What neurotransmitters are involved in anxiety disorders?
Corticotropin-releasing Factor (CRF)
What parts of the brain are involved in anxiety?
locus ceruleus (LC)
medial and dorsal raphe nuclei
periaqueductal gray matter
What plays a critical role in the assessment of fear stimuli and learned response to fear?
What part of the brain is the primary NE-containing site, with widespread projections to areas responsible for implementing fear responses (vagus, lateral and paraventricular hypothalamus)?
the locus ceruleus
What area of the brain is integral to consolidation of traumatic memory and contextual fear conditioning?
What area of the brain is the principle area for integrating neuroendocrine and autonomic response to a threat?
What is the Noradrenergic Model of anxiety?
the ANS of anxious pts is hypersensitive and overreacts to various stimuli
many pt display sx of peripheral autonomic hyperactivity
in response to a threat, the LC serves as an alarm center, activating NE release and stimulating SNS and PNS
chronic central noradrenergic overactivity down-regulates alpha2 receptors in pts with GAD (alpha2 receptors are hypersensitive in some pts with panic disorder)
pts with SAD appear to have hyperreactive adrenocortical response to psychologic stress
LC --> NE --> glutamate -->anxiety
What is the GABA Receptor Model of anxiety?
drugs to reduce anxiety and produce sedation target GABAAGABAA receptors are ligand-gated ion channels
When benzodiazepine ligands bind to GABA, the inhibitory effects of GABA binding to GABAA receptors are enhanced which decreases 5-HT, NE and DA effects
growth hormone response to baclofen in pts with generalized SAD suggests an abnormality in central GABAB receptor function
What is the Serotonin Model for anxiety?
no definitive evidence shows a clear abnormality in 5-HT function
abnormalities in serotonergic functioning through release and reuptake at the presynaptic autoreceptors (1A/1D), the serotonin reuptake transporter (SERT) site, or effect of 5-HT at the postsynaptic receptors (1A, 2A, 2C) may play a role in anxiety disorders
increased 5-HT function may increase avoidance behavior
decreased 5-HT function may increase aggression
What is seen on neuroimaging in pts with GAD?
increased cortical activity
decreased basal ganglion activity
benzodiazepine tx results in increased basal ganglion activity and decreased cortical activity
What is seen on neuroimaging in pts with panic disorder?
abnormal activation of the parahippocampal region and the prefrontal cortex
decreased GABA concentrations in the occipital region
What effect do pharmacotherapy and psychotherapy have on neuroimaging in pts with SAD?
decreased cerebral blood flow in the amygdala, hippocampus, and surrounding cortical areas
Which neurotransmitter is associated with the raphe nuclei?
Which neurotransmitter is associated with the locus ceruleus?
Which area of the brain is responsible for fear response (freezing or "fight or flight")?
the periaqueductal gray matter
What is the consequence of increased release of NE?
What is the most important inhibitory neurotransmitter in the CNS?
What is the consequence of increased glutamate?
What is the consequence of increased cholecystokinin (CCK)?
Which anxiety disorder is characterized by sustained, unrealistic or excessive anxiety or worry about many different things?
What causes GAD?
no identifiable trigger
Which neurotransmitters are involved in GAD?
What is the onset of GAD?
usually early in life (childhood or adolescence)
What is the first line therapy for GAD?
What drugs are used for GAD?
pregabalin (in the European Union)
propranolol - for somatic sx only, not to decrease anxiety
What should be used in patients who requre rapid anxiolytic effect?
What should be avoided in patients with a history of substance abuse?
What should be used in pts with past or current substance abuse
What should pts on buspirone or antidepressants be told to expect?
some pts experience restlessness, jitteriness, increased anxiety sx, insomnia and HA (will go away with time)
Which antidepressants are approved for use in GAD?
Which drug is no good for comorbid conditions (depression, panic, PTSD, OCD, etc)?
Antihistamine used for GAD
mild, dose-dependent anticholinergic SE at high doses
What are the issues with a single dose of a benzodiazepine?
food and anticholinergics slow the onset (good if you experience a rush SE)
lipid soluble drugs have short DOA d/t rapid redistribution out of the brain
What are the issues with multiple doses of BZDs?
accumulation a problem for chronic insomniacs
clinical significance of accumulation is mitigated by tolerance
impaired metabolism with age, liver dysfunction, and alcohol abuse (use one that is glucuronidated, not oxidated)
tolerance can sometimes develop as quickly as one dose
may cause daytime sedation
What are the advantages of BZDs in GAD?
VERY rapid onset of anxiolysis
safer than barbs
generally well tolerated
favorable sleep profile
few significant DI = large therapeutic window
What are the disadvantages of BZDs in GAD?
some pts don't like them
rare disinhibition rxns (usually kids and elderly)