Anti-depressants Flashcards
What is important to remember about Lithium
Strictly, it is not an anti-depressant
It is a mood stabilising drug.
Summarise ECT
Used in cases of ‘black depression’- where the patient is not responding to talking therapies or drugs
Current across temporal lobe
Give a shot of suxamethonium short-acting NMJ blocker- to prevent any damage to the limbs from convulsions.
Describe the different classification of psychoses
Split into: Schizophrenia (thought disorders) Affective disorders (mood-related)- which consist of mania (less common) and depression.
Describe the emotional (psychological) symptoms of depression
Misery, apathy, pessimism
Low self-esteem
Loss of motivation
Anhedonia (inability to enjoy life)
Describe the biological (somatic) symptoms of depression
Slowing of thought & action (psychomotor retardation)
Loss of libido
Loss of appetite, sleep disturbance
What are the two different types of depression
Unipolar depression/ depressive disorder
Bipolar depression/ Manic Depression
Describe unipolar depression / depressive disorder
Mood swings in same direction
Relatively late onset
Reactive depression (75%) - stressful life events (disproportionate response)
- non-familial
Endogenous depression (25%) - unrelated to external stresses
- familial pattern
What is important to remember about the drug treatment for unipolar depression
Same for both reactive and endogenous depression.
Describe bipolar depression
Oscillating depression/mania
Less common; Early adult onset
Strong hereditary tendency
Drug treatment (Lithium- oral lithium carbonate- effects I.C secondary messenger symtpoms (reduces cAMP and IP3)
Symptoms of mania- opposite to that of depression (increased exuberance, aggression etc).
What is the key difference between bipolar depression and unipolar depression
Bipolar depression- symptoms in common with schizophrenia
Unipolar depression- symptoms associated with fear and aggression.
Define what is meant by ‘psychoses’
Severe mental disorders, with or without, organic damage, characterised by derangement of personality and loss of contact with reality, and causing deterioration of normal social functioning.
Describe the monamine theory of depression
§ Monoamine theory of depression – depression is a functional deficit of central MA transmission; Mania is a functional excess of MA transmission.
o Related to NA and 5-HT (serotonin) deficits/excesses.
Summarise the pharmacological evidence that supports the monamine theory of depression
TCAs- block NA and 5-HT reuptake- Increase MOOD
MA oxidase inhibitors – Increase stores of NA and 5-HT – increase MOOD
Reserpine (MA deplete) - inhibits NA and 5-HT storage - decreases mood
a-methyltyrosine and methyldopa- inhibit NA synthesis- decreasing mood (and calming of manic patients)
ECT- increases CNS response to NA and 5-HT- increases mood.
Describe the pharmacological evidence that disagrees with the monoamine theory of depression.
Amphetamine- releases NA and blocks re-uptake- no effect on mood (but causes euphoria in normal subjects).
Cocaine- inhibits NA reuptake- no effect on mood (but causes euphoria in normal subjects)
Tryptophan -increases 5-HT synthesis- mood may increase in some subjects but not all
Alpha and beta adrenoreceptor antagonists - block NA action- mood slightly reduced, but no effect on manic patients
Methysegide- 5-HT antagonist- no effect
L-dopa - increases NA synthesis - no effect
Iprindole- no effect on monamine metabolism- increases mood.
Describe the inconsistency of the biochemical evidence of the monamine theory
Although a reduction of NA metabolites are seen in patients with clinical depression, there is no correlation i.e not necessarily an even greater reduction in NA metabolites for a patient with severe depression as opposed to mild depression.
There is a delayed onset of the clinical effects of drugs, when the reduction in monamines would take place acutely. This may be due to adaptive changes of the neurones of depressed patients (i.e down regulation of a2, beta and 5-HT receptors) which are only targeted by anti-depressants after a couple of weeks.
However the general conclusions remain firm- and many of the anti-depressants target monamine metabolism to have their effect
Describe some other theories for depression
HPA axis (↑ CRH levels)?- Hippocampal neurodegeneration? - anti-depressant drugs have been shown to reverse this.
The plasma cortisol concentration is usually high in depressed patients. Other hormones in plasma are also affected, for example, growth hormone concentration is reduced and prolactin is increased. While these changes are consistent with deficiencies in monoamine transmission, they are not specific to depressive syndromes.
But CRF1 receptor antagonists have not been effective.
Why may cocaine not be effective in treating depression
Adaptive changes of neurones in depressed patients- may not express cocaine receptors.
Describe Reserpine
Originally licenced as an anti-hypertensive- no longer used due to its association with depression.
Monamine depletor- that is it inhibits the synaptic proteins that package and store NA in vesicles- depleting its storage- less released.