Antidepressants

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  • Created by: LBCW0502
  • Created on: 02-10-18 09:05
What are the three types of depression?
Unipolar, bipolar and SAD (Seasonal Affective Disorder)
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Describe features of SAD
Affects 0.5 million people, female > male, linked to circadian genes, treated with light therapy
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Describe features of bipolar
Oscillation between depression and mania. 1-3% lifetime incidence, females = males, young > old, familial (linked to ankryin G and L-type calcium channels), treat with Lithium, ECT
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Describe features of unipolar
2-3% incidence (2007). 5-10% experience depression in lifetime. Prevalence 3% (Japan), 17% USA. F > M. Reactive (75%). 25% familial (SERT). Treat with drugs, ECT, psychotherapy. Major cause of disability worldwide. $83 billion, USA (2002)
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What is a major depressive episode?
When five or more symptoms have been present during the same 2-week period and represent a change from previous functioning (most of the day, nearly everyday)
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What are the main aspects of a major depressive episode (10)?
Mood, pleasure, weight, sleep, psychomotor, energy levels, self-worth, concentration, suicide and cognitive changes
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Describe features of mood and pleasure which lead to a major depressive episode
Depressed mood, subject reports feeling sad or empty. Others appear tearful. In children/adolescents, can be irritable mood. There is diminished interest or pleasure in activities
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Describe features of weight which lead to a major depressive episode
Weight loss when not dieting or weight gain. A change of more than 5% of body weight in a month. Decrease or increase in appetite nearly everyday. In children, consider failure to make expected weight gains
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Describe features of sleep, psychomotor and energy levels which lead to a major depressive episode
Insomnia or hypersomnia. Agitation or retardation. Fatigue or loss of energy nearly everyday
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Describe feelings of self-worth and concentration which lead to a major depressive episode
Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly everyday (not merely self-reproach or guilt about being sick). Decreased ability to think
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Describe features of suicide which can lead to a major depressive episode
Recurrent thoughts of death. Recurrent suicidal ideation without a specific plan. Suicide attempt. Specific plan for committing suicide
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Give an example of a cognitive change which could be a symptom of a major depressive episode
Impaired memory
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What is the percentage for incidence and prevalance?
5-10%
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What are the four main treatments for depression?
Antidepressant drugs, psychology, electroconvulsive treatment and deep brain stimulation
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Give three examples of the types of antidepressant drugs used to treat depression
Enzyme inhibitors (MAOIs), uptake inhibitors and presynaptic receptor antagonists
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State two features of psychology used to treat depression
Psychotherapy and cognitive behaviour therapy
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Describe features of electroconvulsive treatment
When depression resistant to other treatment. Neuromuscular block (suxamethonium) used to reduce pain. Electroshock (unilateral to reduce memory loss)
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Describe features of deep brain stimulation
Treatment resistant depression. Targets include: subgenual cingulate gyrus, posterior gyrus rectus, nucleus accumbens, ventral capsule/ventral striatum, inferior thalamic peduncle, Lateral habenula and medial forebrain bundle
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What are the causes of depression (7)?
Stress (HPA axis and cortisol), gene polymorphism, cardiovascular, GI system and adipose, sex steroids (oestrogen and progesterone), innate immune system
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What are the comorbid illnesses?
Obesity, diabetes and cardiovascular disease
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Which two neurotransmitters are involved in depression?
NE (drive/motivation) and 5HT (dorsal/ventral raphe, control of mood, anxiety, sleep, libido, food intake, pain perception (dorsal horn), defective SERT/limbic pathway)
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Outline the monoamine hypothesis of depression
Depression caused by functional deficit of monoamine transmitters in certain areas of the brain. Mania results from functional excess. Hypothesis based on pharmacology (initially based on NE, subsequently included 5HT)
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Which drugs and treatments support the monoamine hypothesis (6)?
Tricyclic antidepressants, monoamine oxidase inhibitors, tryptophan, methyldopa and alpha-methyl tyrosine, reserpine, ECT (see table)
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Which drugs do not support the monoamine hypothesis (6)?
Amphetamine, cocaine, alpha and beta antagonists, methysergide, L-DOPA, Iprindole (5HT2 antagonist) - see table
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Outline the neuroendocrine mechanism - Hypothalamic - Pituitary - Adrenal - Axis
Hypothalamic neurons control pituitary function. Receive NA and 5HT input, release corticotrophin releasing hormone, CRH stimulates pituitary cells to release adrenocorticotrophic hormone. ACTH - cortisol secretion.
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Depressed patients have which features in the HPA Axis (3)?
High cortisol levels, reduced growth hormone, increased prolactin
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Where is corticotrophin releasing hormone found?
Throughout the brain. Mimics depression in animal models. CRH levels increased in depressed patients
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Depressed patients fail to respond to what?
Dexamethasone (test - dexamethasone suppression test - suppress release of ACTH)
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Describe features of trophic factors, neuroplasticity and glutamate
Depression (reduced BNDF or malfunction of Tyrosine kinase B receptor). Reduced volume of pre-frontal cortex and hippocampus (reduced synapse number in PFC, sustained glucocorticoids decrease synaptic number, stress increases extracellular glutamate)
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What is the effect of antidepressants on BDNF?
Antidepressants increase BDNF (depress and facilitate, acute administration)
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Describe features of neuronal loss
Loss of neurons in hippocampus and prefrontal cortex. Ventricular enlargement. Shrinkage of hippocampus and prefrontal cortex. Reduced activity. Effect mimicked by chronic stress or increase in glucocorticoids
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What is the effect of antidepressants on neuronal loss?
Inhibit or reverse loss. Stimulate neurogenesis via alpha 2 and 5HT1A stimulation via BDNF. Exercise promotes neurogenesis and can be antidepressant
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Describe the desirable features of an antidepressant
Rapid onset. Mechanism of action (neurotransmitter system, receptors/2nd messenger, gene expression, remodelling neuronal pathway. Long term efficacy (chronic), well tolerated (TCA/MAO-serious side effects, new drugs tolerated). Safe in overdose
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When does the onset of antidepressants take place?
2-4 weeks
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What is the function of a monoxidase inhibitor?
Increase levels of NA and 5HT in neurons by blocking mechanism (40% of NA metabolised by MAOA after reuptake)
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What are the two types of irreversible inhibitors?
MAO types A and B (Phenelzine is an example of an irreversible inhibitor)
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Where are MAO type A inhibitors found?
Noradrenergic neves and neurons, glia, gut/liver
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Where are MAO type B inhibitors found?
Glia, gut, liver, neurons
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Describe the cheese reaction (no MAOI)
Tyramine in cheese is metabolised in the gut by MAOB and MAOA. Enters bloodstream and is metabolised. Tyramine doesn't reach adrenergic neurone and NA remains in vesicles
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Describe the cheese reaction (plus MAOI)
Tyramine moves from gut to bloodstream without being metabolised (no MAOB/MAOA). Reaches adrenergic neurone. Exchange tyramine for NA. Increase in NA leads to high BP
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What is the function of a reversible inhibitor (RIMA)
E.g. moclobemide. Reversibly inhibits MAOA in gut and nerve terminals. Only blocks MAOA so some MAOB metabolism possible. Tyramine overcomes block in gut. Block in neurones still effective. Delay (weeks) before full antidepressant response
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Describe the cheese reaction (plus RIMA)
Tyramine metabolised by MAOB in gut. No metabolism in blood stream. No exchange of tyramine for NA. Prevent increase in BP
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Describe features of TCAs
Three think HC ring structure, inhibit NA and 5HT transporters, amine-uptake inhibition is immediate but antidepressant effect takes 2-4 weeks. Antagonist at muscarinic, H1 and alpha 1 adrenoreceptors may cause side effects
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What is the consequence of an overdose of TCAs?
Overdose - fatal cardiac arrhythmias, mechanism use-dependent sodium channel block
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What are the side effects of TCA (6)?
Sedation, postural hypotention, insomnia, weight gain, skin rash, liver damage (rare)
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Describe the function of Serotonin-Selective Re-uptake Inhibitors
Selectively inhibit neuronal 5HT SERT. Elevate and prolong synaptic levels of 5HT. Uptake inhibition immediate but 2-4 week delay in onset of antidepressant effect
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Give examples of SSRIs
Fluoxetine (Prozac), paroxetine, sertraline, citalopram
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What are the side effects of SSRIs?
Nausea/GI disturbance, agitation, sexual dysfunction, weight gain (fewer and less serious side effects than with TCAs)
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Give examples of newer antidepressants
Block NA/5HT SERT (and/or). Noradrenaline selective re-uptake inhibitor (Rebozetine/Edronax). Specific Serotonin and NE reuptake inhbitors (less side effects than TCA). Bupropion inhibits NA/DA uptake (nicotinic antagonist)
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Give examples of noradrenergic and specific serotonergic antidepressants (atypicals)
Flupenthixol, tetracyclic antidepressants, setiptiline, agometantine, tianepine - see table for classes of antidepressant
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What is the proposed mechanism of delayed response?
Normal - 5HT1a receptor inhibits 5HT release. Acute - 5HT1a receptor inhibit release but inhibits re-uptake (more extracellular 5HT). Chronic - 5HT1a receptor inhibition of 5HT release removed and 5H1a receptors desensitise
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Give examples of antidepressants for treatment of specific anxiety states
OCD (clomipramine, SSRIs), PTSD (SSRIs), PD (BDZs, SSRIs), SAD (SSRIs)
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Are antidepressants effective over placebo?
Antidepressants are not very effective due to an onset of 2-4 weeks and side effects are expressed before the therapeutic effect of the antidepressant
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Give examples of future antidepressants
Triple uptake inhibitors (NA, 5HT, DA), NK1 antagonists (SP), glutamate (NMDA antagonists e.g. ketamine, NR2B antagonist), ACh (nicotinic antagonists), antiglucocorticoids. Melatonin agonists (agomelatine)
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Card 2

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Describe features of SAD

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Affects 0.5 million people, female > male, linked to circadian genes, treated with light therapy

Card 3

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Describe features of bipolar

Back

Preview of the front of card 3

Card 4

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Describe features of unipolar

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Card 5

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What is a major depressive episode?

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