So Happy He Could Die
            When Andrew pulled a knife on his dad, his parents knew something was off. The thing was, Andrew and his family already knew that something wasn’t right – he had been diagnosed with depression months earlier, and had started medication immediately. This behavior wasn’t his depression causing him to act out. It was his medication.
Andrew, a junior at Ithaca College, started taking antidepressants during his freshman year of high school after a serious attempt at suicide. Under pressure from his parents, Andrew began a combination of therapy and medication, which he did not resist.
 “I was in such a bad place,” he says. “I knew it was time for help.”
            Starting on Prozac, a selective serotonin reuptake inhibitor antidepressant, Andrew says the medication was helpful at first. But a few weeks into being medicated, he went back to being constantly depressed and began eating more. He had an immense weight change, gaining 120 pounds in only three months, but stayed on the drugs because he thought it was just an adjustment period.
“They just made it okay not to care. I was just kind of coasting through the days, rather than focusing on how depressed I was,” he says.
            The weight gain and zombie-like mood didn’t cause Andrew’s doctor to make any changes. He encouraged him to stay with his regular doses. Andrew began to get progressively more depressed and began cutting his wrists in order to focus on physical pain rather than the emotional pain he couldn’t get away from.
“I started going crazy,” he says. “It was getting so bad.”
Andrew’s erratic behavior such as eating nothing for two weeks and then binge-eating led his doctors to think he was bi-polar.
            “It wasn’t drop-of-a-dime mood swings,” he says. “I’d be really depressed for a while and then really fanatical – going nuts.”
It was thanks to his psychiatrist that he wasn’t diagnosed as bi-polar. His psychiatrist, after making a recommendation to his doctor, had Andrew’s meds switched and he began taking Zoloft, a different type of SSRI. He lost 65 pounds and, “started feeling like how I wanted to feel for so long.”
            Andrew is not alone. One in eight adolescents suffers from depression, and only 30 percent seek medication for it. This means that on the Ithaca College campus, with a student body of 6,409 enrolled in the Fall 2006 semester, 801 may be suffering from depression and 240 of them may be on medication.
Suicide is the third leading cause of death among young people ages 15 to 24, after motor vehicle accidents and homicide. It is also the sixth leading cause of death among children ages 5 to14.
 The problem is some of the people contributing to this suicide statistic are on antidepressants, which is supposed to help them deviate from suicidal behavior. But some studies say that it’s the medication that’s making some adolescents more depressed which causes suicidal thoughts. The National Institutes of Health say the risk of suicidal behavior is linked to certain types of antidepressants, particularly the SSRI category. But some doctors, even those aware of the possible side effects, are continuing to prescribe the antidepressants that create this problem, as Andrew’s doctor did.
            While Andrew admits he continued to cut while on Zoloft, he says it was no longer in order to kill himself. He says he thinks his psychiatrist, and the correct medication he was eventually prescribed, saved him.
“I was falling into a black hole,” he says. “If I hadn’t switched meds, I might not have gotten out.”
             
National Recognition
The first SSRI, Prozac, was released in 1987. With the strong connection between depression and anxiety, SSRIs are prescribed because anxiety responds well to drugs that affect serotonin, and therefore they can alleviate both.  An antidepressant that isn’t classified as an SSRI doesn’t treat the anxiety that goes along with depression as well, which is why SSRIs have become so popular. In 2003, Prozac was the only antidepressant approved for use in children with depression.
Andrew says he sees its approval as “a load of crap.”
            Paxil’s manufacturers sought approval later that year and the U.S. Food and Drug Administration denied its application. This came after the United Kingdom’s 2003 ban of all SSRIs in children with depression, except for fluoxetine (Prozac). Regulators said this was the only drug that had benefits that outweighed the risks. They said the other SSRIs posed increased risks of such problems as self-harm, agitation and suicidal thoughts.
            The FDA took this into account and the added concerns in the U.S. prompted it to launch an investigation. It found that paroxetine (Paxil) created a higher risk of suicidal thoughts and action in children taking this drug over children that took a placebo. So in 2004, it directed manufacturers of this newer class of antidepressants to put a warning on the drugs’ labels. The warning, found on drugs such as Paxil, Prozac and Zoloft, alerts health care providers to an increased risk of suicidal thoughts in children and teens using the medications.
Research continued, and in July 2005, the FDA issued a public health advisory which again raised the possibility that the risk of suicide also applied to adults taking SSRIs. Studies pointed to this after research that focused on users’ suicidal thoughts and actions while on the medication.
While the FDA continues to investigate, new evidence of this phenomenon is still to emerging. In August 2006, faculty at the Columbia University Medical Center published a study on the trend in the “Archives of General Psychiatry,” a publication of the American Medical Association. The study says the use of common antidepressants boosts suicide risks for young adults.
            The study, in which 5,500 adults and children participated, found that children aged 6 to 18 who were treated with antidepressants were 1.5 times more likely to attempt suicide, and 15 times more likely to die of the attempt than individuals not treated with an antidepressant. The risk of suicide attempt varied across antidepressant medications. This was not seen among any of the adults using antidepressants in the study. However, in the study it’s hard to determine what figures the researchers were using for how likely children not treated with an antidepressant are to attempt suicide.
            The study found that during the randomized controlled trials, antidepressant drug treatment of adults was not associated with suicide death. Children and adolescents treated with antidepressant agents were “significantly more likely to complete suicide.”
         The information in this study is consistent with the FDA meta-analysis of pediatric randomized controlled trials of the SSRI antidepressants, which was conducted to obtain overall suicidality risk estimates for each drug individually. The meta-analysis, completed before the Columbia study, concluded the use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.        
         Dr. Mark Olfson, author of the Columbia study, says he hopes the study will have the increase the vigilance of young people as they start antidepressants.

A Professional Predicament
         So if only fluoxetine is approved for use by children, how are other medications getting prescribed? While the FDA can approve a drug for a particular condition in a particular population, it can’t regulate the actual practice of the medicine. This means that doctors can use their judgment in a practice known as off-label use, which allows doctors to legally prescribe antidepressants for children even if they haven’t been specifically approved, something parents may not realize.
         Also, many doctors think the FDA analysis wasn’t extensive enough to justify its conclusions and the reasoning for issuing warnings is weak. The American Psychiatric Association says the FDA was “premature” to issue warnings based on short-term clinical trials that studied children for only four months. The FDA also pooled data from a variety of studies done in different ways and on children with different conditions, so skeptics question the differing variables and their influence.
         One skeptic is Dr. David Newman, director of the Hammond Health Center at Ithaca College. He says he disagrees with Olfson’s study because it used only subjects who had received inpatient treatment for depression, meaning that they were already severely depressed, which is an extreme. Also, the study mentions that the finding that children treated with antidepressants are significantly more likely to complete suicide is based on only eight suicide deaths and since the patients were severely ill, the association should be interpreted with caution.
         Newman says he has not encountered suicidality with his patients on antidepressants, though he says to keep in mind that he sees patients at the very end of adolescence. He has treated patients who have become more depressed while on antidepressants, but he says he has never been able to determine whether it was the result of the antidepressants.
         “Depression is a biological disorder that has a life of its own,” he says. “It can get worse and get better. Sometimes it gets worse even with intensive treatment,” he says.
         When he sees this happen in a patient, he says his approach is to talk with the patient about situations in their life. He says that he often looks for signs of substance abuse that he may not have identified in previous visits. He looks for this because alcohol and other recreational drugs can interfere greatly with the effect of antidepressants.
         Newman also determines whether or not the subjects have responded to the medication. If they have had a response, he adjusts the dosage until they have a positive response again or until a side effect is developed that makes it impractical to continue. The other option is to switch medications or add on an augmenting medication, which is a combination of antidepressants. He says giving a person two forms of antidepressants takes advantage of individual properties of different medications, which can boost the effect of an existing antidepressant.
         Newman says if he starts someone on an antidepressant and they are getting worse rather than better in the initial titration phase, the period after medication has been prescribed and the body begins to respond to the drug, he always seriously considers switching them. He also makes sure he questions whether he has the correct diagnosis.

Clashing Cognition
         Newman says the FDA’s black box warnings have no influence over which drug he chooses to prescribe to a patient.
         “Concern about enhanced suicidality has been dramatically overblown by the media,” he says. “I’m not the only one with that opinion. Experts have it as well.”
         He says the warnings are doing more harm, by frightening people away from what would be effective treatment, than any good they would do by protecting someone from the theoretical possibility of becoming more suicidal.
         “Some people, when they’re depressed, are so deprived of energy that they are not suicidal only because they don’t even care enough or have enough energy to care about suicide,” Newman says.
         Since different symptoms of depression can get better at different rates, there’s always a risk when someone’s energy improves, which may happen before the mood improves.
         He says, “They might go from being depressed and lethargic to being depressed and sufficiently motivated to commit suicide and that’s nothing new.”
         While this is rare, it does coincide with the findings in the studies on SSRIs. Andrew thinks this is what happened to him. “Suddenly I had the energy to want to off myself,” he says.
          “Really this [media attention] has gotten way out of hand,” Newman says. “These are generally very safe and incredibly effective medications.”
         He says he thinks if there were good quality studies that have shown increased suicidality in children that it would clearly be important. But he personally finds too many holes in the Columbia study, including the fact that blood tests were not performed, so there is no way to be sure the children used in the studies were actually taking their medication. He says he hasn’t seen any of the correlations described in the study with any of the students he has treated at Ithaca College.
         “Although I’m definitely encountering more fear,” he says.
         Bryan K., a senior at Ithaca College, says he has had a positive experience with SSRIs and also disagrees with the information he reads about the suicidality link to the drugs.
         “Sure, they may take a bit of time to get used to, but they help you get better,” he says. “And getting better means realizing that you’re not okay and that’s something you have to deal with.”
          Bryan says when he started on his medication, his depression did not immediately improve, but he attributes that to the fact that he wasn’t in a “depression coma” anymore. He says while it did take time for him to get better, he knows the drugs were what gave him that extra push.
         “The drugs can only take you so far,” he says. You have to do the rest on your own.”

A Happy Ending?
         After three years on Zoloft, Andrew has stopped taking his meds and is doing well. He says he finds it ironic that Prozac is an approved drug while it increased his suicidality, and Zoloft isn’t, when it made him better.
          One of the “real arts,” as Newman puts it, of treating depression is choosing which antidepressant to put a patient on. He said it is based on factors like side effects, but SSRIs are usually used as the initial prescription if there are no contraindications, unless a patient is concerned about the sexual side effects or has had a previous negative experience with an SSRI.
         A new form of antidepressant, known as bupropion, was released in 2000. It targets the neurotransmitters dopamine and norepinephrine rather than serotonin. While no official studies have been done solely on this form of antidepressants, they are required by the FDA to carry the black box warnings, and are only approved for adults 18 years and over.
         Andrew’s advice to doctors is to make sure they know their patients. “I do think that them putting me on the wrong drug at first – if I had stayed on it – it would have been really bad,” he says.
         Andrew insists the switch to a drug that worked for him gave him something very important – his life.
          “I’m still here,” he says. “That’s what matters.”