A man began taking Zoloft because of some anxiety over whether he could cope with high school students as a student teacher. By the second day on Zoloft, he was having delusions. By day three, he believed aliens were hiding in the normal bodies of people all around him. He thought the alien leader had taken over his wife’s body. On the seventh day of Zoloft, he became certain that he had to kill the alien inside his wife to save himself and the world. So he drove their car full speed into a road barrier, unbuckling her seatbelt just before the crash. Finding her lying on the ground and alive after the wreck, he began to bang her head against the concrete and choke her. His wife survived, but their marriage did not.

A psychiatrist with a successful practice was stressed because of difficulties that ended up with him taking another psychiatrist to court. She in turn sued his son, who was involved in the business.  He prescribed himself Prozac hoping to relieve some of his tension and raise his spirits, but that didn’t help. He sought out treatment from another psychiatrist who treated him with more antidepressants, which led to further deterioration. Eventually he was placed on Luvox—the same antidepressant one of the Columbine shooters was taking. He became increasingly incensed at the psychiatrist who countersued his son and attacked her with a tack hammer.

These are just two of the case studies described by psychiatrist Peter Breggin in his book, Medication Madness. However, you don’t have to read it to find further examples. Read about the speculation after the Sandy Hook shootings about Adam Lanza. Or read this 2010 article by Moore, Glenmullen and Furberg, “Prescription Drugs Associated with Reports of Violence Toward Others.” Thirty-one different drugs met the study’s criteria for a disproportionate association with violence. The drugs included 11 antidepressants, 5 hypnotic/sedatives, 3 ADHD drugs and varenicline (Chantix). “SSRI Stories” describes over 6,000 stories where it seems prescription drugs  (primarily SSRIs) were linked to adverse outcomes, including violence. Also look at “Drugs, Violence and Revolution” or “Smoke and Mirrors” on this website.

These data provide new evidence that acts of violence towards others are a genuine and serious adverse drug event that is associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and serotonin reuptake inhibitors were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.

Several years ago I attended a conference and heard a presentation by Yolande Lucire on her research into the association of violence and psychiatric medications.  At the time I found her presentation both fascinating and concerning in that she thought she had identified a biomedical association between antidepressant medications and some perpetrators of violence. Could there actually be medical evidence of an association between antidepressants and violence? But I didn’t hear anything more about this finding, despite the parade of case studies and anecdotes like those above that did suggest a connection. Then I saw where she was the coauthor of an article in the April 2016 issue of Forensic and Legal Medicine, describing a forensic investigation of three individuals who committed homicide, two of which also intended suicide while taking antidepressants.

The article by Eikelenboom-Schieveld, Lucire and Fogleman was a forensic investigation of three cases they believed to be instances of antidepressant-induced akathisia-related homicide. They suggested that mutations in the CYP450-encoding genes of these individuals contributed to problems metabolizing psychiatric medications and were thus contributing factors to their homicides. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. “These individuals also had diminishing mutations in the CYP450 family of metabolizing enzymes and all were taking medicines that further decreased metabolism by inhibition.”

None of the three individuals knew they were supposed to take their medication regularly or how to stop taking it safely; and none of them improved on the medications. In addition, none of the prescribers recognized their complaints as adverse drug reactions. Nor were they aware of any impending danger from their patients. Interviews with the individuals indicated they had struggled with akathisia (agitation or distress), confusion, delirium, euphoria, extreme anxiety, obsessive preoccupation with aggression, and an incomplete recall of events. Impulses to kill were acted on without warning. Upon recovery, they all saw their actions as out of character. Their beliefs and behaviors horrified them.

They were all prescribed medications that interacted with one another and one person combined these with alcohol. The drug-to-drug interactions further decreased their metabolizing capacity and increased their risk for adverse events by prolonging the half-life of the medications and raising their blood levels.

Fast-changing levels of psychotropic substances, up or down, can cause behavioural changes, as the neurotransmitters in the brain react to reach some equilibrium. This phenomenon makes starting and stopping medication the most dangerous times for suicide and violence, but both can happen at any time, with stress, provocation, dose change, addition or subtraction of a medication. These toxic responses to antidepressants may occur early or later in treatment.

When reading this paper, I saw that Dr. Lucire had previously published an article in 2011 on anti-depressant-induced akathisia-related homicide and the CYP450 genes. In Lucire and Crotty they found that CYP450 allele frequencies were higher in those individuals who had experienced akathisia/serotonin toxicity after taking psychiatric medications. They presented ten cases whose the use of antidepressants had not mitigated their distress. Every person’s emotional reaction worsened while their treating physician attempted a “trial and error” method of increasing doses and then changing to another antidepressant when the previous one did not work.

The symptoms of antidepressant drug toxicity were not recognized as such by the subjects or their physicians. In many cases, the dosage of the antidepressant was increased while other medications were given to address the side effects Frequently the adverse effects were compounded.

In some cases the violence ensued from changes occasioned by withdrawal and polypharmacy. In all of these cases, the subjects were put into a state of drug-induced toxicity manifesting as akathisia, which resolved only upon discontinuation of the antidepressant drugs.

This paper has detailed and substantiated in specific terms how the metabolism of each of the antidepressant drugs used by the subjects would have been seriously impaired both before and at the time they committed or attempted homicide. They were experiencing severe reported side effects, adverse drug reactions due to impaired metabolism complicated by drug–drug interactions against a background of variant CYP450 alleles.

Eikelenboom-Schieveld, Lucire and Fogleman concluded that CYP450 was an important factor for determining who could tolerate a drug or combination of drugs from who could not. “Testing for cytochrome P450 identifies those at risk for such adverse drug reactions.” They hoped that as awareness of the biological causes of these disastrous side effects became more known, justice would be better served for both the victims and perpetrators of akathisia-related violence. “The medicalization of common human distress has resulted in a very large population getting medication that may do more harm than good by causing suicides, homicides and the mental states that lead up to them.”