Antidepressants

Question 1

What is the first line class of drug treatment for adults with unipolar depression, anxiety or OCD?

Answer 1

SSRIs - selective serotonin reuptake inhibitor

Fluoxetine + citalopram (most commonly preferred), sertraline, escitalopram, paroxetine, fluvoxamine, dapoxetine

Question 2

How do SSRIs work?

Answer 2

Block pre-synaptic serotonin receptors - inhibiting the uptake of serotonin and increasing the amount of serotonin in the synapse

Also downregulate the number of 5-HT receptors

Predominantly acts in the prefrontal cortex

Patients report low feelings are less pronounced, they do not increase ‘happiness’

(though we dont really know and this means literally nothing)

Question 3

What side effects are common?

Answer 3

GI most common:
N+V, abdo pain, silent reflux, GI bleed
Can give omeprazole (also if taking NSAID)

Feelings of agitation, tremor, anxiety, dizziness, blurred vision

Sexual dysfunction - low libido, erectile dysfunction, delayed ejaculation

Emotional numbness

Question 4

What is serotonin syndrome?

Answer 4

Typically resulting from the use of 2+ serotonergic drugs - including SSRIs and other AntiD’s; street drugs - MDMA/amphetamines/cocaine/hallucinogens; St John’s Wort

Uncommon, short lived condition that can be fatal

Symptoms - triad: (SAC)
Cognitive = headache, agitation, hypomania, confusion, hallucination, coma
Autonomic =
tachycardia, sweating, shivering, dilated pupils, HTN, hyperthermia, N+V
Somatic = myoclonus, hyperreflexia, tremor

Management:
Stop drug
IV fluids +/- benzodiazepines if necessary
5-HT2A antagonists such as cyproheptadine in severe

Question 5

What interactions are common?

Answer 5

Almost endless list

Some significant common ones are: aspirin/NSAIDs - GI bleeding risk - must co-prescribe with PPI

Warfarin/heparin - antiplatelet effect - try Mirtazepine

Triptans - just avoid SSRI

MAOIs - risk of serotonin syndrome

Fluoxetine + paroxetine are most commonly associated with interactions

Question 6

How does the treatment plan work?

Answer 6

Started on lowest possible dose thought to improve symptoms

Taken daily for 2-4wks before benefit is felt - 2wk review with doctor is typical; if increased suicide risk - r/v in 1wk

Mild side effects may be present early but will usually settle

If taken for 4-6 weeks with no improvement return to doctor for titration upwards or review/switch if proving ineffective at higher doses

Should remain on for 6m after remission to reduce risk of relapse

Reduce over 4wks to minimise discontinuation symptoms

Question 7

What happens if one SSRI unsuccessful?

Answer 7

Ensure trialled at maximum dose

Try another in the same class before changing type of antidepressant

Switch to mirtazapine, lofepramine, reboxetine etc

Antidepressant effects greatest when medications (in the same class) are mixed, though not in nice guidelines and should never mix with MAOIs as can cause serotonin syndrome

Question 8

What is the relationship between hyponatraemia and antidepressants?

Answer 8

Possible side effect - usually in the elderly

Most commonly associated with SSRIs
Should be considered in all patients who develop drowsiness, confusion or convulsions

Question 9

What are some cautions/contraindications for SSRI prescription?

Answer 9

Bipolar disorder - can precipitate mania
Bleeding disorders - can exacerbate
Epilepsy - only taken if well controlled
Diabetes
Serious kidney, liver or heart problems
Narrow angle glaucoma

Pregnancy:
First trimester - congential heart defects
Third trimester - persistent pulmonary HTN
Weigh up risks/benefits

Breastfeeding:
Paroxetine or sertraline are usually recommended and are considered safe to use

Children + adolescents: higher self harm and suicidal ideation; Fluoxetine is the drug of choice if depressed

Question 10

Which antidepressants should be considered for more severe forms of depression?

Answer 10

Tricyclics

Venlafaxine

Question 11

How do tricyclics work?

Answer 11

Block the reuptake of serotonin and noradrenaline

Various members in the class have different selectivities for each receptor type

They are also classed into more sedating and less sedating

Question 12

What are some sedating tricyclics?

Answer 12

Used for anxious/agitated patients

Amitryptaline, clomipramine, dosulepin, doxepin, trazadone, trimaprimine

Question 13

What are some less sedating tricyclics?

Answer 13

Used for patients who are withdrawn or apathetic

Imapramine, nortripyline, lofepramine

Question 14

What are some side effects of tricyclics?

Answer 14

Antimuscarinic - dry mouth, pupil dilation and photosensitivity, no sweating, constipation, urinary retention, brady/tachy/arrhythmias

Weight gain/loss, postural hypotension, rash, sedation

Question 15

How do you prescribe amitryptaline?

Answer 15

Migraine + chronic tension headache prophylaxis, neuropathic pain including phantom limb pain, abdominal pain in those unresponsive to other drugs

It is not however recommended in major depressive disorder due to an increased risk of fatality in overdose

Question 16

What are SNRIs?

Answer 16

Block the reuptake of serotonin and noradrenaline

Examples are duloxetine, venlafaxine

Question 17

What is Mirtazepine?

Answer 17

Could be a tetracyclic or a noradrenaline and specific serotonergic antidepressants (NASSA) - we dont really know..

Blocks - alpha-2 adrenergic receptors, histamine and serotonin (though doesnt inhibit reuptake)

Similar side effect profile to SSRI but fewer sexual side effects and more sedating/hypnotic initially (so can give for those with insomniac symptoms, take in evening)

Also improves appetite - give if weight/appetite concerns

Question 18

What are MAOIs?

Answer 18

Monoamine oxidase inhibitors

Inhibit breakdown of NAd, 5HT, DA by inhibiting MAO enzyme

Much less frequently used due to diet/drug interactions; specialist prescription only

Examples - tranylcypromine (SE: HTN crisis), isocarboxazid and phenelzine (SE: hepatotoxicity); moclobemide (2nd line)

Indicated in severe refractory depression; also particularly successful if atypical/hypochondriacal/hysterical features

Response after 3+wks, and an additional 1-2 to become maximal

Question 19

What is a washout period?

Answer 19

Time between switching serotinergic antidepressants - detox almost

Cross fading dose titrations here are also possible ie introducing one whilst decreasing the dose of another

Longer washout periods (of abstinence) are needed when switching to or from irreversible MAOIs as serotonin syndrome is more common here (see guidance)

Question 20

What augmenting agents can be used along side antidepressants?

Answer 20

Lithium, quetiapine;
also aripiprazole, olanzapone, rispridone (unlicensed)

Specialist prescription only

Question 21

What SSRI is best used after MI?

Answer 21

Sertraline and citalopram are the safest according to current evidence

Question 22

What effect does citalopram (+escitalopram) have on QT interval?

Answer 22

Associated with dose-dependent QT interval prolongation and should not be used in those with: congenital long QT syndrome; known pre-existing QT interval prolongation; or in combination with other medicines that prolong the QT interval (lots of antipsychotics)

Maximum daily dose is now 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment

Question 23

What are some discontinuation symptoms of SSRIs?

Answer 23

Gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
Increased mood change
Restlessness
Difficulty sleeping
Unsteadiness
Sweating
Paraesthesia

Should reduce SSRI over 4wks to minimise risk (unnecessary with fluoxetine due to longer half life; more common in paroxetine)

Question 24

What is a classic side effect of MAOIs?

Answer 24

Tyramine reaction:

Foods high in Tyramine e.g. cheese - may bring on a hypertensive crisis