W7 30 anti-depressant drugs

Question 1

Mood fluctuates routinely. What is depression?

Answer 1

Mood variation has to be persistent and pervasive.
Time duration is if low/irritable mood lasts for 2 weeks or more (since life events affect mood)

Question 2

What social factors can predispose to depression?

Answer 2

Unemployed, social class 4 and below, urban, moved 2/3 times in last 2 years, social housing, no formal qualifications, losing a loved one (partner or child)

Question 3

What are the diagnostic features of depression - key symptoms?

Answer 3

Persistent sadness or low mood
And/or
Marked loss of interests or pleasure

Question 4

What are the diagnostic features of depression - associated symptoms?

Answer 4

Altered sleep
Decreased or increase appetite and/or weight
Fatigue or loss of energy
Agitation of slowing of movements
Poor concentration or indecisiveness
Feelings of worthlessness or excessive or inappropriate guilt
Suicidal thoughts or acts

Question 5

What is slowing of movements also called?

Answer 5

Slowing of movements is retardation, or psychomotive agitation, where they can’t sit still and keep moving (mainly in elderly)

Question 6

What are the diagnoses for depression, via no. of symptoms?

Answer 6

Subthreshold depressive symptoms - fewer than 5 symptoms of depression
Mild - symptoms in excess of 5 required to make the diagnosis and symptoms result in only minor functional impairment
Moderate - symptoms or functional impairment are between mild and severe
Severe - most symptoms present (>7/8). Markedly interfere with functioning. Can occur with or without psychotic symptoms.

Question 7

What is the diagnosis of depression not solely based on symptom counting?

Answer 7

Severity
Persistence - longer than 2 weeks (pervasive - low in all situations of a persons life)
Presence of other symptoms
Functional and social impairment

Question 8

What are the aetiological risk factors for depression?

Answer 8

Biological vulnerability (genes, brain anomalies etc)
Psychotic vulnerability (eg abuse, neglect etc, fighting parents, neuroticism)
Social vulnerability (eg unemployment, poverty, homelessness etc)
Stress (bereavement, trauma, illness onset etc)
Just risk factors not causative. Resilience factors can prevent depression development.

Question 9

What are the different theories for depression?

Answer 9

Monoamine hypothesis - depression results from low monoamines (serotonin and NA)
Hypothalamus pituitary adrenal axes hyperactivity

Question 10

What is the theory for the HPA axis hyperactivity?

Answer 10

Chronic stress leads to increased HPA axis so increased ACTH, thus increased cortisol levels, and CRF —> reduced hippocampus and neurogenisis
- hippocampus has a negative feedback mechanism on HPA axis, so chronic activity means it reduces the feedback more
- neurogenesis = neuronal death in brain and regeneration occurs usually but hippocampus atrophy reduces neurogenesis

Question 11

What brain areas are implicated in depression?

Answer 11

Prefrontal cortex anterior cingulate cortex, primary and secondary somatosensory cortex, insular cortex, posterior cerebellum, amygdala, hippocampus, thalamus, nucleus accumbens

Question 12

How are monoamines (5HT and NA) neurotransmitted?

Answer 12

Presynaptic neurone has vesicles containing monoamines
When transmission has to occur, monoamines are released into the synaptic cleft
They attach themselves onto the post-synaptic receptors
Signals occur with second generation messenger changes and the signal if propagated through the post-synaptic neurone
Once the activity of the neurotransmitter is completed in the synaptic cleft, they are taken back. There are reuptake transporters for both. Some are metabolised, lots taken back up into presynaptic neurone, some stores back into vesicles

Question 13

According to the monoamine hypothesis, if there are low levels of 5HY and/or NA, how can we increase levels of these in the synaptic cleft?

Answer 13

Inhibit the re-uptake of the monoamines
Increase production of monoamines (eg eating things containing tryptophan, exercise)
Increase release of monoamines

Question 14

Treatments for depression

Answer 14

Antidepressants (most common for severe and moderate)
Adjuvant medication: lithium, antipsychotic medication
Psychological therapies
Electroconvulsive therapy (ECT)

Question 15

What are the NICE guidelines on depression interventions?

Answer 15

Read the diagram PG321

Question 16

What different antidepressants are there?

Answer 16

TCAs - tricyclic antidepressants
Specific 5HT or NA reuptake inhibitors
Dual 5HT/NA reuptake inhibitors
MAOIs - monoamine oxidase inhibitors
Selective MAO-A inhibitors
Reversible MAO-A inhibitors
Newer ‘atypical’ antidepressants

Question 17

What do tricyclic antidepressants do?

Answer 17

Block 5HT and NA reuptake
Increases levels of monoamines in the synaptic cleft, reducing depression

Question 18

What is the problem with TCAs?

Answer 18

Dirty drugs - block not just monoamines but other neurotransmitters including histamine, dopamine and cholinergic receptors, leading to a wide array of side effects eg cardiac side effects.

Question 19

What do specific 5HT or NA reuptake inhibitors do?

Answer 19

Targeted blocking the uptake of 5HT or NA
Less side effects than TCAs
First line drug for antidepressant medication

Question 20

What do dual 5HT/NA reuptake inhibitors do?

Answer 20

Non-specific, so blocks uptake of lots of monoamines.
SNRIs venlafaxine.

Question 21

Why do we use dual 5HT/N reuptake inhibitors with caution?

Answer 21

Use drugs with caution with people with cardiac effects due to blockage of noradrenergic reuptake, leading to increase of NA, which can have cardiotoxic effects.

Question 22

What do monoamine oxidase inhibitors do (MAOIs)?

Answer 22

Blocks the action of enzymes that metabolise the neurotransmitters, so more neurotransmitter available for action.
Either non-specific blocking NA 5HT as well as dopamine and others etc leading to significant side effects, eg hypertensive side effects.

Question 23

What do ‘atypical’ antidepressants do?

Answer 23

Free of major tricyclic side effects
Amplify 5HT and/or NA by a variety of mechanisms

Question 24

What are the first line drugs for depression?

Answer 24

SSRIs - specific serotonin reuptake inhibitors

Question 25

Give some examples of SSRIs

Answer 25

Fluoxetine
Citalopram
Escitalopram
Sertraline
Paroxetine
Fluvoxamine
Vortioxetine

Question 26

Give some examples of TCAs

Answer 26

Amitriptyline
Clomipramine
Dosulpein
Imipramine
Lofepramine
Nortriptyline
Doxepin

Question 27

Give examples of MAOIs

Answer 27

Moclobemide clorgyline
Phenelzine tranylcypromine

Question 28

Examples of SNRIs

Answer 28

Venlafaxine
Duloxetine

Question 29

What is usually the second choice of drug for depression after SSRIs and what do it do?

Answer 29

Mirtazapine - an antagonist at central pre-synaptic a2-receptors, increasing both 5HT and NA
(also helps with sleep at lower doses)

Question 30

What are agomelatine?

Answer 30

Fairly newer - agonist at melatonin receptor and antagonist at 5HT2c receptors

Question 31

What is reboxetine?

Answer 31

Specific noradrenergic reuptake inhibitors, not used as much

Question 32

Some drugs interact with antidepressants. Which antidepressants do NSAIDs interact with and what is their interaction?

Answer 32

Interacts with SSRIs
Increased risk of GI bleeding. Short term use (2-4days) is fine but avoid in elderly and those at risk of GI bleed.

Question 33

Some drugs interact with antidepressants. Which antidepressants do codeine and derivatives interact with and what is their interaction?

Answer 33

SSRIs
SSRIs inhibit CYP2D6 leading to poor analgesia. If opiate pain relief is required use morphine.

Question 34

Some drugs interact with antidepressants. Which antidepressants do benzodiazepines interact with and what is their interaction?

Answer 34

SSRIs
Inhibit oxidation of benzo leading to elevated levels. If required use lorazepam/temazepam.

Question 35

Some drugs interact with antidepressants. Which antidepressants do tramadol and merperidine interact with and what is their interaction?

Answer 35

SSRIs - Serotonin syndrome
Meperidine also interacts with MAOIs - unclear action but seizures and coma occur

Question 36

Some drugs interact with antidepressants. Which antidepressants do epinephrine and levonordefrin interact with and what is their interaction?

Answer 36

MAOIs - ephedrine and nasal decongestants may lead to hypertensive crisis
TCAs - sympathomimetic actions, use with caution, recheck vital signs after use