Antidepressants in Children: What Causes Suicidality - Psychiatricanswers

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Antidepressants in Children: What Causes Suicidality - The Medication or The Underlying Bipolar Spectrum Disease?

The Journal of Bipolar Disorders.
Vol. 6 No. 4

We review our extensive clinical experience with children and adolescents who have received antidepressant(s) or combinations thereof to determine if and under what circumstances these drugs_are involved in suicidality.

Background
Prominent psychiatrists and researchers have questioned1,2 the Food and Drug Administration's (FDA)3 decision to endorse a blank statement that attributes to antidepressants (ADs) a potential to induce suicidal thoughts in children and adolescents. Regrettably, a byproduct of such an announcement by the FDA is that many parents are reluctant to give their children the benefit of a time-honored treatment such as ADs.

Chart Review
To determine what is involved in suicidality, we reviewed the data collected from 1,076 pediatric patients evaluated and treated between 2002 and 2007 in a variety of settings: outpatient community clinics, a residential treatment center, two inpatient facilities, and a private office. The patient population consisted of males and females from the ages of 3 years to 17 years, but the vast majority (91 %) was represented by children between 8 and 15 years of age. From this sample we focused on the outcomes of 344 children (31.9%) who were treated with ADs. Such treatment was initiated either at the time of arrival or after a psychiatric evaluation. About a third of the patients had never seen a psychiatrist before. In most cases, they had been evaluated by a doctor, but had stopped taking medications; however, others were on drugs prescribed by a previous doctor, who in most instances was a primary care physician. One hundred and eleven children (32.3%) out of 344 had suicidal thoughts or made suicidal gestures, i.e., superficial cutting, while taking ADs. The remaining 233 subjects (67.7%) had no thoughts of suicide when they took similar medications for the treatment of primary obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder (GAD), or panic disorder, even after taking high doses of ADs for several years.
All diagnoses of anxiety disorders and unipolar depression were made by the author using DSM-IV criteria, but for diagnoses of the bipolar spectrum disorders, the framework described by Akiskal and Pinto was used.4
A third of the studied population was exposed to ADs, mostly selective serotonin reuptake inhibitors (SSRls), and none of the patients treated for a primary anxjety disorder without a comorbid bipolar spectrum disorder had an adverse response. Ironically, the subjects with the longest exposure to ADs and higher dosages had minimal side effects, including symptoms not associated with suicidality. I consider "minimal side effects" to be symptoms such as nausea, headaches, dry mouth, decreased libido, and increased appetite. I should note that many years ago, other authors found no association between the SSRI fluoxetine and suicidal thoughts when used to treat primary OCD.5

Illustrative Cases
To provide a more accurate picture of these findings, I selected eight patients who are currently stable to illustrate several types of responses to ADs.

  1. A 15-year-old female presented with diagnoses of GAD and major depression, recurrent, for which she was prescribed bupropion and trazodone. She was brought to the emergency department (ED) with suicidal ideation, where I discovered that her real diagnosis was bipolar disorder, mixed. After stopping the two ADs and starting a mood stabilizer, she has been symptom-free for 9 months.
  2. An 8-year-old girl who had a diagnosis of depression NOS was taking venlafaxine when she reported having thoughts of hurting herself. At the ED, her diagnosis was changed to bipolar disorder, based not only on her mood swings, but also on the fact that both her mother and maternal grandmother were bipolar.
  3. A 14-year-old female was taking sertraline for depression. In school she wrote an essay describing a girl who wanted to die. Her father and an uncle have bipolar disorder, and when she was brought to my office I diagnosed her with mood disorder NOS (DSM-IV), but according to family history the patient can be considered bipolar spectrum.
  4. A 10-year-old boy came to my office after he told his mother that he wished he would die. He had been taking sertraline, and became aggressive and experienced insomnia secondary to racing thoughts and hypomania. After a comprehensive evaluation, he was diagnosed with bipolar II disorder. He was given a mood stabilizer and his symptoms have remained stable for more than a year.
  5. A 15-year-old female who was evaluated by me when she was 13 was "Baker Act" (name given in Florida to the involuntary commitment to the hospital) for cutting herself and assaulting her mother. I diagnosed her with bipolar disorder (same diagnosis as her mother) and substituted her escitalopram for two mood stabilizers, but her psychiatrist put her back on her previous medications. A year later she came to my private practice after another hospitalization for defiance, violence, and suicidality. She has been back on the mood stabilizers for a year and is now stable.
  6. A 17-year-old male diagnosed with depression (taking bupropion, venlafaxine, and sertraline) was admitted to the hospital after 2 days without sleep and because he voiced his wish to drive his car in front of an 18-wheeler. When I interviewed him at the hospital, he stated that his mind was racing so fast that he "could not continue living like this." An injection of 10 mg of olanzapine followed by oral mood stabilizers made this agitated young man a calm and relaxed individual who now lives a normal life with his· new diagnosis of mixed bipolar depression.
  7. A 17 -year-old male on bupropion and citalopram came to a residential treatment program for his abuse of marijuana. He admitted using cannabis to fall sleep and reported a significant family history of "moody relatives."  His diagnosis was confirmed as bipolar II disorder. He has done well on one mood stabilizer.
  8. A 15-year-old male on paroxetine came to my office with diagnoses of attention-deficit/hyperactivity disorder and depression because he told his best friend he wanted to die. He had all the typical symptoms of a person with a bipolar spectrum disorder and has been "nonsuicidal" on a mood stabilizer and a nightly dose of clonazepam.

Conclusion
This study also corroborates previous work6,8 suggesting that ADs have a mood destabilizing effect, primarily in bipolar patients, especially those with depressive mixed states. As a matter of fact, in many cases I have witnessed how the patient's racing thoughts and the feeling of "being out of control"  led to an agitated state of mind in which the individual ends up contemplating suicide as the only solution to their perception of being in a hopeless situation. These experiences led me to believe that the so-called "drug-induced activation"9 is a misnomer for this awful feeling described earlier. As other authors have suggested,9,1O the ability to differentiate between subthreshold cases of bipolar spectrum disorder and unipolar depression is a paramount clinical skill in abating suicidality in antidepressant-treated depressives.
Sussman11 has argued that the FDA advisory is counterproductive, as it robs patients with primary depression and anxiety disorders from a life-saving treatment. Shouldn't doctors be more careful when diagnosing unipolar depression to assure that they are not in the presence of a bipolar spectrum disorder,13,14 which could get worse with the use of antidepressants?

Manuel Mota-Castillo, MD
Lake Mary, Florida
(The author wants to acknowledge his gratitude to Ronald W Pies, MD and Margie Grebin, MS for reviewing this paper and making helpful suggestions that were accepted, and to Manuel A. Mota-Mercado, BS for tabulating the cases' data.)

References
  1. Mann JJ, et al. Neuropsychopharmacology 2006;31:473-492.
  2. Rihmer Z, Akiskal H. 1 Affect Disord 2006;94:3-13.
  3. U.S. Food and Drug Administration. FDA Public Health Advisory: Suicidality in Children and Adolescents Being Treated With Antidepressant Medications, October 15, 2004. Available at: http://www.fda.gov/cder/drug/antidepressants/ssripha200410.htm. Accessed December 11, 2007. (Current information is available at: Antidepressant Use in Children, Adolescents, and Adults. http://www.fda.gov/cder/drug/antidepressants/default.htm. Accessed December 11, 2007.)
  4. Akiskal HS, Pinto 0. Psychiatr Clin North Am 1999;22:517-534.
  5. Beasley CM Jr, et al. 1 Affect Disord 1992;24:1-10.
  6. Wehr TA, Goodwin FK. Arch Gen Psychiatry 1979;36:555-559.
  7. King RA, et al. 1 Am Acad Child Adolesc Psychiatry 1991;30:179-186.
  8. Akiskal HS, et al. 1 Affect Disord 2005;85:245-258.
  9. Akiskal HS, B

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