Presented by: Erika, Kristin and Nola. History How do SSRIs work? Selected Indications and Dosages Side effects/Interactions Alternative uses for Children/Adolescents.

Selective Serotonin Re-Uptake Inhibitors (SSRIs)Presented by: Erika, Kristin and Nola

SSRI Presentation Overview

• History• How do SSRIs work?• Selected Indications and Dosages• Side effects/Interactions• Alternative uses for Children/Adolescents • Risks of SSRIs

A Brief History

Development of SSRIs

• Relatively new class of anti depressant medications (Prozac was introduced in the U.S. in 1987)

• Developed due to significant side effects of other antidepressants that effected a broad range of neurotransmitters

• SSRI is a targeted medication-focused on serotonin

• Provides relief of symptoms with less side effects and less risk of overdose

• Considered first line treatment for anxiety disorders

• Most widely prescribed type of anti-depressant in the world

How do SSRIs Work?

Mechanisms of Action

• In a typical brain, sufficient neurotransmitters are released to stimulate neighbouring cells

• Neurotransmitters are consistently reabsorbed into

the brain where they are broken down by an enzyme called monoamine oxidase

• Depression, anxiety, and severe stress are associated with low serotonin levels

• SSRIs act by blocking the re-uptake of serotonin. As a result the levels of the neurotransmitter is increased by blocking their reabsorption

SSRIs block the reuptake of serotonin at the presynaptic membrane

Increasing the concentration in the synaptic cleft that can bind to the receptors

Selected Indications and Dosages

Citalopram (Celexa)

• Restores the balance of serotonin in the brain

• Treatment of: Major Depression and Panic Disorder

• Adult dose: 20-40mg per day

• Not deemed safe or effective for those under 18

• Slow onset

• Leaves system in 35 hours

• May improve: energy level and feelings of well-being

Citalopram (Celexa)

• Other Uses: Obsessive-compulsive Disorder (OCD), Panic Disorder

• Drug Specific Effects:• Heart rhythm • Fast or irregular heart beat

Fluoxetine (Prozac/Gen-Fluoxetine)

• Treatment of: Major Depression, OCD, Panic Disorder, PTSD, Bulimia Nervosa, Premenstrual Dysphoric Disorder

• Adult dose: 20-60 mg/day, not to exceed 80mg/d• Child dose: 10-20 mg/day• Onset: slow• Duration: 10 to 12 hours and leaves system in 1-3 days• May improve: mood, sleep, appetite, energy level, restore

interest in daily life • May decrease:• fear, anxiety, unwanted thoughts,• premenstrual symptoms (irritability, increased appetite,

depression),• binging, purging, (bulimia) • number of panic attacks, compulsions (hand-washing,

counting, checking• Liquid form contains alcohol

Fluoxetine (Prozac/Gen-Fluoxetine)

• Other Uses: Anorexia, Post Traumatic Stress Disorder (PTSD), Certain nervous system/sleep disorders (Cataplexy, Narcolepsy)

• Drug Specific Effects:• May effect blood sugar levels

Fluvoxamine (Luvox)

• Treatment of: Obsessive Compulsive Disorder (OCD)• Adult dose: 50-300mg/d• Onset: rapid• Duration: 14-16 hours• Leaves system in 13-15 hours

• Other Uses:• Depression• PTSD

• Drug Specific Effects: • None listed

• Not deemed safe or effective for those under 18

Paroxetine (Paxil)

• Treatment of: Major Depression, OCD, Panic Disorder• Can be used to treat GAD and Social Phobia• Adult dose: 20-50 mg/d• Child dose: not deemed safe or effective for those under 18• Onset: 5 hours• Duration: 12-16 hours• Leaves system in 21 hours

• Other Uses: • Premenstrual Dysphoric Disorder

• Drug Specific Effects: • Weight gain

* Avoid alcohol

Sertraline (Zoloft)

• Treatment of: Major Depression, OCD, Anxiety (with depression), Social Anxiety Disorder, Panic Attacks, PTSD, Premenstrual Dysphoric Disorder

• Adult dose: 50-200mg/day• Child dose: 25-200 mg/d for OCD• Onset: 4-8 hours• Duration: 12-20 hours• Leaves system in 26 hours

• Other Uses:• None listed

• Drug Specific Effects: • None listed

* Avoid alcohol

Side Effects and Interactions

Starting and Ending Treatment

• The effects of anti depressants occur after 10 to 14 days and may take 6 to 8 weeks before full effect is observed

• Side effects are generally mild and brief, and subside in 1-2 weeks:• Gastrointestinal disturbances, anxiety, headache, and

restlessness are most common• May induce suicidal thinking in children and adults (or

may increase energy before elevating mood, allowing the depressed individual to act on their depressed mood)

• Ending Treatment: • F.L.U.S.H symptoms ending treatment

Potential Ongoing Side Effects

• Compared to tricyclics, SSRIs have fewer adverse anticholingergic and cardiovascular effects and generally do not cause weight gain

• May cause disturbance in sexual functioning, which is the most frequent reason for terminating treatment (10-15%)

• May cause drowsiness (recommended to take SSRI’s in the evening)

Serious Reactions

• Serotonin Syndrome/Toxicity:• Too much serotonin• Potentially life-threatening• Caused by taking multiple drugs that increase serotonin

and/or drug interactions Taking • St John’s wort or a MAOI

• Allergic Reaction:• Rare• Rash, itching, swelling (face, tongue, throat), severe

dizziness, trouble breathing

Potential Interactions

• Consuming caffeine may increase stimulant sensation

• Smoking may increase the metabolism of the SSRI

• Drinking alcohol may cause central nervous system (CNS) depression

• Used with caution for those with compromised liver functions

SSRI’s for Children & Adolescents

• One third of all medications prescribed in the United States are anti-depressants

• An estimated 72% of cases do not have a psychiatric diagnosis

• Concerns regarding the increased risk of suicidality has been reported

• Fluoxetine (Prozac) - labeled for use with children has the highest efficacy of all SSRIs and should be considered the first line of treatment

• Does untreated depression presents as a greater risk than its treatment?

Alternate Uses for Children/Adolescents

Alternate Uses for Children/Adolescents

• Alternate Uses:• Anxiety• Generalized Anxiety Disorder, Social Anxiety Disorder• Good evidence to support the use of SSRIs in treatment

• PTSD• Attributed to an overall improvement in quality of life

• Psychiatric Disorders• Bipolar, OCD, Panic Disorder• Bipolar studies are inconsistent

• Headaches• To be used with caution for migraine prevention• Considered an integral part of practice to use off-label

medications to treat complex headache conditions

Alternate Uses Continued• Bulimia• Highly effective for treating bulimia• Combination of psychotherapy and antidepressants

was significantly superior to psychotherapy alone• Sleep Disorders• Insomnia (late night insomnia)• Not approved by FDA, but prescribed anyways• Longer lasting effects than sleeping medication

• Pain• Fibromyalgia• Not yet approved • Supports the transmission of pain signals through

nerve fibers

Risks of SSRIs

Pre-Natal Risks• Majority of new SSRI medications remain relatively safe to use

• Studies indicate that nearly 85% of cases are not impacted by pre-natal pharmacological use

• Concerns around:• Low birth weight• Cardiovascular malformation• Premature births (low gestational age)• Behavioural issues • Neonatal adaptation difficulties

• Identification of the severity of depression should be explored prior to medical intervention

Suicide & Self Harming• In 2003, the FDA warned against the use of SSRIs with pediatric

patients

• Concerns included:• Short-term risk of self harm• Increased risk of suicide attempts

• Risk of self harm is highest during the initial month of intervention

• Close monitoring of symptoms is encouraged

• Children with depression noted higher suicidal tendency than those with other psychiatric conditions

• Less than 1% of the pediatric population experienced suicidal ideations in the studies reviewed

In Conclusion

• SSRIs are the most commonly prescribed anti-depressant (anti-anxiety) medication

• Easy to prescribe, low risk of overdose, non addictive • Multiple uses for various disorders

• Continued debate regarding use during pregnancy and with the pediatric population

• Risks are still relatively unknown

References• Aschenbrenner, D. S, & Venable, S. J. (2009). Drug Therapy in Nursing (3rd

Ed.) Philadelphia, PA: Wolters Kluwer Health and Lippincott Williams & Wilkins.

• Barry, C., & Busch, S.H. (2010). News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics, 125(1), 88-95. doi:

10.1542/ peds.2009-0792

• Breggin, P.R. (2005). Recent U.S, Canadian, and British regulatory agency actions concerning antidepressant-induced harm to self and others: A review and analysis. Ethical Human Psychology & Psychiatry, 7(1), 7-22.

• CNS Drugs. (2009). Effectiveness of lithium in children and adolescents with conduct disorder. Author, 23(1), 59-69.

• Einarson, A., Choi, J., Einarson, T.R., & Koren, G. (2010). Adverse effects of antidepressant use in pregnancy: An evaluation of fetal growth and preterm birth. Depression & Anxiety, 27(1), 35-38. doi:

10.1002/da.20598• Gentile, S. (2010). Neurodevelopmental effects of prenatal exposure to

psychotropic medications. Depression & Anxiety, 27(7), 675-686. doi: 10.1002/da.20706

• Hauser, W., Wolfe, F., Tolle, T., Uceyler, N., & Sommer, C. (2012). The role of antidepressants in the management of fibomyalgia syndrome. CNS Drugs, 26(4), 297-307

• Isacsson, G., Holmgren, P., & Ahlner, J. (2005). Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: A controlled forensic database study of 14 857 suicides. Acta Psychiatrica Scandinavica, 111(4), 286-290. doi: 10.1111/j.1600-0447.2004.00504.x

• Masi, G. (2004). Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs, 18(14), 1031-1052.

• Spina, E., Trifiro, G., & Caraci, F. (2012). Clinically significant drug interactions with newer antidepressants. CNS Drugs, 26(1), 39-67, 29.

• Raman-Wilms, L. (Ed.) (2008) Canadian Pharmacists Association: The Canadian Guide to Drugs and Supplements. Toronto, ON: Readers Digest Association.

• Vitiello, B. (2008). An international perspective on pediatric psychopharmacology. International Review of Psychiatry, 20(2), 121-126. doi: 10.1080/0954026080188710