Anxiety & depression III Existing drug Treatments

Question 1

5HT system

Answer 1

cell bodies in the raphe nucleus
roles in: widespread distribution/feeding behaviours/body weight regulation/aggressive behaviour/anxiety/depression

Question 2

NA system

Answer 2

cell bodies in the locus coeruleus
roles in: widespread distribution/arousal/reward/bp regulation/anxiety/depression

Question 3

overview of the types of antidepressants

Answer 3

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

Question 4

agromelatine (Valdoxan)

Answer 4

melatonin R antagonist
selective 5HT2c R antagonist

Question 5

Mirtazapine

Answer 5

presynaptic a2 adrenoreceptor antagonist
increases NA/5HT neurotransmission
NA and specific 5HT antidepressant (NaSSA)
tetracyclic antidepressant (TeCA)

Question 6

Flupentixol

Answer 6

D2/5HT2a R antagonist (antipsychotic)
antidepressant effects (D2/D3 R blockade) extrapyramidal side effects
increased post-synaptic activation

Question 7

Trazadone hydrochloride

Answer 7

depressive illness (if sedation required)
5HT2a R antagonist and reuptake inhibitor (SARI)

Question 8

side effects of antidepressants

Answer 8

increased appetite and weight
dry mouth
blurred vision
oedema
postural hypotension

Question 9

what is required for the successful treatment of depression

Answer 9

early diagnosis and treatment
treatment combined with psychotherapy
sufficient dose and length of treatment
taper withdrawal
deal with co-morbidities (drug use, diabetes)

Question 10

benzodiazepines

Answer 10

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

Question 11

GABAa Receptor

Answer 11

ligand gated chloride channel (postsynaptic)
5 protein subunits (2a 2b y)
GABA binds to b subunit
GABAA channel opens, Cl- enters, reduces cell excitability

Question 12

types of benzodiazepines

Answer 12

diazepam (valium) - GAD
clonazepam - social phobia/GAD
lorazepam - panic disorder
alprazolam (xanax) - panic disorder and GAD

Question 13

beta-blockers

Answer 13

propranolol
adrenergic neurone blockers (reduces sympathetic activity)
decreases arousal
social phobias cause physical symptoms
feared situations can be predicted

Question 14

busipirone

Answer 14

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

Question 15

limitations of anxiolytics and antidepressants

Kirsch et al., 2008

Answer 15

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)

Question 16

Broich, 2008

Answer 16

dismissed kirsch et al., 2008
states findings were based on robust evidence

Question 17

delayed onset of actions for antidepressants

Answer 17

immediate adverse effects
increased suicide risk
decreased 5-HT/NA activity in early stages of treatment (autoreceptor activation)
combine SSRI+pindolol - blocks somatodendritic autoreceptors

Question 18

individual differences

Answer 18

genetic/environmental factors not necessary/sufficient for cause
different aetiological pathway = different biological differences = difference responses
effective treatment is trial and error - personalised medicine

Question 19

other treatments for severe depression

Answer 19

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

Question 20

SSRIs

antidepressants for anxiety

Answer 20

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

Question 21

TCAs

antidepressants for anxiety

Answer 21

panic disorders/GAD: imipramine
OCD: clomipramine
low to gradually high dose
side effects: dizziness/drowsiness/dry mouth/weight gain/change to other treatment

Question 22

MAOIs

antidepressants for anxiety

Answer 22

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)

Question 23

non pharmacological treatment

Answer 23

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