Misinformation abounds when it comes to antidepressants, say Dutch researchers. Their investigation of the drug uncovered troubling information: Children and teens prescribed one of the most common antidepressants experienced a doubled risk of aggression and suicide, new evidence reveals.

Yet for adults, the risk of these same negative side effects as well as others — including hostility, assault — remains unknown, the researchers say.

The Rise of Antidepressants

Depression is painfully common. According to the World Health Organization, this mental disorder strikes women more often than men and is the leading cause of disability worldwide. At its best, depression leads to numb suffering. At its worst, depression leads to suicide.

The most commonly prescribed drugs for this malady are two slightly different forms of antidepressants. Prozac, approved by the Food and Drug Administration in 1988, was the first of the selective serotonin reuptake inhibitors or SSRIs, which also include brands Celexa, Lexapro, Paxil, Pexeva, and Zoloft. Serotonin-norepinephrine reuptake inhibitors or SNRIs entered the fray in 1993, when the FDA first approved Effexor, yet brands Cymbalta and Pristiq soon followed. Both drugs increase levels of the neurotransmitter serotonin in the brain, while SNRIs also influence amounts of norepinephrine.

Antidepressants were the third most common prescription drug in 2005 through 2008 for all ages, according to the Centers for Disease Control and Prevention, and the most frequently used drug among 18 to 44 year olds. Apparently, these drugs are used most of all by middle-aged American women — one in four take them.

Doubts about antidepressant safety have begun to taint their reputation, despite their popularity.

Violence

One 2004 review showed “increased suicidal behavior in children and teens” who were taking antidepressants, the study authors explain, while another analysis revealed involvement of these drugs “in cases of violence, including murder.”

“Perpetrators of school shootings and similar events have often been reported to be users of antidepressants and the courts have in many cases found them not guilty as a result of drug induced insanity,” wrote the University of Copenhagen researchers.

Led by Dr. Tarang Sharma, who currently works for the Nordic Cochrane Center, the research team set out to understand potential harms associated with these drugs. They reviewed and analyzed 68 clinical studies — documents submitted by drug companies seeking approval from regulatory agencies — including 18,526 patients for the antidepressants duloxetine, fluoxetine, paroxetine, sertraline and venlafaxine. To gain a more complete and potentially less-biased picture of the drug, the researchers also read patient narratives and appendices to the clinical studies.

Their findings are sobering.

True Risks Unknown

Drug companies misrepresented adverse events, the team reports.

“Several deaths were misclassified, and more than half the instances of suicide attempts and suicidal ideation were coded as ‘emotional liability’ or ‘worsening of depression,’” wrote Dr. Joanna Moncrieff, a psychiatrist, in an accompanying editorial.

Though they could not demonstrate a relationship between antidepressants and suicide or aggression among adults, a doubling of the risk for aggression and suicides occurred among children and teens, the researchers say.

The limitations in both design and reporting of clinical trials may have led to “serious under-estimation of the harms,” wrote the authors. For example, akathisia, a form of restlessness that may increase suicide and violence, appeared to be inconsistently coded and so, too, inaccurately estimated. While some evidence indicates withdrawal syndrome can be severe and prolonged, the shortcomings of drug company reports suggest the frequency of this side effect may have been incorrectly recorded.

“The true risk for serious harms is still uncertain,” Sharma and her colleagues concluded.

Daily prescribed by doctors round the globe and daily swallowed by patients, antidepressants are only "modestly more effective than placebo in depression," wrote Moncrieff. Worse, in terms of overall patient improvement, she explains, any differences between these potentially damaging drugs and sugar pills are not even detectable.

Source: Sharma T, Guski LS, Freund N, Gøtzsche PC. Suicidality and aggression on antidepressant drugs: systematic review and meta-analyses based on clinical study reports. BMJ. 2016.