Nursing 3100- The Nervous System: Drugs for Anxiety and Sleep Disorders

Limbic System

responsible for emotional expression, learning, and memory.

Hypothalamus

- Autonomic NS/ “Fight or Flight”

- Activates the sympathetic NS

- Causes the release of corticosteroids during anxiety.

Reticular formation

- connected to hypothalamus

- stimulation causes alertness/arousal; inhibition causes drowsiness/induction of sleep.

Cingulate gyrus

- Limbic system

- formation/processing emotions.

Locus Coeruleus

- Releases NE during periods of anxiety or stress to activate fight-or-flight

Thalamus

- regulate consciousness, sleep, and alertness.

Hippocampus

long-term storage of memory related to emotions.

Amygdala

Recognizes harmful stimuli and generates emotional responses (fear/anxiety)

Histamine receptors

- Some meds target histamine receptors for anxiety and insomnia

- can affect serotonin and other neurotransmitters

Which neurotransmitters is anxiety related to?

serotonin, norepinephrine, and GABA.

Types of anxiety disorders

1. generalized anxiety disorder

2. panic disorder

3. phobias

4. separation anxiety disorder

Related disorders to anxiey

OCD & PTSD

Generalized Anxiety Disorder (GAD)

- Persistent anxiety/fear related to daily life.

- Physical symptoms: palpitations, sweating, muscle tension due to limbic system activation of the sympathetic nervous system.

Panic Disorder

- Sudden panic attacks; recurrent and unexpected without triggers.

- Symptoms: palpitations, sweating, shortness of breath, hyperventilation, numbness, collapse.

Phobias

- Persistent, irrational fears.

- ie Social anxiety disorder

Separation Anixety Disorder

- Primarily affects children.

- Anxiety when separated from parents/caregivers

- crying and inconsolability.

obsessive-compulsive disorder (OCD)

Uncontrolled thoughts or repetitive behaviors.

Post-Traumatic Stress Disorder (PTSD)

Result of traumatic events.

Essentials for diagnosis

1. Persistent excessive anxiety or chronic fear with behavioral disturbances.

2. Somatic symptoms

3. Not due to physical disorders, schizophrenia, or drug abuse

Insomnia

Inability to fall or stay asleep; commonly associated with anxiety disorders.

Sleep disorders related to insomnia (3)

- Narcolepsy: Excessive daytime sleepiness.

- Obstructive Sleep Apnea (OSA): Airway obstruction during sleep.

- Restless Legs Syndrome (RLS): Urge to move legs.

Medications for insomnia/anxiety

- Benzodiazepines

- Nonbenzodiazepines

- Antidepressants

- Barbiturates

- First generation antihistamines

BAN FB

Sedative-hypnotics

- For insomnia/anxiety

- Calming effect at low doses; induce sleep at higher doses.

- Sublingual

Anxiolytics

Reduce anxiety by altering NE and serotonin levels.

Benzodiazepines

- Short-term therapy for anxiety and insomnia (due to risk for addiction/tolerance)

- Bind to GABA receptors, enhancing GABA's effects (don't mimic, so limited CNS depression)

Adverse effects of benzodiazepines

- Drowsiness/sedation/lethargy/confusion, headache, respiratory depression

- Use cautiously in older adults and pregnant women (↑ fall risk, cognitive impairment, teratogenic).

Chlordiazepoxide (librium)

- Benzodiazepine

- Side effect = lethargy

FDA approved benzodiazepines for anxiety

Alprazolam, Diazepam, Clonazepam, Lorazepam

CLAD

FDA approved benzodiazepines for insomnia

- Temazepam

- Triazolam

- Estazolam

TET

Flumazenil

- reversal agent for benzodiazepines

- competitively binds to the GABA receptor, blocking benzodiazepines

Nonbenzodiazepines

- Buspirone (FDA approved for anxiety)

- Z-drugs (FDA approved for insomnia).

Barbiturates

- Rarely used due to narrow therapeutic index/toxicity

- Bind to/mimic GABA (unlimited CNS depression potential)

- High addiction risk.

- No antidote; withdrawal managed with phenobarbital.

Types of barbiturates

Pentobarbital, Phenobarbital, Methohexital, Secobarbital.

First generation antihistamines

- Hydroxyzine (FDA approved for anxiety)

- Doxepin (FDA approved for anxiety)

- Diphenhydramine (FDA-approved for insomnia).

Types of antidepressants for anxiety and insomnia

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

2. Atypical antidepressants- serotonin norepinephrine reuptake inhibitor (SNRIs)

3. Tricyclic Antidepressants (TCAs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

- First-line for anxiety/depression.

- also treat eating disorders, panic disorder, OCD

- Block serotonin reuptake → increase serotonin availability/binding

- Fewer anticholinergic side effects.

SSRI Common side effects

Nausea, dry mouth, sleep disturbance, headache, GI upset, dizziness, fatigue, sexual dysfunction, weight gain

SSRI serious adverse affects

- Suicidal ideation

- Serotonin Syndrome

- Stevens-Johnson Syndrome (SJS)

Serotonin Sydrome

Hypothermia, tachycardia, hypertension, clonus, hyperreflexia, loss of consciousness, altered mental status.

Examples of SSRIs

- Fluoxetine, Citalopram, Escitalopram, Paroxetine, Sertraline, Fluvoxamine

- All FDA approved for anxiety

Serotonin norepinephrine reuptake inhibitor (SNRIs)

- inhibit reuptake of serotonin and NE

- More side effects than SSRIs.

- May require longer titrations

Examples of SNRIs

Duloxetine, Venlafaxine (FDA approved for anxiety), Desvenlafaxine

Venlafaxine

- SNRI

- Short half-life → fast effect but withdrawal risk if doses missed.

- Causes hypertension

Serotonin modulator

- SSRIs that partially agonize/antagonize 5-HT receptors.

- Used for treatment-resistant depression.

- Black Box Warning: Suicidality.

- SNRI/SSRI more effective

Trazodone

- serotonin modulator (old drug)

- off label for insomnia

- FDA approved for depression

- not typically used due to cardiac/anticholinergic effects

Nefazodone

- serotonin modulator (old drug)

- discontinued due to hepatotoxiicty

Examples of serotonin modulators- newer drugs

- vortioxetine

- vilazodone

- FDA-approved for depression only.

Tricyclic Antidepressants (TCAs)

- Affect serotonin and other neurotransmitters.

- Strong anticholinergic and cardiac toxicities.

Examples of TCAs

- Doxepin (FDA-approved for insomnia at low dose)

- Imipramine (off-label)

- Amitriptyline (off-label)

Z drugs

- non-benzodiazepine

- Bind to GABA receptor at benzodiazepine-binding site

- FDA-approved for insomnia: Zolpidem, Zaleplon, Eszopiclone

Non-benzodiazepine anxiolytics

Hydroxyzine, Buspirone, Meprobamate.

First-generation antipsychotics with anxiolytic effects

Prochlorperazine, Perphenazine, Quetiapine, Trifluoperazine.

Hydroxyzine (Atarax, Vistaril)

- First-gen antihistamine.

- FDA approved for anxiety

- Very sedating, highly anticholinergic; use with caution in pregnancy, avoid in lactation.

Buspirone (BuSpar)

- Partial agonist of serotonin receptors.

- now FDA approved for anxiety.

- Do not use with MAO inhibitors

Monoamine Oxidase Inhibitors (MAOIs)

- Nonselective inhibition of monoamine oxidase.

- Inhibit breakdown of tyramine (food-drug interaction risk)

- FDA Approved For: Depression only

- For patients unresponsive to SSRIs or TCAs.

MAOIs examples

phenelzine

tranylcypromine

selegiline transdermal

isocarboxazid

PITS

MAOI side effects

Drowsiness, orthostatic hypotension, vision changes, nausea, constipation, dry mouth, urinary retention, sexual dysfunction.

MAOI serious events

Suicidal ideation, hypertensive crisis, serotonin syndrome, circulatory collapse.

Antiseizure medications

Valproic acid.

Beta Blockers

- Propranolol- used for situational anxiety/migraines

- crosses BBB

Ramelteon

- melatonin receptor agonist; regulates wake-sleep cycles.

- FDA approved for insomnia