Adolescent Depression and Suicide

1. Adolescent Depression and Suicide Amy Cheung, MD Department of Psychiatry University of Toronto

2. Outline Issues with Diagnosis Suicide in Adolescence Focus on Treatments Clinical Implications Case Presentation

3. Depression in Adolescence Nationally, 8% endorsed depressive disorder 4% in males, 11% in females Maritimes 4% (lower than national average) 1.6% in males, 7% in females 60% recurrence rate before reaching adulthood Only 50% are diagnosed before adulthood and only ½ of those who are diagnosed receive appropriate treatment

4. Depression in Adolescence Provider Attitude Lack of confidence in treatment Lack of understanding of research evidence Natural History Fluctuating nature Significant role of psychosocial stressors Nature of adolescence

5. Depression in Adolescence Difference from Depression in Adults Irritability most likely presenting mood symptom versus low mood in adults Reactivity of mood Less neurovegetative symptoms Response to medications Remission rates same as placebo with TCA’s Slightly better rates than placebo with SSRI’s

6. Depression in Adolescence Gender Differences Prepuberty-males>females Post-puberty-females>males ?cause of differences Self-esteem Hormonal Vulnerability to stressors

7. Depression in Adolescence Differential Diagnosis Normal mood swings Bipolar Disorder Anxiety Disorder Comorbid Disorders Eating Disorder Substance Abuse Personality disorders

8. Depression in Adolescence Normal mood swings Functional impairment Family history/traits Scales/instruments Collateral information Time

9. Depression in Adolescence Bipolar Disorder Time limited episodes of elevated mood Family history Collateral information Time Scales

10. Depression in Adolescence Anxiety Disorder Temporal association between symptoms Which is more dysfunctional Family history/traits Collateral information Treatment

11. Depression in Adolescence Comorbid Disorders Personality Disorders (including Conduct) Self-harm/Suicidality Poor judgment Irritability Substance Abuse Amotivation Eating Disorders Low mood due to nutritional deficiencies

12. Suicide in Adolescence What do we know? Survey of adolescents in Canada in 2002 13.5% nationally Males 8.8%, Females 18.4% Rate lower in the Maritimes = 11.1% Males 8%, Females 14.5% Survey of adolescents in US in 2001 19% had seriously thought about suicide 15% had a specific plan for suicide

13. Suicide in Adolescence What do we know about diagnoses? >90% had at least one psychiatric diagnosis >50% had more than 2 diagnoses 49% with affective disorder 24% with comorbid substance abuse 18% with comorbid conduct disorder 21% with comorbid anxiety disorder

14. Suicide in Adolescence Males Higher rates of Conduct Disorder and Substance Abuse Older males more likely to be intoxicated Males more likely to use irreversible means Females Higher rates of mood disorder Higher rates of past attempts More likely to use overdose as means of self-harm

15. Suicide in Adolescence What about other risk factors? Younger victims had less intent Younger victims affected by parent-child conflict Older victims affected by romantic relationships and legal/disciplinary issues No evidence of differential risk from family history

16. Suicide in Adolescence What do we know about other risk factors? “Contagion Effect” Anecdotal reports of clusters Statistical support for time-space clusters Evidence of media influence-increased rates after media coverage of real or fictional suicide Social desirability Increase in clinically significant suicidal ideation (associated with depression)

17. Treatment Goals Resolution of symptoms Functional Improvement Relationships Academic/Vocational

18. Treatment Options Psychotherapy Cognitive Behavioural Therapy Interpersonal Therapy Other Antidepressants SSRI’s

19. Psychotherapies Cognitive Behavioural Therapy (CBT) Examines cognitions and its’ influence on mood Numerous studies (individual or group) showing effectiveness Question about comparison group TADS results

20. Psychotherapies Interpersonal Therapy Examines the connection between interpersonal relationships and mood Few studies - in “normal” settings Other Family Therapy Psychodynamic Psychotherapy Supportive Therapy/Counselling

21. Interpretation of Efficacy Data

22. Efficacy Data (CGI)

23. OVERALL Medication and therapy both can be effective Best is combination treatment Better acute improvements in symptoms More complete remission of disorder Better functional status Better self-reported quality of life

24. SAFETY: Psychotherapy “Adverse events” with psychotherapy Incidence of emergent suicidality was 12.5% Self-reported suicidal thoughts at intake were a significant predictor of emergent suicidality, even when suicidality was denied at intake interview Bridge et al., 2005

25. IN THE NEWS… FDA Public Health Advisory (2004): Black box warnings that recommend close observation of adult and pediatric patients treated with antidepressants for worsening of depression or the emergence of suicidality

26. SAFETY: Medications General Safety and Adverse Events Treatment Group Range from 47.5 to 92.5% Placebo Group Range from 35.3 to 79.3% Most common are neurological (i.e., dizziness, headache) and GI disturbance (i.e., nausea)

27. SAFETY Discontinuation due to Adverse Events Up to 12% Serious Adverse Events Up to 12% Mania Up to 6%

28. SAFETY Suicide Related Events Treatment Group Range from 2 to 12% Placebo Group Range from 0 to 7% Most studies reported Different terminology/definitions Example of ‘emotional lability’ Previously not considered an AE

29. Overall relative risks (RR) of suicidal behaviour or ideation by drug This table shows the relative risks for suicidal behavior or ideation by drug. It has three columns. This one shows the brand names of the drugs, which are listed here in alphabetic order, first the SSRIs then the atypicals This column shows the overall RR in depression trials of each drug. This column shows the overall relative risk for all the trials, regardless of indication, which is a summary for what I just showed you before ? go over it drug by drug comparing the two columns (There were no events in Serzone and Wellbutrin. For the remaining drugs the “RR” is more than one for all drugs, regardless of indication However, note that the only drug that has a CI that does not include one is Effexor.)This table shows the relative risks for suicidal behavior or ideation by drug. It has three columns. This one shows the brand names of the drugs, which are listed here in alphabetic order, first the SSRIs then the atypicals This column shows the overall RR in depression trials of each drug. This column shows the overall relative risk for all the trials, regardless of indication, which is a summary for what I just showed you before ? go over it drug by drug comparing the two columns (There were no events in Serzone and Wellbutrin. For the remaining drugs the “RR” is more than one for all drugs, regardless of indication However, note that the only drug that has a CI that does not include one is Effexor.)

30. Overall relative risks of treatment-emergent agitation or hostility by drug in depression trials Note that there is a trend towards an association for most drugs, but Paxil is the only drug with CI that does not include one. In addition, the CI of the overall estimate also does not include one. Evaluation of the risk of suicidal behavior or ideation among patients with “activation” symptoms was not evaluable ? because information on the timing of the latter events were not in the FDA datasets Note that there is a trend towards an association for most drugs, but Paxil is the only drug with CI that does not include one. In addition, the CI of the overall estimate also does not include one. Evaluation of the risk of suicidal behavior or ideation among patients with “activation” symptoms was not evaluable ? because information on the timing of the latter events were not in the FDA datasets

31. Data From Meta-Analyses Based on emergence of suicidality Number needed to Treat = 9 Number needed to Harm = 56 Bridge et al., 2005

32. Data From Other Studies (Epidemiological/Observational) Areas with increased antidepressant prescription rates have lower rates of completed suicides Olfson et al., 2003 Treatment of at least 6 months reduced the likelihood of suicide attempt compared with antidepressant treatment for <8 weeks Valuck et al., 2004

33. Data From Other Studies (Epidemiological/Observational) Post-Mortem toxicology of adolescents after suicide showed few had taken antidepressants Gray D et al., 2003; Isacsson G et al., 2005; Leon AC et al., 2004; Leon et al., 2006

34. Clinical Recommendations A careful assessment is critical in cases where the clinician suspects depression in children and adolescents. If a diagnosis is made, patients and families need to be educated about the illness and the options available for treatment. It is also vital for clinicians to evaluate for any prior history of suicidal behaviours and to evaluate this frequently in subsequent visits. If medication is required, families and patients need to be fully informed about the risks and benefits of antidepressant treatment. Antidepressants should be initiated at a low dose (equivalent of 5-10 mg of fluoxetine) with increases every 2 weeks if no significant adverse events emerge.

35. Clinical Recommendations Families and patients need to be fully informed about the possible risk of the emergence of suicidal behaviours with antidepressant treatment. Families should closely monitor for worsening depression, worsening or new onset of suicidality, and other behavioural side effects. Families may wish to utilize tools available (i.e., National Alliance for Mental Illness; Families for Depression Awareness) to aid in this process. The FDA suggests weekly face-to-face monitoring for the first 4 week of antidepressant treatment or with any subsequent dose adjustments in children and adolescents.

36. SOURCES Published clinical trials Unpublished reports of clinical trials ACNP Task Force: http://www.acnp.org/exec_summary.pdf FDA: http://www.fda.gov/ohrms/dockets/ac/cder04.html MHRA: http://www.mhra.gov.uk/news/2003.htm