Affective disorders: neurobiology and treatment

Question 1

Aetiology of depression

Answer 1

Multifactorial

Incompletely understood

Interactions of genetic factors, childhood adversities, past history of mood disorders, psychological predisposition

Often precipitated by stressful life events

Question 2

Monoamine dysfunction in depression

Answer 2

All traditional antidepressants affect 5-HT/NA systems

Question 3

Serotonin dysfunction in depression

Answer 3

All traditional antidepressants affect 5HT/NA systems

Decrease 5-HT concentrations

Reduced 5-HT transporter in post mortem suicide studies

Question 4

1st generation antidepressants

Answer 4

Monoamine oxidase inhibitors

Tricyclic antidepressants

Question 5

Monoamine oxidase inhibitors

Answer 5

Non-selectively inhibit enzymes involved in the breakdown of monoamines, including serotonin, dopamine and norepinephrine

Question 6

Tricyclic antidepressants

Answer 6

Non-selectively inhibit the reuptake of monoamines, including serotonin, dopamine and noreepinephrine

Question 7

2nd generation antidepressants

Answer 7

SSRI

SNRI

Alpha2 and 5HT2C antagonist

Dopamine- noradrenaline reuptake inhibitor

Question 8

SSRI examples

Answer 8

Sertraline

Citalopram

Escitalpram

Fluoxetine

Question 9

SNRI

Answer 9

Venlafaxine

Duloxetine

Question 10

Alpha2 and 5-HT2C antagonist

Answer 10

Modulate serotonin and Na release

Mirtazapine

Question 11

Dopamine-noradrenaline reuptake inhibitor

Answer 11

Bupropion

Not approved as antidepressant in UK

Question 12

SSRI

Answer 12

Efficacy equal to tricyclics in outpatients

Large spectrum of action

Low toxicity and safe in overdose

Initial treatment phase is most delicate due to prevalence of side effects over benefits

Question 13

SSRI side effects

Answer 13

GI symptoms (nausea and diarrhoea)

Headache

Irritability

Anxiety

Reduction of libido

Sexual dysfunction

Question 14

Side effects of tricyclics

Answer 14

Constipation

Orthostatic hypotension

Dry mouth

Drowsiness

Cardiac toxicity in overdose

Question 15

MAOi side effects

Answer 15

Dry mouth

GI side effects

Headache

Drowsiness

Insomnia

Dizziness

Food interactions

Question 16

Venlafaxine side effects

Answer 16

Nausea

Vertigo

Headache

Insomnia

Question 17

Mirtazapine

Answer 17

Drowsiness

Sedation

Hypotension

Increased appetite

Weight gain

Question 18

HPA dysfunction in mood disorders

Answer 18

Lack of dexamethasone suppression

Glucocorticoid receptor alterations

Depression in Cushing’s disease

Question 19

Inflammation and depression

Answer 19

Raised plasma cytokine levels (IL6, TNFa) and inflammatory markers

High comorbidity between chronic inflammation and depression

Administration of cytokines provokes depressive symptoms

Microglial activation in brain of depressed patients

Question 20

Neural systems involved in depression

Answer 20

Increased activity to negative emotional stimuli

Decreased activity to positive emotional stimuli and during receipt and anticipation of reward

Bias of attention towards negative emotional stimuli, and away from positive emotional and reward-related stimuli

Question 21

Short term treatment of bipolar disorder

Answer 21

To reduce the severity and shorten the duration of the acute episodes and achieve remission of symptoms

Question 22

Long term treatment of bipolar disorder

Answer 22

Prevention of new episodes and to achieve adequate inter-episode control of residual or chronic mood symptoms

Question 23

Drug categories for bipolar disorder treatment

Answer 23

Antipsychotics

Lithium

Anticonvulsants

Antidepressants

Question 24

Antipsychotics

Answer 24

D2/3 antagonists
DA partial agonists

Rapid anti-manic effect

Often used long term to maintain same treatment effective in acute episodes

Long term adverse effects on weight, glucose regulation and lipids

Full D2 antagonism may cause EPSEs

Question 25

D2/3 antagonists

Answer 25

1st generation: haloperidol 2nd generation: olanzapine, risperidone, quetiapine, lurasidone, asenapine, amisulpride, clozapine

Question 26

Lithium

Answer 26

Multiple mechanisms of action - multiple neurotransmitters - cellular signalling - neurotrophic factors Anti suicidial effects Possible efficacy on impulsive and violent behaviours Strongest evidence for prevention of relapses Narrow therapeutic index Blood tests every 3 months for 1st year Adverse long term effects on kidney function Risk of lithium toxicity

Question 27

Anticonvulsants

Answer 27

Valproate Lamotrigine Carbamazepine

Question 28

Valproate

Answer 28

Actions via GABA, intracellular signalling, Na+ channel blockade, epigenetic modulation Anti-manic and effective in prevention of mania Useful in combination but potential pharmacokinetic interactions Not to be used for women of child bearing potential due to teratogenesis

Question 29

Latmotrigine

Answer 29

Actions via GABA, glutamate and Na+ channel blockade Mostly effective in prevention of depressive relapses Ineffective as anti-manic agent

Question 30

Carbamazepine

Answer 30

Less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective Almost exclusively effective against manic relapse Pharmacokinetic interactions

Question 31

Treatment of depressive episodes

Answer 31

Antipsychotics (quetiapine, lurasidone) Fluoexetine/ olanzapine combinations Antidepressants to be co-prescribed with an anti-manic drug Consider lamotrigine

Question 32

Treatment of acute manic episodes

Answer 32

Dopamine antagonists (haloperidol, olanzapine, risperidone, quetiapine) Valproate Discontinue any antidepressant treatment

Question 33

Long term treatment: prevention of new episodes

Answer 33

Consider long term treatment following a single severe manic episode Lithium as initial monotherapy Alternatives: - valproate - dopamine antagonists/ partial agonists - carbamazepine

Question 34

Adverse effects of long term pharmacological treatments

Answer 34

WEight gain Metabolic syndrome Hyperprolactinemia Tardive dyskinesia Liver damage Kidney and thyroid dysfunction