Mood disorders and antidepressant drugs

Question 1

What are the signs of major depression?

Answer 1

• Fatigue/loss of energy
• Diminished ability to concentrate
• Feelings of guilt and worthlessness
• Suicidal ideation
• Insomnia
• Weight loss and decrease in appetite
• Lack of interest + anhedonia
• Depressed mood
• Psychomotor agitation
• Social withdrawal
• Psychomotor retardation

Question 2

Name some of the genes that have been linked to depression.

Answer 2

CRHR1
SLC6A4
MAOA
5-HT transporter polymorphisms (short allele)

Question 3

Name some of the noradrenaline projection sites.

Answer 3

Thalamus 
Hypothalamus
Amygdala 
Hippocampus 
Lateral tegmental area 
Locus coeruleus

Question 4

Name some of the serotonin projection sites.

Answer 4

Caudate 
Putamen 
Globus pallidus
Amygdala 
Hippocampus 
Raphe nuclei 
Superior central nucleus

Question 5

What brain regions are associated with depression?

Answer 5

Ventrolateral prefrontal cortex
Dorsolateral prefrontal cortex
Medial prefrontal cortex
Striatal regions (ventral striatum) 
Hippocampus

Question 6

How does the grey matter of the subgenual anterior cingulate cortex in someone with MDD differ from someone without MDD?

Answer 6

Grey matter volume of the subgenual anterior cingulate cortex is reduced in someone with MDD

Question 7

What other structural differences of the brain are seen in someone with depression?

Answer 7

Reduced cortical thickness

Reduced thickness of the rostral orbitofrontal area 10-47 and the middle orbitofrontal area 47

Question 8

Give examples of TCAs.

Answer 8

Clomipramine 
Imipramine 
Desipramine
Amitriptyline 
Nortriptyline 
Protriptyline

Question 9

What receptors do TCAs have an affinity for?

Answer 9

Noradrenaline + serotonin transporters
5-HT2a + 1a
H1
Alpha 1 + 2 adrenoreceptors

*TCAs inhibit the reuptake of monoamines

Question 10

What are some of the adverse effects of TCAs?

Answer 10

Dry mouth 
Blurred vision
Constipation 
Urinary retention 
Fatigue + sedation 
Weight gain 
Postural hypotension 
Dizziness 
Loss of libido
Arrhythmias

Question 11

Give examples of irreversible monoamine oxidase inhibitors

Answer 11

Phenelzine
Tranylcypramine
Iproniazid

Question 12

Give an example of a reversible MAOI. What are the adverse effects?

Answer 12

Moclobemide (increased selectivity for MAOa)

S/E: nausea, agitation, confusion

Question 13

Give examples of SSRIs. What are the adverse effects?

Answer 13

Citalopram, fluoxetine, paroxetine

Adverse effects: nausea
headahces
GI problems 
Increased aggression 
Insomnia
Anxiety 
Sexual dysfunction

Question 14

Name other classes of antidepressants and give an example for each.

Answer 14

Serotonin Noradrenaline reuptake inhibitors –> Venlafaxine

Noradrenaline reuptake inhibitors –> Reboxetine

Noradrenaline and specific serotonergic antidepressants –> Mirtazapine

Serotonin antagonist and reuptake inhibitor –> Trazodone

MT1 and MT2 receptor antagonists –> agomelatine

Question 15

Why is there a delay in the action of antidepressants?

Answer 15

• Due to changes in autoreceptors
• The immediate increase in synaptic concentration of amine may lead to activation of somatic neuronal autoreceptors (5-HT1a)
• Activated autoreceptors reduce firing of neurones
• During the first weeks of treatment the autoreceptors desensitise
• Neurones will eventually return to normal firing rate

Question 16

What is discontinuation syndrome? How can it be prevented?

Answer 16

Condition that occurs after a decrease in the dose of drug taken, an interruption of treatment or abrupt cessation of treatment

Can be prevented by a very gradual discontinuation of treatment by using a very slow tapering of the doses taken by the patient

Question 17

What are the symptoms of discontinuation syndrome?

Answer 17

Diarrhoea/abdominal cramps
Insomnia 
Anxiety 
Nausea
Headaches
Electric shock sensations 
Agitation 
Mood swings

Question 18

What mood disorder is treated with lithium? What are the side effects?

Answer 18

BPD

S/E: thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne

Question 19

Describe the different phases of treatment.

Answer 19

Acute treatment: first 6-12 weeks of treatment; aims at remission - an inadequate early response indicates poor prognosis

Continuation treatment: for 6 months after full symptom control - to maintain remission status and prevent relapse

Maintenance treatment: prevention of recurrence of a further episode - maintenance dose for >/=1 year

Question 20

What type of depression is electroconvulsive therapy used for?

Answer 20

Refractory depression with suicide risk

Question 21

What area of the brain is stimulated in DBS for depression?

Answer 21

Subcallosal cingulate white matter - area 25

Question 22

When might vagal nerve stimulation be used to treat depression?

Answer 22

If it is chronic (>2 years)

Question 23

Which drugs are used to treat atypical depression?

Answer 23

irreversible monoamine oxidase inhibitors:

• Phenelzine
• Tranylcypramine
• Iproniazid

Question 24

What is the ‘cheese-effect’? How is it avoided?

Answer 24

Interaction of irreversible MAO inhibitors with tyramine-containing foods (cheese, wine, red meat etc)
Causes high BP, headaches and hypertensive crises
Avoided by avoiding these foods
*these foods must be avoided for at least 2 weeks after discontinuation