1. 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

2. 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?

3. What are antidepressants? Activity 2 http://www.biopsychiatry.com/antidepressants/ Three main types tricyclic antidepressant (example doxepin) monoamine oxidase inhibitor (example iproniazid) SSRI (serotonin specific reuptake inhibitor, example Paxil and Prozac)

4. What is depression? http://www.itmonline.org/arts/ssri.htm

5. What causes depression? http://165.112.78.61/Teaching/Teaching4.html Lack of serotonin Pre-courser L-Tryptophan Receptors all over the brain

6. What else causes depression? Depressed, suicide Depressed No information

7. 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

8. How are antidepressants administered? How much is used? Activity 3 Doses vary, person to person, drug to drug. Example TI: Zoloft – approximately 100 Prozac – approximately 25

9. Antidepressant metabolism? Activity 4 DrugEnzymeHalf life ProzacCYP2D6~100 hours ZoloftCYP2D6, CYP3A4 and others ~50 hours WellbutrinCYP2B6 (which is inhibited by prozac) ~12 hour

10. What’s the connection between serotonin and depression? (Effects on neurons) Activity 5 Overly-efficient removal due to - enzyme break down - rapid reuptake

11. How do different anti-depressants compare? DrugMechanismSpecificitySide-effects & drug interactions MAO-I Tricyclics SSRIs Inhibit enzyme Inhibit transporter Inhibit SPECIFIC transporter All monoamines Only serotonin Numerous – MANY drugs, even foods Some, more general mood symptoms Few, specific to serotonin

12. 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

13. Antidepressant addiction? Activity 6 Not generally, although those that influence dopamine have a potential to be addictive if abused.

14. 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 discussion posted on Edmodo

15. 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

16. 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.

17. Who takes antidepressants?

18. 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. Abstract Reduced 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

19. 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