Lecture 18: treatments of depression

Question 1

Is electroconvulsive therapy effective? List one advantage and one disadvantage.

Answer 1

Yes, it is effective
- induce seizure in temporal lobe
- advantage: relief occurs very quickly, which is very good when a person is experiencing suicidal thoughts
- disadvantage: risk of memory loss

Question 2

Why are electroconvulsive therapy and ketamine NOT first choices in the treatment of depression?

Answer 2

ECT:
- very invasive, risk of memory loss
Ketamine:
- easy to be abused, very difficult to be approved
- very expensive, often insurance won’t cover it

Question 3

How is ketamine’s mechanism of action different from SSRIs mechanism of action

Answer 3

Ketamine:
- glutamate antagonist
- increases release* of glutamate from pre-synaptic neuron

SSRIs:
- serotonin reuptake inhibitors
- prevent serotonin from returning to the pre-synaptic neuron

Question 4

What is the key advantage of ketamine treatment?

Answer 4

1. works extremely fast
2. amount you need to experience relief goes down over time, which prevents tolerance and dependence/abuse

Question 5

How do SSRIs and SSNRIs work?

Answer 5

• selectively block/inhibit the reuptake of serotonin / serotonin and norepinephrine

Question 6

What are the advantages of SSRI’s over MAOi or tricyclics?

Answer 6

• SSRI’s have very few side effects and are very safe (low therapeutic index)
• MAOis are less effective than SSRIS and have side effects on your diet
• tricyclics are effective for melancholic features (rather than atypical), but have much more side effects than SSRIs (heart failure) and higher therapeutic index

Question 7

How do MAOis work? Why do they interfere with your diet?

Answer 7

• MAOis = monoamine oxidase inhibitors
• monoamine oxidase is an enzyme that breaks down monoamines such as DA, NE, and 5-HT
• by inhibiting the enzyme, MAOis prevent the breakdown of monoamines in the neuron
• MAO is also present in other places in the body
• its used to digest food
• when you’re inhibiting it, it can’t digest food as well, which can cause toxic reactions to certain foods

Question 8

Tricyclics have lower therapeutic index than SSRIs making them less safe. What does it mean to have a lower therapeutic index?

Answer 8

therapeutic index is the ratio of the dose of a drug needed to be effective compared to the dose that is toxic. A lower therapeutic index means that a small difference in dosage can be dangerous, which makes tricyclics less safe.

Question 9

By now, you know what SSRis do, using the same approach, what do you think NDRIs do?

Answer 9

• Norepinephrine & dopamine re-uptake inhibitors
• they inhibit the reuptake of NE and DA NTs

Question 10

What are the 3 hypotheses of depression?

Answer 10

• diathesis-stress
• monoamine hypothesis (NTs)
• allergies

Question 11

Last week we talked about different hypothesis of depression. Which of those hypotheses are supported by the fact that tricyclics are an effective treatment of depression? Explain your answer

Answer 11

• allergies
• tricyclics have 2 parts
  –> 1st – identical to SSNRIs – block reuptake of 5-HT & NE
  –> 2nd – block receptors of acetylcholine and histamine
• histamine = allergies