Anxiety Disorders Flashcards
List the components of the current understanding of the biological basis of anxiety and anxiety disorders
Neuroanatomy: hippocampus, amygdala, PFC
NT’s
Hypothalamic-Pituitary-Adrenal Axis (HPA)
Anxious temperament
Explain the current understanding of the biological basis of anxiety and anxiety disorders based on neuroanatomy
Hippocampus • In temporal lobe • Involved in memory and learning • Sensors for cortisol • May become dysregulated in anxiety and depression
Amygdala
• Processes sensory info
• Role in negative emotions = fear and learning new fear associations
• Activation → activates HPA → autonomic and behavioral responses
• Responses = innate (evolutionarily conserved); selective (genetically determined)
PFC
• Inhibits amygdala → regulates expression of fear
• Helps “unlearn” fear associations
Explain the current understanding of the biological basis of anxiety and anxiety disorders based on neurotransmitters
o Glutamate = excitatory; GAGA = inhibitory
o Noradrenergic and serotonergic systems likely involved in anxiety disorders
Explain the current understanding of the biological basis of anxiety and anxiety disorders based on the HPA axis
o Normal stress response = activates HPA:
• Result: metabolic mobilization; increased HR, BP and respiration; redistribution of blood flow; suppression of immune, inflammatory, and digestive systems
o Chronic stress = abnormal HPA activation
• Result: HT, obesity, diabetes, osteoporosis, suppressed immune function, memory impairment, changes in brain structure, depression, anxiety
• Adrenal cortex hypertrophy
• Hippocampus neuronal atrophy and volume reduction
Explain the current understanding of the biological basis of anxiety and anxiety disorders based on temperament
Genetically determined = 40% heritable
• Hippocampus = heritable determinants
• Amygdala = not heritable
o Have extreme behavioral inhibition (freezing) in response to new situations or strangers
o Can be identified early in life (2 years old)
o Predicts development of anxiety, depression, co-morbid substance use
Describe agoraphobia
- Intense anxiety about 2 or more of: using public transportation, being in open spaces, being in enclosed spaces, standing in line or being in a crowd, being outside of home alone
- May be co-morbid with panic disorder, social phobia, GAD, MDD, PTSD, alcohol use disorder
Recognize the substance and medication induced and other medical etiologies of anxiety.
Medical conditions o Hyperthyroidism o Hyperparathyroidism o Pheochromocytoma o Hypoglycemia o Cardiac arrhythmias o Mitral valve prolapse o Pulmonary embolus o Myocardial infarction
Substance-induced o Caffeine intoxication o Stimulant abuse o Alcohol withdrawal o Sedative-hypnotic withdrawal
Medications o Asthma drugs (albuterol) o Steroids (prednisone) o Thyroid drugs o Some antidepressants (bupropion) o Stimulants (methylphenidate) o Decongestants (pseudoephedrine) o Caffeine-containing drugs (No-Doz)
Panic disorder: epidemiology
Lifetime prevalence: 2-3% females; 0.5-15% males
Panic disorder: pathophysiology
Biological disturbances: • Increased catecholamines in CNS • Abnormal locus ceruleus (area in brainstem regulating alertness and procuces NE) • CO2 hypersensitivity • Lactate metabolism disturbances • Abnormal GABA NT system
Abnormal brain structure:
• Temporal lobe (hypothalamus)
• Cerebral vasoconstriction
Hereditary
• Risk = 20% in 1st-degress relatives
Panic disorder: common comorbidities
Higher rates peptic ulcer disease, HT, death
Increased risk of other psychiatric conditions
o Depression
o Alcohol abuse
Higher rates suicide
Other types anxiety disorders
GAD: epidemiology
Lifetime prevalence: 4-7%
More common in women
GAD: pathophysiology
- Unknown underlying cause
- Environmental factors > hereditary role
- Frontal lobe and limbic system disturbances in NE, GABA, and serotonin may be factors
GAD: common comorbidities
- Often exists with other psychiatric disorder
* Increased risk depression and substance abuse
OCD: epidemiology
Lifetime prevalence: 2-3%
Equally prevalent in males and females
OCD: pathophysiology
- Serotonin dysfunction
- Associated neurological disorders: TBI, epilepsy, Huntington’s
- Genetically linked to Tourette’s
Other findings:
• Abnormal electroencephalographic findings
• Abnormal auditory evoked potentials
• Growth delays
• Abnormal neuropsychological test results
PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections)
• Strong heritable component
ODC: common comorbidities
- Recurrent major depression episodes (70-80%)
- History of tics (20-30%)
- Tourette’s (5-7%)
OCD: prognosis
Poor prognostic indicators: • Yielding to compulsions • Childhood onset • Bizarre compulsions • Need for hospitalization • Coexisting major depression or personality disorder
Favorable indicators:
• Good social and occupational adjustment
• Presence of precipitating event
• Episodic symptom course
Recognize the clinical presentations of social phobia and specific phobias.
- Social phobia: strong persisting fear of situations in which embarrassment can occur
- Specific phobia: strong persisting fear of an object or situation
- Both result in avoidance, anxious anticipation, or distress
Somatization disorder
o Presence of distressing and impairing somatic symptoms that can’t be explained on basis of physical and lab exam
o Ex: pain, GI symptoms, sexual symptoms, neurological symptoms
o Lifetime prevalence = 0.2-2%; 5:1 female to male ratio
o Begins before age 30
o Course can be chronic and debilitating
o Episodes typically last 6-9 months, may be separated periods of 9-12 months
o Genetic component; otherwise etiology is unclear
o Must rule out other medical disorders: MS, myasthenia gravis, SLE, HIV/AIDS, acute intermittent porphyria, hyperthyroidism, hyperparathyroidism and chronic systemic infections
Conversion disorder
Presents with one or more neurological symptoms without identifiable neurological cause; caused by psychological factors
GAD: treatment
o Combo of medication and psychotherapy
o 1st line = SSRIs
o Also effective = SNRIs
o May use SSRI and benzodiazepine, then taper benzodiazepine once SSRI has taken effect
o CBT: restructure patient’s distortion about environment
o Other behavioral interventions: deep breathing, progressive muscle relaxation, imagery
Panic disorder: treatment
o Combo of medication and psychotherapy
o 1st line = SSRIs
o Also effective = SNRIs; may use older tricyclic and MAOI antidepressants but not as safe or tolerable
o Benzodiazepines to prevent attacks
o CBT: education to help make more appropriate attributions to somatic symptoms
o Exposure therapy: expose to feared stimulus to desensitize themselves
OCD: treatment
o Combo of medication and psychotherapy
o 1st line = SSRIs
o Clomipramine = gold standard but lots side effects so try SSRIs first
o Refractory OCD: antidepressants + antipsychotics; psychosurgery (cingulotomy)
o CBT: Exposure and response prevention; family therapy to prevent reinforcement of compulsions
List the benzodiazepines
Alprazolam Clonazepam Diazepam Lorazepam Midazolam Oxazepam
List the benzodiazepine antagonists
Flumazenil
List the serotonergic anxiolytic
Buspirone
List the hypnotics
Eszopiclone
Zolpidem
MOA of benzodiazepines vs barbiturates
Overall MOA:
o Affect GABAA receptors
o GABA = major inhibitory NT in CNS
o Stimulate GABAA receptors → opens Cl- pore → Cl- entry into neuron → hyperpolarization → less likely to fire
Benzodiazepine agonists
o Positive GABAA receptors modulators
o Increase affinity of GABAA receptors for GABA
o Increase frequency of GABA-induced Cl- channel opening
o Do NOT directly activate GABAA receptor
Barbiturates
o Increase duration of GABA-induced channel opening
o At high concentrations = directly activate GABAA receptor
• Overall result: neuron hyperpolarized, less excitable
Benzodiazepines: effects & uses
Agonist effects: sedating, hypnotic, anxiolytic, amnesiac, spasmolytic, anti-seizure
Therapeutic uses Do NOT: • Produce surgical anesthesia • Depress respiration in normal patients • Induce CYP enzymes Indicated for short-term use (2-4 weeks)
Benzodiazepines: adverse effects
o Minimal effects on CV function, slight decrease in BP
o Withdrawal syndrome with sudden DC: insomnia, anxiety, seizures (Need to taper to avoid)
o Paradoxical excitement especially in children and elderly
CNS:
• Dose related effects: drowsiness, ataxia, slurred speech
• Additive CNS depression with ethanol and other sedatives and hypnotics
o Highly teratogenic (Pregnancy Risk Category D and X)
Buspirone
Serotonergic anxiolytic
• Non-Benzodiazepine anxiolytic
• Partial agonist at 5-HT1A receptors; moderate affinity/partial agonist effects for D2 receptors
• Treats GAD
• NO sedation, anticonvulsant effects or psychomotor impairment
Explain why there is a difference in the duration of action of diazepam and lorazepam when these drugs are administered chronically.
Diazepam
o Long-acting
o Hepatic metabolism via CYP2C19 & CYP3A4
o Has two active metabolites
Lorazepam
o Metabolized by glucuronidation
o Glucuronide excreted in urine
o No active metabolites (avoids hangover effect)
Explain why the benzodiazepines are not the drugs of choice for the chronic treatment of generalized anxiety disorder and insomnia.
- Adverse effects
- Tolerance and dependence with chronic use
- Withdrawal symptoms = occur more commonly with shorter-acting drugs like benzodiazepines
Explain why the benzodiazepines may be the drugs of choice the treatment of acute anxiety.
• Shorter acting
List other clinical uses of benzodiazepines
Insomnia
Sedation
Anesthesia = at higher doses
Alcohol withdrawal
o Benzodiazepines can substitute for alcohol
o Treat with long-acting benzodiazepine to prevent withdrawal
o Gradually taper dose
Antispasmodic = treatment for seizure disorders; need higher doses so also get sedative effect
Describe the types of insomnia
Transient insomnia
• Lasts 3 weeks
• Caused by major psychiatric illnesses (e.g. mania), sleep apnea, chronic medical illnesses (e.g. CHF)
• “Learned” insomnia
Describe the 2 hypnotics
Zolpidem
• Non-benzodiazepine sedative-hypnotic for short-term treatment
• MOA: within GABAA receptor complex
• Both immediate and controlled release forms
Eszopiclone
• Non-benzodiazepine sedative-hypnotic for long-term treatment
• MOA: within GABAA receptor complex
Describe the indications for the use of flumazenil and potential hazards associated with its use.
Indications:
o Treats benzodiazepine overdoses
o Reverses benzodiazepine sedation during anesthesia
o Antagonizes sedative actions of zolpidem and eszopiclone
o No effect on barbiturate activity
Adverse reactions
o CNS: dizziness, headache
o Injection site pain
o Patients shouldn’t engage in activities requiring complete alertness (residual sedative effects from benzodiazepines)
