T3 L6 Affective disorders Flashcards
What was the first MAOi?
Iproniazid
What was the first tricyclic?
Imipramine
What studies show a decrease in serotonin concentrations?
Acute tryptophan depletion studies
What study showed a reduction in serotonin transporter?
Post mortem suicide studies
Where are serotonin cell bodies located?
In raphe nuclei
Where are NA cells located?
In locus coerulus
What does the monoamine theory of depression suggest?
Relative deficiency in synaptic levels of serotonin & noradrenaline in key CNS pathways underlies depressive illness
What is the prefrontal cortex involved in?
Executive functions
What is the limbic system involved in?
Behaviour
Motivation
Emotion
What structures are included in the limbic system?
Hippocampus
Anterior cingulate cortex
Hypothalamus
Amygdala
What types of drugs are primary generation antidepressants?
Monoamine oxidase inhibitors
Tricyclic antidepressants
Give some examples of MAOi drugs
Phenelzine
Tranylcypromine
How do MAOis work?
Non-selectively inhibit enzymes involved in the breakdown of monoamines including serotonin, dopamine and noradrenaline
What are the side effects of MAOi?
Dry mouth GI side effects Headache Drowsiness Insomnia Dizziness Food interactions
Give some examples of tricyclic antidepressants
Amitriptyline
Clomipramine
How do tricyclic antidepressants work?
Non-selectively inhibit reuptake of monoamines including serotonin, dopamine and noradrenaline
What are the side effects of tricyclic antidepressants?
Constipation Orthostatic hypotension Dry mouth Drowsiness Cardiac toxicity in overdose
What types of drugs are secondary generation antidepressants?
SSRI
SNRI
Alpha & 5-HT2c antagonist
Dopamine-noradrenaline reuptake inhibitor (not approved as antidepressant in UK)
Give some examples of SSRIs
Sertraline
Citalopram
Escitalopram
Fluoxetine
What can SSRIs be used for?
OCD PTSD Panic GAD social anxiety
What are the side effects of SSRIs?
GI symptoms - nausea, diarrhoea Headache Irritability Anxiety Reduction in libido & sexual dysfunction Worse in first few weeks
What SSRIs produce the worst withdrawal symptoms?
Venlafaxine
Paroxetine
Due to their short half life
Give examples of SNRI drugs
Venlafaxine
Duloxetine
What are some side effects of venlafaxine?
Nausea
Vertigo
Headache
Insomnia
What do alpha & 5-HT2c antagonists do?
Modulate serotonin and noradrenaline release
Example is mirtazapine
What are the side effects of mirtazapine?
Drowsiness Sedation Hypotension Increase appetite Weight gain
Describe the link between inflammation and depression
Raised plasma cytokine levels (IL-6, TNF-alpha) and inflammatory markers
High comorbidity between chronic inflammation and depression
Administration of cytokines provokes depression
What are the medical prefrontal and anterior cingulate cortical regions involved in?
Processing emotion and automatic or implicit regulation of emotion
What are lateral prefrontal cortical systems involved in?
Cognitive control and voluntary or effortful regulation of emotion
What structures are in the medial prefrontal-limbic network?
Amygdala
Anterior cingulate cortex
Medial prefrontal cortex
Give an example of a 1st generation D2/D3 antagonist antipsychotic drug?
Haloperidol
Give examples of 2nd generation D2/D3 antagonist antipsychotic drugs?
Olanzapine Risperidone Quetiapine Lurasidone Asenapine Amisulpride Clozapine
What long term effects do antipsychotics have?
Weight gain
Glucose regulation
Lipids
Except for aripiprazole, amisulpride and lurasidone
What are the mechanisms of action of lithium?
Multiple neurotransmitters including dopamine
Cellular signalling
Neurotrophic factors
Give examples of anticonvulsants
Valproate
Lamotrigine
Carbamazepine
Describe valproate mechanism
Actions via GABA, intracellular signalling, sodium channel blockage, epigenetic modulation
What can valproate be used for?
Anti-manic and prevention of mania
What is the concern with valproate?
Risk of foetal teratogenesis and impaired intellectual development
What is the mechanism of Lamotrigine?
Action via GABA, glutamate and sodium channel blackage
What is Lamotrigine useful in?
Preventing depressive relapses
What is Lamotrigine not useful in?
Anti-manic agents
Describe Carbamazepine use
Less effect in maintenance treatment than lithium but may be used as mono therapy if lithium is ineffective
Especially in patients who don’t show classical pattern of episodic euphoric mania
Almost exclusively effective against manic relapse
What is the treatment for depressive episodes?
Antipsychotics - quetiapine, lurasidone
Fluoxetine / olanzapine combinations
Antidepressants co-prescribed with anti-manic drug
Condiser lamotrigine with anti-manic drug
What is the treatment for acute manic episodes?
Dopamine antagonists - haloperidol, olanzapine, risperidone, quetiapine
Valproate
Discontinue any antidepressant treatment
What alternatives can be used to prevent new episodes if lithium is ineffective?
Valproate
Dopamine antagonists / partial agonists
Carbamazepine
What are the side effects of long term treatment?
Weight gain - most medications, especially olanzapine & quetiapine
Metabolic syndrome - olanzapine, queitapine, risperidone
Hyperlactinemia - dopamine antagonists
Tardive dyskinesia - much lower risk with newer agents
Liver damage - valproate
Kidney & thyroid dysfunction - poorly regulated lithium
