Drugs used in affective disorders: antidepressants Sarah & Clara

If have those, check for these: 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) Majority of these all based on the monoamine theory of depression (i.e. depleted levels of serotonin or noradrenaline cause development of low mood and vice versa). 1st line: SSRIs/2nd: MAOI-As or TCAs due to side effects

SSRIs MAOI-As TCAs Atypical Fluoxetine Moclobermide Amitryptiline Buspirone Paroxetine Phenelzine Nortripyline Bupropion Citalopram Isocarboxadize Cocaine Reboxetine Setraline Venlafaxine Citalopram Nortriptyline Buspirone Reboxetine Phenelzine Venlafaxine Sertraline Amitryptiline Paroxetine Moclobermide Fluoxetine 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. Newer ones tend to be selective and reversible so less nasty side effects (eg. Moclobermide)

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 What else can they sometimes be used for? Treatment of neuropathic pain. Side effects are mostly due to effect on the autonomic nervous system.

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 Lithium Non-pharmacological: 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. Agomelatine: light therapy known to enhance mood plus sleep disruption decreases mood, so two-fold targets.

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!)