Top ten most read in July: re-analysis of the STAR*D antidepressant study and combination drug therapy among US adult users of CNS stimulants

"February 22nd" by Carsten Schertzer (CC BY 2.0)
“February 22nd” by Carsten Schertzer (CC BY 2.0)

Only one new entry made its way into our top ten most read articles in July—Pigott et al’s re-analysis of patient-level data from the STAR*D study, which reached seventh place in the top ten despite its publication towards the end of the month.

STAR*D re-analysis

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was a major trial in the treatment of depression, funded by the US National Institute of Mental Health, the initial results of which were first reported in 2006. The study provided up to four antidepressant treatments per patient and was intended to provide guidance on the selection of the best next-level treatment option for patients who did not gain sufficient relief from their initial (and subsequent) treatments. In their new re-analysis of the study, Pigott et al attempt to examine what they describe as “key methodological deviations” from the original study protocol and related publications, and the impact of these on the reported outcomes. Their re-analysis was conducted following the guidelines of the Restoring Invisible and Abandoned Trials (RIAT) initiative and used the trial’s patient-level dataset and followed the analysis outlined in the original protocol.

According to the authors, the original study investigators did not use the protocol-stipulated Hamilton Rating Scale for Depression (HRSD) to report the cumulative remission and response rates and instead used a non-blinded, clinic-administered assessment. They also point to the inappropriate inclusion in the original analysis of 99 patients who already scored as remitted on the HRSD at the start of the study and 125 who scored as remitted when initiating their next-level treatment. Re-analysing the data without these deviations, Pigott et al report that the cumulative remission rate was approximately half of that originally reported.

Combination drug therapy among US adult users of CNS stimulants

While not a new entry, Moore et al’s study of medical use and combination drug therapy among US adult users of central nervous system stimulants, currently in tenth place, has been featured in our top ten most read articles consistently since its publication in late April. In this cross-sectional analysis using data for prescription drug claims for US adults from a commercial insurance claims database, the researchers examined patterns of medical use of amphetamine and methylphenidate stimulant drugs. Among those patients using these Schedule II stimulants during 2020, the researchers found that 45.5% combined use with one or more additional CNS active drugs for a median of 213 treatment days, while 24.3% used two or more additional CNS-active drugs for a median of 182 days. The authors conclude by expressing concern about the lack of approved indications and limited clinical trial assessment of these multidrug combinations.

Below are the top ten most-read papers in BMJ Open during July 2023:


*Most read figures are based on pdf downloads and full text views. Abstract views are excluded.
Rank* Author(s) Title
1 Walker et al. Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study
2 Wang et al. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019
3 Hall et al. Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population
4 Beidelschies et al. Polycyclic aromatic hydrocarbons and risk of rheumatoid arthritis: a cross-sectional analysis of the National Health and Nutrition Examination Survey, 2007-2016
5 Hong et al. Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials
6 Kaneko et al. Development and validation of a rurality index for healthcare research in Japan: a modified Delphi study
7 Pigott et al. What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol
8 Wang et al. Sexual well-being among older adults in China (SWELL): protocol for a multicenter cross-sectional study
9 Erviti et al. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data
10 Moore et al. Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis

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