Anxiety and Depression Flashcards
What is anxiety disorder? What is it characterised by>
“an inappropriate or excessive, anticipatory manifestation of the fear response, often to a stressor’
- defensive behaviours
- autonomic reflexes
- corticosteroid secretions
- negative emotions
= pathology if interferences with normal life
What are the types of anxiety disorder?
- general anxiety disorder –> somatic and autonomic effects e.g. restlessness, agitation, tachycardia, sweating, sleep disturbance
- phobic anxiety
- panic disorder
- post-traumatic stress disorder
- obsessive compulsive disorder
Draw the hypothalamic-pituitary-adrenocortical axis and describe how it might be altered in anxiety disorders
see lecture
- may be overactive in anxiety
- presence of the stressor may not be necessary to activate it
what are the 3 options for treatment of anxiety disorders?
- self-help
- psychological e.g. CBT
- pharmacological
What are the 3 classes of anxiolytic drugs?
- B blockers
- Benzodiazipines
- Antidepressants
How do beta blockers reduce anxiety?
- reduce somatic symptoms by blocking affects of released adrenaline and NA
What are the useful effects of benzodiazepines?
- reduce anxiety
- induce sleep
What is the mechanism of action of benzodiazepines?
What areas of the brain to they act on?
- increases affinity for GABA at the GABAa receptor –> increase Cl –> hyperpolarisation
- these act in amygdala and prefrontal cortex
What are the short and long term problems with benzidiazipine use?
Short term - sedation - acute overdose, esp. with alcohol Long term - tissue tolerance - dependence and withdrawal
Which class of antidepressants can be used in anxiety?
SSRIs
serotonin selective reuptake inhibitors
What are the symptoms of unipolar depression?
- misery, despair, loss of motivation, appetite, suicidal throughts, move less
What are the two types of causes of depression
reactive (75%)
endogenous (25%)
What are the 4 classes of antidepressants?
- SSRIs
- TCAs
- MAOIs
- atypical
What is the monoamine theory of depression?
Which Its are monoamines?
- depression is due to hypoactivity at monoaminergic (NA and 5-HT) synapses in the brain
What is the evidence for and against the monoamine theory of depression?
Evidence for:
- ADs increase MA in brain rapidly
Evidence against:
- ADs take >1-3 weeks to work
How do you choose which antidpressant to use?
- efficacy
- side effect profiles
Describe the action of MAOIs using the biochemistry of the central monoaminergic synapse
MAO inhibitor prevents breakdown of NA and 5-HT and so increases intraterminal MA and intrasynaptic MA
What are the immediate effects of MAOIs?
When does the antidepressant action start?
- euphoria
- 4 weeks in
Give an example of a MAOI
- moclobemide
- reversible binding, MAO-A selectivity
What are some unwanted effects of MAOIs?
- the cheese reaction, unmetabolised tyramine from diet displaces NA and increases BP
- antimuscarinic effects
- alpha1 antagonism
Give examples of SSRIs
fluoxetine
What is the mechanism of action of SSRIs?
- block re-uptake 5-HT
How long do SSRIs take to have an AD effect?
What are their unwanted effects?
- 2-4 weeks delay to clinical effect
- serotonin syndrome –> suicidal thoughts
- GI and N+V
Give an example of a TCA?
What are their mechanism of action?
amitriptyline
5-HT/NA reuptake inhibition
What are the unwanted effects of TCAs?
- anti-muscarininc
- sedation (H1 antagonism)
- overdose
Newer drugs proposed MoA
NEW = melatonin receptor antagonists
- various uptake/receptor mediated effects for 5-HT, NA, dopamine
- better adverse effect profile
Do AD drugs work?:
- How many patients may not respond?
- Why is it difficult to evaluate efficacy
- 30% of patients may not respond Difficult to evaluate efficacy - trial and error required so studies are difficult to conduct - slow onset of action - mood is variable - high placebo effect
Describe the new theory - the network hypothesis
- depression leads to an increase in CRF (from hypothalamus) and cortisol in the CSF
- this is reversed by ADs
- hyperactivity/sensitivation of the neuroendocrine stress reponse –> depression
Mechanism - chronic stress
- decrease glucocorticoid receptors and BDNF
- decrease neurogenesis and neuroplasticity
AD –> increase MA –> increase neurogenesis –> restore neuronal network - this is the reason for the delay
What is BDNF?
- a neurotrophic factor that helps to maintain healthy synapses
