Anxiety and Insomnia RAT NT

ANXIETY

Lifetime prevalence of anxiety related disorders in adults ages 18-64

~33%

Median age of onset of GAD

31

Most frequent psychiatric comorbidities with anxiety disorders

Depression

Alcohol and substance use disorders

What causes anxiety

Environmental factors (stressful life events, illness, parental relationships, trauma)

Female, loneliness, adverse parenting, and chronic somatic illness (cardiovascular disease, diabetes, asthma, obesity)

Symptoms of GAD

Feeling nervous, anxious, frightened, worried, on edge

Feeling panic or being frightened

Avoiding situations that make you anxious

Medical conditions that contribute to symptoms

Medications associated with symptoms

Goals of therapy for GAD

Acutely reduce severity and duration of symptoms and restore overall functioning

Long-term → achieve and maintain remission

Nonpharmacologic therapies for GAD

Exercise, stress management, psychosocial therapies (cognitive behavioral therapy)

Avoid agents that may potentiate anxiety, including caffeine, decongestants, diet pills, and excessive alcohol use

Why are antidepressants the drugs of choice for GAD

Tolerable side effect profiles, no risk for dependency, and efficacy in common comorbid conditions

Which symptoms do antidepressants reduce

Cognitive symptoms (worry and apprehension)

Onset of antianxiety effect with antidepressants

2 to 4 weeks

Treatment algorithm for GAD

Antidepressants used in the management of GAD

Benzodiazepine duration in GAD treatment

2-3 weeks

Symptoms benzos are most effective for

Somatic symptoms (pain, fatigue, muscle tension)

Disadvantages of benzos

Risk for withdrawal and potential need for taper, as well as potential interdose rebound anxiety, especially with short-acting benzodiazepines (alprazolam)

Benzodiazepines - MOA

Enhance transmission of the inhibitory neurotransmitter GABA through interaction with the GABA_A-receptor complex

Benzos preferred in reduced hepatic function secondary to aging or disease

Lorazepam

Oxazepam

Benzodiazepines - side effects

Central nervous system depressant effects (drowsiness, sedation, psychomotor impairment, and ataxia)

Cognitive effects (poor recall and anterograde amnesia)

Gabapentinoids - MOA

Calcium channel modulators with anxiolytic properties due to the selective binding to the α₂-delta subunit of voltage-gated calcium channels

How do the gabapentinoids differ in GAD efficacy

Gabapentin - strong efficacy

Pregabalin - Limited/mixed efficacy

Buspirone - MOA

5-HT_1A partial agonist

How does buspirone differ from benzos

Does not have abuse potential, cause withdrawal symptoms, or potentiate alcohol and sedative-hypnotic effects

Buspirone - onset of action

2 weeks (no immediate anxiety relief)

Buspirone - adverse effects

Dizziness, drowsiness, nausea, and headaches

May increase BP when co-administered with MAOI

INSOMNIA

How many adults report symptoms of insomnia

1/3

How many (%) meet DSM-5 criteria

10%

Conditions that coexist with insomnia

Psychiatric (depression, anxiety)

Chronic pain disorders

How is insomnia characterized

Difficulty falling asleep, frequent nocturnal awakenings, and early morning awakenings

Treatment goals of sleep disorders

Restoration of normal sleep patterns

Elimination of daytime sequelae

Improved quality of life

Prevention of complications and adverse effects from therapy

How to improve sleep hygiene and stimulus control

Agents recommended for complaints of sleep onset difficulty and sleep maintenance

Eszopiclone or zolpidem

Agents recommended for complaints of sleep onset difficulty only

Zaleplon, ramelteon, or triazolam

Agents recommended for complaints of difficulty maintaining sleep only

Doxepin or suvorexant

Difference between nonbenzodiazepine receptor agonists and benzodiazepines

NBRAs are highly selective for GABA_A receptors containing the specific α₁ subtype of the α subunit known to produce sedation and promote sleep

Nonbenzo and benzo adverse effects

Residual sedation, grogginess, and psychomotor impairment into the waking hours after sleep

Antidepressants used in management of insomnia

Sedating antidepressants (trazodone, amitriptyline, mirtazapine, doxepin)

Why are sedating antidepressants appealing for insomnia

Appealing option in patients with concomitant depression

What are the drawbacks of sedating antidepressants

Quality clinical studies demonstrating efficacy for insomnia are lacking

Adverse effects from antidepressants can be frequent, including next-day sedation, grogginess, anticholinergic effects, and weight gain

Ramelteon - MOA

Melatonin receptor agonist

Orexin Receptor Antagonists (suvorexant, lemborexant, and daridorexent) - MOA

Inhibits brains orexin neuropeptide signals

Eszopiclone - half life

6 hours

Eszopiclone - daily dose range

2-3 mg

Temazepam - half life

10-15 hours

Temazepam - daily dose range

7.5-30 mg

Zaleplon - half life

1 hour

Zaleplon - daily dose range

5-10 mg

Zolpidem - half life

2-2.6 hours

Zolpidem - daily dose range

5-10 mg

Zolpidem CR - half life

2.8 hours

Zolpidem CR - daily dose range

6.25 - 12.5 mg