Antidepressant Drugs Flashcards
How many people worldwide have depression?
What % of the total burden of disease worldwide does this account for?
350 million
10%
What is the DSM-IV classification for depression? (4)
Major depression
Bipolar disorder
Dysthymic disorder
Depressive disorder not otherwise specified
What is the DSM-V classification for depression?
Depressive Disorders
Disruptive Mood Dysregulation Disorder
Major Depressive Disorder
Persistent Depressive Disorder (Dysthymia)
Premenstrual Dysphoric Disorder
Substance/Medication-Induced Depressive Disorder
Depressive Disorder Due to Another Medical Condition
Other Specified Depressive Disorder
Unspecified Depressive Disorder
List the symptoms of depression.
Psychomotor retardation Fatigue or loss of energy Diminished ability to concentrate Diminished interest in social activity Psychomotor agitation Depressed mood Feelings of guilt and worthlessness Suicidal ideation Insomnia Weight loss and decreased appetite Lack of interest and anhedonia
What is the lifetime risk of having major depression for a first degree relative of someone who has bipolar disorder? What about of having bipolar disorder themselves?
12%
6%
Name some genes for which there is evidence of a link of depression.
GRIK4 (glutamate receptor)
CRHR1 (corticotrophin releasing factor receptor 1)
SLC6A4 (serotonin transporter)
MAOA (monoamine oxidase A)
What area of the prefrontal cortex is particularly affected in depression? How?
Subgenual prefrontal/anterior cingulate cortex
Decreased metabolism and reduction in glucose consumption, as well as a reduced mean grey matter volume
Which pathways are dysfunctional in depression?
Ascending monoaminergic pathways
Which main two neurotransmitters are affected in depression?
Noradrenaline and serotonin
Where (nuclei) are the 5-HT neurons located? Do they have faster activity during waking phase or during sleep?
Raphe nuclei
During waking – it decreases during sleep
Which areas of the brain are linked to depression? (6)
Amygdala Ventrolateral prefrontal cortex Dorsolateral prefrontal cortex Medial prefrontal cortex Ventral striatum Hippocampus
What can also be said about the cortex in major depression?
Decreased cortical thickness
What is default mode network? What is different about it in depression?
Network of brain regions active when the brain is at wakeful rest
Increased functional connectivity
Genetic variation modulates the response to stress in terms of significant life events. For which transporter is there evidence for this? Which genotype?
S genotype 5-HT transporter polymorphism (associated with different levels of transcription of the transporter) is associated with higher risk of major depression following significant life events.
A genetic variation in which gene (which encodes an enzyme that controls monoaminergic signalling) may affect the course of major depression? How?
MAOA gene
By disrupting cortico-limbic connectivity
What does rumination mean?
Recurring negative thoughts
There is hyperactivity in…? There is hypoactivity in…? This causes rumination.
Hyper – amygdala, hippocampus, subgenual cingulate, MPFC
Hypo – VLPFC, DLPFC
What type of drug are the following?
Clomipramine, imipramine, desipramine, amitriptyline, nortriptyline, protriptyline
TRICYCLIC ANTIDEPRESSANTS
How do tricyclic antidepressants work?
Inhibit reuptake of amines
Why do TCAs have so many adverse effects?
They have affinity for many different targets - H1, muscarinic, alpha 1 and 2 adrenoreceptors
What are the issues/adverse effects of TCAs?
Cardiotoxicity Dry mouth Blurred vision Constipation Urinary retention Aggravation of narrow angle glaucoma (Others: Fatigue, sedation, weight gain, postural hypotension, dizziness, loss of libido, arrythmias)
What type of drug is iproniazid? Name two others.
MONOAMINE OXIDASE INHIBITOR
Phenelzine and tranylcypromine
Interaction with pethidine and sympathomimetic compounds
Hepatotoxicity
How do MAO inhibitors work?
Irreversible inhibition of the enzyme (non-selective for A versus B).
What type of depression are MAO inhibitors used to treat?
Treatment of atypical depression (with anxiety, phobia and hypochondria)
What is the main concern (a reaction) with irreversible MAO inhibitors?
Interactions with tyramine-containing food (mature cheese, red wine, beer, broad bean pods) - this is the ‘cheese reaction’. Patients have to change their diet when taking these drugs and the restrictions continue at least 2 weeks after discontinuation of the drug.
What type of drug is citalopram? Name 2 others.
SELECTIVE SEROTONIN REUPTAKE INHIBITOR
Fluoxetine and paroxetine
How do SSRIs work? Which one is most selective?
The prevent the re-uptake of serotonin.
Citalopram
What is the S-isomer of citalopram called? It has recently been introduced as a new SSRI.
Escitalopram
List some adverse effects of SSRIs.
Nausea, headaches, gastrointestinal problems, increased aggression, insomnia, anxiety, sexual dysfunction
What are the three major positives of SSRIs?
No anticholinergic activity
No cardiotoxic effects
Safe in overdose
Name a reversible MAO inhibitor. Which isoform does it have an increased selectivity for?
Moclobemide
Increased selectivity for MAOA
What are the adverse side effects of reversible MAO inhibitors? What is the benefit?
Nausea, agitation, confusion
Safer than irreversible inhibitors
What is agomelatine?
Agonist at melatonin MT1 and MT2 receptors and antagonist at 5-HT2c receptors. It may act as a NA/dopamine disinhibitor.
What are the benefits of agomelatine compared to other antidepressants?
The onset of effect is in the first week of treatment, it improves sleep quality, there is less sexual dysfunction than with SSRIs, it has anxiolytic effects and norisk of discontinuation syndrome.
What is venlafaxine?
SEROTONIN NORADRENALINE REUPTAKE INHIBITOR
SEROTONIN ANTAGONIST AND REUPTAKE INHIBITOR (SARI) (mainly antagonism at 5-HT2 receptors and serotonin reuptake inhibition) Trazodone
Overall, fewer unwanted effects with these various other drugs than with older drugs such as TCAs, MAOI, SSRI…
What is reboxetine?
NORADRENALINE REUPTAKE INHIBITOR
What is mirtazapine? How does it work?
NORADRENERGIC AND SPECIFIC SEROTONERGIC ANTIDEPRESSANTS - antagonism at 5-HT2 and alpha 2 adrenergic receptors
What effect does buspirone have?
Anxiolytic drug
Explain why there is a delayed onset of action with antidepressants, focusing on the case of TCAs.
Tricyclic drugs inhibit reuptake of amines - the immediate increase in synaptic concentration of amines may lead to activation of somatic neuronal autoreceptors (e.g. 5-HT1A type), which will decrease the firing of neurones. The autoreceptors will become desensitised after a few weeks and the normal firing rate of neurones will return. However, the inhibition of reuptake continues and the level of amines continues to be high, resulting in full efficacy.
Explain antidepressant drug discontinuation syndrome - when can it occur and how can it be prevented?
A condition that can occur after a decrease in the dose of drug taken, an interruption of treatment or abrupt cessation of treatment.
It 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 antidepressant drug discontinuation syndrome?
Insomnia Anxiety Nausea Headaches Electric shock sensations Agitation Mood swings Diarrhoea/abdominal cramps
What is bipolar disorder?
A mood disorder characterised by cycles of depression and mania
What is lithium used for?
Used as maintenance treatment in bipolar disorder (and also acute mania and drug-resistant depression).
What are the adverse effects of lithium?
Thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne
What must be checked for bipolar patients on lithium BEFORE treatment and also during?
Renal and thyroid function
Carbamazepine and sodium valproate can be used to treat… (3)
Epilepsy, neuropathic pain and bipolar disorder
Antidepressant drugs used in bipolar precipitate mani episodes in how many % of patients?
How many patients experience an increased frequency in mood change cycles?
35%
26%
Which drug has the highest risk of mania switch?
Which drug has the least?
TCAs
SSRIs
How many patients treated for depression fail to achieve remission?
Approximately 2/3
How many % of patients receiving antidepressants stop treatment in the first month?
50%
What are the three phases in treatment of depression?
Acute Treatment (first 6-12 weeks) Continuation Treatment (for 6 months after full symptom control) Maintenance Treatment
How many patients have treatment-resistant depression?
What non-pharmacological treatment can be particularly effective for these patients?
25-30%
Electroconvulsive therapy
What are the non-pharmacological treatments for depression? (4)
Electroconvulsive therapy
Cognitive behavioural therapy
Deep brain stimulation (subcallosal cingulate white matter – area 25)
Vagal nerve stimulation
What areas does the subgenual cingulate cortex link to?
Striatum, dorsal frontal cortex, orbitofrontal cortex
What can be said about the hippocampus in depressed patients?
Reduced hippocampal white matter due to neuronal loss and decreased neurogenesis caused by increased cortisol and proinflammatory cytokines (IL-6).
Subcallosal cingulate metabolism was higher in…?
Non-responders to either CBT or escitalopram
