Antidepressant Use and Risk of Recurrent Stroke: A Population-Based Nested Case-Control Study

Approximately 30% of individuals that have had a stroke are also diagnosed with depression, and although antidepressant therapy is recommended in patients with post-stroke depression, there are no guidelines for choosing therapy options. For this reason, a study was conducted to determine the relationship between the use of various classes of antidepressant medications and the recurrence of stokes. This longitudinal study analyzed health insurance database information of adults over the age of 18 who had a stroke and were readmitted with this condition. Around 10,000 patient cases were included in the study results (6,679 controls; 3,536 cases).  The study found that there was not an increased risk of stroke recurrence in patients taking SSRIs for depression; however, a correlation was found in patients being treated with TCAs (1.41 times increase). The risk for stroke recurrence in patients taking TCAs did not show much differentiation when analyzing dose and treatment duration variations. As a result, the study highly recommends using alternative methods of treatment for depression symptoms in patients who have experienced a stroke.

I believe this article is important to the understanding of pharmaceutical care due to the fact that antidepressants are one of the most commonly prescribed classes of medications. As healthcare professional that prioritize on the safety of treatment methods, we should be aware of medication contraindications so that we can provide the best patient care. Although all healthcare professionals look out for the best interests of the patient, pharmacists specialize on medications and thus will have the best knowledge on the potential dangers associated with treatment methods. This study makes me want to learn more about specific medication contraindications so that I will no how to protect patients health after graduation from pharmacy school.



SSRIs May Increase the Risk of Violent Behavior in Young People

Selective serotonin reuptake inhibitors, or SSRIs, are among the most commonly prescribed antidepressants. These drugs are not generally used in adolescents and young adults as several studies have suggested that SSRIs increase the risk of suicidal ideation in these age groups, but not in adults. SSRIs are also believed by some to cause violent behavior, particularly in adolescents and young adults, although the data on this is much more inconclusive. Therefore, one group of researchers in Sweden designed a study to try and determine a possible correlation between SSRI use and violence in adolescents. The researchers used records available from the Swedish Prescribed Drug Register to identify 856,493 patients over the age of 15 who had been prescribed SSRIs in the period between January 1, 2006 and December 31, 2009. The researchers then examined the arrest records of these patients and compared individual patient records when they were on SSRI treatment to when they were not on an SSRI treatment.

Of the entire patient population studied, 9.9% were between the ages of 15 and 24, and these individuals were considered adolescents or young adults. Upon examining the arrest and conviction records of this population, it was determined that this group was more likely to be convicted of a violent crime while on SSRI treatment, although only low doses of SSRIs produced this result. Patients in this age group on moderate or high doses of SSRIs and patients in other age groups on any dose of SSRI did not show a significant increase in violent crime. Within the 15 to 24 age group, the use of medications that could serve as an alternative to SSRIs, such as venlafaxine, was also associated with an increase in violent crime. The study could not determine the cause of this association, and recommended that further studies should be conducted to corroborate their findings.

Given their potential to increase suicidal ideation and possibly the rate of violent crime among adolescents and young adults, is there any case for using SSRIs in adolescents? Would giving a young person large doses of an SSRI really be the most effective treatment option?  With this study’s suggestion that other antidepressant treatments may also increase violent behavior in adolescents, is it possible that antidepressant medication as a whole may not be appropriate for adolescents or young adults?



Molero Y, Lichtenstein P, Zetterqvist J. Selective serotonin reuptake inhibitors and violent crime: a cohort study. PLoS Med. DOI: 10.1371/journal.pmed.1001875 (published 15 September 2015)

Antidepressants’ Black Box Warning: 10 Years Later

Almost ten years after the antidepressant black-box warning was first issued by the FDA, the impact of this labeling is now being weighed against the growing number of untreated cases of depression in the United States. This review article considers how drastically the FDA’s decision to warn the public of this risk has influenced prescribing patterns and rates of depression with the epidemiological data now available.

This article first discusses the increased risk of suicidal thinking, feeling, and behavior in young people taking antidepressants and the basis for issuing the black box warning. The initial 372 clinical trials showed that 4% of patients receiving the antidepressant displayed suicidal thinking compared with 2% of placebo, and age analyses did show that this increased risk was higher in children under the age of 18.

Now, a cohort study revealed that there has been a reduction in antidepressant use within two years after the FDA advisory was issued. Reductions of 31%, 24.3%, and 14.5% in adolescents, young adults, and adults were seen, respectively. It was also found that the number of adults with depression who did not receive an antidepressant medication increased from 20% to 30% from 2003 to 2004. Other trends that have seem to emerged since the FDA advisory include an increase in psychotropic-drug poisoning, although trends are not directly proven to be related to intentional suicide attempts. This review really calls for an increased knowledge and education, most importantly for primary care providers, to know the risk posed by untreated depression – and how to balance this risk with the small risk associated with antidepressant treatment to best help their patients.

This article really brought to light something I had never thought about before in regards to antidepressant pharmacotherapy. Black-box warnings are obviously important in helping the public understand the risks associated with their medications. I personally had never thought that such a warning on antidepressants may really reverse the goal of using SSRIS. A question I have is how pharmacists may be able to bridge this gap between the benefits of using antidepressants and the reluctance of patients to want to start medication therapy because of this black box warning?

New England Journal of Medicine. 2014;371:18. Link to Article

Antidepressants may double the risk of aggression and suicide in children

It is has been researched that suicidal behavior may be increased with children aged <18 who take popular antidepressants such as SSRIs and SNRIs, however, few systemic research has been done to correlate the effects of aggressive behavior with popular antidepressants.  This systematic review and meta-analysis was conducted to analyze the mortality, suicidality, aggression, and akathisia associated with five popular antidepressants—duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine—using clinical study reports.  Akathisia is an extreme state of restlessness, agitation, and distress that can increase the risk of suicide and violence. No patients were involved in the study.  The methods included obtaining clinical study reports from the European Medicines Agency and Modern Humanities Research Association.  Out of the 198 clinical study reports, only 68 were used.  Using the reports that contained double bind placebo controlled trials and patient narratives, primary outcomes (mortality and suicide) and secondary outcomes (aggressive behavior and akathisia) were assessed by searching for specific terms, such as those used by the FDA.

Quality of the clinical study reports were varied, such as the number of trials conducted and the length of the study designs.  The results of the study showed that 16 deaths occurred in adults, and 155 suicidality events occurred with an odds ratio in children and adolescents doubled to that in adults.  The odds ratio for children and adolescents was also double that to adults for aggressive behavior.  The odds of akathisia were roughly the same for both adults and children and adolescents.  Thus, the data from this study shows that there is indeed an increased risk of suicide in children and adolescent taking antidepressants.  However, the study also found that there was a significant increase in aggressive behavior in children and adolescents.  This was a comprehensive review of randomized controlled trial data and is the first to note this finding of increased aggressive behavior.

My questions posed to colleagues are: Do you feel that this is a significant, valuable finding, despite the limitations in the research study?  Do you feel that this information could benefit pharmacists, and if so, how?

BMJ. 2016; 352(65): .