Affective Disorders (NM) (DONE)

Question 1

Depression

Answer 1

Leading cause of disability in developed countries
Approximately 1 in 7 people will suffer a depressive episode at some point in their life
More common in women than men
Strong association with suicide

Question 2

Characteristics of depression

Answer 2

Low mood
Loss of interest/pleasure from normally pleasurable activities
Reduced energy (fatigue)
Low self esteem, feelings of guilt, inability to concentrate, altered psychomotor activity, sleep disturbance, altered appetite, suicidal thoughts
Two core symptoms plus two or more of the others present for most of the day and on most days for at least two weeks

Question 3

Diagnosis of depression

Answer 3

The symptoms are not attributable to physical illness, alcohol, medication or illicit drugs
There has never been a manic episode, or a hypomanic episode

Question 4

Aetiology of depression

Answer 4

Biological: genetic factors, monoamine hypothesis, alterations in the hypothalamic-pituitary axis and immune system
Environmental/psychological: early life adversity, personality traits (anxiety, impulsivity, obsessionality), stressful life events, physical illness

Question 5

Psychopharmacology of depression

Answer 5

A reduction in monoamine (serotonin, noradrenaline, dopamine) neurotransmission (depletion of neurotransmitters and change in receptor function)
Tryptophan depletion which reduces 5HT synthesis can lead to depressive symptoms
Increased activity in the subgenual cingulate cortex- antidepressants and deep brain stimulation reduce the activity of this area

Question 6

Prognosis of depression

Answer 6

Episodes tend to last for 3-6 months
Approximately 50-80% of patients who have one episode of major depression will go on to have a second
80-90% of those having a second episode will have a third episode
Significant risk of suicide
Risk of recurrence increased by family history, female gender, social factors, co-morbid psychiatric illness, longer duration of episode, co-morbid medical illness

Question 7

Treatment of depression

Answer 7

Assessment and accurate diagnosis
Psychological- CBT, behavioural activation, interpersonal psychotherapy, problem solving therapy
Social- identifying stressors and working on strategies/signposting to other supporting organisations
Biological- antidepressant medication or antidepressants and antipsychotics in psychotic depression

Question 8

Antidepressants

Answer 8

Usually divided according to mechanism of action
All potentiate neurotransmission and are effective but with different side effect profiles
All can cause hyponatraemia (caution in elderly)

Question 9

Tricyclic antidepressants

Answer 9

Amitriptyline, nortriptyline, dosulepin
5HT and NA transporter blockade
Side effects: short lasting sedation, confusion and incoordination in both normal and depressed patients, antimuscarinic effects
Potentiation of the effects of alcohol

Question 10

SSRIs

Answer 10

Fluoxetine, paroxetine, citalopram (escitalopram), sertraline
Inhibits 5HT transporter
Side effects: nausea, anorexia, insomnia, loss of sexual function
Less anticholinergic side effects and less dangerous in overdose than TCAs
Interactions: NSAIDs, anticoagulants, triptans

Question 11

SNRIs

Answer 11

Venlafaxine and duloxetine
Inhibits 5HT and NA transporter
Side effects: withdrawal effects
Interactions: NSAIDs, anticoagulants

Question 12

MAOIs

Answer 12

Irreversible- tranylcypromine
Reversible- moclobemide
Inhibits monoamine oxidase, non-selective (MAO-A and B)
Side effects: anti-muscarinic effects, restlessness as a result of CNS excitation
Interactions: food/drug interactions- cheese effects

Question 13

Atypical antidepressants

Answer 13

Mirtazapine
a2 autoreceptor antagonism, 5HT receptor blockade
Side effects: sedation, weight gain, increased appetite, blood disorders, withdrawal
Interactions: alcohol

Question 14

Other antidepressants

Answer 14

Trazodone- weak reuptake inhibitor and 5HT antagonist
Mianserin- 5HT histamine and NA a2 receptor antagonist
Agomelatine- melatonin receptor agonist
Reboxetine- noradrenaline reuptake inhibitor
Tryptophan- serotonin precursor

Question 15

Treatment approach for depression

Answer 15

Mild symptoms: psychological therapy
Persistent mild symptoms or moderate to severe symptoms: antidepressant and psychological therapy
First line drug treatment usually SSRI
Second line switch to alternate SSRI
Third line switch to an agent from a different class

Question 16

Practical issues

Answer 16

Initiating an antidepressant can increase feelings of anxiety; consider co-prescribing a short course of BZDs
First few weeks of treatment can have worsening suicidal thoughts with improved motivation
Consider prescribing limited supply of medication
Side effects often transient and improve with time
Caution when switching antidepressants

Question 17

Serotonin symdrome

Answer 17

Rare but potentially life threatening adverse drug reaction as a result of excessive stimulation of CNS and peripheral serotonin receptors
Antidepressants, analgesics, anti-emetics, recreational
Triad of:autonomic hyperactivity (hypertension, tachycardia, hyperthermia), neuromuscular abnormality (tremor, clonus, hypertonicity), mental status changes

Question 18

Further depression therapy

Answer 18

If no response to 3 antidepressants then check concordance, review diagnosis and consider if social problems are maintaining depression
Consider augmentation: mirtazapine, quetiapine, aripiprazole, lithium, lamotrigine, ECT

Question 19

Antidepressant efficacy

Answer 19

Generally the more severe the symptoms, the more effective the antidepressant (compared to placebo)
Usually used for moderate- severe illness
20% recover with no treatment
30% respond to placebo
50% respond to antidepressant

Question 20

Response to antidepressants

Answer 20

2-4 weeks to see response (longer in elderly patients)
Improvement greatest during weeks 1-2
If no response during that period consider switching to alternative
Extending duration of treatment trial will lead to additional benefit in some

Question 21

Preventing relapse

Answer 21

Relapse rate 3-6 months post remission is 50% with no drug treatment
A/D treatment reduces absolute risk of relapse by about 50%
After first episode continue for 6-9 months
After second episode continue for 12 months
After third episode continue for 2 years

Question 22

Novel treatment options

Answer 22

Repetitive transcranial magnet stimulation (rTMS)
Vagal nerve stimulation
Light therapy- useful in seasonal affective disarder
Modulation of glutamate neurotransmission
Ketamine

Question 23

Electroconvulsive therapy

Answer 23

Used in severe treatment resistant depression or treatment resistant mania. Can also be used to treat catatonia and severe postnatal depression.
Up to 70% efficacy, most effective in older people with depression or people with psychotic depression
Patient is given anaesthetic and muscle relaxant and electric current passed through the brain to cause seizure
Usually given twice weekly and response seen within first few weeks
Risks- associated with general anaesthesia, can cause memory loss, usually short term

Question 24

Bipolar disorder

Answer 24

Chronic, severe mental illness affecting 0.5% population, more common in women
Characterised by two or more episodes where the patient’s mood and activity is disturbed
Disturbance may be elevation of mood with increased energy and activity, or low mood with decreased energy/activity
Episodes are separated by a period of euthymia or a switch to the opposite symptom type

Question 25

Manic episode

Answer 25

Elevated mood out of keeping from person’s circumstance
Characterised by: increased energy/activity, pressure of speech, flight of ideas, reduced sleep, distractability, inflated self esteem, loss of inhibitions, reckless/risk taking behaviour

Question 26

Aetiology of bipolar

Answer 26

Usually presents in young adulthood
Causes include:
Genetic- stronger inheritance than any other psychiatric disorder (10% risk in first degree relatives)
Less evidence for environmental factors/life events
Possible role of the hypothalamic pituitary adrenal axis

Question 27

Psychopharmacology of bipolar

Answer 27

Mania: increased dopamine activity- amphetamine can induce a manic state; antipsychotics are effective antimanic agents; lithium withdrawal can precipitate mania, with only an indirect effect on dopamine
Depression: serotonin may play a part- SSRIs can be used to treat bipolar depression; tryptophan depletion does not induce symptoms; noradrenaline may also play a role

Question 28

Prognosis of bipolar

Answer 28

A chronic disorder which may have an episodic course- periods of mania/depression separated by euthymia
Chronic symptoms especially depression may persist
Suicide is common- 15%

Question 29

Treatment of bipolar disorder

Answer 29

Short term treatments: used to manage acute episodes of mania or depression, subsequently discontinued
Long term treatments: used to prevent relapse, continued indefinitely

Question 30

Treatment of mania

Answer 30

Antipsychotic or sodium valproate: olanzapine may be superior to valproate, may be more susceptible to adverse effects, usually treat for 2-3 months then maintenance
Usually BZD, either as required or regular for a short period to provide sedation
If patient is prescribed an antidepressant this should be discontinued
Lithium is effective, but difficult to initiate in a manic patient

Question 31

Treatment of bipolar depression

Answer 31

CBT for mild symptoms
SSRI or other antidepressant 
Lamotrigine
Lithium
Antipsychotics

Question 32

Lithium

Answer 32

Effect on neurotransmitters and second messenger systems
Effectiveness if closely associated with treatment continuation- discontinuation gives high risk of relapse
Risk of suicide in bipolar is 15%, lithium reduces risk by 80%

Question 33

Side effects of lithium

Answer 33

Rapidly absorbed from GI tract, excreted unchanged via kidney
Narrow therapeutic range 0.4-1.0mmol/L
Signs of toxicity: nausea, diarrhoea, ataxia, confusion, coarse tremor, seizures, loss of consciousness
Long term increases risk of: hypothyroidism, hyperparathyroidism, renal impairment

Question 34

Lithium counselling

Answer 34

Lithium card
Prior checks on renal, thyroid and cardiac function
Keeping appointments for regular monitoring
OTC NSAIDs
Seek medical attention if they develop diarrhoea and or vomiting
Maintain fluid intake
Seek advice about stopping lithium for up to 7 days if they become severely ill

Question 35

Valproate

Answer 35

NICE recommends as first line for mania, with antidepressant for depression and prophylaxis of BPD
As effective as lithium
Lithium non-responders may respond to valproate
Available in different formulations

Question 36

Lamotrigine

Answer 36

Voltage dependent Na+ channel blocker, reduces glutamate release
Considered effective for treating bipolar depression and for prophylaxis (as effective as citalopram)
Dose: slow increase very important

Question 37

Carbamazepine

Answer 37

Blocks voltage dependent Na+ channels, reduces glutamate release and transmitter turnover
Not recommended first line by NICE for mania, may be useful fro bipolar and unipolar depression
Less effective than Li+ for prophylaxis
RCT showed 40% relapse per year
Narrow therapeutic range
Hepatic enzyme inducer

Question 38

Antiepileptic adverse events

Answer 38

Minor but common: fever, flu-like symptoms, drowsiness
Serious but rare: blood disorders, liver disorders, pancreatitis
Weight gain
Teratogenicity
Rash in lamotrigine
Hyponatraemia