The Food and Drug Administration on May 2 proposed that the manufacturers of all antidepressant medications update the existing black box warning on their products' labeling to include a warning about the increased risk of suicidal thinking and behavior in young adults aged 18 to 24 during initial treatment.
The risk of suicide thinking and behavior in children and adolescents associated with use of antidepressants was acknowledged in 2005 by the FDA, which required that a black box warning be put on the labeling to address that potential risk.
But the FDA did not prohibit children and adolescents from receiving antidepressants to treat depression and other psychiatric disorders. Rather, the agency asked the drug makers to develop Medication Guides to help patients, families and caregivers monitor the behaviors of those who were on antidepressants and believed at a high risk of suicide.
The use of antidepressants were on sharp decline after the black box waning was put on the drug labeling to alert doctors and patients of the suicide risk, according to the American Psychiatric Association (APA).
The updated warning alerts that those aged 18 to 24 are also at an increased risk of the suicide attempts when they are using any antidepressant.
But those older than 24 are not at increased risk and those who are older than 65 are actually at a decreased risk of suicide when they are using antidepressants.
Additionally, the updated labeling requirements also add a warning that depression and psychiatric disorders are the most important causes of suicide, suggesting that older people with depression may be better off taking antidepressants.
The FDA proposal is based on the recommendations by the FDA's Psychopharmacologic Drugs Advisory Committee, which found all antidepressants increase the risk of suicide in young adults aged 18 to 24.
The committee also noted that the antidepressants' labeling needed to be updated to reflect the apparent benefits of antidepressants in older adults and to remind health care professionals that the depression and other psychiatric disorders are the most important cause of suicide.
The Committee made the recommendation after reviewing hundreds of antidepressant trials of 77,000 adult patients with major depressive disorders and others that examined the risk of suicide thinking and behaviors in adults who were prescribed antidepressants.
In response to the FDA proposal, APA quickly issued a statement to welcome the agency's proposal that addresses the risk of untreated depression and other psychiatric disorders.
"We welcome today's announcement from the FDA as a major step in the right direction. Specifically, we are pleased that the agency is changing the label on antidepressants to acknowledge, for the first time, that it is untreated depression that puts people at the greatest risk for suicide," Carolyn Robinowitz, M.D., president-elect of the APA says.
The statement says that "Studies have shown that the old labeling - a black box warning label that the agency had issued in 2004 - was associated with a steep decline in treatment rates. Worse, the 2004 labeling change was followed by an increase in the suicide rate, reversing a decade-long decline in suicide deaths in the
United States."
Those who are concerned about the side effects of antidepressants may try alternative treatments. For instance, taking omega-3fats may help prevent and treat major depression.
Interested readers may find compelling evidence in a book titled The Omega-3 Connection by Andrew L. Stoll, M.D., the director of the psychopharmacology research lab at
Boston's
McLean
Hospital and assistant professor of psychiatry at
Harvard
Medical
School.
Questions and answers from the FDA
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What is FDA announcing regarding the use of antidepressants?
FDA is announcing a request to manufacturers of all antidepressant medications to update the existing “black box” on their product labeling to include warnings about increased risks of suicidal thinking and behavior (suicidality) in young adults ages 18 to 24 during initial treatment.
The labeling also will point out that scientific data did not show this increased risk in adults older than 24 and that adults ages 65 and older taking antidepressants actually have a decreased risk of suicidality. The warning statements will emphasize that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide.
Drug manufacturers will have 30 days to submit their revised labeling and revised Patient Medication Guides to the FDA for review. Medication Guides are FDA-approved user-friendly information for patients, families and caregivers that could help improve monitoring. Medication Guides are intended to be distributed at the pharmacy with each prescription or refill of a medication.
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Why is FDA making this announcement now?
In December 2006, the FDA’s Psychopharmacologic Drugs Advisory Committee
agreed that labeling changes were needed to inform health care professionals about the increased risk of suicidality in younger adults using antidepressants. Additionally, the committee recommended that product labeling note that no increased risk of suicidality was seen in adults older than 24 and that adults ages 65 and older taking antidepressants actually had a decreased risk of suicidality. Finally, the committee recommended that labeling remind health care professionals that depression and other disorders being treated with these drugs are serious illnesses that need to be recognized and effectively treated.
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What products are involved in this announcement of a labeling change?
The requested labeling changes apply to the entire category of antidepressants. Products involved in today’s action include: Anafranil (clomipramine), Asendin (amoxapine), Aventyl (nortriptyline), Celexa (citalopram hydrobromide), Cymbalta (duloxetine), Desyrel (trazodone HCl), Elavil (amitriptyline), Effexor (venlafaxine HCl), Emsam (selegiline), Etrafon (perphenazine/amitriptyline), fluvoxamine maleate, Lexapro (escitalopram hydrobromide), Limbitrol (chlordiazepoxide/amitriptyline), Ludiomil (maprotiline), Marplan (isocarboxazid), Nardil (phenelzine sulfate), nefazodone HCl, Norpramin (desipramine HCl), Pamelor (nortriptyline), Parnate (tranylcypromine sulfate), Paxil (paroxetine HCl), Pexeva (paroxetine mesylate), Prozac (fluoxetine HCl), Remeron (mirtazapine), Sarafem (fluoxetine HCl), Seroquel (quetiapine), Sinequan (doxepin), Surmontil (trimipramine), Symbyax (olanzapine/fluoxetine), Tofranil (imipramine), Tofranil-PM (imipramine pamoate), Triavil (perphenazine/amitriptyline), Vivactil (protriptyline), Wellbutrin (bupropion HCl), Zoloft (sertraline HCl), and Zyban (bupropion HCl).
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Are the drugs mentioned above approved for use in children and adolescents?
Prozac (fluoxetine) is approved for use in children and adolescents for the treatment of major depressive disorder. Prozac (fluoxetine), Zoloft (sertraline), and fluvoxamine maleate are approved for use in children and adolescents for the treatment of obsessive compulsive disorder. The other drugs have no approved uses in children.
- I am currently taking an antidepressant. What should I do?
If you observe worsening depression, or the emergence of suicidal thinking, or if you are experiencing other symptoms that you are concerned might be related to taking your medication, you should consult your doctor to discuss the best course of action. It is very important that you do not stop taking your antidepressant without first checking with your doctor. Also, some of these medications may be associated with discontinuation symptoms if stopped abruptly. If your doctor advises that your medication should be stopped, be sure to follow your doctor’s advice about how to accomplish this.
- My child or adolescent, or someone else I am caring for, is currently taking an antidepressant. What should I do?
If you observe worsening depression, or the emergence of suicidal thinking, or if you observe other symptoms that you are concerned might be related to taking medication, you should consult the doctor responsible for your child’s or this person’s medications to discuss the best course of action. It is very important that you do not stop your child’s or this person’s antidepressant without first checking with the prescribing doctor. Also, some of these medications may be associated with discontinuation
symptoms if stopped abruptly, so that, if the doctor advises that the medication should be stopped, be sure to follow the doctor’s advice about how to accomplish this.
