Pharmacology of Antidepressants and Mood Stabilisers

Question 1

What are some uses of antidepressants?

Answer 1

Moderate/severe depression, dysthymia, generalised anxiety disorder, panic disorder, OCD, PTSD, premenstrual dysphoric disorder, bulimia, neuropathic pain

Question 2

What are some common groups of antidepressants?

Answer 2

Monoamine oxidase inhibitors, monoamine reuptake inhibitors and atypical drugs

Question 3

What are some examples of monoamine reuptake inhibitors?

Answer 3

Tricyclics, SSRIs and noradrenaline reuptake inhibitors

Question 4

What is the monoamine hypothesis?

Answer 4

Depression results from a functional deficit of monoamine transmitters, especially 5-HT and noradrenaline

Question 5

What effect can drugs that deplete stores of monoamines have?

Answer 5

Cause low mood

Question 6

What does the CSF of depressed patients show?

Answer 6

Reduced levels of monoamines or metabolites

Question 7

What are the serotonin (5-HT) projection pathways?

Answer 7

Rostral = mood, sleep, feeding behaviour, sensory perception

Caudal raphe = analgesia

Question 8

What is the noradrenaline projection pathway?

Answer 8

Locus coeruleus = arousal and emotion

Question 9

What are some examples of monoamine oxidase inhibitors?

Answer 9

Phenelzine = irreversible
Moclobemide = reversible

Question 10

What is the action of monoamine oxidase inhibitors?

Answer 10

Inhibit MAO-A and B

Question 11

What are the side effects of monoamine oxidase inhibitors?

Answer 11

Hypertensive crisis, insomnia, postural hypotension, peripheral oedema, potentiate effects of other drugs by decreasing their metabolism

Question 12

How do monoamine oxidase inhibitors cause hypertensive crisis?

Answer 12

Irreversible inhibition of MAO-A in the gut prevents breakdown of dietary tyramine

Question 13

What are some examples of tricyclics?

Answer 13

Imipramine, dosulepin, amitriptyline, lofepramine

Question 14

What is the mode of action of tricyclics?

Answer 14

Block reuptake of mainly noradrenaline and 5-HT into presynaptic terminals

Question 15

What are the anticholinergic side effects of tricyclics?

Answer 15

Blurred vision, dry mouth, constipation, urinary retention

Question 16

What are some general side effects of tricyclics?

Answer 16

Sedation, weight gain, postural hypotension, tachycardia, arrhythmia, cardiotoxic in overdose

Question 17

What are some examples of SSRIs?

Answer 17

Fluoxetine, citalopram/escitalopram, sertraline

Question 18

What is the action of SSRIs?

Answer 18

Selectively inhibit reuptake of 5-HT from the synaptic cleft

Question 19

What are the side effects of SSRIs?

Answer 19

Nausea, headache, worsened anxiety, sexual dysfunction, sweating, vivid dreams
Transient increase in self harm/suicide in <25 y/o
Hyponatraemia in elderly

Question 20

What are some features of dual reuptake inhibitors (SNRIs)?

Answer 20

Agents = venlafaxine, duloxetine
Block reuptake of noradrenaline and 5-HT into the presynaptic cleft
Similar side effects to SSRIs

Question 21

What are some noradrenaline selective antidepressants?

Answer 21

Reboxetine, maprotiline, despiramine, protriptyline, nortriptyline

Question 22

What are some examples of non-selective antidepressants?

Answer 22

Amitriptyline, imipramine, clomipramine

Question 23

What are some examples of 5-HT selective antidepressants?

Answer 23

Venlafaxine, paroxetine, fluvoxamine, sertraline, fluoxetine, citalopram

Question 24

What are some examples of atypical antidepressants?

Answer 24

Mirtazapine and bupropion = mixed receptor effects

Question 25

What are some features of mirtazapine?

Answer 25

Blocks alpha2, 5-HT2 and 5-HT3 Side effects = weight gain, sedation Can block serotonergic side effects if given with SSRIs

Question 26

What is the action of bupropion?

Answer 26

Dopamine uptake inhibitor

Question 27

What are some features of current antidepressants?

Answer 27

Most have similar clinical efficacy = 40-70% Most have delayed onset of action = several weeks Clearer evidence for usefulness in more severe cases Caution in young adults due to transient increases in suicidal tendencies

Question 28

What drug is used to treat bipolar affective disorder?

Answer 28

Lithium = usually given as lithium carbonate

Question 29

What are the proposed actions of lithium?

Answer 29

may block phosphatidylinositol pathway, inhibit glycogen synthase kinase 3beta or modulate no signalling

Question 30

Why must the 12 hour post dose blood levels of lithium be monitored?

Answer 30

Has narrow therapeutic index = target range is 0.4-1.0 mmol/L with higher end of range being associated with better response

Question 31

What are the side effects of lithium?

Answer 31

Dry mouth, strange taste, polydipsia, polyuria, tremor, hypothyroidism, long term reduced renal function, nephrogenic diabetes insipidus, weight gain

Question 32

What are the toxic effects of lithium?

Answer 32

Vomiting, diarrhoea, ataxia, course tremor, drowsiness, altered conscious level, convulsions, coma

Question 33

What are some anticonvulsants used as mood stabilisers in bipolar disorder?

Answer 33

Valporic acid, lamotrigine and carbamazepine

Question 34

What is the mode of action of anticonvulsants?

Answer 34

Unclear = may potentiate GABA transmission and therefore block overactive pathways

Question 35

What are the side effects of valproate and carbamazepine?

Answer 35

Drowsiness, ataxia, CV effects, induces liver enzymes

Question 36

What is the most concerning side effect of valproate?

Answer 36

Teratogenicity = neural tube defects

Question 37

What is a potential side effect of lamotrigine?

Answer 37

Very small risk of Stevens-Johnson syndrome

Question 38

What are some antipsychotics used as mood stabilisers?

Answer 38

Quetiapine, aripiprazole, olanzapine, lurasidone

Question 39

What is the action of antipsychotics?

Answer 39

Dopamine and 5-HT antagonsim

Question 40

What are the side effects of antipsychotics?

Answer 40

Sedation, weight gain, metabolic syndrome, extrapyramidal side effects (aripiprazole)