Depression + Antidepressants Flashcards
What are the depressive symptoms?
Depressed mood
Loss of interest
Weight loss/gain
Insomnia
Agitation
Fatigue
Feeling worthless
Decreased concentration
Thoughts of death/suicide
What is mild depression?
Minimum of 5 symptoms
Mild functional impairment
What is moderate depression?
More symptoms
More functional impairment
What is severe depression?
Most symptoms present
Marked functional impairment
What is aetiology of depression?
Stress - early-life + on-going
Drugs/alcohol
Medicines
Genetics - more likely if relation has it
What is the pathology of depression?
UNCERTAIN
BUT increased cortisol levels
How do you treat mild depression?
Lifestyle changes
Counselling
How do you treat moderate/severe depression?
Lifestyle changes
Counselling
Pharmacotherapy
Non-drug treatments
What is Iproniazid?
Inhibits monoamine oxidase
What is Imipramine?
Inhibits reuptake of 5-HT + noradrenaline
Describe the biochemistry of 5-HT terminal
Activity of TPH determine synthesis rate
Activity of MAO determines breakdown
Synthesis + breakdown determine vesicular content
Content of vesicles determines amount of 5-HT released per AP
Firing activity determines release rate
Transporter activity determines reuptake rate
Release + reuptake determine level + duration of 5-HT in synaptic cleft + activation of receptors
What does the inhibition of MAO do?
Increased neurotransmitter in vesicles
Increased release per impulse
What does the inhibition of reuptake do?
Increased duration + concentration of 5-HT/NA in synaptic cleft
What targets metabolism?
MAO inhibitors
What targets the reuptake?
TCAs
SSRIs
NARIs = noradrenaline reuptake inhibitors
SNRIs
What does MAOa target the most?
5-HT>NA>DA
What does MAOb target the most?
DA>NA>5-HT
What are the MAOa drugs?
Clorgyline
Moclobemide
What are the MAOb drugs?
Selegiline
What are the MAOa+b drugs?
Pargyline
Iproniazid
Tranylcypromine
What are the interactions for MOA inhibitors?
Interaction with foods
Serotonin syndrome = interact with other serotonergic drugs
What is the patient advice for MOA inhibitors?
Avoid certain foods
Avoid OTC cold remedies + drugs of abuse
Do NOT take any other antidepressants
What is the main problem with MOA inhibitors?
Irreversible enzyme inhibitors
= their effects outlast the clearance of the drug
= take around 6 weeks for enzyme protein turnover
What are the side effects of TCAs/SSRIs/SNRIs?
GI disturbance
Sexual dysfunction
Dry mouth
What are the TCAs side effects?
Sedation
Hypotension
Weight gain
Dry mouth
Urinary retention
What is the problem with antidepressants?
Delayed action (4-8 weeks)
What is the 1st line treatment for depression?
SSRI
eg. Sertraline, Citalopram
What do you need to do with SSRIs?
Low dose first
THEN increase if tolerated
BUT must be safe
What to do if there is a poor response to treatment?
Ensure positive lifestyle changes
Increase dose - BUT safe
Switch antidepressant
Additional drug
Additional non-drug therapy = CBT therapy
Other drug treatments = transcranial magnetic stimulation (TMS)
Why is TCAs NOT 1st line?
More side effects
More dangerous in overdose
Why is SNRIs NOT 1st line?
More efficacious in treatment of resistant depression
BUT less well tolerated
Why is MAO inhibitors NOT 1ST line?
Effective
BUT difficult to take
What can happen of you come off antidepressants suddenly?
Withdrawal symptoms
Associate with relapse
Why do you come off antidepressants?
Depression is episodic + recurrent
Discontinuation associated with relapse
What are the withdrawal symptoms?
Flu-like symptoms
Nausea
Anxiety
Electric shocks
Difficulty sleeping
How do you avoid discontinuation syndrome for long half life drugs?
eg. Fluoxetine
Gradually decrease amount of tablets
= plasma levels fall very slowly
How do you avoid discontinuation syndrome for short half life drugs?
eg. Paroxetine
Switch to fluoxetine
Reduce doses slowly over several weeks
Treat symptoms -eg. constipation
