Dispensing of psychotropic medications to Australian children and adolescents before and during the COVID-19 pandemic, 2013-2021: a retrospective cohort study.

OBJECTIVE: To determine longitudinal patterns of dispensing of antidepressant, anxiolytic, antipsychotic, psychostimulant, and hypnotic/sedative medications to children and adolescents in Australia during 2013-2021. DESIGN: Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. PARTICIPANTS, SETTING: People aged 18 years or younger dispensed PBS-subsidised psychotropic medications in Australia, 2013-2021. MAIN OUTCOME MEASURES: Population prevalence of dispensing of psychotropic medications to children and adolescents, by psychotropic class, gender, and age group (0-6, 7-12, 13-18 years). RESULTS: The overall prevalence of psychotropic dispensing to children and adolescents was 33.8 per 1000 boys and 25.2 per 1000 girls in 2013, and 60.0 per 1000 boys and 48.3 per 1000 girls in 2021. The prevalence of psychotropic polypharmacy was 5.4 per 1000 boys and 3.7 per 1000 girls in 2013, and 10.4 per 1000 boys and 8.3 per 1000 girls in 2021. Prevalent dispensing during 2021 was highest for psychostimulants (boys, 44.0 per 1000; girls, 17.4 per 1000) and antidepressants (boys, 20.4 per 1000; girls, 33.8 per 1000). During 2021, the prevalence of dispensing was higher than predicted by extrapolation of 2013-2019 data for many classes, including antidepressants (boys: +6.1%; 95% CI, 1.1-11.1%; girls: +22.2%; 95% CI, 17.4-26.9%), and psychostimulants (boys: +14.5%; 95% CI, 8.0-21.1%; girls: +27.7%; 95% CI, 18.9-36.6%). The increases were greatest for girls aged 13-18 years (antidepressants: +20.3%; 95% CI, 16.9-23.7%; psychostimulants: +39.0%; 95% CI, 27.9-50.0%). CONCLUSIONS: The prevalence of both psychotropic dispensing and psychotropic polypharmacy for children and adolescents were twice as high in 2021 as in 2013. The reasons and appropriateness of the marked increases in psychotropic dispensing during the COVID-19 pandemic, particularly to adolescent girls, should be investigated.

Industry-corrupted psychiatric trials. / Zjawisko korupcji w badaniach psychiatrycznych.

The goal of this paper is to expose the research misconduct of pharmaceutical industry sponsored clinical trials via three short case studies of corrupted psychiatric trials that were conducted in the United States. We discuss the common elements that enable the misrepresentation of clinical trial results including ghostwriting for medical journals, the role of key opinion leaders as co-conspirators with the pharmaceutical industry and the complicity of top medical journals in failing to uphold standards of science and peer review. We conclude that the corruption of industry-sponsored clinical trials is one of the major obstacles facing evidence-based medicine.

The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance.

OBJECTIVE: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. METHODS: Approximately 750 documents from the Celexa and Lexapro Marketing and Sales Practices Litigation: Master Docket 09-MD-2067-(NMG) were deconstructed. RESULTS: The published article contained efficacy and safety data inconsistent with the protocol criteria. Procedural deviations went unreported imparting statistical significance to the primary outcome, and an implausible effect size was claimed; positive post hoc measures were introduced and negative secondary outcomes were not reported; and adverse events were misleadingly analysed. Manuscript drafts were prepared by company employees and outside ghostwriters with academic researchers solicited as 'authors'. CONCLUSION: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety.

Aripiprazole in the maintenance treatment of bipolar disorder: a critical review of the evidence and its dissemination into the scientific literature.

BACKGROUND: Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. METHODS AND FINDINGS: We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. CONCLUSIONS: A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature. Please see later in the article for the Editors' Summary.

Conflicted medical journals and the failure of trust.

Journals are failing in their obligation to ensure that research is fairly represented to their readers, and must act decisively to retract fraudulent publications. Recent case reports have exposed how marketing objectives usurped scientific testing and compromised the credibility of academic medicine. But scant attention has been given to the role that journals play in this process, especially when evidence of research fraud fails to elicit corrective measures. Our experience with The Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) illustrates the nature of the problem. The now-infamous Study 329 of paroxetine in adolescent depression was negative for efficacy on all eight protocol-specified outcomes and positive for harm, but JAACAP published a report of this study that concluded that "paroxetine is generally well tolerated and effective for major depression in adolescents." The journal's editors not only failed to exercise critical judgment in accepting the article, but when shown evidence that the article misrepresented the science, refused either to convey this information to the medical community or to retract the article.

Industry-sponsored ghostwriting in clinical trial reporting: a case study.

In this case study from litigation, we show how ghostwriting of clinical trial results can contribute to the manipulation of data to favor the study medication. Study 329 for paroxetine pediatric use was negative for efficacy and positive for harm. Yet the ghostwritten publication from this study concluded that paroxetine provided evidence of efficacy and safety and continues to be influential. Despite the role of named authors in revisions of the manuscript, the sponsor company remained in control of the message.

The ethics of pharmaceutical industry relationships with medical students.

Little research has been done on the extent of the relationship between the pharmaceutical industry and medical students, and the effect on students of receiving gifts. Potential harms to patients are documented elsewhere; we focus on potential harms to students. Students who receive gifts may believe that they are receiving something for nothing, contributing to a sense of entitlement that is not in the best interests of their moral development as doctors. Alternatively, students may be subject to recognised or unrecognised reciprocal obligations that potentially influence their decision making. Medical educators have a duty of care to protect students from influence by pharmaceutical companies.

Childhood tetanus in Australia: ethical issues for a should-be-forgotten preventable disease.

Refusal of a parent to have a child vaccinated against tetanus raised ethical issues for the treating clinicians. The clinicians felt their duty to the child was compromised, but recognised that our society leaves the authority for such decisions with the parents. As there was no reason, other than different beliefs about vaccination, to doubt the parent's care for the child, the clinicians limited their response to providing strong recommendations in favour of vaccination. Other issues raised by this case include community protection, and the costs to the community of treating a vaccine-preventable disease.