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Anti-depressants and suicidality in adolescents

Is there a link?

 

A close-up of red antidepressant pills.

http://www.npr.org/templates/story/story.php?storyId=9627377

-Liana Larcada

 

The Problem…

 

Depression, often called “the common cold of psychiatry”, has various treatment options available. Most psychiatrists will argue that the combination of psychological therapy coupled with medication proves to be the most effective treatment. “Therapy” and “anti-depression medication” are broad terms that include many types.  This includes behavioral therapy, cognitive therapy, psychoanalysis, and group therapy among others. Examples of anti-depressants include selective serotonin reuptake inhibitors (SSRIs), tricyclics, or monoamine oxidase inhibitors (MAOIs). As in any medication, many side-effects are associated with anti-depressants and what works for one person may not work for another due to genetics and other extraneous factors (http://www.healthyplace.com/Communities/depression/treatment/antidepressants/index.asp). Therefore, anti-depressants continue to be a hot topic in psychological research.

 

The susceptibility of children and adolescents to be diagnosed with depression has risen in the latter part of the 20th century most likely due to multiple factors including environmental reasons. Prevalence rates for children are as high as 2.4% and up to 8.3% for adolescents. Suicide rates are also increasing drastically, especially in adolescents. The suicide rate for adolescents has increased 4-fold since 1950, which causes great concern for psychiatric researchers (Birhamer et. al, 1996). Due to the drastic increase in depression and suicidal incidence among children and adolescents, research over the last several years has focused on anti-depressant use within this population. It has been demonstrated in various studies that SSRIs are effective in treatment against depression (Ryan, 2003).  Anti-depressant prescriptions have increased up to 5-fold since the 1990’s (Zito et. al, 2003).

 

FDA Takes Action…

 

On October 15, 2004, the Food and Drug Administration (FDA) changed the path of anti-depressant medication for children and adolescents. Results following a review of 24 trials found Zoloft bottlea 2-fold increase in suicidality (defined as suicidal behavior or suicidal ideation) with children and adolescents taking SSRI anti-depressant medications versus placebos (Bridge, 2007). (There were no actual suicides reported.)  The FDA felt that action was required after results from this study were released. SSRIs for children and adolescents under the age of 18 were required to hold a “black-box” warning. This warning stated:

 

Antidepressants increase the risk of suicidal thinking and behavior (suicidality)

in children and adolescents with major deprive disorder (MDD) and other

psychiatric disorders. Anyone considering the use of (drug name) or any other

antidepressant in a child or Text Box: Figure 1: http://www.antidepressantsfacts.com/zoloft-side-effects-lawyer.htmadolescent must balance this risk with the clinical

need. Patients who are started on therapy should be 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. (Drug name) is not approved for use in pediatric patients except

for patients with (approved pediatric claim). 

http://www.antidepressant-drugs-and-suicide.com/fda-warning.htm

 

Is this necessary?

           

Ever since this warning was put into place, pediatricians and child psychologists and psychiatrists have debated the necessity of this warning. A black-box warning will inevitably cause demand for these anti-depressants to decrease as parents and caregivers are hesitant in giving their children a medication that appears to make them more susceptible to suicide. As demand for anti-depressants goes down, the number of child and adolescents with depression remains. The necessity for the emergence of other depression treatments has presented itself through these FDA regulations. The question and controversy remains with many child psychiatrists as to whether it truly is the anti-depressant medications that is causing this increase in suicidality or if it is the environment among other extraneous factors that are causing this increase among depressed children and adolescents.

           

Research says…                                      

Beginning with an overall picture of the problem, Rihmer and Aiskal performed an analysis on a general population (including adults). They looked at various countries, especially ones with high suicide rates. Addressing this problem globally allowed for an expansive analysis of raw data. With 27 countries, results showed that with an increase in prescriptions of SSRI pills, there was a decrease in suicide rates (Rihmer et. al, 2006). In another study concentrated on adolescents, it was demonstrated that an increase in SSRI prescriptions, caused a decrease in suicide rates among adolescents alone (Gibbons et. al, 2006).

 

In a study focusing on children and adolescents, researchers Olfson and colleagues used children and adolescents between 10-19 years of age and analyzed data on prescription rates and completed suicide rates in 588 different United States zip code regions. Many different variables were found to affect the results in this study. Gender, age and socioeconomic status, were all found to have an effect on suicide rates. This study did not control for factors such as substance use and psychotherapy, which are also likely to have an effect on suicide rates. These researchers believe that regional areas with high rates of suicide may prescribe more anti-depressants than areas with lower rates of suicide. Solid conclusions cannot be drawn from this study except in saying that the problem is likely very complex involving many variables (Olfson et. al, 2003).

 

Hammad and colleagues used randomized, placebo-controlled studies in order to examine the relationship between anti-depressants in children and adolescents and “suicidality”. Suicidality here was defined as “suicidal ideation and behavior” and measured using suicide item scores on depression scales as well as analysis of behavior. All individual SSRIs were analyzed for drug affects and as a whole (See Figure 2). Results were not statistically significant with a risk ratio for SSRIs in depression trials averaging 1.66. This means that the suicidality risk of anti-depressants in children and adolescents is moderate, yet still statistically insignificant. Many of the studies that he used were from the FDA’s report. More information is needed to draw distinct conclusions (Hammad et. al, 2006).

 

Table 502553

Figure 2:  http://archpsyc.ama-assn.org/cgi/content/full/63/3/332

 

Different perspectives often provide insight that is not easily seen by researchers. Sharp and Hellings, two practitioners, analyzed both published and unpublished studies regarding this relationship between suicidality and anti-depressant medication. Using various data sources, they found that the SSRIs were safe and efficient in treating depression. Again, the FDA studies, among others, were used in this analysis. The practitioners analyzed the methods used in the previous reports and found them to be valid. They sought to answer the question of what practitioners are to do with this available data. Anti-depressants work in treating major depressive disorder and therefore, cannot be taken off the market without a solid relationship established between suicidality and these medicines. These two conclude that psychiatrists and care-givers should be aware of the risks and watch out for relevant warning signs (Sharp & Hellings, 2006).

 

Bridge, Iyengar and others were interested in the overall scope of the research on this topic. They performed a literature search and only included studies that they viewed as complete, placebo-controlled and randomized studies. This analysis included 15 studies with a total of 3,430 children and adolescents with major depressive disorder. Using random-effects, rather than the fixed-effects used in the FDA reports, the results were less striking than the original FDA data, yet still apparent. Anti-depressants, however, were not statistically significant in increasing suicide ideation/suicide attempts in children and adolescents. This design is limited in that it was a meta-analysis and there were variables that were unavailable. The limitations from each of the individual studies were also present in this analysis (Bridge et. al, 2007).

 

            A huge problem remains with combining all of this research to reach conclusions. The FDA uses the term “suicidality”. The definition of this term varies across studies; there is not one solid, observable, operational definition (Wong et. al, 2004). Therefore, one must be careful and keep this in mind when looking over all of this research comprehensively. The FDA warning does not deal with suicide rates, only suicidal behavior, which is difficult to measure and often subjective.

 

But what happened?

 

            Since this controversial black-box warning has been initiated, the results have been the opposite of what the FDA has expected. Adolescent SSRI prescriptions have fallen by 22% and adolescent suicide rates have increased by 14% from 2003-2004, the largest year-to-year increase in suicide rates since the start of data collection in 1979 (Gibbons et. al, 2005).  The director of the FDA described these statistics as a “dilemma” and “not what you would want to see”. (http://www.chicagotribune.com/news/nationworld/chi-suicide_07sep07,0,5371930.story?coll)

 

The Bottom Line…                              

            The facts are clear: suicide rates and suicidality in children and adolescents are increasing. The question remains: Why? Does this have to do with SSRIs or other anti-depressant medications? Many researchers believe in the multi-variable role of this problem. “Suicidal behavior results from complex interactions in which individual and psychosocial factors, as well as depression and other mental health problems, play a role” (Rey et. al, 2005) Health and psychological problems are typically multi-dimensional and not easily explained with one variable alone. The contradicting data from FDA reports before the black-box warning and the post black-box warning data concerning adolescent suicide rates are striking and a cause of concern for psychiatrists. This issue needs to be researched more extensively as depression in children and adolescents becomes a greater problem. Maybe the black-box warning was not warranted without sufficient data. It’s up for interpretation….

 

 

 

 

 

 

References

 

1. Birmaher, B., Ryan, N.D., Williamson, D.E., Brent, D.A., Kaufman, J., Dahl, R.E., Perel, J.,        

Nelson, B. (1996). Childhood and adolescent depression: a review of the past 10 years,          

part I. Journal of the American Academy of Child and Adolescent Psychiatry, 35(11),   1427.

2. Bridge, J.A., Iyengar, S., Salary, C.B., Barbe, R.P., Birhamer, B., Pincus, H.A., Ren, L., Brent,   

D.A. (2007). Clinical response and risk for reported suicidal ideation and suicide attempts         

in pediatric antidepressant treatment. Journal of American Medical Association, 297(15),         

1683-1696.

 

3. Gibbons, R.D., Brown, C.H., Hur, K., Marcus, S.M., Bhaumik, D.K., Erkens, J.A., Herings,        

R.M., Mann, J.J. (2007). Early evidence on the effects of regulators’ suicidality warnings    

on SSRI prescriptions and suicide in children and adolescents.  The American Journal of  Psychiatry,

164(9), 1356-1363.

4. Gibbons, R.D., Hur, D., Bhaumik, D.K., Mann, J.J. (2006). The relationship between       

antidepressant prescription rages and rate of early adolescent suicide. The American     

Journal of Psychiatry, 163(11), 1898-1904.

5. Hammad, T.A., Laughren, T., Racoosin, J. (2006). Suicidality in pediatric patients with    

antidepressant drugs. Archives of General Psychiatry, 63(3), 332-9. 

 

6. Olfson, M., Shaffer, D., Marcus, S.C., Greenberg, T. (2003). Relationship between           

antidepressant medication treatment and suicide in adolescents. Archives of General   

Psychiatry, 60, 978-982.

 

7. Rey, J.M., Dudley, M.J. (2005). Depressed youth, suicidailty and antidepressants. The Medical   

Journal of Australia, 182(8), 378-379.

 

8. Rihmer, Z., Akiskal, H. (2006). Do antidepressants t(h)reat(en) depressives? Journal of Affective  

Disorders, 94(1), 3-13.

 

9. Ryan, N.D. (2003). Child and adolescent depression: short-term treatment effectiveness and       

long-term opportunities. International Journal of Methods in Psychiatric Research,    

12(1), 44-53.

 

10. Sharp, S.C., Hellings, J.A. (2006). Efficacy and safety of selective serotonin reuptake inhibitors  

in the treatment of depression in children and adolescents: practitioner review. Clinical           

Drug Investigation, 26(5), 245-55.

11. Wong, I.C., Besag. F.M., Santosh, P.J., Murray, M.L. (2004). Use of selective serotonin reuptake inhibitors in children and adolescents. Drug Safety, 27(13), 991-1000.  

 

12. Zito, J.M., Safer, D.J., DosReis, S., Gardner, J.F., Magder, L., Soeken, K., Boles, M., Lynch, F., 

Riddle, M.A., (2003). Psychotropic practice patterns for youth: a 10-year perspective.      

Archives of Pediatric Adolescent Medicine, 156, 17-25.

 

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