Applid

• Anxiety disorders (eg, generalized anxiety disorder [GAD] and panic disorder [PD]) have prominent features of anxiety and avoidance that are irrational or that impair functioning
• In posttraumatic stress disorder (PTSD), there is previous exposure to trauma and the occurrence of intrusive, avoidant, and hyperarousal symptoms
• Evaluation of anxiety


  • Requires a physical and mental status examination; complete psychiatric diagnostic exam; appropriate laboratory tests
• Medical illnesses associated with anxiety symptoms


  • Cardiovascular
  • Endocrine and metabolic
  • Gastrointestinal
  • Neurologic
  • Respiratory system
  • Others
• Medications and substances associated with anxiety symptoms


  • Antiseizure medications
  • Antidepressants
  • Antihypertensives
  • Antibiotics
  • Bronchodilators
  • Corticosteroids
  • Dopamine agonists
  • Herbals
  • Unhealthy substance use
  • Nonsteroidal antiinflammatory drugs
  • Stimulants
  • Sympathomimetics
  • Thyroid hormones
  • Toxicity
• Noradrenergic model


  • Autonomic nervous system is hypersensitive and overreacts to stimuli; Locus ceruleus activates norepinephrine release and stimulates sympathetic and parasympathetic nervous systems
• GABA receptor model


  • GABA is the major inhibitory neurotransmitter in the central nervous system; Benzodiazepines enhance GABA's inhibitory effects
• 1. HT model


  • Greater 5-HT function facilitates avoidance behavior; Reducing 5-HT increases aggression
• Cortisol

  • Reduces the stress response by tempering the sympathetic reaction; Patients with PTSD have subnormal levels of cortisol
• Neuroimaging studies


  • Support the role of the amygdala, anterior cingulate cortex, and insula in the pathophysiology of anxiety
• GAD


  • Abnormal increase in the brain's fear circuitry and activity in the prefrontal cortex
• PD


  • Midbrain structural abnormalities
• PTSD


  • Amygdala plays a role in the persistence of traumatic memory; Hypofunctioning in the ventromedial prefrontal cortex prevents extinction
• Glutamate signaling abnormalities


  • May distort amygdala-dependent emotional process under stress, contributing to dissociative and hypervigilant symptoms in PTSD
• Psychological and cognitive symptoms of GAD


  Excessive anxiety, worries that are difficult to control, feeling keyed up or on edge, and trouble concentrating or mind going blank
• Physical symptoms of GAD


  Restlessness, fatigue, muscle tension, sleep disturbance, and irritability
• Diagnosis of GAD


  Excessive anxiety and worry most days for at least 6 months with at least three physical symptoms present; Significant distress or impairment in functioning; Not caused by a substance or another medical condition
• Females are twice as likely as males to have GAD
• GAD has a gradual onset at an average age of 21 years and a chronic course with multiple exacerbations and remissions
• Goals of treatment for anxiety disorders


  Reduce severity, duration, and frequency of symptoms; Improve functioning; Minimal or no anxiety symptoms, no functional impairment, prevention of recurrence, and improved quality of life
• Nonpharmacologic therapy for GAD


  • Psychotherapy, short-term counseling, stress management, psychoeducation, meditation, and exercise
• Cognitive behavioral therapy (CBT) is the most effective psychological therapy for GAD
• Nonbenzodiazepine antianxiety agents for GAD


  • Duloxetine, Escitalopram, Imipramine, Paroxetine, Sertraline, Venlafaxine XR, Vilazodone, Vortioxetine, Buspirone, Hydroxyzine, Pregabalin, Quetiapine XR
• Dosing considerations for older patients


  Usually treated with approximately one-half of the dose except Buspirone
• Paroxetine should be avoided in pregnancy
• Vilazodone has drug-drug interaction with itraconazole, clarithromycin, voriconazole
• Pregabalin needs dosage adjustment in patients with renal impairment
• Antidepressants for GAD


  Effective for acute and long-term management, especially in the presence of depressive symptoms; Response rates between 60% and 68%, and remission rates of ~30%
• Antidepressants more likely to achieve remission of GAD symptoms


  Venlafaxine, escitalopram, paroxetine, duloxetine, and quetiapine; Sertraline may be the best tolerated
• Antidepressants may require small initial doses to limit transient increased anxiety (jitteriness syndrome)
• Antidepressants carry a black box warning regarding suicidal thinking and behaviors in children, adolescents, and young adults less than 25 years
• Antidepressants recommended for pregnant persons


  Fluoxetine, sertraline, or citalopram; Paroxetine should be avoided due to cardiovascular malformation risk
• Benzodiazepines for GAD


  Most effective and frequently prescribed treatment for acute anxiety; About 65%–75% of patients have a marked to moderate response, with most improvement in the first 2 weeks; More effective for somatic and autonomic symptoms, whereas antidepressants are more effective for psychic symptoms
• Antidepressants


  Fluoxetine, sertraline, or citalopram recommended for pregnant persons; paroxetine should be avoided due to cardiovascular malformation risk
• Jitteriness, myoclonus, and irritability in the neonate and premature infant have been reported with antidepressants
• Benzodiazepines


  All possess anxiolytic properties, 7 are FDA-approved for GAD treatment
• Benzodiazepines


  • Most effective and frequently prescribed treatment for acute anxiety
  • About 65-75% of patients with GAD have a marked to moderate response, with most improvement in the first 2 weeks
  • More effective for somatic and autonomic symptoms of GAD, whereas antidepressants are more effective for the psychic symptoms (eg, apprehension and worry)
• Dose of benzodiazepines


  Must be individualized, older patients are more sensitive and may experience falls
• Adverse effects of benzodiazepines


  • CNS depression, but tolerance usually develops
  • Others include disorientation, psychomotor impairment, confusion, aggression, excitement, ataxia, and anterograde amnesia
• Benzodiazepine dosing


  1. Start with low doses, adjust weekly

  2. Use a regular dosing regimen, not on an as needed basis

  3. Treatment of acute anxiety generally should be 2-4 weeks

  4. Manage persistent symptoms with antidepressants