Newly published research is calling for doctors to be careful when handing out prescriptions to treat depression in teens and young adults, and when they do they should monitor the youngsters closely, particularly if they are on an elevated dose, due to an increased risk of suicidal behavior and self harm.

Twice as kindly

The research, which was published in the Journal JAMA Internal Medicine at the end of April 2014, found that among the ages of 10 and 24 receiving very high doses of drugs known as SSRI antidepressants (Selective Serotonin Reuptake Inhibitors) were twice as likely to try to harm themselves as those receiving lower or the recommended doses of these drugs.

The risk also appeared to be age dependent with those under the age of 25 and on higher than normal doses the most at risk. The risk was also highest during the first three months of taking the drugs. The same risk was not found in older people on high doses of these drugs.

SSRIs nearly 70 percent of all prescriptions

The study was led by Dr. Matthew Miller from the Harvard School of Public Health and involved over 162,000 people aged between 10 and 64 who had been treated for depression with one of three different types of SSRI drugs; citalopram hydrobromide, sertraline hydrochloride, and fluoxetine hydrochloride. These drugs are also sold under the trade names of Celexa, Zoloft and Prozac and were chosen for the study because these are the drugs that account for nearly 70 percent of all prescriptions initially issued to treat depression.

The researchers compared those who were taking an average or recommended dose of these drugs with those who were receiving higher than normal doses between 1998 and 2010.
They checked at intervals of one month, quarterly and a year after initially being prescribed these drugs for evidence of attempted suicide or accidents of deliberate self harm.

After analysis of the results, they found that one out of every 150 patients who were treated with high dose antidepressants decidedly self harmed.

“If I were a parent, I definitely would not want my child to start on a higher dose of these drugs” said Dr. Miller.

Alarm bells

It is not the first time alarm bells have been rung because of the risk of suicidal behavior when taking antidepressants. Back in October 2004 after a government review the FDA issued a warning about the risk of self harm in children prescribed SSRIs. The FDA directed manufacturers to add a 'black box' warning to the healthcare professional labeling of all antidepressant medications to describe this risk and emphasize the need for close monitoring of patients started on these medications.

However, one research study published in the Journal of the American Medical Association in 2007 concluded that the benefits of prescribing antidepressants to young people suffering from depression far outweighed the risks. Yet another study published in the American Journal of Psychiatry in the same year found that suicide rates in the young had increased despite a drop in the number of SSRI prescriptions issued. Some researchers reckon that this is evidence that SSRIs actually offer some protection against suicidal behavior.

However, no studies have ever looked at the dosages of these antidepressants and the risks of suicidal behavior and self harm like this most recent US study did.

Unanswered questions

There are still questions that remain unanswered though. For example, it's not clear exactly why high doses lead to an increased risk of suicide in younger people. It is also not clear why some people are affected and not others or because some types of drugs carry a greater risk than others. We also do not know if the same risks apply when treatment is started at the average or recommended dose and is progressively progressively afterwards.

The results also do not explain why some people in the study were prescribed very high doses of these antidepressants in the first place. The requirement was that those included in the study should not have been prescribed an antidepressant in the previous year, however, that did not preclude people who may have been prescribed them prior to that. It could be that these people had different circumstances than those newly prescribed antidepressants.

Regardless, it would seem clear that doctors should look for other alternatives than starting children and young adults on very high doses of these drugs.

Official Recommendations

According to NICE (National Institute for Health and Clinical Excellence) the CHMP (Committee for Human Medicinal Products) noted that suicidal behavior and hostility were seen more frequently in clinical trials where children and adolescents were treated with these antidepressants compared to those treated with a placebo and advised that SSRIs “should not be used in children and adolescents except in their approved indications – usually not depression”.

However, doctors can make a decision based on the individual needs of a patient. In these cases, CHMP recommends that patients are monitored carefully, especially at the beginning of treatment, for signs of suicidal behavior, self harm and / or hostility.