Week 10. Antidepressants 8/23/2013 2:30:00 PM
• At times, we’ve all felt sad/depressed
• What are some causative factors (in terms of life) in depression?
Loss of activity/ability
Nothing clear - genetic disposition
Insomnia/too much sleep
• How do we deal with it?
Talk to people
Remove yourself from negative/triggering environment
Drugs (e.g. antidepressants)
• Periods of sadness/despair are a normal part of life
• Can argue an important part of life?
Develop coping skills
Strengthen social bonds
Prompt self-reflection and learning (for the next time)
• When periods of sadness are intense and persistent depression
• Affective disorder
• Defined by a loss of interest/pleasure in usual things/activities
intense and persistent sadness
• Serious depression, if left untreated, can be fatal (suicide)
• Recent stats for depression rates = 1 in 6 NZs, 1 in 7 before the age of
24 • High levels of depression in NZ, and suicide rate too – not good!!!!
• What constitutes depressive behaviour?
Talking about feelings
Recall the definition of behaviour in week 1 – depressive
behaviour can be seen…but most of it comes from feelings being
How to treat depression?
• 1. Recognition of depression (within self, and/or within someone else)
• 2. Agreement to some course of therapy
Or both combined
• 3. Adherence to therapy
Pharmacotherapy to treat
• To treat depression pharmacologically, need to know what’s going on
at the biochemical level
• Biological (or biogenic) Amine Hypothesis
Developed in 1960s
Idea = if you increase NE and 5HT in the brain, can treat
therefore, if this is true, then a deficiency of NE and 5HT must
account for depression???
o Consistent deficits in biological amines not always seen in
o Mismatched time course in therapy between amine
increase and improved affect
If this hypothesis was true, then in every depressed brain you
should see low levels of these neurotransmitters (not the case)
and you should see improved mood if you increase these (not
• Receptor Sensitivity Hypothesis
Imbalance of receptors
Idea = Receptors have been sensitized and you’ve created an
imbalanced system = causes depression • Today, we’re seeing a shift towards examining long-term, network
(e.g. changes in BDNF, CREB-mediated transcription,
Disequilibrium in the amine…
Nevertheless, antidepressant drugs still primarily target the
amine neurotransmitters (NE and 5HT etc)
Remember four targets:
• This lecture, focus is on NE and 5HT
• Comes from DA
• MAO-A = breaks down NE
• NET – transporter
alpha 1 - Gq
alpha 2 (2a, 2b, 2c) (want to know this one)
o can find it presynaptically = metabotropic, Gi
o Dont worry about 3 subtypes of it
beta - Gs
• Comes form tryptophan
• Loaded into vesicles
• 5 subtypes:
3 – ionotropic (excitatory)
1 - autoreceptor (presynaptically, Gi, inhibitory)
MAO-A to breakdown
History of antidepressants • Prior to the development of these antidepressant drugs, what were
some other drugs used to treat depression
MAO inhibitors (MAOIs brought to market)
Tricyclic antidepressants (TCAs) brought to market
o didn’t work for psychosis, but did for depression
Biological amine hypothesis developed
2nd generation antidepressants developed
antidepressant drug design today – lots and lots being made
(make a lot of money)
Rates of depression
• Are more people depressed in 2011 than say 1980?
Prescription rates for antidepressant drugs are steadily
E.g., NZ Rx = 700,000 in 2002, Rx = 1.2 million in 2008
• Why are we seeing higher rates of depression in 21 century?
Recent world events?
o e.g. Chch earthquake
Public awareness and decline of stigma to seek help?
o There are a number of ads today, may increase public
Better recognition and diagnosis?
o By self and/or GP
Application to other disorders?
o Huge pushes for adverts
An undermining of the Westernized life? o E.g. “The American nightmare” – expecting too much out
Four major classes of drugs we talk about today:
Dual action SSRI + 5HT2
Monoamine Oxidase Inhibitors (MAOIs)
Binds non-selectively and irreversibly to MAO
What’s another MAOI we’ve talked about?
What’s another irreversible enzyme inhibitor weve talke about?
o Nerve gases
Improve affect and activity levels in depressed individuals
Use is limited by serious drug-drug and drug-food interacti