Drugs used in affective disorders: antidepressants

Sarah & Clara

• Depression: Most common mental health issue. ICD-10: Mood [affective] disorders (F30-F39).

• Key symptoms:• 1) Persistent low mood/sadness and/or• 2) marked loss of interest or pleasure

• If have those, check for these: – disturbed sleep (decreased or increased compared to usual)– decreased or increased appetite and/or weight– fatigue or loss of energy– agitation or slowing of movements– poor concentration or indecisiveness– feelings of worthlessness or excessive or inappropriate guilt– suicidal thoughts or acts

Pharmacological treatments for depression – 4 main classes:

• Selective Serotonin Reuptake Inhibitors (SSRIs)• Monoamine Oxidase Inhibitors (MAOI-As)• Tricyclic Antidepressants (TCAs)• Atypical Antidepressants (e.g. NRIs, SNRIs)

SSRIs MAOI-As TCAs Atypical

Fluoxetine Moclobermide Amitryptiline Buspirone

Paroxetine Phenelzine Nortripyline Bupropion

Citalopram Isocarboxadize Cocaine Reboxetine

Setraline Venlafaxine

Citalopram

Venlafaxine

Nortriptyline

Moclobermide

Sertraline

Fluoxetine

Buspirone

Amitryptiline

Reboxetine Phenelzine

Paroxetine

Bupropion Isocarboxadize Cocaine

Explain the MoA of SSRIs:

• Serotonin is released into the synaptic cleft.• Under normal circumstances, some of this serotonin is taken back

up into the pre-synaptic nerve ending by a re-uptake pump.• SSRIs inhibit this re-uptake pump.• Therefore serotonin levels in the cleft are increased…• …and more serotonin is available to bind to receptors• = HAPPY (NB: Serotonin often referred to as 5HT)

Side effects of SSRIs/5HT modulation (5):

• Slow onset (2-3 weeks earliest)• Sleep disorders• Sickness• Sexual dysfunction• ‘Serotonin Syndrome’ (hyperthermia, cardiovascular

problems, aggression, tremor and rigidity)

• REMEMBER THE 5 S’s!

Explain the MoA of MAOI-A’s:• Increase levels of

NA/5HT by inhibiting their enzymatic breakdown by monoamine oxidase.

• =HAPPY

• Some are selective/non-selective and reversible/irreversible.

Side effects of MAOI-A’s (5):• Postural hypotension• Convulsions• Restlessness• Sleep disorders• CHEESE REACTION• + not to be used with either SSRIs or TCAs = bad mix

• Cheese reaction: • Cheese, red wine etc contain tyramine – another substance

usually broken down by monoamine oxidase. A build up of tyramine can cause a hypertensive crisis.

The 5 main actions of TCA’s:• 5HT reuptake blocker• NA reuptake blocker• α1 adrenoreceptor antagonist

• H1 receptor antagonist

• M1 receptor antagonist

• Biggest effect is the increase in NA levels. Bit iffy with the effect on 5HT…

• And they have side effects to match!• H1: Sedation and weight gain• A1: Vasodilation and tachycardia• M1: Constipation, dry mouth, glaucoma

Atypicals (don’t worry too much)

• NRIs (e.g. Ruboxetine) work in exactly the same way as SSRIs to up 5HT levels.

• SNRIs (e.g. Venlafaxine) are multitaskers and up levels of NA and 5HT by reuptake inhibition

• 5HT partial agonists reduce neuronal impulse firing to allow serotonin levels to replete:

• Buspirone• Trazodone• Tandospirone

A final few others…• Agomelatine

• Melatonin agonist• Increases slow-wave sleep

• Lithium• Historical general mood stabilizer, CNS mechanisms not well understood.

• Non-pharmacological:• CBT• Counselling• Electro convulsive therapy (ECT)• Trans-cranial magnetic stimulation (TMS)

NICE recommendation: a combined treatment programme of CBT + AD.

Any questions?https://www.cnsforum.com/educationalresources/imagebank/antidepressants

Exam style questions• List: the two main symptoms & additional symptoms required

for the diagnosis of depression• List the types of pharmocological treatment used for

depression. Name two drugs for each class of drugs. • Name some non-pharmacological treatments for depression• What is the MOA for SSRIs?• Name some side effects of SSRIs• What is the “Serotonin Syndrome”?• Describe the MOA of Monoamine Oxidase Inhibitors. • What are the side effects of MOA-I?• Which receptors do Tricyclic Antidepressants work on? Name

the effects for each receptors, and therefore the side effects for this type of drug (actual exam question!)