulant medications​

-clonidine

• enhances precortical function for better mental focus​

• appetite neutral​

• may help with sleep disturbances, administer at bedtime​

• adverse effects: sedation, brain fog​

• monitor of BP closely during initial titration​

• tapered to avoid rebound hypertension post discontinuation​

-guanfacine​

• may also be used for children with tics, sleep disturbances, or aggression

• ​tolerability and convenience enhanced by once-daily oral controlled-release formulation

• ​adverse effects: sedation, headache, decreased appetite

​• reduced side-effect profile comparable to clonidine

• ​bedtime administration to avoid daytime sedation

Norepinephrine Dopamine Reuptake Inhibitor​

bupropion (Wellbutrin) ​

-off-label use for ADHD in adults

-appropriate for clients with concurrent depression or tobacco abuse

Non-Stimulant Medication patient education

-Common side effects include nausea, vomiting, diarrhea, fatigue, mood swings, dizziness, worsening of symptoms, changes in heart rate (HR) and blood pressure (BP), sedation, and dry mouth.

-Most subside with continued use over several weeks.

-Insomnia may develop over time and can be significant.

ADHD and Comorbidities tx order:

1. alcohol/stimulant/substance abuse

2. mood disorders

3. anxiety disorders

4. ADHD

Children and adolescents

1. Nicotine dependence

2. ADHD

ADHD Lifespan Considerations: Pregnancy

Stimulants may cause fetal harm including increases in low birth weight and pregnancy.

ADHD Lifespan Considerations: Breastfeeding

Stimulants are not recommended while breastfeeding.

ADHD Lifespan Considerations: Children

-ADHD medications are not approved for children under 6.

-Consider short-acting medications for children who have significant appetite loss or are underweight; this may improve appetite for lunch and dinner.

Cora is an 11-year-old who presents to the clinic with her mom. Cora's teachers report that she has difficulty staying on task and is disruptive in class. She is argumentative and oppositional at times, will not stay in her seat, and is often impulsive. Her mom started noticing hyperactivity symptoms two years prior. The PMHNP decides to start her on 5mg methylphenidate IR in the morning. Within a few days, there is an improvement in Cora's symptoms; however, the medication seems to wear off within a few hours.

Which of the following changes would you make to Cora's initial prescription?

increase dose to 5 mg methylphenidate IR twice daily

Rationale: Methylphenidate's immediate release has a duration of action of 3-4 hours. Increasing the dose to twice daily is an appropriate first step. Consider a second dose after lunch if appetite is affected. A non-stimulant drug is not appropriate for this client.

Cora's mom reports that the new dose of medications seems to alleviate symptoms of ADHD, but Cora experiences irritability close to the time when her next dose is due. Cora's mom asks if there is something that can be done to help reduce the irritability. Which change would you make to Cora's prescription?

change dose to methylphenidate 10 mg ER once daily

Rationale: Cora's irritability may be due to the immediate release of methylphenidate wearing off prior to her next dose. Changing to a long-acting form may decrease irritability. Increasing the dose of methylphenidate IR, switching to a different stimulant medication, or adding guanfacine 1mg daily will not help decrease Cora's irritability.

After 3 months, Cora's mom reports that her irritability has decreased somewhat with the implementation of the extended-release methylphenidate, but her teacher notes that she remains argumentative and oppositional at times. Her appetite remains good, but she is having difficulty sleeping. Which of the following medication changes might you consider at this time for Cora?

add guanfacine 1mg daily

Rationale: While methylphenidate is somewhat effective for Cora, her irritability and ADHD may be better controlled by adding a non-stimulant medication, such as guanfacine, to her daily medication regimen. Guanfacine taken at bedtime may also help with sleep.

Disruption of healthy sleep is a significant cause of:

societal morbidity

lost productivity

reduced quality of life

Center in the brain that tells you to go to sleep

VLPO (Ventrolateral preoptic area)

-tells the 7 wakefulness areas of the brain to "shut off"

excitatory neurotransmitters that stimulate wakefulness:

acetylcholine

norepinephrine

histamine

serotonin

orexin

dopamine

sleep-promoting neurotransmitters:

Gamma aminobutyric acid (GABA)

melatonin

insomnia

dissatisfaction with either the quality or quantity of sleep associated with one or more of the following:

-Difficulty initiating sleep

-Difficulty maintaining sleep

-Early morning awakenings with the inability to go back to sleep

-Difficulty sleeping at least 3 times a week for 3 or more months

• ​increases with age, one-third of clients older than age 65 years have persistent insomnia

• frequently triggered by acute stress and resolves when the stress resolves

• coexisting medical conditions can cause

*can exacerbate the symptoms of most psychiatric diagnoses; considered a psychiatric "vital sign" requiring frequent assessment and symptomatic treatment when sleep problems are encountered

Sleep Hygiene

sleep hygiene measures should be explored prior to prescribing medications:

-Limit screen time

-Limit caffeine

-Limit nicotine

-Dark, cool room

-Reduce noise

Sleep Medications

-Over-the-Counter Sleep Aids

• antihistamines such as diphenhydramine (Benadryl)

• Valerian root

-Melatonin Agonist Medications

-ramelteon (Rozerem)

• prescription melatonin

-Orexin Receptor Antagonists​

• Suvorexant (Belsomra)

• Lemborexant (Dayvigo)

-Sedating Antidepressants​

• trazodone (Desyrel)

• amitriptyline (Elavil)

• mirtazapine (Remeron)

-Z-drugs (Sedative/hypnotic drugs) First-line agents for insomnia include:

• zolpidem (Ambien)

• zaleplon (Sonata)

• eszopiclone (Lunesta)

• PEARLS: potential for abuse/dependence, Drugs may increase suicidal ideations, Abrupt discontinuation can result in rebound insomnia and withdrawal symptoms

-Benzodiazepines (BZOs)

• not considered a first-line treatment due to the potential for misuse

• when first-line agents fail, benzodiazepines may be used with caution for insomnia

Sleep meds Lifespan Considerations: Pregnancy

-Consider the risk-benefit ratio.

-Avoid z-drugs when possible

• use them for the shortest duration possible.

Sleep meds Lifespan Considerations: Older Adult

2019 American Geriatric Society (AGS) Beers Criteria include the following recommendations: ​

-Consider nonpharmacologic strategies.​

-Avoid combining z-drugs with other central nervous system (CNS) medications to prevent falls.​

-Avoid using z-drugs or antihistamines in clients with dementia, cognitive impairment, or a history of falls. ​

-Consider melatonin as an alternative.

Scott is a 69-year-old with a history of major depressive disorder well controlled with sertraline 50 mg daily. He complains that he has a hard time falling asleep some nights and has been taking Benadryl 50 mg at bedtime to help him sleep. He complains of dry mouth and dry eyes the mornings after he takes Benadryl, and states sometimes he feels a little confused after waking. He wonders if he should continue taking Benadryl for sleep. What recommendations would you have for Scott?​

No

Rationale: Scott is experiencing mild adverse effects from Benadryl most likely due to the muscarinic antagonism which can cause anticholinergic effects. Scott should discontinue the use of this medication.​

Which of the following are other acceptable medication options for Scott? Select all that apply.

melatonin OTC

suvorexant (Belsomra)

limit caffeine intake to early in the day

Rationale: Other options for Scott include melatonin, suvorexant, and sleep hygiene including limiting caffeine intake. Zolpidem is not recommended for older adults. Amitriptyline may help induce sleep but would not be first-line since his MDD is controlled with sertraline. Amitriptyline is also a tricyclic antidepressant and is not well tolerated in the elderly due to its risks for falls. Exercising before bed does not increase sleep, is stimulating, and may further impact sleep. ​

A common cause of insomnia is ____________

restless legs syndrome (RLS)

restless legs syndrome (RLS)

typically occurs in the evening or at night

-causes uncomfortable uncontrollable urge to move the legs.

-may be idiopathic or associated with other conditions such as pregnancy, end-stage renal disease, fibromyalgia, iron deficiency, arthritis, or peripheral neuropathy

-Tx:

• Dopamine agonists​: pramipexole (Mirapex), ropinirole (Requip)​

• Iron

• Gabapentin/ pregabalin​ for severe or painful RLS

Jessica is a 28-year-old client with a diagnosis of generalized anxiety disorder. Her anxiety is well-controlled with escitalopram and therapy. She presents with new complaints of insomnia and states, "I have constant itching and need to move my legs while I am in bed."

Which of the following diagnostic tests should be completed next? Select all that apply.

caffeine intake

ferritin level

computerized tomography (CT) scan

pregnancy test

tyrosine intake

caffeine intake

ferritin level

pregnancy test

Rationale: Caffeine, alcohol, and nicotine may all increase the risk for RLS. Pregnancy and iron deficiency anemia may cause RLS. Foods high in tyrosine are not associated with RLS. A CT scan is not indicated for this client. ​

Jessica's lab work is within normal limits, and her pregnancy test is negative. She reports drinking two cups of coffee each morning and denies alcohol or nicotine use. Based on her assessment and diagnostic data, which of the following is the best medication choice to treat Jessica's RLS?

ropinirole

Rationale: Ropinirole is a first-line agent for RLS. Iron is not appropriate in a client unless serum ferritin indicates deficiency. Gabapentin is appropriate for RLS but is a second-line medication. Diazepam is not appropriate for this client.

Matching ADHD symptoms to circuits:

Problems with selective attention

-dorsal anterior cingulate cortex (dACC)

problems with sustained attention

-dorsolateral prefrontal cortex (DLPFC)

Hyperactivity

-prefrontal motor cortex

impulsivity

-orbital frontal cortex