18. Depression and antidepressants

Question 1

What are the different general types of depression? (DSM-IV classification)

Answer 1

Major depression
Bipolar disorder
Dysthymic disorder
Depressive disorder not otherwise specified

Question 2

What are the different specific types of depression?

Answer 2

Lifelong anxious depression
Acute depression
Depression after childhood trauma
Depressive reaction to stress
Postpartum depression
Late-life depression
Psychotic depression
Atypical depression
Bipolar depression
Secondary depression (substance abuse, medical illness)

Question 3

What are the key symptoms in people with depression?

Answer 3

Psychomotor retardation (slowing down)
Fatigue or loss of energy
Diminished ability to concentrate
Diminished interest in social activity 
Psychomotor agitation
Depressed mood
Feelings of guilt and worthlessness
Suicidal ideation
Insomnia
Weight loss and decreased appetite
Lack of interest and ahedonia

Question 4

What is the role of genetics in developing depression?

Answer 4

There is a strong genetic component of depression and there is a shared genetic risk between the different forms of depression i.e. there is a cross heritability between e.g. the inheritance of bipolar disorder and of major depression

Question 5

What are the different theories to explain the pathophysiology of depression?

Answer 5

Monoamine theory
Role of dopamine
Decreased grey matter

Question 6

What is the pathophysiology of depression in terms of the monoamine theory?

Answer 6

This is currently the most widely accepted theory
Supports that monoaminergic pathways i.e. noradrenergic and serotonergic pathways are key players in the pathophysiology of depression
These both innervate cortical and subcortical structures and pathways and dysfunctions in these can result in a higher risk of the development of depression

Question 7

What is the pathophysiology of depression in terms dopamine?

Answer 7

Reduced levels of dopamine are thought to result in the development of depression

Question 8

What is the pathophysiology of depression in terms decreased grey matter?

Answer 8

At the subgenual cingulate prefrontal cortex - shown to be a decreased level of grey matter thought to be due to a loss of tissue
There is also a decreased rate of metabolism in this region

There is a decreased decortical thickness of more than 10% which is suggestive of neurodegeneration

Question 9

What are the different regions of the brain that are associated with depression?

Answer 9

These are the regions linked to functional circuit abnormalities in depression:
Amygdala
Ventrolateral prefrontal cortex
Dorsolateral prefrontal cortex
Medial prefrontal cortex
Striatal regions e.g. ventral striatum 
Hippocampus

Question 10

What environmental factors can result in the development of depression?

How is this linked to genetics?

Answer 10

Widely accepted that depression can be triggered by a significant adverse life event e.g. divorce, bereavement
In some individuals, these events will result in the development of the disease

Suggested that different genotypes of the 5-HT transporters play a role in this - there are some genetic factors which can cause individuals to react to a greater extent to certain life events

Question 11

What is the role of negative thoughts in depression?

Answer 11

People with depression are more likely to go over and over negative stimuli and negative thoughts in their mind
Generally, negative stimuli activate the amygdala and the hippocampus and then the sebgenual cingulate but the prefrontal cortex then stops this from becoming a major issue via the regulation of the thought process
BUT in those with depression, the function of the prefrontal cortex is impaired and the control of the negative thoughts is impaired - results in the continuous cyclic negative thoughts

Question 12

What are the different types of antidepressants that can be administered to a patient?

Answer 12

Tricyclic antidepressants
Irreversible monamine oxidase inhibitors
Selective serotonin reuptake inhibitors
Reversible monomamine oxidase inhibitors

Question 13

How do tricyclic antidepressants work and what are their adverse effects?

Answer 13

These inhibit the reuptake of amines and so they increase the monoaminergic cell transmission
These have a different degree of selectivity for amines between them

Have an affinity for many other receptor types e.g. H1, muscarinic, a1 and a2 adrenorecptors
Can result in dry mouth, blurred vision, constipation, urinary tract infection, fatigue, sedation, weight gain, postural hypotension, dizziness, loss of libido

Question 14

How do irrevserible monoamine oxidase inhibitors work and what are their adverse effects?

Answer 14

Irreversible inhibition of the MAO enzymes – non-selective for MAOa and MAOb
So this will work to increase the monoaminergic signalling

Can result in the cheese effect – the MAO enzymes are required for the digestion of certain food types and if this cannot occur then these patients must avoid these foods to avoid adverse reactions to them

Question 15

How do selective serotonin reuptake inhibitors work and what are their adverse effects?

Answer 15

These have an increased selectivity for serotonin uptake and do not have any selectivity for other receptor types
These are also safe in overdose

Adverse effects include nausea, headaches, GI problems, increased aggression, insomnia, anxiety, sexual dysfunction

Question 16

How do reversible monomamine oxidase inhibitors work and what are their adverse effects?

Answer 16

These work in the same way as irreversible monoamine oxidase inhibitors except they have an increased selectivity for MAOa
Irreversible so there is no risk of the cheese effect

Adverse effects of nausea, agitation and confusion

Question 17

What is the delay of onset associated with antidepressants?

Answer 17

With all antidepressants, there is a delay in the onset of time by which it has an action and produces a change in the mood of the individual
Their initial limited effect may be due to the action of autoreceptors which control the monoaminergic receptors
These autoreceptors act to decrease the sudden increased firing of the neurones to return the neurones to the normal firing rate
However overtime, these may become desensitised and then the increased monoamine levels can have their effect

Question 18

What is the antidepressant drug discontinuation syndrome?

Answer 18

This is where in some patients, an abrupt interruption of the treatment can result in the development of extreme adverse side effects such as:
Insomnia, anxiety, nausea, headaches, electric shock sensations, agitation, mood swings, diarrhoea/abdominal cramps

Question 19

What is bipolar disorder?

Answer 19

This is a mood disorder characterised by cycles of depression and mania i.e. cycles of hyperactivity and of severe depression

Question 20

What is the main treatment option for people with bipolar disorder?

What are the potential adverse effects?

Answer 20

Lithium
This is used as a maintenance treatment in bipolar disorder to decrease these cycles
NB. this has a narrow therapeutic margin

Adverse effects of thirst, nausea, fine tremor, polyuria, weight gain, oedema and acne

Question 21

What other treatment options can be used for bipolar disorder?

Answer 21

Other mood stabilisers may be used such as carbamazepine, sodium valproate

Question 22

Why is it difficult to provide accurate treatment to people suffering from bipolar disorder?

Answer 22

Because you don’t really want to use pure antidepressants or pure antipsychotics - these can increase one of the depressive/manic cycles more than the other
You don’t want to precipitate more mania or push the patient further into depression

Question 23

How long should a patient continue to take antidepressants after remission and why?

Answer 23

For at least six months to limit the risk of relapse of depression

Question 24

What percentage of patients fail to respond to antidepressant medication?

Answer 24

About 25-35%

Question 25

What non-pharmacological treatment options are available for depression and mood disorders?

Answer 25

Electroconvulsive therapy - can have adverse long lasting cognitive effects
Cognitive behavioural therapy (CBT)
Vagal nerve stimulation
Deep brain stimulation
Interpersonal psychotherapy - identify reason for the downward spiral of mood and develop ways to overcome this

Question 26

When is vagal nerve stimulation most likely to be used to treat depression?

Answer 26

In chronic depression

Question 27

What is the advantage of using CBT to treat depression?

Answer 27

This can augment the effects of pharmacological treatment

Question 28

What structure is the target for the treatment of depression in deep brain stimulation (DBS)?

Answer 28

Subcallosal cingulate white matter/area 25/subgenual cingulate cortex
(All the same place but with different names)

Question 29

How is electroconvulsive therapy administered?

When may this be most useful as a treatment option?

Answer 29

Induced shock for two weeks - may be multiple times per day

This has a high efficacy in severe treatment-resistant depression

Question 30

What is the effect of depression on brain matter?

Answer 30

Major depression can structurally effect the brain - results in a reduced volume of hippocampal white matter

Can also result in a loss of grey matter due to a persistent neuroinflammaotry state - neuronal loss and decreased neurogenesis in the grey matter of the hippocampus too

Question 31

What criteria are used to diagnose depression?

Answer 31

DSM-IV: There are 9 symptoms and if the patient presnts with 5 of these then they can be diagnosed with depression

ICD-10: 10 different symptoms and these subcategorise depression - mild, moderate and severe

Question 32

What is the problem with the monoamine theory for depression?

Answer 32

Antidepressants act to increase the number of monoamines present within a few days however, the beneficial effects do not occur until after at least a few weeks after
Suggests that the pathophysiology of depression is more complex that just lacking level of monoamine neurotransmission at the synapse

Question 33

What is hyponatremia and how does this relate to depression?

Answer 33

This is where there are abnormally levels of sodium within the bloodstream
This is a very common side effect of most antidepressants

Question 34

What are the differential diagnoses for depression and what investigations will be administered to check for these?

Answer 34

TSH and thyroxine – hypothyroidism
Basic electrolytes and serum calcium – metabolic disturbance
Full blood count – systemic infection or chronic disease
Testosterone – hypogonadism (cause of depression in men)
Vitamin D – low vitamin D levels are associated with greater risk of depression

Question 35

What is citrulline and what is it’s role in treating depression?

Answer 35

SSRI

This is the medication that should be administered in patients with heart arrhythmia or history of MI

Question 36

What is the relationship between diabetes and depression?

Answer 36

Depression has a negative affect on metabolic control
Patients with a depression diagnosis should be screened for diabetes

Fluxotine - SSRI - has been associated with improvements in HBA1C