18. Depression and antidepressants Flashcards
What are the different general types of depression? (DSM-IV classification)
Major depression
Bipolar disorder
Dysthymic disorder
Depressive disorder not otherwise specified
What are the different specific types of depression?
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)
What are the key symptoms in people with depression?
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
What is the role of genetics in developing depression?
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
What are the different theories to explain the pathophysiology of depression?
Monoamine theory
Role of dopamine
Decreased grey matter
What is the pathophysiology of depression in terms of the monoamine theory?
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
What is the pathophysiology of depression in terms dopamine?
Reduced levels of dopamine are thought to result in the development of depression
What is the pathophysiology of depression in terms decreased grey matter?
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
What are the different regions of the brain that are associated with depression?
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
What environmental factors can result in the development of depression?
How is this linked to genetics?
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
What is the role of negative thoughts in depression?
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
What are the different types of antidepressants that can be administered to a patient?
Tricyclic antidepressants
Irreversible monamine oxidase inhibitors
Selective serotonin reuptake inhibitors
Reversible monomamine oxidase inhibitors
How do tricyclic antidepressants work and what are their adverse effects?
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
How do irrevserible monoamine oxidase inhibitors work and what are their adverse effects?
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
How do selective serotonin reuptake inhibitors work and what are their adverse effects?
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
How do reversible monomamine oxidase inhibitors work and what are their adverse effects?
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
What is the delay of onset associated with antidepressants?
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
What is the antidepressant drug discontinuation syndrome?
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
What is bipolar disorder?
This is a mood disorder characterised by cycles of depression and mania i.e. cycles of hyperactivity and of severe depression
What is the main treatment option for people with bipolar disorder?
What are the potential adverse effects?
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
What other treatment options can be used for bipolar disorder?
Other mood stabilisers may be used such as carbamazepine, sodium valproate
Why is it difficult to provide accurate treatment to people suffering from bipolar disorder?
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
How long should a patient continue to take antidepressants after remission and why?
For at least six months to limit the risk of relapse of depression
What percentage of patients fail to respond to antidepressant medication?
About 25-35%
What non-pharmacological treatment options are available for depression and mood disorders?
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
When is vagal nerve stimulation most likely to be used to treat depression?
In chronic depression
What is the advantage of using CBT to treat depression?
This can augment the effects of pharmacological treatment
What structure is the target for the treatment of depression in deep brain stimulation (DBS)?
Subcallosal cingulate white matter/area 25/subgenual cingulate cortex
(All the same place but with different names)
How is electroconvulsive therapy administered?
When may this be most useful as a treatment option?
Induced shock for two weeks - may be multiple times per day
This has a high efficacy in severe treatment-resistant depression
What is the effect of depression on brain matter?
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
What criteria are used to diagnose depression?
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
What is the problem with the monoamine theory for depression?
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
What is hyponatremia and how does this relate to depression?
This is where there are abnormally levels of sodium within the bloodstream
This is a very common side effect of most antidepressants
What are the differential diagnoses for depression and what investigations will be administered to check for these?
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
What is citrulline and what is it’s role in treating depression?
SSRI
This is the medication that should be administered in patients with heart arrhythmia or history of MI
What is the relationship between diabetes and depression?
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
