Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study

In an article published by Ladson, et al. the effects of metformin on adolescents with polycystic ovary syndrome (PCOS) were studied. PCOS is a disorder that causes irregular menstruation, increased levels of testosterone, and very often metabolic issues in females of reproductive age. These metabolic issues can lead to increased rates of obesity and diabetes.

The study was looking to see if metformin is an effective treatment for PCOS. Two groups of adolescent females were gathered and educated about lifestyle interventions they could make in order to help cope with their disorder, such as improving diet and increasing exercise. One group was then given increasing doses of metformin, while the other was given a placebo. At the end of the study, the metformin group showed no major difference from the placebo group other than decreased levels of serum testosterone and an increased number of adverse effects. They recommended that metformin not be used to treat adolescents with the disorder.

I feel that this article is important to pharmacy because it deals with off label usage of a drug. Metformin is well known to be indicated for type 2 diabetes, but it has been shown to be useful for other disorders. I think that it is imperative as pharmacists that we try and research studies like these in order to learn about drugs that may be helpful in treating a disorder it is not originally intended for. Although this article recommended not using metformin on PCOS in adolescents, I have read other articles that have highly suggested that adult females with PCOS be put on metformin therapy. What do you think? Should one study like this stop a drug from being used off label?

Link to the article

Ladson, Gwinnett, William C. Dodson, Stephanie D. Sweet, Anthony E. Archibong, Allen R. Kunselman, Laurence M. Demers, Peter A. Lee, Nancy I. Williams, Ponjola Coney, and Richard S. Legro. “Effects of Metformin in Adolescents with Polycystic Ovary Syndrome Undertaking Lifestyle Therapy: A Pilot Randomized Double-blind Study.” Fertility and Sterility 95.8 (2011): n. pag. Clinical Key. Web. 25 Feb. 2016.

Methylphenidate for ADHD in children and adolescents

Methylphenidate is often prescribed to children and adolescents for the treatment of ADHD, or attention-deficit/hyperactivity disorder, however, there is no known comprehensive systematic review on the harms and benefits of administering the medication to the young patients.  Previous reviews have bias or contain flaws, thus, this research study agrees to use guidelines following the Cochrane Handbook and PRISMA guidelines.  Full texts of randomized clinical trials that compared methylphenidate with or without a placebo in the age range of about 3 to 18 years were selected.  Pharmaceutical companies were contacted for additional information.  Primary outcomes included serious adverse effects and symptoms of ADHD, while secondary outcomes included non-serious adverse effects.  No patients were involved in the study.  The data was extracted from the trials by reviewers and the authors were contacted for more information.  The dose of methylphenidate, design of trials, bias, sex of participants, type of ADHD, and other factors were analyzed in the clinical trials.  Concerning quality of evidence, the potential levels of bias associated with the trials evaluated.

Out of 14,431 records, 761 of the publications were included in this review.  In the results, a high possibility of bias was found in most trials due to the passion, failure of full coverage blinding, choosy in reporting data, etc.  Thus, although many of the outcomes suggest that methylphenidate shows benefits, this cannot be deemed as a true conclusion due to the high risk of bias associated with many trials.  Conclusions show that symptoms associated with methylphenidate may be improved and may not cause increase serious adverse effects.  However, methylphenidate may result in a high risk of non-serious adverse effects, such as decreased appetite and sleep problems.

I hope to see a future trial that has little risk of bias, which accounts for all the adverse effects that occur as a result.  This could help with children and adolescent patients who are currently diagnosed with ADHD and could potentially unveil that they are not receiving the benefits that they believe they are supposed to receive.

BMJ. 2015 ; 351(5203): .

 

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): .