Depression and Anxiety Flashcards
How effective is drug treatment for depression and anxiety?
drug treatment is about 30% effective and complete remission is not common
-drug treatment takes weeks to work
What are some symptoms of major depression?
feelings of sadness, tearfulness, emptiness or hopelessness
angry outbursts, irritability or frustration even over small things
loss of interest or pleasure in normal activities
sleep disturbances
tiredness and lack of energy
reduced appetite or cravings and weight loss or gain
anxiety, agitation or restlessness
slowed thinking, speaking, movements
feeling of worthlessness
trouble thinking or concentrating
suicidal thoughts
physical problems
What are psychological symptoms of generalized anxiety?
persistent worry
overthinking plans and solutions
perceiving events as threatening
difficulty handling uncertainty
indecisiveness and fear of making wrong decision
inability to let go of worry
inability to relax
difficulty concentrating
What are the physical symptoms of generalized anxiety?
fatigue
trouble sleeping
muscle tension/aches
trembling
nervousness
sweating
nausea, diarrhea or IBS
irritable
What are the treatment modalities for depression and anxiety?
medications (particular those involved in serotonergic system)
counseling
exercise, meditation, light therapy, relaxation
multimodal approach creates synergy, one method alone is not sufficient
Describe the serotonergic system.
14 subtypes of receptors organized into 7 classes
receptor classes coupled to G proteins except for 5-HT3 which is ligand gated ion channel
Where does serotonin work in the body?
brain: mood, happiness, sleep
periphery
gut
CV system and platelets
What are the major brain regions involved in serotonergic pathways and their respective roles?
hippocampus: learning & memory
amygdala: fear & emotions
hypothalamus: neuroendocrine functions
Where is 5-HT produced?
several raphe nuclei in the brainstem
What does serotonin do in the body?
mood and emotion processing
sleep/wake cycling (promotes sleep)
aggression and impulsivity
appetite and obesity
platelet response
effects on CV system
reduces airway inflammation
GIT (modulates enteric nervous system)
How does serotonin reduce appetite?
activation of 5HT2C in hypothalamus
How is serotonin involved in vasodilation and the platelet response?
activates 5HT1 resulting in NO release=vasodilation
activates 5HT2=platelet aggregation + vasoconstriction
How does serotonin reduce airway inflammation?
5HT2 receptor activation
Describe serotoninergic signaling.
depolarization of presynaptic neuron=entry of Ca and Na
vesicles full of serotonin fuse with plasma membrane releasing 5HT into the synaptic cleft
serotonin traverses the cleft and binds with serotonin receptor on the postsynaptic nerve terminal
intracellular signaling occurs in the postsynaptic nerve resulting in a downstream effect
What is the monoamine hypothesis of depression?
depletion of monoamines causes depressive symptoms
-NE, serotonin, and dopamine
the dysregulation may have a genetic link and/or may be affected by stress or trauma, whereby receptor density or sensitivity is altered and brain function is impacted
restoring monoamines improves depression
What is a neurotropic factor that may be involved in depression?
brain-derived neurotrophic factor (BDNF)
-regulates plasticity, resilience, and neurogenesis
What is the impact of stress and pain on BDNF?
decreases BDNF
-antidepressants enhance BDNF-induced neurogenesis and
synaptic connectivity in areas like hippocampus
-structures affected may be affected anatomically by
persistent, untreated major depression due to neuronal loss
-electroshock treatment=increased BDNF
What are the hormonal factors associated with major depressive disorder?
elevated cortisol
low thyroid hormone
low estrogen
low testosterone
these may reduce BDNF transcription
How quickly does treatment with antidepressants increase monoamine levels?
quickly but the antidepressive effect lags by several weeks
-due to time required to upregulated expression of
neurotrophic factors and modulated serotonin receptors to a
more normal physiologic state
What are drugs that affect serotonergic signaling?
reserpine
-prevents vesicular accumulation of serotonin
triptans
-agonist at 5HT 1D/1B to reduce pain and reduce vasodilation
MAOIs
-inhibit serotonin breakdown
SSRIs/SNRIs/TCAs
-block 5HT reuptake at the synaptic cleft
busiprone
-partial agonist at 5HT 1A
antipsychotic drugs
-block 5HT 2A/C
anti-emetics
-block 5HT3 receptors (Na ion channel)
What are SSRIs the main therapy for?
major depression
anxiety
panic attacks
OCD
PTSD
How do SSRIs work?
inhibiting serotonin reuptake into the pre-synaptic terminus (SERT) and a reduction in “autoreceptors” in the axon and terminus of the pre-synaptic nerve so they no longer reduce serotonin release
What are the long term changes of SSRIs on neurotropic factors?
BNDF increases
SERT decrease
takes weeks
What are some pharmacokinetic properties of SSRIs?
CYPD2D, CYP 2C19 inhibitors
avoid with St Johns Wort and other serotonergic drugs
-risk of serotonin syndrome
OD dosing
