Anxiety & depression III Existing drug Treatments Flashcards
5HT system
cell bodies in the raphe nucleus
roles in: widespread distribution/feeding behaviours/body weight regulation/aggressive behaviour/anxiety/depression
NA system
cell bodies in the locus coeruleus
roles in: widespread distribution/arousal/reward/bp regulation/anxiety/depression
overview of the types of antidepressants
monoamine oxidase inhibitors (MAOIs)
tricyclic antidepressants (TCAs)
selective serotonin reuptake inhibitors (SSRIs)
serotonin noradrenaline reuptake inhibitors (SNRIs)
noradrenaline-dopamine reuptake inhibitor (NDRI)
4-6 weeks for full effect
agromelatine (Valdoxan)
melatonin R antagonist
selective 5HT2c R antagonist
Mirtazapine
presynaptic a2 adrenoreceptor antagonist
increases NA/5HT neurotransmission
NA and specific 5HT antidepressant (NaSSA)
tetracyclic antidepressant (TeCA)
Flupentixol
D2/5HT2a R antagonist (antipsychotic)
antidepressant effects (D2/D3 R blockade) extrapyramidal side effects
increased post-synaptic activation
Trazadone hydrochloride
depressive illness (if sedation required)
5HT2a R antagonist and reuptake inhibitor (SARI)
side effects of antidepressants
increased appetite and weight
dry mouth
blurred vision
oedema
postural hypotension
what is required for the successful treatment of depression
early diagnosis and treatment
treatment combined with psychotherapy
sufficient dose and length of treatment
taper withdrawal
deal with co-morbidities (drug use, diabetes)
benzodiazepines
binds to GABAa R (a subunit)
21 mil prescriptions in 1989 (UK)
present: 2-4 weeks
alternative to previously used Barbiturates (1950s)
panic disorder
tolerance and risk of dependence
side effects: amnesia/drowsiness/withdrawal
GABAa Receptor
ligand gated chloride channel (postsynaptic)
5 protein subunits (2a 2b y)
GABA binds to b subunit
GABAA channel opens, Cl- enters, reduces cell excitability
types of benzodiazepines
diazepam (valium) - GAD
clonazepam - social phobia/GAD
lorazepam - panic disorder
alprazolam (xanax) - panic disorder and GAD
beta-blockers
propranolol
adrenergic neurone blockers (reduces sympathetic activity)
decreases arousal
social phobias cause physical symptoms
feared situations can be predicted
busipirone
newer medication to treat GAD
5HT1a R partial agonist (presynaptic DA agonist at D2/3/4 R)
side effects: dizziness/headaches/nausea
2 weeks for effect
limitations of anxiolytics and antidepressants
Kirsch et al., 2008
meta analyses of antidepressants only report modest benefits over placebo
when unpublished data is included, the benefit falls below significance
clinicians monitor severity of depression using the Hamilton rating scale of depression (HRSD) SSRIs improved HRSD 1.8 points more than placebo (signifcant difference is 3 points)
Broich, 2008
dismissed kirsch et al., 2008
states findings were based on robust evidence
delayed onset of actions for antidepressants
immediate adverse effects
increased suicide risk
decreased 5-HT/NA activity in early stages of treatment (autoreceptor activation)
combine SSRI+pindolol - blocks somatodendritic autoreceptors
individual differences
genetic/environmental factors not necessary/sufficient for cause
different aetiological pathway = different biological differences = difference responses
effective treatment is trial and error - personalised medicine
other treatments for severe depression
vagus nerve stimulation (VNS)
repetitive transcranial magnetic stimulation (rTMS)
deep brain stimulation - implanted electrodes, limbic cortex stimulated, specifically subgenual anterior cingulate cortex (sgACC), depolarising block
SSRIs
antidepressants for anxiety
panic disorder/OCD/PTSD/social phobia: fluoxetine (prozac)/sertraline/citalopram/paroxetine/escitalopram
GAD: SNRI/venlafaxine
less side effects than older antidepressants/sexual dysfunction/jitters/nausea/can be corrected by changing to other treatment
TCAs
antidepressants for anxiety
panic disorders/GAD: imipramine
OCD: clomipramine
low to gradually high dose
side effects: dizziness/drowsiness/dry mouth/weight gain/change to other treatment
MAOIs
antidepressants for anxiety
panic disorder/social phobia: phenelzine/tranylcypromine/isocarboxazid
side effects: no food/drinks with tyramine, cannot consume other types of medication (birth control/pain relief/cold medicines)
non pharmacological treatment
psychotherapy
CBT
exposure based therapy - change thinking patterns, moderate effects (carpenter et al., 2018)
interpersonal therapy (IPT) - 12 weeks
ECT (shocks) causes memory loss/confusion/disorientation (short term), patient is anaesthetised so doesnt feel electrical impulses, lasts few minutes, combined with antidepressants
