Antidepressants Flashcards
2 things which impact depression mood?
normal high/low mood but
- duration
- intensity of feeling
diagnostic features of depression (symptoms)
persistent sadness/low mood
and/or
marked loss of interests or pleasure
associated symptoms of the 2 major symptoms of depression?
physical - Altered sleep - change in appetite and/or weight - fatigue/loss of energy - agitation/slowing of movements - poor concentration or indecisiveness
psychological
- feelings of worthlessness or excessive or inappropriate guilt
- suicidal thoughts or acts.
diagnosis of depression
Subthreshold depressive
symptoms: < five symptoms of
depression.
• Mild: >five symptoms and result in only minor functional impairment. • Moderate: between ‘mild’ and ‘severe’. • Severe: Most symptoms present; markedly interfere with functioning.
Not solely based on symptom counting but on • Severity • Persistence • Presence of other symptoms • Functional and social impairment
aetiology and neurobiology of depression
what are the risk factors for vulnerability to depression?
3
biological vulnerability:
-genes, brain abnormalities, disordered biochem
psychological:
- Abuse, Neglect, Parental discord, poor attachment, Neuroticism
social:
- Unemployment, poverty, homelessness, chronic illness, poor relationships
the 3 risk factors of vulnerability to depression may lead to what which could lead to depression?
not always
- Stress Bereavement Trauma Onset of illness Chronic stress
3 hypothesis of neurobiology of depression.
not been validated
Monoamine hypothesis– low
monoamines (Serotonin & Nor Adrenaline)
(HPA) axes hyperactivity –
repeated Stress ->increased cortisol levels, & CRF -> reduced hippocampus (volume) & neurogenesis.
Brain areas implicated indepression - : prefrontal cortex (PFC), anterior cingulate cortex (ACC), primary and secondary
somatosensory cortex, insular cortex, posterior cerebellum,
amygdala, hippocampus, thalamus, nucleus accumbens
do most antidepressants work?
inc/reduce levels of NTs: serotonin…
normally what is the action of NTs e.g. serotonin?
normal neurotransmission.
- elect activity passed through neuron
- NT release from pre synaptic vesicles?
- NT come into synaptic cleft (jnction between 2 neurons)
- act on post synaptic receptors
and activity from this to post synaptic neuron
what happens to NT when activity done i.e. reached synaptic cleft and postsynaptic neuron?
NTs e.g. serotonin are metabolised by enzymes in synaptic cleft/ in pre synaptic neurone
or
taken back into pre synaptic neurone by reuptake transporter. metab/stored back into cell
name of the enzymes that break down NTs once used?
monoamine (5HT and NA) enzymes !!!!
treatment of depression?
• Medical: antidepressants • Adjuvant medication • Psychological therapies • Electroconvulsive therapy (ECT) • Vagal Nerve Stimulation* • Transcranial Magnetic Stimulation (TMS)* • Deep brain stimulation* * Experimental and yet to be recommended by NICE
Examples of Adjuvant medication to antidepressants?
Lithium, Antipsychotic medication,
nature of intervention for step 1 focus: All known and suspected
presentations of depression
Assessment, support, psycho-education, active
monitoring & referral for assessment & interventions
nature of intervention for step 2 focus: Persistent subthreshold
depressive symptoms; mild to moderate
depression
Low-intensity psychosocial interventions,
psychological interventions, medication and
referral for assessment & interventions
nature of intervention for step 3 focus: Persistent subthreshold
symptoms or mild to moderate
(inadequate response to initial intervn)
moderate and severe depression
Medication, high-intensity psychological
interventions, combined treatments,
collaborative care, and referral for further
assessment and interventions
nature of intervention for step 4 focus: Severe and complex
depression; risk to life; severe
self-neglect
Medication, high-intensity psychological
interventions, ECT, crisis service,
combined treatments, MDT & inpatient
care
first line pharm treatment of depression?
give example and mechanism of action
SSRIs (specific 5HT or NA reuptake inhibitors)
e.g. Citalopram
block presynaptic uptake rec = increases serotonin/ NAd
no anticholinergic effects
what are tricyclic antidepressants?
non-specific in uptake of serotonin/ NAd
amplify 5HT and NA
anticholinergic and other SE. e.g. cardiac therefore not first line
affect other recpetors
what are dual 5HT/NA reuptake inhib antidepressants?
and give example
SNRIs e.g. venlafaxine
block both serotonin and NAd.
amplify 5HT AND NA
no anticholinergic effects
why are dual 5HT/NA reuptake inhib antidepressants reserved for 2nd/3rd line treatment?
very powerful and have SEs such as cradiac. caution w patients w heart problems
what do atypical antidepressants do?
increase serotonin and NAd by diff mechanism
free of major tricyclic SEs
mechanism of atypical antidepressants?
and give an example drug for each mechanism
- stimulate 5HT1A rec (buspirone)
- or disinhibition of NA/5HT by blockade of inhibitory receptors e.g. mirtazapine
what do MAOIs depressants do?
block MAO receptors so less break down of NTs and more available in synaptic cleft for NTransmission
what do MAOIs depressants do?
block MAO receptors so less break down of NTs and more available in synaptic cleft for NTransmission
two types of MAOIs: selective and reversible
how do they differ?
selective
- amplify 5HT, NA
- dietary SEs (wine and cheese)
reversible
- amplify 5HT, NA
- no dietary SEs
two types of MAOIs: selective (reversible) and (non-selective) irreversible
give example of each
selective:
- clorgyline
reversible:
- moclobemide
non-selective… irreversible
- phenelzine
- tranylcypromine
7 types/examples of SSRIs?
- Fluoxetine
- Citalopram
- Escitalopram
- Sertraline
- Paroxetine
- Fluvoxamine
- Vortioxetine
mechanism of action of SSRIs
Blockade of reuptake
of 5HT
SSRIs licensed uses?
Depression Generalized anxiety disorder Social phobia OCD Eating disorders
adverse/ side effects of SSRIs?
Nausea, Vomiting, Dyspepsia, diarrhoea, sweating, agitation, headache, insomnia Sexual dysfunction Hyponatremia (elderly!!) Cutaneous bleeding disorders
GI SEs
7 types/ examples of Tricyclic Antidepressants (TCAs)?
- Amitriptyline
- Clomipramine
- Dosulpein
- Imipramine
- Lofepramine
- Nortriptyline
- Doxepin
mechanism of action of TCAs?
Non-selective inhibitors of amine
(5HT, NA) transporters
TCAs licensed uses?
Depression
Nocturnal enuresis
OCD
Cataplexy
adverse/ side effects of TCAs?
Dry mouth, blurred vision, constipation, urinary retention. Postural hypotension Sedation Poor dental health Tachycardia / arryhtymia
heart SEs
non selective MAOIs particularly useful in?
atypical depression
how do the side effects differ for the two types of MAOIs?
MAO-A selective, reversible:
- transient, stop when treatment stops
non-selective, irreversible:
- irreversible SEs
actual SEs are the same
side effects of any MAOIs?
post hypotension dry mouht blurred vision urinary retention (atropine like effects)
weight gain
restlessness
insomnia
(CNS stimulation)
SNRIs 2 examples
Venlafaxine
Duloxetine
mechanism of action of SNRIs
Serotonin- norepinephrine
reuptake inhibitor
similar to tricyclic
SNRIs licensed uses?
Depression
Generalized
Anxiety disorder
SNRIs adverse effects?
Nausea, dry mouth, constipation, increased BP. Somnolence, sweating, sexual dysfunction, headaches
mechanism of action of the newest antidepressant: Agomelatine?
Agonist at melatonin
receptor and
antagonist at 5HT2c
receptor
only licensed for depression
Adverse effects of Agomelatine?
Nausea, dizziness,
headaches,
somnolence, changes
in Liver function tests
Mirtazapine SE that is good for people with what specific symptom of depression?
known to cause sedation good if have insomnia
Mechanism of action of Mirtazepine?
antagonist at central
pre-synaptic alpha(2)
-receptors. Increases
both 5HT and NA
Mechanism of action of Reboxetine?
Specific Noradrenergic
reuptake inhibitors
Mirtazepine adverse effects?
Increased appetite,
weight gain,
drowsiness, oedema,
headache, dizziness
Reboxetine adverse effects?
Insomnia, sweating,
dizziness, dry mouth,
constipation, urinary
hesitancy, headache.
summary: treatment of Recent onset mild depression?
active monitoring, guided self help, CBT or exercise
summary: treatment of Moderate to severe depression?
Antidepressants (SSRIs)
summary: treatment For refractory depression?
antidep (SSRIs)
and add Lithium, or antipsychotic or another antidepressant
onset of action of antidepressants and what to warn patients about?
Onset of action 10-14 days, warn about withdrawal symptoms
duration of treatment with antidep?
After recovery from 1st episode treatment continued for 6-9 months, if 2 or more episode, continue treatment for 2 years
