P18: Antidepressant Drugs Flashcards
Give examples for manic symptoms
- Euphoria
- Over-confidence
- Grandeur delusions
- Irritability
- Anger
Give examples for depressive symptoms
- Misery, apathy
- Pessimism
- Indecisiveness
- Loss of appetite
- Insomnia
- Avolition
What can cause secondary mood disorders?
- Illness
- Medication
What are the classes of primary mood disorders?
- Bipolar
- Unipolar
What symptoms do you show if you have a Bipolar mood disorder?
Both mania and depressive symptoms
What symptoms do you show if you have a Unipolar mood disorder?
Only depressive symptoms
Name some of the genetic risk factors of MDD
- No single genes identified
- Familial component exists (twins)
- Genes regulating 5-HT transmission (weak)
Name some of the social risk factors of MDD
- Bereavement
- Financial strain
- Emotional, physical or sexual abuse
- Childhood trauma/abuse
- Social exclusion – e.g. being LGBT in an unsupportive environment
Name some of the medical risk factors of MDD
- Alcohol or illegal drug use
- Serious or chronic ill health
- Medicinal drugs, e.g. antihypertensive medication
What is the Monoamine Theory of Depression?
- Deficiency in one or more key monoamines [Serotonin, NorAd, Dopamine]
- Pre-synaptic neurone upregulates these key MAs
- Abnormally functioning gene causes depression
What is the evidence for the Monoamine Theory of Depression?
- Treatment of patients with the noradrenaline packaging blocker reserpine for hypertension caused depression
- Treatment of tuberculosis with the monoamine oxidase inhibitor iproniazid improved patients’ moods
- Majority of antidepressant drugs potentiate monoamine (noradrenaline, 5-HT, dopamine, adrenaline) signalling
Patients with MDD often show over-activity in which part of the brain?
Thalamus, which has strong connections to the amygdala (fear and anxiety)
How do Tricyclic Antidepressants (TCAs) work?
Inhibit the uptake of both 5-HT and NA, prolonging their synaptic lifespan
Give some examples of Tricyclic Antidepressants
I am Despacito
- Imipramine (NA»_space; 5-HT)
- Amitriptyline (5-HT and NA)
- Desipramine (NA, active metabolite of imipramine)
slow onset
What are the side effects of TCAs?
- Epilepsy
- anti-muscarinic - dry mouth, constipation, urinary retention
- α-adrenoceptor antagonism - postural hypotension
- Sedation (H1 antagonism)
- cardiotoxic in overdose
How do Monoamine Oxidase Inhibitors (MAOI) work?
Inhibit MAO-A, so NA and 5-HT are not broken down.
Give some examples of MAOIs
- Phenelzine (non reversible)
- Tranylcypromine [Non-reversible]
- Moclobemide [MAO-A, Rev]
What are the side effects of MAOIs?
- Hyperthermia
- Hypotension
- Coma
- Respiratory depression
How do Serotonin Selective Reuptake Inhibitors (SSRIs) work?
Inhibit reuptake of 5-HT therefore prolong synaptic lifespan of 5-HT
2-3 week onset
Give some examples of SSRIs
- Fluoxetine (prozac)
- Paroxetine
- Citalopram
- Fluvoxamine
What are the side effects of SSRIs?
- Epilepsy
- Lacks sedative and anti-muscarinic effects of TCAs
What causes serotonin syndrome?
Use of two (or more) types of monoamine modulators can in rare instances induce an acute toxic reaction
rapid onset
What are the symptoms of serotonin syndrome?
- High body temperature (>41C)
- Agitation
- Sweating
- Dilated pupils
- Diarrhoea
- Seizures
What is Venlafaxine?
Potent blocker of both serotonin and noradrenaline reuptake (SNaRI)
What is Nefazodone?
- Potent 5-HT2 receptor antagonist, with weak SNaRI activity
- More sedating than venlafaxine
- Causes nausea
What is Mirtazapine?
- α2, 5-HT2 and 5-HT3 receptor antagonist
- Increases both noradrenaline and serotonin transmission
What is Reboxetine?
- Selective noradrenaline reuptake inhibitor
- Anti-muscarinic and pro-sympathetic side effects (e.g. dry mouth, insomnia, constipation, urinary retention, tachycardia)
What are the structural changes to the brain with someone with Bipolar affective disorder?
Increased volume of the pallidum and lateral ventricles
What are the functional changes to the brain with someone with Bipolar Affective Disorder?
Abnormal modulation of the amygdala is likely to underlie emotional and mood regulation
How does Lithium work as a drug to treat MDD?
- Mood stabilising drug, more effective in bipolar than unipolar affective disorder
- Reduces the frequency and severity of relapses by half, reduces the likelihood of suicide
What is the Lithium Mechanism of Action?
- Affects the Inositol cascade
- Li+ inhibits inositol recycling, limiting actions of Gq-coupled receptors
- Reduces CNS glutamate, GABA, glycine, 5-HT, ACh, dopamine and noradrenaline signalling
What are the 2 major categories of depressive disorder
dysthymia - mild
major depressive disorder (MDD) - severe
What are the major flaws of the monoamine theory of depression
- Treatment with monoamine interacting drugs has an immediate neurochemical effect, but behavioural effects take 3-4 weeks to appear
- No evidence for a primary deficit in monoamine transmission in MDD patients
- Atypical antidepressants do not target the monoamine systems but are effective
How might the Hypothalamo-Pituitary-Adrenal Axis result in depression
- Adapts to stressors over time and releases more GCs
- GCs in patients with MDD can’t regulate their own production
- Evidence that HPA axis is over active in MDD patients
- GC over-exposure thought to damage serotonergic pathways in the brain, leading to neuronal retraction
What classes of drugs and treatments are used to treat MDD
Tricyclic antidepressants (TCAs)
Serotonin Selective Re-uptake Inhibitors (SSRIs)
Serotonin & Noradrenaline RIs, Noradrenaline Selective RIs
Monoamine Oxidase Inhibitors (MAOIs)
Cognitive Behavioural Therapy - milder forms
Electro-convulsive therapy - severe forms
Why are TCAs not suitable for suicidal patients
Easy and severe effects of overdose
How do TCAs interact with alcohol
Strongly potentiates its sedative properties
What are the 2 isoforms of MAO and how they differ
MAO-A - noradrenaline and serotonin
MAO-B - noradrenaline, dopamine and serotonin
What is the cheese reaction
When irreversible MAOIs interact with tyramine in foods like blue cheese, smoked fish and cured meats - caises acute hypertension
How do MAOIs interact with drugs like barbiturates and alcohol
reduces the metabolism of them and prolongs and exaggerates their effects.
In which patients are SSRIs used
first line treatment for patients who don’t respond to CBT
How is serotonin syndrome treated
Treatment is cessation of monoamine modulators, and administration of a serotonin antagonist, e.g. cyproheptadine
How is Electroconvulsive Therapy carried out
Induction of an epileptic seizure
Electric current applied through two electrodes attached to the anterior temporal areas of the scalp
Performed under general anaesthetic, and after administration of a muscle relaxant - prevents injury during the fit
