Depression and Antidepressants Flashcards
Define depression
A state of low mood and avoidance of activity that can affect a person’s behaviour
and feelings.
Name 4 types of depression from the DSM-IV class-action and describe them
- Major depression = this is a continuous low mood for 2 weeks or longer
- Bipolar disorder = this is a cycle of depression and then manic highs
- Dysthymic disorder = this is depression that has lasted for around 2 years
- Depressive disorder = this is depression that is otherwise unspecified
Name the difference types of depression from DSM V
sion of the system DSM V
- Depressive disorders
- Disruptive Mood Dysregulation Disorder
- Major Depressive Disorder, Single and Recurrent Episodes
- 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
name some 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(lack of pleasures)
define anhedonia
lack of interest and pleasure
there is a strong….
genetic link to depression
Describe how depression and genetics can be linked
depression has a strong genetic component
- there is also a shared genetic risk between forms of depression for example if you are related to a patient with major depression disorder you can have a chance of developing that or something like bipolar disorder
Name some genes that are linked to depression
- HTR2A
- GRIK4
- CRHR1
- HTR1A
- MAOA
- all these genes code for monoamines such as serotonin, noradrenaline and dopamine
describe how noradrengic pathways and serotonergic pathways are linked to depression
depression can be linked to a decrease in transmission of noradrenaline and serotonin as these are linked to the emergence of depression
What brain regions are associated with depression
- Amygdala
- Ventrolateral prefrontal cortex
- Dorsolateral prefrontal cortex
- Medial prefrontal cortex
- Striatal regions (ventral striatum)
- Hippocampus
These areas have shown decreased metabolism due to significant reductions in
glucose consumption.
in terms of inflammation what does depression also show a link to
Depression is associated with an increase in cortisol and pro-inflammatory cytokines
such as IL-6.
how are depression and mean grey matter linked
- The mean grey matter volume of the subgenual anterior cingulate cortex is reduced in patients with major depressive disorder and bipolar disorder
what area is important in the default mode network
left subgenual cingulate cortex
what is the default mode network (DMN)
network of brain regions active when the brain is at wakeful rest
How is the DMN linked to depression
- if we look at studies looking at depressed subjects we can access hot spots in the brain that have areas of activity that are different from control subjects
what does DMN stand for
default mode network
what polymorphism is associated with a higher risk of major depression after signciant life events
5-HT transporter polymorphism is associated with a higher risk of major depression
after significant life events
describe how genes can lead us to getting depression
- some genetic weakness exposes us to depression for example it can reduce our ability to be able to deal with stress
what is another word for negative thoughts
rumination
what can cause rumination (negative thoughts)
- When rumination (negative thoughts) occurs this is due to hyperactivity of the amygdala and hippocampus which causes hyperactivity in the VLPFC and DLPFC
name 4 main antidepressant drugs
Tricyclic antidepressants
MAO inhibitors
SSRIs – selective serotonin reuptake inhibitors
Reversible MAO inhibitors
Tricyclic antidepressants
- examples
- mechanism of action
- side effects
- other notes
Examples; - clomipramine, imipramine, desipramine, amitriptyline, nortriptyline, protriptyline
Mechanism of action;
- Inhibit reuptake of amines (noradrenaline and serotonin)
Side effects;
• Adverse effects: dry mouth, blurred vision, constipation, urinary retention, aggravation of narrow angle glaucoma, fatigue, sedation, weight gain, postural hypotension, dizziness, loss of libido, arrhythmias = mainly due to binding of cholinergic receptors
• Dangerous in overdose – they can cause cardiotoxicity
Characteristics
• Different degree of selectivity for amines between them (5-HT vs. noradrenaline)
• Have affinity for H1, muscarinic, α1 and α2 adrenoceptors
MAO inhibitors
- examples
- mechanism of action
- side effects
Examples; phenelzine, tranylcypromine, iproniazid
- Treatment of atypical depression is what they are more effective in
Mechanism of action;
• Non-selective MAOA versus MAOB
• Interaction with pethidine and sympathomimetic compounds
Side effects
• Cheese reaction - Interactions with tyramine-containing food (mature cheese, pickled fish and meat, red wine, beer, broad bean pods, yeast extract)- restrictions continue at least 2 weeks after discontinuation = can cause hypertensive crisis
• Hepatotoxicity
Selective serotonin reuptake inhibitors
- examples
- mechanism of action
- positives about the drug
- side effects
Examples; Clitalopram, fluoxetine, paroxetine
- Efficacy comparable to tricyclic compounds
Mechanism of action
- Increased selectivity for serotonin reuptake (citalopram the most selective)
- Inhibit serotonin reuptake increasing the amount of serotonin
Positives;
- No anticholinergic activity
- No cardiotoxic effects
- Safe in overdose
Side effects
- Adverse effects: nausea, headaches, gastrointestinal problems, increased aggression, insomnia, anxiety, sexual dysfunction
what is a recently introduced drug
More recently introduction of S-isomer of citalopram; escitalopram
reversible monamine oxidase inhibitors
- examples
- mechanism of action
- side effects
Examples = Moclobemide
Mechanism of action;
• Increased selectivity for MAOA
• Safer than irreversible MAOIs
• Efficacy comparable to MAOIs
Side effects
• Adverse effects: nausea, agitation, confusion
• can start medication straight away
• Reduced cheese effect as they have less time present in body
What is another name for reversible monamine oxidase inhibitors
RIMA
name a serotonin noradrenaline reuptake inhibitor
Venlafaxine
- Block monoamine reuptake but they have no affinity for other targets
name a noradrenaline reuptake inhibitor
Reboxetine
name a noradrenergic and specific serotonergic antidepressant
- mechanism of action
- side effects
- other
Mirtazapine
Mechanism of action
- Antagonist at alpha-2 adrenergic receptors
Side effects
- Cause drowsiness as they have an affinity for H1 receptors
- Sedation
- Dry mouth
- Constipation
Other
Exert antagonist effects at 5HT2 and 5HT4 receptors
name a serotonin agonist and reutpake inhibitor
mainly antagonism at 5-HT2 receptors and serotonin reuptake inhibition) = trazodone
Tianeptine (enhancer or positive allosteric modulator of 5-HT uptake; also atypical mu opioid receptor agonist)
what is the mechanism of action of agomelatine and what does the treatment do
Mechanism of action
- agonist at melatonin MT1 and MT2 receptors and antagonist at 5-HT2c receptors
- (may act as a noradrenaline/dopamine disinhibitor);
- onset of effect in the first week of treatment;
- improves sleep quality;
- less sexual dysfunction than SSRIs;
- anxiolytic effects; no discontinuation syndrome
why do antidepressant drugs have a delayed onset of action
Antidepressants have a delayed onset of action.
This is believed to be because of somatic neuronal auto receptors.
Their activation by the drugs causes decreased neuronal firing.
It takes some time for these auto receptors to de-sensitize, but when they do the
neurones will return to firing at a normal rate.
Inhibition of reuptake continues, and the level of amines rises.
why might some patients stop taking antidepressants in the first few weeks
- only feel the negative effects of the drug first until the auto receptors become densistise and then they feel the positive effects
what is antidepressant drug discontinuation syndrome
- 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
- see the symptoms
What are the symptoms of antidepressant drug discontinuation
- Insomnia
- Anxiety
- Nausea
- Headaches
- Electric shock sensations
- Agitation
- Mood swings
- Diarrhoea/abdominal cramps
what is the definition of bipolar
– A mood disorder characterised by cycles of depression and mania
what is the main choice of drug for bipolar disorder
lithium
describe how lithium works and the characterises of it
- Used as maintenance treatment in bipolar disorder (and also acute mania and drug-resistant depression) – gets rid of the bipolar cycles
- Narrow therapeutic margin (0.6-1 mM)
what are the adverse effects of lithium
- Renal and thyroid function must be checked before treatment (and then at regular intervals during maintenance treatment)
- Adverse effects: thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne
name some mood stabilisers that can be used in bipolar
carbamazepine
sodium valproate
what is important to note for antidepressant drugs used in bipolar
- they can precipitate the manic episodes or mixed affective states
- can also increase the frequency in mood change cycles
what are the order of risk for mania switch
TCAs > SNRIs > MAOIs > SSRIs
What are the phases of treatment for depression
Acute treatment
- First 6-12 weeks of treatment; aims at remission (control of symptoms)
- Inadequate early response is associated with poor prognosis
Continuation treatment
- for 6 months after full symptom control; to maintain remission status and prevent relapse
Maintenance treatment
- Aims at prevention of recurrence of a further episode of depression. - Indicated when higher risk of these recurrence; “maintenance dose”.
What is the criteria for choosing an antidepressant drug
- The clinical characteristics of depression
- The adverse effects profile
- The danger of suicide/overdose
- The response to previous treatments
How do you define resistance to drugs treatment in depression
- Lack of clinical response after adequate pharmacotherapy has been prescribed (at least two different antidepressant drugs)
- Affects a large number of patients (conservative estimate: 25-30%)
What are the non pharmacological approaches for depression treatment
- electroconvulsive therapy (treatment-refractory severe depression with suicide risk)
- Cognitive behavioural therapy (CBT) (can augment the effects of pharmacological treatment)
- Vagal nerve stimulation (especially in chronic depression)
- Deep brain stimulation (subcallosal cingulate white matter – Brodmann area 25)
Describe how deep brain stimulation can be used to treat depression
- Focuses on areas 25 the subgenual cingulate cortex –
- Links of this area to striatium, dorsal frontal cortex, orbitofrontal cortex
name a scale that can be used to rate depression
Hammerton depression scale
