Mood disorders and antidepressant drugs Flashcards
What are the signs of major depression?
- 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
Name some of the genes that have been linked to depression.
CRHR1
SLC6A4
MAOA
5-HT transporter polymorphisms (short allele)
Name some of the noradrenaline projection sites.
Thalamus Hypothalamus Amygdala Hippocampus Lateral tegmental area Locus coeruleus
Name some of the serotonin projection sites.
Caudate Putamen Globus pallidus Amygdala Hippocampus Raphe nuclei Superior central nucleus
What brain regions are associated with depression?
Ventrolateral prefrontal cortex Dorsolateral prefrontal cortex Medial prefrontal cortex Striatal regions (ventral striatum) Hippocampus
How does the grey matter of the subgenual anterior cingulate cortex in someone with MDD differ from someone without MDD?
Grey matter volume of the subgenual anterior cingulate cortex is reduced in someone with MDD
What other structural differences of the brain are seen in someone with depression?
Reduced cortical thickness
Reduced thickness of the rostral orbitofrontal area 10-47 and the middle orbitofrontal area 47
Give examples of TCAs.
Clomipramine Imipramine Desipramine Amitriptyline Nortriptyline Protriptyline
What receptors do TCAs have an affinity for?
Noradrenaline + serotonin transporters
5-HT2a + 1a
H1
Alpha 1 + 2 adrenoreceptors
*TCAs inhibit the reuptake of monoamines
What are some of the adverse effects of TCAs?
Dry mouth Blurred vision Constipation Urinary retention Fatigue + sedation Weight gain Postural hypotension Dizziness Loss of libido Arrhythmias
Give examples of irreversible monoamine oxidase inhibitors
Phenelzine
Tranylcypramine
Iproniazid
Give an example of a reversible MAOI. What are the adverse effects?
Moclobemide (increased selectivity for MAOa)
S/E: nausea, agitation, confusion
Give examples of SSRIs. What are the adverse effects?
Citalopram, fluoxetine, paroxetine
Adverse effects: nausea headahces GI problems Increased aggression Insomnia Anxiety Sexual dysfunction
Name other classes of antidepressants and give an example for each.
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
Why is there a delay in the action of antidepressants?
- 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
What is discontinuation syndrome? How can it be prevented?
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
What are the symptoms of discontinuation syndrome?
Diarrhoea/abdominal cramps Insomnia Anxiety Nausea Headaches Electric shock sensations Agitation Mood swings
What mood disorder is treated with lithium? What are the side effects?
BPD
S/E: thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne
Describe the different phases of treatment.
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
What type of depression is electroconvulsive therapy used for?
Refractory depression with suicide risk
What area of the brain is stimulated in DBS for depression?
Subcallosal cingulate white matter - area 25
When might vagal nerve stimulation be used to treat depression?
If it is chronic (>2 years)
Which drugs are used to treat atypical depression?
irreversible monoamine oxidase inhibitors:
- Phenelzine
- Tranylcypramine
- Iproniazid
What is the ‘cheese-effect’? How is it avoided?
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
