What Information Will be Covered for EVERY Drug- REMINDER

What is drug?Why is it used?How is it administered?How much is used?Metabolism?Affects on the cell?Addiction?Benefits?Harms?Individual experience may vary

What do you already know about antidepressants?

Which neurotransmitter is most impacted by antidepressants?

Some target all monoamines. How could ONE drug influence MANY neurotransmitters?

What is one side effect of antidepressants seen more in adolescents than adults?

Prescribed antidepressants were used starting in the late 1950s. Why are there so many more prescriptions written today compared to then?

What are antidepressants? Activity 2

http://www.biopsychiatry.com/antidepressants/

Three main typestricyclic antidepressant (example doxepin)monoamine oxidase inhibitor (example iproniazid)SSRI (serotonin specific reuptake inhibitor, example

Paxil and Prozac)

What is depression?

http://www.itmonline.org/arts/ssri.htm

What causes depression?

http://165.112.78.61/Teaching/Teaching4.html

Lack of serotonin

Pre-courser L-Tryptophan Receptors all over the brain

What else causes depression?

Depressed, suicide

Depressed

No information

Connect depression’s cause to ADHD. Which might explain why some people are predisposed to ADHD?

1. They can’t be connected, they involve different neurotransmitters

2. They must both involve enzymes that metabolize monoamines

3. ADHD risk is elevated among people who use cocaine

4. ADHD risk could be linked to TOO efficient dopamine recycling

How are antidepressants administered?How much is used? Activity 3

Doses vary, person to person, drug to drug.

Example TI:Zoloft – approximately 100Prozac – approximately 25

Antidepressant metabolism? Activity 4

Drug Enzyme Half life

Prozac CYP2D6 ~100 hours

Zoloft CYP2D6, CYP3A4 and others

~50 hours

Wellbutrin CYP2B6 (which is inhibited by prozac)

~12 hour

What’s the connection between serotonin and depression? (Effects on neurons) Activity 5

Overly-efficient removal due to- enzyme break down- rapid reuptake

How do different anti-depressants compare?

Drug Mechanism Specificity Side-effects & drug interactions

MAO-I

Tricyclics

SSRIs

Inhibit enzyme

Inhibit transporter

Inhibit SPECIFIC transporter

All monoamines

All monoamines

Only serotonin

Numerous – MANY drugs, even foods

Some, more general mood symptoms

Few, specific to serotonin

Why would MAO-Is have more side effects than tricyclic antidepressants?

1. MAO-Is will cause there to be more serotonin in the synapse

2. MAO-Is impact more neurotransmitters

3. They will interfere with breakdown of monoamines found anywhere (including food)

4. Interfering with metabolism has more effect than interfering with reuptake

Antidepressant addiction? Activity 6

Not generally, although those that influence dopamine have a potential to be addictive if abused.

Do antidepressants REALLY work? Activity 7

Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. PLoS Medicine Vol. 5, No. 2, pmid.0050045

47 studies

>5000 patients

4 drugs

Please watch link to complete discussionposted on Edmodo

Beyond therapy, benefits?New neurons are born in the adult hippocampus (one of only a few places where this occurs)

Exercise and Rich environments maximizes the amount of new neuron birth.

Anti-depressants do too. PMID: 18256257

What are antidepressants harmful side effects? Activity 8

• Anticholinergic effects• Antagonize acetylcholine pathways, primarily reducing parasympathetic nervous system function.• Sedation• Serotonin is known to influence sleepiness.• Orthostatic effects• Dizziness due to low blood pressure upon standing upright.• Sexual effects• Serotonin is also known to influence libido.• GI upset• The parasympathetic system is the “rest and digest.” To antagonize it is to reduce digestive function.• Cardiac arrhythmias• A disruption of the synchronized contraction of heart muscle. This is being investigated among fetuses of

pregnant women who use antidepressants (opening story).• Agitation/ Insomnia• These medications increase the concentration of excitatory neurotransmitters which can cause increased

function in the reticular pathway making a person wakeful. • Weight gain• No direct explanation—could be related to improved mood leading to increased appetite.

Who takes antidepressants?

Antidepressant use by adolescents

http://www.paxil-side-effects-lawsuits.com/

Science. 2004 Oct 29;306(5697):879-81.Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice.

Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA.

AbstractReduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders.

PMID: 15514160

Ansorge, et al. (2004) suggests that antidepressants used early in life:

1. Low sertonin levels during development can lead to adult psychiatric problems

2. Low serotonin transporter function during development can lead to adult psychiatric problems

3. Fluoxetine (prozac) results in low levels of serotonin transporters

4. Fluoxetine use in developing animals protects adults from eventual psychiatric problems