Exam 3 Gutierrez (Bipolar and Sleep Disorders)

What are the symptoms of bipolar mania?

DIG FAST (Mania)

• ________

• ________ - poor judgement, spending sprees, reckless driving

• ________ - inflated self esteem

• Flight of ideas - ________

• Activities - ________

• ________ - decreased need

• ________ - pressured speech

Distractibility, Impulsivity, Grandiosity, racing thoughts, psychomotor agitation, Sleep, Talkativeness

• Bipolar 1: hit the ________, ________

• Bipolar 2: ________, no ________

• ________ use monotherapy

highs, hypermania, bipolar depression, hypomania, do not

 T/F: There are more women than men with bipolar disorders. (________)

False, equal amount

What is the average age of onset of bipolar disorders?

• Takes up to ________

10 years

What is the danger of a misdiagnosis of ADHD instead of bipolar disorder?

• Note the similarity with some sxs between bipolar mania and ADHD.

• Danger of misdiagnosis of ADHD instead of bipolar disorder is it can ________ symptoms → ________

  • Distractibility

  • Impulsivity 

  • Grandiosity

  • Flight of Ideas

  • Activity Increase

  • Sleep Deficit

  • Talkativeness

worsen BD, suicide

The symptoms experienced during bipolar depression and major depression are the same (D/A+SIGECAPS). What is the main difference with treatments?

• Major depression —> ________

• Bipolar disorder —> ________ + ________

antidepressants, mood stabilizers, atypical antipsychotics

What is your recommendation for a bipolar patient with manic symptoms on Prozac 20 mg QAM?

• Shouldn’t use an ________ for ________ patient

• ________

antidepressant, bipolar, stop the dose

What baseline labs are needed for lithium therapy? Why? 

• ________ and ________: to assess renal function; ________ eliminate by kidneys

• Urine specific gravity: lithium can ________ kidney’s ability to concentrate urine

• CBC with differential: lithium → leukocytosis

• Serum sodium: hyponatremia → ________ elimination of lithium

• T3, T4, TSH: R/O hyperthyroidism → ________; lithium → ________

Lithium - Optional Baseline Labs

• Electrocardiogram (EKG) (________ + ________):

  • For patients over __ y/o or with hx of cardiac problems

  • Lithium => ________ flattening => QRS widening (i.e., bradycardia)

• Pregnancy test:

  • For females of childbearing potential

  • Lithium => ________ risk of fetal cardiovascular malformation; 11x higher risk than women ________ lithium; absolute risk < 10%

  • Avoid use in ________

BUN, SCr, lithium, decrease, decreased, mania, hypothyroidism, Sodium, lithium, 40, T wave, increases, without, 1st trimester

What is the usual therapeutic lithium level range?

• ________ mEq/L

0.6-1.2

How many hours post-dose would you educate your patient on lithium to go get labs for their lithium levels? Why?

• ________ hours post-dose levels due to ________ lithium levels 

10-12, increased

What common DDIs can cause higher and possible toxic lithium levels?

• ________, ________, ________ restriction, ________, renal ________

Lithium + other Drugs:

• ________ (Non-steroidal anti-inflammatory drugs)

  • Most NSAIDs

  • Reduce lithium clearance

  • ________ and possibly sulindac appear to be exceptions

• ________

  • Reduce lithium clearance

  • Increase ________ concentrations

ACE inhibitors, NSAIDs, sodium, dehydration, impairment, NSAIDs, aspirin, thiazide diuretics, serum

What are the symptoms of lithium toxicity? What can be recommended for a patient with lithium toxicity?

• Coase ________, ________, persistent ________ + ________ – confusion, ataxia, slurred speech, lethargy

• Hold lithium dose for ________

Lithium - Toxic Sxs

• If > 1.5 mEq/L => coarse hand tremor, vomiting, persistent diarrhea + CNS toxicity - confusion, ataxia, slurred speech, lethargy. Tx - Hold lithium doses for 1 day, and reevaluate

• If > 2.0 mEq/L = profound ________, ________, ________, ________. Tx - 0.9% sodium chloride solution IV infusion or hemodialysis (as last resort)

  • Chronic exposure (days) to ________ toxic levels 2.0 mEq/L is more dangerous than acute exposure (hours) to ________ toxic levels 4.0 mEq/L

  • After treatment, lithium levels in the brain can still be ________ (d/t slow release from the brain). Watch for complete resolution of toxic sxs before restarting lithium

hand tremor, vommiting, diarrhea, CNS toxicity, 1 day, CNS depression, arrhythmias, seizures, coma, low, high, high

Lithium has a delay in onset of action (2-3 weeks). What medications are usually prescribed for acute mania before lithium’s onset of action?

Atypical Antipsychotics + Approved FDA Bipolar Indication

• ________ (asenapine) (S)

  • Acute treatment of manic or mixed episodes associated with ________Disorder; >__ years

• ________ (________) (L)

  • Depressive episode associated with ________ Disorder (________); Adults

• ________ (________) (Z)

  • ________ Disorder (Manic or Mixed Episodes (mono or adjunctive therapy); >__ years

  • Depressive episodes associated with BD I (with ________)

• ________ (________) (R)

  • ________; >__ years

• ________ (________) (S)

  • Seroquel XR

  • ________; >__ years

  • Bipolar disorder, depressive episodes

  • Maintenance tx of BD I as adjunct to Li or VPA

• ________ (________) (G)

  • ________ Disorder (acute mixed or manic and maintenance as adjunct to Li or VPA); Adults

• ________ (________) (A)

  • ________ Disorder (acute or maintenance); >__ years Agitation associated with bipolar mania; Adults

Saphris, Bipolar I, 9, Latuda, lurasidone, Bipolar I, bipolar depression, Zyprexa, olanzapine, Bipolar I, 13, fluoxetine, Risperdal, risperidone, bipolar mania, 12, seroquel, quetiapine, bipolar mania, 9, Geodon, Ziprasidone, Bipolar I, Abilify, aripiprazole, Bipolar I, 10

Which atypical antipsychotics are FDA-approved for bipolar depression?

Atypical Antipsychotic:

• ________ (Vraylar)

• Indication: ________, ________

• Dosage per Day: ___ mg/d (depression), ___ mg/d (mania)

• ________ (Latuda)

• Indication: ________, ________ (off-label)

• Dosage per Day: 20-120 mg/d with > 340 kcal meal; 40-80 mg range is typical

Varies with intensity of mixed features

• ________ combo (Symbyax)

• Indication: ________

• Dosage per Day: 6/25-12/50 mg/d; mean 7.4/39.3 mg/d

• ________

• Indication: ________

• Dosage per Day: 5-20 mg/d (mean 10-15 mg/d)

• ________ (Seroquel)

• Indication: ________, ________

• Dosage per Day: ___ mg/d (depression), ___ mg/d (mania)

Cariprazine, depression, mania/mixed, 1.5, 3, Lurasidone, depression, mixed, Olanzapine-Fluoxetine, depression, olanzapine monotherapy, mania/mixed, quetiapine, depression, mania/mixed, 300, 400-800

What indications is Caplyta® (lumaterperone) approved for? What are 2 common ADRs?

Caplyta (lumateperone) is Approved for Broad Range of ________ Patients with ________

(Indications: ________, ________ associated with bipolar I or II disorder)

• Quetiapine/Quetiapine XR → Bipolar ________ (w/Lithium or Valproate)

• Olanzapine/Fluoxetine → Bipolar ________

• Lurasidone → Bipolar ________ (w/Lithium or Valproate)

• Cariprazine → Bipolar ________

• The ________ and ________ treatment indicated for depressive episodes associated with Bipolar I and II Disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with ________ or ________

• Common ADRs → Somnolence/Sedation (________) and ________

adult, bipolar depression, schizophrenia, depressive episodes, 1+2 Monotherapy and Adjunctive, 1+2 Monotherapy, 1 Monotherapy and Adjunctive, 1 Monotherapy, 1st, only, lithium, valproate, sleepiness, dizziness/nausea

Patients with CrCl < ___ ml/min should not be on lithium therapy.

0.9

Explain the effects of a 2-gm sodium restriction diet for your patient on lithium. Explain the mechanism of action for this effect.

• More reabsorption of Na+ & Li+ → ________ concentration → increased ________ or ________

higher Li+, ADR, toxicity

Which anticonvulsants are prescribed for the treatment of bipolar disorder?

________

• FDA-Approved (2014), US and UK Guidelines (2005) → ________, ________, ________

________

• US Guidelines → ________, ________, ________

________

• FDA-Approved → ________

• US Guidelines → ________, ________, ________, ________

• UK Guidelines → Same as US guidelines BUT also ________

• ________

• FDA-Approved → ________

• US and UK Guidelines → ________, ________, ________

Carbamazepine, mania, mixed, maintenance, Oxcarbamazepine, mania, mixed, maintenance, Divalproex, mania, Mania, mixed, rapid cycling, maintenance, depression, Lamotrigine, maintenance, Depression, Rapid Cycling, Maintenance

What is the advantage of Depakote® vs. Depakene®? What is the problem with using antacids with Depakote®?

• Depakote – ________ release

• Depakene – ________ release formulation, ________ & ________

• Using antacids with Depakote® (divalproex sodium) —> minor to moderate ________ where the antacid may slightly ________ the absorption of valproic acid, potentially raising its ________ in the blood.

slower, faster, capsules, syrups, drug interaction, increase, concentration

What is the problem with using CBZ or VPA during pregnancy?

• Carries significant risks to the developing ________, with ________ (________) generally considered the most dangerous

Which of the following anticonvulsant mood stabilizers can cause neural tube defects? (Spina bifida - fetal spinal column did not close completely).

• ________ and ________

fetus, valproate, VPA, valproic acid, carbamazepine

You have a patient with a new Rx for carbamazepine (CBZ). She is also on oral contraceptives. What do you need to inform the patient and her provider?

• ________

Carbamazepine

“Lamotrigine is FDA-approved for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy.” Is lamotrigine effective for acute bipolar mania?

• ________, Drug of choice for ________

Yes, pregnancy

What is an important patient education point for patients starting on lamotrigine? Why?

• Report ________ → ________, start ________, go ________

rash, SJS, low, slow

What is the dosing precaution with the use of lamotrigine (Lamictal®) for patients on valproic acid (Depakene®) or divalproex sodium (Depakote®). Why?

• ________ lamotrigine

• Valproic acid ________ lamotrigine metabolism, leading to ________ clearance and ________ half-life, so lamotrigine must be started at a ________ dose and titrated ________ to avoid ________.

not eliminating, inhibits, decreased, increased, lower, slowly, toxicity

What is the best mood stabilizer for a pregnant patient with Bipolar 2 disorder?

Lamotrigine

Which antipsychotic(s) are FDA-approved for bipolar mania and depression?

Vraylar (Cariprazine) and Caplyta (lumateperone)

Which mood stabilizer is neuroprotective and being studied for Parkinson's and Alzheimer's disease?

Lithium

What is the recommendation for advanced sleep phase disorder associated with many geriatric people (e.g., asleep by 7pm and wake up at 3am)?

• Exposure to ________ later in the ________, ________ of melatonin.

sunlight, evening, delay secretion

What is the recommendation for delayed sleep phase disorder associated with many teenagers (e.g., not sleepy until 3 am and sleep till noon)?

• Gradually advancing the bedtime by ________ minutes nightly, morning ________ (bright light/sunlight), evening ________ supplements, and strict ________ (no screens at night).

15-30 minutes, light therapy, melatonin, sleep hygeine

REM rebound from d/c of alcohol or BZDs can cause what sleep disturbances?

Vivid nightmares

What is sleep apnea? What is the treatment of choice? Why is it important to avoid CNS depressants (including alcohol) for people with sleep apnea?

Sleep Apnea: A condition characterized by ________ of cessation of ________, lasting 20 to 30 seconds, terminated by a brief arousal from sleep during which the patient gasps for air and resumes breathing; there may be several hundreds of the “mini-arousals” during a single night

• For sleep apnea, if continuous ________ (________) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating ________. If ________ is used adjunctively with CPAP, the encouragement of and periodic assessment of CPAP compliance are necessary.

• Avoid ________!

• Avoid all ________ →inhibit the “mini-arousals”; can be potentially lethal

episodes, breathing, positive airway pressure, CPAP, modafinil, provigil, hypnotics, CNS depressants

What stages of sleep are considered restorative sleep (AKA delta sleep)? Explain why patients with sleep apnea are so tired in the daytime despite appearing to sleep for 7-8 hours?

• Stage _ (________)

• Never reach ________ → very ________ (________ CPAP machine)

3, N3, deep sleep, tired, without

Which hypnotic classes should be avoided for treatment of insomnia for the elderly? Why?

• In the elderly, avoid long-term use of ________ (b/c ________ SEs) and ________ (leading to accumulation in ________, cognitive and motor impairment). Use the lowest dose of ________.

OTC diphenhydramine/antihistamines, anticholinergic, long-acting BZDs, fat, Ambien

How does caffeine work to increase wakefulness? What is the half-life of caffeine?

• With Caffeine: Caffeine blocks ________ from the receptors that would ________ the body down and signals the ________ instead.

• Caffeine (t ½ = ____ hours)  → ________

adenosine, slow, release, 5-7, adenosine antagonist

What medications can cause insomnia?

• Drugs – antidepressants (________, ________), caffeine, alcohol rebound, ________, ________. OTCs → ________ 

bupropion, fluoxetine, psychostimulants, oral decongestants, nasal decongestants

What is narcolepsy and the treatment options?

Narcolepsy: A condition characterized by excessive ________ with irresistible attacks of sleep anytime during the day (sleeping 10-20 minutes; up to 1 hour if uninterrupted). Often preceding with episodes of ________ (brief loss of muscle tone, triggered by strong ________, that can result in ________ and possible injury to ________ and others)

• Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of ________ neurons in the ________

Treatments:

• __ minute ________

• Excessive daytime sleepiness usually treated with ________, ________ (________) and ________ (________)

daytime sleepiness, cataplexy, emotions, falls, self, orexin-producing, hypothalamus, 30, power naps, psychostimulants, Modafinil, provigil, armodafinil, Nuvigil

Which FDA-approved benzodiazepines hypnotics would be a better choice for patients with hepatic impairment?

LOT

Among the 3 Z-hypnotic agents (Ambien – zolpidem, Sonata – zaleplon, Lunesta – eszopiclone), which one is FDA-approved for long-term use? What is a common side effect of this Z-hypnotic agent?

• ________ (________) → FDA approved for ________ 

Common SEs

• HA, ________, dry mouth, nausea, dizziness,

Eszopiclone, Lunesta, 12 months, bitter taste

Name the 2 melatonin receptor agonist hypnotic agents that are FDA-approved for long- term use. Which one is FDA-approved for non-24 hour sleep wake disorder (e.g., blind people)?

• ________ (Rozerem) and ________ (Hetlioz). ________ (________) is a FDA-approved for blind people and non-24 hour sleep wake disorder

Ramelteon, Tasimelteon, Tasimelteon, Hetlioz

Which Z-hypnotic can be taken in the middle of the night provided they have 4 hours before time to wake up?

• ________ (________) has the shortest half-life.

Sonata, Zalepon

Patients taking the Z-hypnotics should not drink alcohol and grapefruit juice. Explain why?

• They all enhance ________-mediated ________ → ________ → ________, impaired ________, and risk of ________.

GABA, CNS depression, sedation, respiratory depression, coordination, overdose

Which class of hypnotics has the most reported CNS ADRs, such as sleep eating, walking, or driving?

Z-Hypnotics

Your patient asked if she could take 2 of the 8 mg ramelteon if she cannot stay asleep with this medication. What would you recommend?

• Max dose is ___ mg and talk to the prescriber to consider another medication. Do not ________ the dose.

8, double

Which is the most common hypnotic agent prescribed now that is used to be a sedating antidepressant? What is the most common side effect, other than sedation, associated with this agent?

• ________ (50-150 mg) → Most common SE: ________ (________ blocker)

Trazodone, orthostasis, alpha-1

Patient brings in a new Rx for Provigil 200 mg po q6pm. What is the most likely indication in this case?

• ________ Disorder (________). (Provigil dose is 200 mg given ________. For patients with ________ and ________, a single dose QAM. For patients with SWSD, take ________ to the start of their work shift.)

Shift work sleep, SWSD, once a day, narcolepsy, apnea, 1 hour prior

Why do you need to inform patients on Provigil (modanfinil) or Nuvigil (armodafanil) to report rashes?

Cause serious, life-threatening skin reactions, including:

• ________ (________)

• ________ necrolysis (________)

Stevens-Johnson Syndrome, SJS, Toxic Epidermal, TEN

Why is it important to taper temazepam 30 mg po qhs prn insomnia (used nightly for > 1 year) to zolpidem 10 mg po qhs prn insomnia?

• Takes ________ for onset of action. A __-day trial showed a positive difference over ________ in inducing sleep.

• To prevent severe ________ (seizures, anxiety, rebound insomnia) due to physical ________.

weeks, 28, placebo, withdrawal symptoms, dependence

What is the active ingredient in Unisom? In Advil PM for sleep? What are the common side effects?

• Unisom Active Ingredient → ________ (look at active ingredient)

  • Common SEs: ________ effects

• Advil PM Active Ingredient: ________ + ________

  • Common SEs: next-day ________, ________, ________, ________, and ________ vision

Doxylamine, anticholinergic, Ibuprofen, Diphenhydramine, drowsiness, dizziness, dry mouth, constipation, blurred

Comment on the dose of this Advil PM product with instructions to take 2 caplets QHS.

• __ mg Diphenhydramine. So taking _ caplets QHS → Ibuprofen ___ mg + Diphenhydramine ___ mg

• Within OTC dosing limits, BUT caution is advised in older adults or those with ________ disease, ________ risk, or concurrent ________.

76, 2, 400, 76, kidney, GI, CNS depressants

What is Silenor? Comment on Silenor’s dosing vs. its use in the past as an antidepressant.

• Silenor: ________ used in much ________ doses than its use as an ________ 

• Silenor is a _____-dose formulation of ________ used specifically for insomnia (sleep maintenance).

• Adults: __ mg po __ prn sleep. 

• Geriatrics: 3 mg/night prn sleep taken __ mins before bedtime

• At low doses (Silenor) → primarily blocks ________ receptors → promotes sleep with minimal anticholinergic effects

• At higher antidepressant doses → affects ________ & ________ + more ________ and ________ side effects

TCA, lower, antidepressant, low, Doxepin, 6, qhs, 30, H1 histamine, SE, NE, anticholinergic, cardiac

What are the potential DDIs associated with Provigil (modanfinil) or Nuvigil (armodafanil)?

• Potent CYP____ inducer → decrease CYP____ substrates’ ________ and ________ → ________ (statins) won’t be effective

3A4, 3A4, concentrations, efficacy, oral contraceptives

Your patient with Alzheimer’s disease was given Tylenol PM for sleep. Any potential problem?

• ________ → Worsens ________, ________, and increases ________ (worsens AD)

anticholinergic effects, confusion, cognition, fall risk

What is the mechanism of action of suvorexant (Belsomra), lemborexant (Dayvigo), daridorexant (Quiviviq)? What is the interaction with grapefruit juice? (orexin receptor antagonists)

• Metabolism via CYP________. 

• Efficacy can decrease with CYP________. 

• AVOID grapefruit juice with Belsomra, Dayvigo, and Quviviq because grapefruit inhibits CYP3A4 → increases drug levels → ↑ risk of excessive ________ and next-day ________.

3A4, 3A4 inducers, sedation, impairment

What is the max dose of Belsomra (suvorexant)? Why did FDA lowered the max dose by half before it was approved.

• Max Dose: __ mg

• FDA cut the max dose in half to reduce ________ and ________.

20, next-day drowsiness, driving impairment

What are the non-pharmacologic options for the treatment of insomnia?

• Cognitive behavioral therapy (________)

  • Helps change unrealistic beliefs about sleep

  • Sleep only as much as needed to feel refreshed and alert during the day

• ________ (Relaxation Response)

• ________ (YouTube, Calm App)

CBT, meditation, sleep hypnosis

Other than the FDA-approved hypnotics, name the 3 psychiatric drugs that are commonly used at lower doses off-label for insomnia. 

The 3 commonly used psychiatric drugs (off-label, low dose) for insomnia are:

• ________ (Desyrel)

• ________ (Remeron)

• ________ (Seroquel)

Trazodone, Mirtazapine, Quetiapine

How many hours of sleep is considered adequate for an adult? How many REM cycles are considered healthy per night?

7-8 hours and 4-6 REM cycles

REM sleep cycles every ___ minutes. Why is REM (rapid eye movement sleep) important?

90

What are the effects of lack of sleep (< 5 hours/night) on testosterone? Sleep deprivation can decrease testosterone levels to __ years their senior.

Testosterone is mostly produced during ________ (slow-wave) sleep.

Chronic sleep deprivation reduces total and free ________, affecting:

• Brain → increased ________ drive, improved ________, ________, ________ function

• Muscles → Muscle ________, increased ________ + ________

• Bones → Bone ________ maintenance

• Bone Marrow → ________ production

• Sex Organs: ________ production, ________ dysfunction, ________ growth

• Skin: ________ growth,

10, deep, testosterone, sex, mood, confidence, memory, growth, strength, endurance, mass density, RBC, sperm, erectile, prostate, hair/collagen

What are the effects of sleep deprivation on learning? What is the potential difference in testing results after staying up to study all night for an exam vs. those who slept 8 hours before the exam?

• Testing results: Had two groups, a group that was deprived of sleep, and one that got a normal amount of sleep.

  • 1. Sleep Deprived: ____% deficit of brain to make new memories with no significant hippocampus activity.

  • 2. Normal sleep: normal amounts of hippocampus activity; deep sleep and sleep spindles allow you to make memories.

40-50

Which part of the brain is a “memory inbox” and can shut down with lack of sleep?

Hippocampus

What are the effects of sleep “daylight saving time” shift? March decreases 1 hour of sleep! What can one do to decrease the March “Spring forward” sleep loss?

• Losing even 1 hour of sleep from DST can impair memory, mood, and CV health, highlighting how sensitive the body is to small circadian disruptions.

• ________ 1 hour sleep loss - Spring forward: 24% increase in ________ the following day. Fall back (gain 1 hour of sleep): 21% decrease.

• Also increases in ________, ________ rates!

March, heart attacks, auto accidents, suicide

How does lack of sleep affect your immune system? On the risks of cancer? Why?

• Decreases production of ________ → decrease ________

• ________ → type of lymphocyte in the immune system that rapidly identifies + destroys ________-infected cells and ________ cells. There is a 70% drop in NK cell activity with only __hours of sleep!

• Lack of sleep → Increases risk of ________ (bowel, prostate, breast)

• ________ shift work increases cancer risks

NK cells, immune health, NK cells, virus, tumor, 4, cancer, nighttime

What are the other negative effects of sleep deprivation?

• ________

• Higher levels of ________

• ________ risk

• ________

• Increased ________

• Increased ________, ________ cancer, and ________ disease risk

impaired condition, anxiety, stroke, weight gain, depression Sxs, diabetes, breast, heart

What is the effect of the lack of sleep on DNA gene activities? Which ones are upregulated and downregulated?

• No sleep → ________ → genes associated with production of ________, ________ responses, ________ diseases

• ________ → immune system genes

upregulations, tumors, inflammatory, CV, Downregulation

What is the best temperature for good sleep? Cooler or hotter?

• Cooler → need at least ___º F ____ in core temperature to fall asleep and stay asleep.

• __ºF(18º C)

2-3, drop, 65

What is the first-line treatment for insomnia for all age range?

• ________ → 1st line treatment for insomnia across all ages; focuses on behavioral and cognitive strategies rather than medications.

CBT-I

T/F: Melatonin is considered safe and effective for the treatment of insomnia. How many mg of hormonal melatonin is usually secreted per night?

• Melatonin is technically not the recommended treatment for ________ bc it regulates ________ (circadian rhythm) RATHER than acting as a ________.

• While effective for jet lag, it lacks the clinical evidence to outperform therapies like ________ for long-term sleep issues.

• Long-term use → more ________

False, chronic insomnia, sleep timing, sedative, CBT-I, prolactinemia

Your 15 yo patient is on fluoxetine 20 mg QDay for depression and anxiety for 2 months. He is doing well overall but complains about insomnia every night. He purchased diphenhydramine 50 mg and takes it every night to sleep. What are the current issues in this case?

• ________ insomnia in an adolescent.

  • Stimulating for some patients, especially adolescents, and can cause insomnia

• Unsafe self-treatment with ________.

  • In adolescents, anticholinergic side effects can include cognitive impairment, confusion, dry mouth, urinary retention.

• Lack of non-pharmacologic sleep strategies.

  • ________adapted for adolescents is first-line for chronic insomnia.

• Potential long-term side effects from nightly ________.

  • Medication ________

  • DDIs are minimal with ________, but caution with other sedating agents.

fluoxetine-induced, diphenhydramine, CBT-I, diphenhydramine, misuse, fluoxetine

A 12 yo is on fluvoxamine for OCD and is given melatonin 10 mg QHS for sleep. His parents read that melatonin is good for insomnia for their child with ASD. Any issues in this case?

• ________ (CYP___) dose (__ mg) for a child — potentially excessive.

• ________ + ________ → 20x more higher ________ levels

high melatonin, 1A2, 10, melatonin, fluvoxamine, melatonin concentration

Which 2 antidepressants are used off-label for insomnia? These should be avoided in patients with ________ disorder.

• ________ and ________ (Silenor)

• Bipolar mania → NO ________ (worsens mania), use ________ (2nd gen) + ________

Bipolar, Trazodone, Doxepin, antidepressants, mood stabilizers, hypnotics

Which anticonvulsant has been studied for restless leg syndrome and can be considered for RLS related insomnia?

Gabapentin

Which TCA is FDA-approved in low doses (3-6 mg) for insomnia? Is this medication still used for depression at high therapeutic doses (150-300 mg)?

______ (______)

• Approved at a low-dose for insomnia 

• ______: High-dose for depression: 150–300 mg/day, TCA (SNRI, more anticholinergic + cardiac effects).

Doxepin, Silenor, Yes

There are 5 FDA-approved benzodiazepine hypnotics. These are not usually considered first-line treatments for chronic insomnia. Why?

• ________, ________, ________, ________, and ________

Not first-line for chronic insomnia because:

• Risk of ________ + ________ with long-term use

• ________ + ________ insomnia after discontinuation

• Cognitive impairment, daytime sedation, fall risk (especially in older adults)

• Do NOT address underlying behavioral causes of insomnia (sleep hygiene, circadian issues)

Estazolam, Temazepam, Triazolam, Quazepam, Flurazepam, dependence, tolerance, W/d, rebound

The concentrations of which classes of hypnotics can be increased with CYP3A4 inhibitors?

• ALL ________

• ________: zolpidem (________), eszopiclone (________), zaleplon (________) — partially CYP___ metabolized

• ________: ________ (Belsomra), ________ (Dayvigo), ________ (Quviviq)

BZDs, Z-drugs, Ambien, Lunesta, Sonata, 3A4, Orexin receptor antagonists, suvorexant, lemborexant, daridorexant

What is the most common childhood neurodevelopmental disorders in the U.S.?

Attention-deficit/hyperactivity disorder

What is the most effective class of medications for the treatment of ADHD? Name the 2 main active medications in this class.

• ________ are either ________-based or ________-based medications.

Stimulants, methylphenidate, amphetamine

T/F: There is a higher prevalence of ADHD in males than females.

True

T/F: Majority of individuals with ADHD are treated with pharmacotherapy.

• Of the 7.1 million ever diagnosed, 92.6% (6.5 million) had current ADHD, and within that population 53.6% were taking ADHD medication currently and 44.4% received behavioral treatment for ADHD within the past year.

False

What are the common co-occurring conditions seen in children with ADHD?

• Almost 78% had a co-occurring condition (e.g., behavioral or conduct problems, anxiety, depression, learning disorders) → lots of ________ and ________

• KNOW: ________ (low doses at night) → non-________ → helps with agitation + aggression → FDA-approved for monotherapy and adjunct ________

• Mild ________ + ________ → ________ (________)

agitation, aggression, Clonidine, stimulant, therapy, ADHD, depression, Bupropion, Wellbutrin

Which neurotransmitters are involved in the etiology of ADHD? Are there excessive or deficiencies with these 2 NTs?

• ________ + ________ neurotransmitters

• Medications targeting these NTs are ________ pharmacotherapy.

Dopaminergic, adrenergic, 1st line

T/F: Children 16 yo or younger need more symptoms (> 6) for the dx of ADHD than for those 17 yo or older ((> 5). Why?

• As people get older, ADHD symptoms often become ________ in number, even though impairment may still be significant.

• Adults and older adolescents tend to develop ________ mechanisms and may show more ________ symptoms (e.g., internal restlessness instead of obvious hyperactivity).

True, fewer, coping, subtle

An individual’s ADHD categorization can change with age. Adult ADHD has less ________ symptoms.

hyperactivity

True or False: There must be at least 6 ADHD symptoms for 6 months for the dx of ADHD in a 12 yo boy. 

• Must appear in two or more settings (e.g., school, home, social settings, work); must interfere with or reduce the quality of functioning in these settings; and are not explained by another mental disorder.

True

If parent training in behavior management fails (< 6yo), what ADHD meds can be considered?

• In preschool-aged children (age 4-5) with ADHD, 1st line intervention is evidence-based ________ (PTBM), with or without behavioral classroom interventions. If these interventions are inadequate, ________ may be considered.

parent training in behavior management, methylphenidate

Name some commonly prescribed methylphenidate medications for the treatment of ADHD.

• ________ + ________ → ER and IR tablet formulations

• ________ → ONLY transdermal methylphenidate Patch (2 hrs to work)

• ________ → last 10-12 hours → tablet → osmosis-controlled release

• ________ → at night → lasts 12 hours → doesn’t get absorbed until 10 hours later

Ritalin, Focalin, Daytrana, Concerta, Jornay PM

Name some commonly prescribed amphetamine-based medications for the treatment of ADHD.

• ________ → + ________ → commonly abused 

• ________ (lisdexafetamine) → ________ → doesn’t act until ___ hours later (dissolved in stomach and absorbed by RBCs) → strawberry taste

Addreall, dextroamphetamines, Vyvanse, prodrug, 1-2

Explain why Jornay PM can be taken at night. What is a potential advantage of this formulation?

• Avoid breakfast interaction (________ in fruit juices) → cause ________ to be ________ absorbed. (around 8 pm)

Vitamin C, psychostimulants, less

Which of the amphetamine-based medications is a prodrug that needs to be metabolized to dextroamphetamine? Why is this medication less abused than other amphetamines (e.g., Adderall)?

• ________ (Lisdexafetamine) → takes ________ to work (lots of processes it goes thru bc it’s a prodrug)

Vyvanse, longer

T/F: Amphetamine-based stimulants are slightly more efficacious than methylphenidate-based agents, yet methylphenidate-based stimulants have shown better overall tolerability.

True

1. What are the common ADRs of stimulant medications? WILL BE QUESTIONS ON SEs and C/Is

• SEs: 

  • ________ distress

  • Decrease ________, ________, & ________

  • Increase ________

  • ________

  • ________, High BP, 

  • Hallucinations + tics

• C/Is: 

  • Advanced ________

  • Symptomatic ________ disease (uncontrolled, high BP)

  • ________

  • Known hypersensitivity to the sympathomimetic amines

  • ________

  • Agitated states (worsens)

  • History of drug abuse (Worsens)

  • During or within 14 days following the administration of ________.

• SEs - Psychiatric

  • Warnings from FDA

    • May cause ________ (to much dopamine), ________ (worsen), ________ (worsen), ________ (worsen), and/or ________ disorder

  • Patients with pre-existing psychotic illnesses

    • Clonidine (FDA approved) or ________: less likely to cause ________, ________, or ________

GI, growth hormone, appetite, weight, nervousness, insomnia, tachycardia, ateriosclerosis, CV, hyperthyroidism, glaucoma, MAO-Is, psychosis, mania, anxiety, aggression, panic, Guanfacine, psychosis, mania, anxiety

What are the 4 nonstimulant medications that are FDA-approved for ADHD?

• ________ (Atomoxetine)

• ________ (Viloxazine)

• ________ (brand name no longer marketed; generic Clonidine ER available)

• ________ (Clonidine ER)

• ________ (Guanfacine ER)

Strattera, Qelbree, kapvay, onyda, intuniv

True/False: Clonidine is an alpha-2 adrenergic agonist for the treatment of ADHD sxs of hyperactivity/impulsivity and agitation/aggression.

• Check BP + HR bc it’s the OPPOSITE of ________ → causes ________ and ________

True, psychostimulants, hypotension, bradycardia

True/False: ________ can acidify the urine and significantly decrease the ________ of psychostimulants (________, ________) as ________.

True, Vitamin C, concentration/efficacy, Addreall, Ritalin, weak bases