1. Suicidality and Risks of Medications Used to Treat Mental Illness A workshop presented by the College of Psychiatric and Neurologic Pharmacists

2. Presenters Steven Burghart, DPh, MBA, BCPP (Moderator) Director of Pharmacy, Rolling Hills Hospital, Franklin, TN Jennifer Zacher, PharmD, BCPP Captain James A. Lovell Federal Health Care Center, North Chicago, IL Kimberly Lintner, PharmD, BCPP Meriter Hospital, Madison, WI

3. Objectives Identify common signs and symptoms that should raise concerns about a person’s safety and the risk of self harm. Explain how medications used to improve depression can contribute to suicidal behavior. Describe how consumers, families and support networks can help manage the risk of medications in light of current regulatory actions regarding antidepressant and antiepileptic medications.

4. Disclosures Steven Burghart has no relevant conflicts of interest to disclose.

5. Definitions Suicide- intentionally killing oneself. Suicidality- the likelihood of an individual committing suicide. Suicidal Ideation- mental thoughts and images which hinge around committing suicide.

6. Suicide Facts Suicide is the eleventh leading cause of death for all age groups. Over 34,000 suicides in 2007. –One suicide every 15 minutes. Over 376,000 emergency room treatment for self-inflicted injuries that same year. One suicide for every 25 attempted suicides. www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

7. Suicide Facts-Gender Males four times as likely as females to complete suicide –78.8% of all suicides. Females attempt suicide 2-3 times as often as males. Males use firearms (55.7%). Females use poisons or medications (40.2%). www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

8. Suicide Facts-Age Suicide is second leading cause of death among 25-34 year olds. Third leading cause of death among 15-24 year olds. 13.8% of students in grades 9-12 considered suicide in the past 12 months. 6.3% of students reported at least one suicide attempt in that same time period. Rate among those age 75 or older was 16 per 100,000, compared to 11.26 per 100,000 for all age groups. www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

9. Suicide Facts-Race Rates among Native Americans aged 15-34 were 1.8 times higher than national average. Hispanic and Black high school students reported higher percentage of suicide attempts compared to White, non Hispanics. –11.1% and 10.4% compared to 6.5%. www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

10. Suicide Affects Families Suicides and attempts devastate families. Family and friends feel shock, anger, guilt, depression. Suicide survivors often face chronic health problems. –Injuries –Organ failure –Brain damage www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

11. Suicide Risk Factors Adults –Mood Disorders such as depression More than 90% of suicide completers have diagnosable illness at the time of death. –Alcohol or other drug abuse Youth –Same as adults, but also –History of aggressive or disruptive behaviors –History of physical or sexual abuse AHRQ Systematic Evidence Review No.32 May 2004

12. Suicide Risk Factors Other risk factors include –Previous suicide attempts –Family history of suicide or violence –Physical illness –Feeling alone www.cdc.gov/violencepreventionwww.cdc.gov/violenceprevention accessed 5/13/2011

13. Suicide Warning Signs Suicide threats Previous suicide attempts Sudden changes in behavior Depression Final arrangements The Jason Foundation 2001

14. Video Warning Signs PSA http://www.youtube.com/watch?v=pZhVuZHD8po&feature=youtube_gdata_player

15. IS PATH WARM? How do you Remember the Warning Signs of Suicide? Here’s an Easy-to-Remember Mnemonic: http://www.suicidology.org/web/guest/stat s-and-tools/warning-signs accessed 5/16/2011 I Ideation S Substance Abuse P Purposelessness A Anxiety T Trapped H Hopelessness W Withdrawal A Anger R Recklessness M Mood Change

16. IS PATH WARM? IDEATION Threatening to hurt or kill him or herself, or talking of wanting to hurt or kill him/herself; and/or, Looking for ways to kill him/herself by seeking access to firearms, available pills, or other means; and/or, Talking or writing about death, dying or suicide, when these actions are out of the ordinary. SUBSTANCE (alcohol or drug) use No reason for living; no sense of PURPOSE in life ANXIETY, agitation, unable to sleep or sleeping all the time Feeling TRAPPED - like there’s no way out HOPELESSNESS WITHDRAWING from friends, family and society Uncontrolled ANGER, seeking revenge or rage Acting RECKLESS or engaging in risky activities, seemingly without thinking Dramatic MOOD changes http://www.suicidology.org/web/guest/stats-and-tools/warning-signs accessed 5/16/2011

17. Jennifer Zacher, PharmD, BCPP How medications used to improve depression can contribute to suicidal behavior Jennifer Zacher has no relevant conflicts of interest to disclose.

18. Symptoms of Depression Symptoms of depression –Low mood –Lack of interest in activities –Guilty feelings –Low energy –Poor concentration –Changes in appetite –Changes in sleep pattern –Slowed movements –Suicidal thoughts DSM IV- TR

19. FDA Concerns Regarding Antidepressants and Suicide Risk Case reports in 1990 that new antidepressant medications were associated with increased risk of suicidal thoughts. From June 2003-2004, the FDA released 5 different safety warnings related to increased risk of suicide in children treated with antidepressants CNS Neurosci Ther 2010. Aug;16(4):227-34.

20. Suicidality and Antidepressants WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Pristiq or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Pristiq® Prescribing Information

21. Mechanisms for Antidepressant- Induced Suicidality Timeline of antidepressant action Unrecognized bipolar disorder Side effects Worsening of depression Other psychiatric or medical conditions CNS Neurosci Ther 2010. Aug;16(4):227-34.

22. Timeline of Antidepressant Action It may take up to 6-8 weeks to see full therapeutic effects of antidepressants. Some patients may have suicidal thoughts prior to starting antidepressants but lack the energy to carry out a plan Energy levels usually improve before mood and guilty feelings.. CNS Neurosci Ther 2010. Aug;16(4):227-34.

23. Undiagnosed Bipolar Disorder Many patients have depressed episodes prior to manic episodes. Bipolar patients who take antidepressant medications without an additional mood stabilizer are at risk of becoming manic of hypomanic. Patients may attempt suicide due to mania. CNS Neurosci Ther 2010. Aug;16(4):227-34.

24. Side Effects of Antidepressants Antidepressant medications can cause jitteriness or akathisia (feeling of intense restlessness). Akathisia may result in agitation and an increase in suicide attempts. Antidepressants may also cause insomnia, which increases risk for suicide. CNS Neurosci Ther 2010. Aug;16(4):227-34.

25. Worsening of Depression About 70% of patients will have some effect from an antidepressant medication  the rest of patients may have no effect or worsening depression. Patients with different types of depression may have worsening of symptoms such as agitation, inner tension, and racing thoughts, which may increase suicide risk. CNS Neurosci Ther 2010. Aug;16(4):227-34.

26. Impact of FDA Warning on Antidepressant Prescribing In 2005, a 20-30% decrease in antidepressant prescribing was seen in children and adolescents with an increase seen in adolescent suicide rates. Decrease in diagnosis of new cases of pediatric depression seen in US. CNS Neurosci Ther 2010. Aug;16(4):227-34.

27. Suicidality and Antidepressants Nemeroff et al. Arch Gen Psychiatry 2007;64:466-72.

28. Suicidality and Antidepressants CDC,MMWR Weekly Report 2007;56:905-908

29. Take Home Points Data on risk of suicidality with antidepressant use is mixed. Children, adolescents, and young adults seem to be at highest risk. Monitoring is key –Frequent contact with provider is necessary when starting an antidepressant or increasing the dose. –Patients should be observed closely for changes in behavior or signs of suicidality by friends and family as well. CNS Neurosci Ther 2010. Aug;16(4):227-34.

30. Kimberly Lintner, PharmD, BCPP Manage the risk of medications in light of current regulatory actions regarding antidepressant and antiepileptic medications. Disclosure: Kimberly Lintner has no relevant conflicts of interest to disclose.

31. Monitoring for safe outcomes FDA (U.S. Food and Drug Administration) –Responsible for protecting the public health by assuring the safety, efficacy, and security of human drugs. –Advances public health by making medications more effective, safer, and more affordable. www.fda.govwww.fda.gov accessed 4/12/11

32. Monitoring for safe outcomes Initial studies Final studies General use Some safety information More safety information Best safety information

33. Resources FDA Medwatch

34. Understanding those leaflets Consumer information Patient package insert Medication guides How do you pick out what is important? –What it is used for, common side effects, serious side effects, when should it start working

35. Understanding those leaflets Study done with adults, education up to high school Asked seven questions and could use the materials to answer (less than half did)  The key information relating to suicide risk in teens (emphasized in all materials) was identified by 60% More is not better, recommendation to FDA to have a single standardized document Shiffman S, Gerlach KK, Sembower MA, Rohay JM. Consumer understanding of prescription drug information: an illustration using an antidepressant medication. Ann Pharmacother. 2011;45:452-458.

36. Resources

37. Pharmacists involvement Provide medications Help sort through “information” –Commercials –Newspaper ads –Printed and Internet resources Is it working? How do you/we know? Safe use –Selecting particular medications/amounts –Supervision and assistance

38. Resources

39. Abuse of prescription medications Nonmedical uses of prescriptions are dramatically rising –Visits to Emergency Departments doubled in 5 years (600,000 -> 1.2 million) Oxycodone 250% Alprazolam 150% Hydrocodone 125% Sources- friends, family members prescriptions, visitors to the home www.drugabuse.govwww.drugabuse.gov accessed 5/26/11

40. Resources

41. Safe medication disposal Appropriate removal will help ensure safety for people, pets and the environment Community collection events are becoming more common-best option At home you can crush and mix with coffee grounds/kitty litter and place in sealed container in the trash –Strong pain medications should be flushed down the toilet –If you are not sure, ask your pharmacist

42. Resources One page (two-sided) handout available for your use.

43. Take action! Information and education Advocate for yourself/others Be willing to ask questions “Ask the Pharmacist” sessions Let others help- keep those appointments Have the tools you need Refilling medications, safety plan

44. Take home messages Medications are more helpful than harmful, but not without risks Everyone involved should be watchful of the responses to medications The pharmacist plays a key role in maximizing treatment

45. Questions and Discussion

46. What Would You Do? You have a (family member, friend, acquaintance) who shares that a week ago they started taking an antidepressant. They have an urge to hurt themselves- maybe even kill themselves. What information would you share with them based on today’s presentation?