Antidepressants

Question 1

Talk to me about biological explanations of depression

Answer 1

• centred around the role of 5-HT, DA and NE-these are NTs particularly important in areas of mood, sexual function/desire, sleep, memory, appetite and social behaviour.
• Biological explanation proposed after invention of ADs!
  
  • stimulant drugs which increased 5-HT were used to treat!
• Little evidence to suggest that imbalances in levels of NTs cause depression?
  
  • perhaps, people vulnerable to depression have less or less sensitive 5-HT Receptors than others?
  • more MAOs so less NT available for release?
  • rapid firing of neurons may lead to depletion?
• Timing is off again-NT levels increase mere hours after taking, but noticeable effect only after 2-6 weeks
  
  • epigenetics?
  • no current convincing biological explanation!
• n.b. most theories have been concerned with CNS-however, 95% of 5-HT is produced in the gut (enteric nervous system)
  
  • newer theories are exploring this connecting
  • new school of throught that depression is a syndrome, with many different subtypes, each with specific biological markers

Question 2

What does SSRI stand for and please name three?

Answer 2

Selective Serotonin Re-uptake Inhibitor

• Citalopram
• Fluoxetine
• Sertraline

Question 3

What does SNRI stand for and please name one?

Answer 3

Serotonin and Norepinephrine Reuptake Inhibitor

• Venlafaxine

Question 4

What does MAOI stand for and please name two?

Answer 4

Monoamine Oxidase Inhibitor

• Phenylzine
• Moclobemide

Examples of Monoamines include;

• DA
• 5-HT
• Adrenaline

Question 5

What does TCA stand for and please name three?

Answer 5

Tricyclic Antidepressant

• Amitryptaline
• Dosulepin
• Clomipramine

Question 6

How are SSRIs thought to work?

Answer 6

• Serotonin theory of depression-increase 5-HT levels lead to elevated mood and decreased anxiety
• They inhibit the reuptake of 5-HT by the amine reuptake pump into the presynaptic neuron, therefore increasing amount in synaptic cleft-allows levels to build up
• no known effect on NE and little affinity for cholinergic sites.

Question 7

How are SNRIs thought to work?

Answer 7

• They prevent the reuptake of both 5-HT (slightly different mechanism*) AND NE-thus increased levels
• (extended release form that does away with multiple daily doeses required with regular form)

Question 8

How are MAOIs thought to work?

Answer 8

• Related to Monoamine Theory of Depression
  
  • Increased levels of Monoamines in key areas of brain (5-HT, NE and DA) elevate mood
• Inhibit the enzyme oxidases which normally break down excess NT
  
  • Mainly target MAO-A (prefers to break down 5-HT but also some NE and DA)
• allows amines to accumulate in synaptive cleft and in presynaptic neuronal vesicles
  
  • increased stimulation of postsynaptic receptors and relief of depression

Question 9

How are TCAs thought to work?

Answer 9

• They increase the production of 5-HT and NE
• Also stop the production of ACh
  
  • Which itself inhibitis 5-HT leves
    
    • (hence antimuscarinic effects)

Question 10

When would each of the ADs be used?

Answer 10

• SSRIs-First line pharmacological treatment
  
  • Newer, less side effects
• SNRIs-used in more complex cases (inc hypochondria)
  
  • also newer, less side effects
• MAOIs-most likely to be used in older people
• TCAs-should only be used in those who have not responded to SSRIs
  
  • Most severe side effects
  • lowest risk of harm to baby during pregnancy

Question 11

What are SSRIs indicated for?

Answer 11

• Depression
• OCD
• GAD
• BN
• PTSD

Question 12

What are MAOIs indicated for?

Answer 12

• Phobias
• Co-morbid Anxiety and Depression
• hypocondriac patients

Question 13

What are TCAs indicated for?

Answer 13

• ONLY clomipramine recommended for relief of depression and anxiety
• Enuresis/pain treatment!

Question 14

What are the general contraindications of ADs?

Answer 14

• Cardiac Arrhythmia
  
  • or immediately after myocardial infarction
• Uncontrolled Hypertension
  
  • risk of hypertensive crisis
• Patients with or susceptible to elevated mood
  
  • risk of triggering mania
• liver and kidney impairments
  
  • where metabolised and excreted
• Pregnancy
  
  • first three months and final month most vulnerable to harm
    
    • withdrawal if in last month
  • SSRIs worst
  • premature birth and miscarriage

Question 15

What are the specific contraindications for ADs?

Answer 15

• SSRIs: Patients under the age of 18 due to increase in suicidal ideation + SH
  
  • also possible effect on brain development
  • possible use of fluoxetine when closely monitored
• TCAs: High risk of suicide
  
  • very toxic-substantial risk of fatality in overdose

Question 16

What drug interactions are particularly dangerous with ADs and why?

Answer 16

• Not to be used with other ADs
  
  • at least 2 weeks non-overlap with MAOIs
  • St John’s Wort (increased photosensitivity. induce liver metabolising enzymes reducing other drugs’ duration of action).
    
    • Serotonin Syndrome
• Carbamazepine
• Typical APs
  
  • Cardiac complications

Question 17

What are the side effects of SSRIs?

Answer 17

SHADY ANTACIDS

(really horrible hangover)

• sexual dysfunction (fluoxetine-premature ejaculationt treatment)
• headaches
• anxiety
• dizziness
• yawning
• anorexia nervosa
• nausea
• tremors
• agitation
• constipation
• insomnia
• dry mouth
• sweating

Question 18

What are the side effects of SNRIs?

Answer 18

• • BP
• sleep disturbances
• constipation
• sweating

Question 19

What are the side effects of MAOIs?

Answer 19

• Dry mouth
• Postural Hypotension
• Restlessness
• Dizziness

Question 20

What are the side-effects of TCAs?

Answer 20

• Risk of EPSEs
• Sedation
• Antimuscarinic effects (dry mouth, blurred vision, confusion)
  
  • because of inhibition of ACh
    
    • Doses at bedtime because of these last two

Tolerance to some of these side effects after a few weeks

Question 21

What is the difference in dosages of SSRIs for depressive and anxiety disorders?

Answer 21

Depressive disorders require much higher doses

Question 22

Name the symptoms of Serotonin syndrome

Answer 22

DADSHIT

• diarrhoea
• agitation
• dilated pupils
• sweating/shivering
• high body temperature (over 38)
• increased reflexes
• tremor

CALL 999-MEDICAL EMERGENCY

Question 23

Talk to me about withdrawal syndrome?

Answer 23

• All ADs require gradual reduction and close monitoring
• Venlafaxine more likely to cause effects
  
  • 82%
  • 6-8 weeks after discontinuation
• Increased anxiety is most common (70%)
• electric shocks/’brain zaps’
• low mood/suicide
• disturbing dreams

Question 24

What is another reason for avoiding MAOIs?

Answer 24

Patient education

• Over the counter meds (coughs and colds)
• Foods containing Tyramine (cheeses, alcohol, cured meats, yoghurt)
  
  • Tyramine normally broken down by MAOs in wall of GI tract, if on MAOIs will absorb lots more into circulation, therefore
    
    • increased bp, risk of hypertensive crisis
      
      • cheese reaction!

Question 25

What could you use in conjunction with ADs regarding side effects and why?

Answer 25

Antidepressant side effect checklist (ASEC)

Side effects are most common reason for non-concordance

May be an indication of non-concordance (if no side effects)

May be an indication of need to stop medication