Antidepressants I

Question 1

Why is treating depression significant?

Answer 1

• Depression is a major cause of work days lost to disability, and a major cause of premature death.

Question 2

What are symptoms of depression?

Answer 2

A. Emotional

• misery, apathy, pessimism
• low self-esteem (feelings of guilty, inadequacy and ugliness)
• indecisiveness, loss of motivation

B. Other domains

• retardation of thought and action
• loss of libido
• sleep disturbance and loss of appetite

Question 3

What are the major types of depression?

Answer 3

A. Unipolar (mood always swings in the same direction)
- most of the cases are classified under reactive depression, which is:
» non-familial
» associated with life events
» accompanied by symptoms of anxiety and agitation
- fewer number of cases are classified under endogeneous depression.
» familial pattern
» not directly related to external stress

B. Bipolar depression or affective disorder (alternating depression and mania)
» strongly familial

Question 4

What is the monoamine theory?

Answer 4

The belief that deficits in monoamine transmitters (noradrenaline and 5-HT) cause depression.

Question 5

A patient has been prescribed a drug that prevents the degradation of monoamines/targets the reuptake of monoamines but is in remission months later. Why?

Answer 5

Monoamine deficit may not be his main cause of depression.

There are complex interactions with other neurotransmitter systems as well.

Question 6

What do MAO-A and MAO-B neurotransmitters mainly work on?

Answer 6

• 5-HT is broken down mainly by MAO-A.

- MAO-B acts on noradrenaline (NA) and dopamine.

Question 7

What is selegiline used to treat, and what class of inhibitors does it fall under?

Answer 7

Parkinson’s disease, MAO-B selective inhibitors

Question 8

What is the mechanism of action for phenelzine?

Answer 8

• Non-selective for MAO-A versus MAO-B.

- An irreversible MAO inhibitor.

Question 9

What are some adverse effects of MAOIs?

Answer 9

• Postural hypotension
• Restlessness and insomnia due to CNS stimulation
• Should not be combined with or other drugs enhancing serotoninergic function (e.g. pethidine)
  » hyperexcitability, increased muscular tone, jerking, involuntary movements etc.

Question 10

What is the cheese reaction?

Answer 10

• Drug-food interaction
• Major limitation on the use of MAOIs
• Acute hypertension, giving severe throbbing headache, and occasionally intracranial haemorrhage.
• Major danger is from cheeses and concentrated yeast products (e.g. marmite)

Question 11

What is the cheese reaction less likely to occur with?

Answer 11

Reversible, MAO-A selective (e.g. moclobemide) inhibitors as compared with irreversible, non-selective MAOIs

Question 12

Why shouldn’t patients on antidepressants consume cheese?

Answer 12

• Cheese contains tyramine that are usually broken down by MAO in the intestines and liver.
• Antidepressants like MAOIs can lead to the accumulation of tyramine and a sympathomimetic effect.
• Tyramine is taken up into adrenergic terminals and competes with NA for vesicular compartment –> this increases release of NA into synapses and results in acute hypertension.

Question 13

Which of the TCAs are non-selective for SERT/NET and which of them are selective for NET?

Answer 13

Non-selective for SERT/NET:
- Imipramine, Amitriptyline, nortriptyline
Selective for NET:
- Desipramine

Question 14

What are some characteristics of nortriptyline?

Answer 14

• Second generation TCA
• Milder side effects compared to amitriptyline and imipramine
• Improved compliance

Question 15

What are some adverse effects of TCAs?

Answer 15

• sedation
• postural hypotension
• dry mouth, blurred vision, constipation
• drug-drug interactions
  » plasma protein bound
  » rely on hepatic metabolism for elimination

Question 16

Imipramine, amitriptyline, nortriptyline. Which of the drugs are first-class, which of them are second-class?

Answer 16

First class: imipramine

Second class: amitriptyline, nortriptyline