Ch. 8-12 Anxiety, Sleep Disorders, ADHD, and Dementia (Mod 3)

GABA (Function & Imbalance Effects)

Main inhibitory neurotransmitter ("brake pedal"). Too much causes sedation

Serotonin (Function & Imbalance Effects)

Mood stabilization. Too much causes GI upset

Norepinephrine (Function & Imbalance Effects)

Fight-or-flight neurotransmitter. Too much causes panic

Glutamate (Function & Imbalance Effects)

Main excitatory neurotransmitter. Too much causes anxiety

Anxiety Disorders

Generalized Anxiety Disorder (GAD), Panic Disorder, Social Anxiety Disorder, PTSD, and OCD.

First-Line Medications for Long-Term Anxiety

SSRIs and SNRIs (SSRIs are preferred over benzodiazepines because they treat the underlying disorder without causing tolerance, dependence, or withdrawal).

SSRIs (Mechanism, Examples, Pros & Cons)

Mechanism: Increases serotonin by blocking reuptake.

Examples: Sertraline, Escitalopram, Fluoxetine, Paroxetine.

Pros: Non-addictive, good for long-term treatment. Cons: Sexual dysfunction, GI upset, initial anxiety worsening, takes 2–6 weeks to work ("slow but steady").

SNRIs (Mechanism, Examples, & Uses)

Mechanism: Increases serotonin and norepinephrine.

Examples: Venlafaxine, Duloxetine. Uses: Anxiety, depression, and neuropathic pain.

Buspirone (Mechanism, Mnemonic, & Characteristics)

Mechanism: Partial serotonin (5-HT1A) agonist.

Characteristics: Preferred for GAD

Benzodiazepines (Short, Intermediate, & Long-Acting Examples)

Short-acting: Alprazolam, Oxazepam.

Intermediate-acting: Lorazepam, Temazepam.

Long-acting: Diazepam, Clonazepam.

Benzodiazepines (Mechanism, Advantages, Disadvantages)

Mechanism: Increase GABA-A receptor activity, causing decreased anxiety, muscle tension, seizures, and insomnia.

Advantages: Rapid onset / works immediately. Disadvantages/Risks: Tolerance, dependence, withdrawal, falls (increased risk in older adults), memory impairment, respiratory depression (especially when combined with opioids).

PTSD Pharmacotherapy (First-Line & Nightmares)

First-Line SSRIs (FDA approved): Sertraline and Paroxetine. Nightmares/Hyperarousal: Prazosin (alpha-1 blocker

Benzodiazepine Tapering Indications

Required for anyone taking daily benzodiazepines for >1 month, especially older adults, those with polypharmacy, substance use disorder, or those on high doses.

Risks of Abrupt Benzodiazepine Discontinuation

Anxiety, insomnia, tremor, seizures, delirium, and (rarely) death.

ASAM General Benzodiazepine Tapering Protocol

Never stop suddenly. Assess prescribed reason, duration, dose, withdrawal risk, and patient goals. Typical taper: reduce dose 5–10% every 2–4 weeks. Avoid reductions of 25% every 2 weeks. Slow down if withdrawal occurs.

Benzodiazepine Withdrawal Symptoms (Mild, Moderate, Severe)

Mild: Anxiety, sweating, insomnia, restlessness. Moderate: Nausea, tremor, palpitations. Severe: Seizures, psychosis, delirium.

Role of Long-Acting Benzodiazepines in Tapering

Patients are often switched to Diazepam before tapering due to its long half-life, which results in less severe withdrawal.

Wake-Promoting Neurotransmitters

Orexin ("on switch"), Histamine, Norepinephrine, Acetylcholine, Dopamine.

Sleep-Promoting Neurotransmitters

GABA, Melatonin.

Types of Insomnia & First-Line Non-Pharmacological Treatment

Types: Difficulty falling asleep (onset), difficulty staying asleep (maintenance), and early awakening. First-Line: Cognitive Behavioral Therapy for Insomnia (CBT-I) and sleep hygiene.

Temazepam (Class, Pros, Cons)

Class: Benzodiazepine for sleep. Pros: Effective. Cons: Dependence, fall risk, memory impairment.

Z-Drugs (Examples, Mechanism, Advantages, Risks)

Examples: Zolpidem, Eszopiclone, Zaleplon. Mechanism: Selective GABA agonists. Advantages: Less dependence, better sleep architecture than benzos. Risks: Can cause sleepwalking and complex sleep behaviors.

Ramelteon (Mechanism, Best Use, Safety)

Mechanism: Melatonin agonist. Best Use: Sleep onset insomnia. Safety: Safe in the elderly

Orexin Receptor Antagonists (Examples, Mechanism, Best Use)

Examples: Suvorexant, Lemborexant, Daridorexant. Mechanism: Blocks orexin (turns off wakefulness signal). Best Use: Sleep maintenance insomnia.

Sedating Antidepressants for Sleep

Trazodone, Mirtazapine, Doxepin (useful when depression and insomnia co-occur).

ADHD Pathophysiology & Brain Region

Deficit of Dopamine and Norepinephrine, primarily in the prefrontal cortex.

ADHD Core Symptoms

Inattention, Hyperactivity, Impulsivity.

Methylphenidate Class (Examples, Mechanism, Mnemonic)

Examples: Ritalin, Concerta, Daytrana. Mechanism: Blocks dopamine and norepinephrine reuptake. Mnemonic: "Makes neurotransmitters stay".

Amphetamine Class (Examples, Mechanism, Mnemonic, Comparison)

Examples: Adderall, Vyvanse, Dexedrine. Mechanism: Releases dopamine and norepinephrine. Mnemonic: "Push neurotransmitters out". Comparison: Generally stronger than the methylphenidate class.

Stimulant Side Effects & Contraindications

Side Effects: Decreased appetite, insomnia, weight loss, increased heart rate, increased blood pressure. Contraindications: Glaucoma, current/recent MAOI use, serious cardiac disease.

Atomoxetine (Mechanism, Indications)

Mechanism: Selective norepinephrine reuptake inhibitor (non-stimulant). Indications: ADHD in patients with co-occurring anxiety or a history of stimulant misuse/substance abuse.

Alpha-2-Adrenergic Agonists for ADHD (Examples & Indications)

Examples: Guanfacine, Clonidine. Indications: Good for children with ADHD, hyperactivity, or tics.

Alzheimer's Disease Pathophysiology

Decreased Acetylcholine, neuronal loss, Amyloid plaques, and Tau tangles.

Alzheimer's Disease Core Symptoms

Memory loss, executive dysfunction, language impairment, behavioral changes.

Cholinesterase Inhibitors (Examples, Mechanism, Effects, Side Effects)

Examples: Donepezil, Rivastigmine, Galantamine. Mechanism: Prevent acetylcholine breakdown (inhibits acetylcholinesterase) -> increases acetylcholine. Mnemonic: "Don't destroy acetylcholine". Side Effects: Nausea, vomiting, bradycardia, weight loss.

Memantine (Mechanism, Indication, Mnemonic)

Mechanism: NMDA receptor antagonist

Alzheimer's Combination Therapy

Donepezil + Memantine: Common treatment strategy in moderate-to-severe disease.

Prognostic Reality of Alzheimer's Medications

Neither cholinesterase inhibitors nor memantine reverse Alzheimer's disease

Sertraline (Class, Use, Side Effect)

Class: SSRI. Use: Anxiety, PTSD. Side Effect: Sexual dysfunction.

Venlafaxine (Class, Use, Side Effect)

Class: SNRI. Use: Anxiety. Side Effect: Hypertension.

Alprazolam (Class/Mechanism, Use, Side Effect)

Class/Mechanism: Benzodiazepine / GABA enhancer. Use: Panic disorder. Side Effect: Dependence.

Prazosin (Class/Mechanism, Use, Side Effect)

Class/Mechanism: Alpha-1 blocker. Use: PTSD nightmares and hyperarousal. Side Effect: Orthostatic hypotension.

Suvorexant (Class/Mechanism, Use, Side Effect)

Class/Mechanism: Orexin receptor antagonist. Use: Insomnia (maintenance). Side Effect: Daytime drowsiness.

Zolpidem (Class/Mechanism, Use, Key Side Effect)

Class/Mechanism: Z-drug / Selective GABA agonist. Use: Insomnia. Key Side Effect: Complex sleep behaviors / sleepwalking.

Adderall (Class/Mechanism, Use, Key Side Effect)

Class/Mechanism: Amphetamine stimulant / Releases DA and NE. Use: ADHD. Key Side Effect: Appetite loss / weight loss.

Methylphenidate (Class/Mechanism, Use, Key Side Effect)

Class/Mechanism: Stimulant / Blocks DA and NE reuptake. Use: ADHD. Key Side Effect: Insomnia.

Atomoxetine (Class/Mechanism, Use, Rare Warning)

Class/Mechanism: Selective NE reuptake inhibitor (Non-stimulant). Use: ADHD. Rare Warning: Suicidal ideation.

Donepezil (Class/Mechanism, Use, Key Side Effect)

Class/Mechanism: Cholinesterase inhibitor / Prevents ACh breakdown. Use: Alzheimer's disease. Key Side Effect: Bradycardia (along with nausea/vomiting).

Memantine (Class/Mechanism, Use, Key Side Effect)

Class/Mechanism: NMDA antagonist / Blocks glutamate toxicity. Use: Moderate-to-severe Alzheimer's disease. Key Side Effect: Dizziness.

GABA Mnemonic

"Brake pedal" -> More GABA equals a calmer brain (mechanism for benzodiazepines and Z-drugs).

SSRIs Mnemonic

"Slow but steady" -> Takes weeks to work, but preferred for long-term anxiety management.

Orexin Mnemonic

"On switch" -> Orexin promotes wakefulness

Prazosin Mechanism of Action

Alpha-1-adrenergic receptor blocker used to reduce sympathetic overdrive, specifically targeting trauma-related nightmares and hyperarousal in PTSD.

Benzodiazepines in Older Adults

High-risk medication class due to increased fall risk, cognitive impairment/memory impairment, and motor incoordination.

Benzodiazepine + Opioid Co-Prescribing Risk

Severe risk of additive CNS depression resulting in severe respiratory depression, coma, or death.

ADHD Stimulants Comparison (Amphetamines vs. Methylphenidate)

Amphetamines push neurotransmitters out (increase DA/NE release), whereas methylphenidate makes neurotransmitters stay (blocks DA/NE reuptake)

Clinical Strategy: Alzheimer's Progression on Donepezil

If memory worsens while on donepezil alone, add Memantine to provide dual-action neuroprotection against glutamate excitotoxicity in moderate-to-severe disease.

Practice Question: Why are SSRIs preferred over benzodiazepines for chronic anxiety?

Answer: SSRIs treat the underlying disorder without causing tolerance, dependence, or withdrawal, whereas benzodiazepines are best reserved for short-term symptom relief.

Practice Question: A patient has taken clonazepam daily for 18 months. What is the safest approach if discontinuation is desired?

Answer: Use a gradual taper (typically 5–10% dose reductions every 2–4 weeks, individualized based on symptoms) to minimize withdrawal risk.

Practice Question: Which ADHD medication is most appropriate for a patient with a history of stimulant misuse?

Answer: Atomoxetine is often preferred because it is non-stimulant and has no abuse potential.

Practice Question: A patient with Alzheimer's disease has worsening memory despite donepezil. What medication might be added?

Answer: Memantine for moderate-to-severe disease, as it targets glutamate-mediated excitotoxicity through NMDA receptor antagonism.

Practice Question: A patient reports recurrent nightmares related to PTSD despite an SSRI. Which medication is commonly used to target this symptom?

Prazosin, particularly for trauma-related nightmares and sleep disruption.