Anti-depressants

The pathophysiological basis of depression is depletion in the levels of serotonin, noradrenaline, and/or dopamine in the central nervous system.

Enhance monoaminergic activity in central synapses:

1.Inhibit monoamine reuptake

2.Inhibit enzymatic degradation

3.Block presynaptic autoreceptors

TCAs - Tricyclic antidepressants

SNRIs- Serotonin and Noradrenaline Reuptake Inhibition

SSRIs- selective serotonin reuptake inhibitors

MAOI- monoamine oxidase inhibitors

Benzodiazepines

NaSSA/ alpha 2 antagonist

Clomipramine

Amitriptyline

• Depressive disorder

• Phobic or obsessional states

serotonin and/or noradrenaline reuptake inhibition

• overdose → block Na+ channels → cardiac arrest

• Weight gain

• Sexual dysfunction

• Depersonalisation

Citalopram

• Depressive disorder

• Panic + anxiety

Blocks SERT (serotonin re-uptake tranposters)

Serotonin will remain in the synaptic cleft for longer

Leads to repeated activation of 5-HT receptors (post)

QT interval prolongation

GI disturbances

sexual dysfunction

sleep disorders

If poorly controlled epileptic or pre-existing long QT interval, or manic

Reboxetine

major depression

Mostly blocks noradrenaline but also some blocking of serotonin

Palpitations

Sexual dysfunction

Decreased appetite

Nausea

dry mouth

dizziness

excessive sweating

Moclobemide

Depressive disorder

Social anxiety

Moclobemide

Inhibit monoamine oxidase A, preventing breakdown of 5HT and NA

A selective (reversible) monoamine oxidase inhibitor which can prevent MAO-mediated clearance of serotonin, noradrenaline and dopamine from synaptic clefts

Confused states (agitation), dizziness, dry mouth, CHEESE CRISIS

If thyrotoxicosis, if bipolar

Selegiline

A type of Parkinson’s drug

Inhibit monoamine oxidase B, preventing breakdown of dopamine

A selective (reversible) monoamine oxidase inhibitor which can prevent MAO-mediated clearance of serotonin, noradrenaline and dopamine from synaptic clefts

Confused states (agitation), dizziness, dry mouth

Irritability

Sleep disorder

Nausea + vomiting

Mirtazapine

NaSSAs bind to and inhibit both noradrenaline a2-autoreceptors and noradrenaline a2-heteroeceptors.

This action prevents the negative feedback effect of synaptic noradrenaline on 5-HT and noradrenaline neurotransmission, sustaining neurotransmission.

NaSSAs also block 5-HT2 and 5-HT3 receptors on the post-synaptic membrane, which causes enhanced 5-HT1 mediated neurotransmission.

5HT3 antagonist: increased appetite

H1 (histamine) antagonist: drowsiness, weight gain

5-HT1: Gi/Go-protein coupled

5-HT3: Ligand-gated Na+ and K+ channels

5-HT2: Gq/G11-protein coupled

5-HT4: Gs-protein coupled

Increased 5HT activity in the CNS

Caused by drug overdose or interaction between two 5HT-enhancing drugs (more common)

It's usually triggered when you take an SSRI or SNRI in combination with another medicine (or substance) that also raises serotonin levels, such as another antidepressant or St John's wort.

Avoid sympathomimetic and dopaminergic drugs (monoamine overload)

• Mental state: anxiety, agitation, disorientation

• Autonomic (SNS) symptoms: diaphoresis, raised HR/RR/BP/temp, vomiting/ diarrhoea/ increased bowel sounds; dilated pupils

• Neuromuscular: tremor, rigidity, hyperreflexia, bilateral Babinksi