EU Regulators Resume Attacks on HCQ

The recent spike in the COVID-19 hospitalizations is caused by seasonality, and, probably, by hydroxychloroquine denial to the patients. The EU regulators attempted to link HCQ to psychiatric disorders, based on historical cases of chloroquine (usually overdosed), and fake science. The following Newsweek article has an appropriately ambiguous title:

Hydroxychloroquine for COVID Treatment Linked to Suicidal Behavior by European Regulators

The article is based on the Meeting Highlights from the latest PRAC meeting. This meeting was held by the Pharmacovigilance Risk Assessment Committee (PRAC) on November 23-26, 2020. The European Medicines Agency published Meeting Highlights., claiming that PRAC conducted “a review of all available data that confirmed a link between the use of these medicines and the risk of psychiatric disorders and suicidal behavior.” No link, nor any reference to the alleged review was provided. The same document also claimed that “chloroquine and hydroxychloroquine have not shown any beneficial effects in treating COVID-19 in large randomized clinical trials.

In addition to disparaging HCQ and providing no corresponding evidence, this same committee also ignored ample evidence of Remdesivir (Veklury), a competing COVID-19 treatment, causing serious kidney damage. PRAC published notes from its October meeting: Meeting Highlights from October, where they discussed “reports of acute kidney injury in some patients with COVID-19 taking Veklury (remdesivir)”. Kidney injury is a well-known side-effect of this drug, yet, PRAC still failed to provide any warnings and concluded:

“At this stage, it has not been determined whether there is a causal relationship between Veklury and the reports of acute kidney injury. … Kidney injury can be caused by other factors as well, e.g. diabetes; importantly, COVID-19 is itself known to be a cause. The PRAC will now carefully assess all available data to evaluate if the medicine may have been responsible for the kidney problems and if there is a need to update the existing information for Veklury. Recommendations for the use of this medicine have not changed.”

See a list of PRAC’s Meeting Highlights.

The alleged review was not provided by PRAC or anyone else and could not be found in any peer-reviewed literature. Since no links or evidence was provided, I used Google Scholar to find the most relevant review:

Brandon S. Hamm, Lisa J. Rosenthal, Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of Coronavirus Disease-2019: Psychopharmacological Interactions and Neuropsychiatric Sequelae, Psychosomatics Journal, July 8, 2020

This review points to the completely opposite conclusion about HCQ – that it is safe. After decades of use, and more than a hundred million patients, there are only a few anecdotal cases of neuropsychiatric side effects. Severe COVID-19 causes psychiatric and/or neurological symptoms very frequently.

Below are some quotes form the HCQ review:

“neuropsychiatric side effects [of chloroquine and hydroxychloroquine] are very uncommon but possible and include a potentially prolonged phenomenon of ‘psychosis after chloroquine’ [not hydroxychloroquine]”

“No studies were found regarding the incidence of hydroxychloroquine-induced psychotic symptoms. “

“psychiatric presentations are expected to be common in hospitalized patients with COVID-19 because of etiologies other than chloroquine- or hydroxychloroquine-induced neuropsychiatric side effects. Delirium has, anecdotally, been frequent in patients requiring intensive care … Prevalence of neurological symptoms was increased to 45.5% in severe COVID-19 cases. In addition, a study of 58 patients with COVID-19 and acute respiratory distress syndrome showed that 69% of patients had agitation… “

“Psychiatric symptom presentation during hospitalization for COVID-19 infection is much more likely to be due to delirium and adjustment disorder than neuropsychiatric side effects of chloroquine and hydroxychloroquine.”

After additional research, I stumbled upon one study that may have been used to substantiate the PRAC allegations.

Garcia, P., Revet, A., Yrondi, A. et al. Psychiatric Disorders and Hydroxychloroquine for Coronavirus Disease 2019 (COVID-19): A VigiBase Study. Drug Safety, October 19, 2020

This is a typical “database study.” It used VigiBase, a World Health Organization database containing reports of adverse drug side effects.  The database currently has more than 20 million reports. Reporting is voluntary, and there appear to be no quality controls.

The authors of this study do not distinguish between cases in which HCQ was dosed correctly and cases of overdoses. Even so, from January to June 16, there were only 3 (three) reported cases with a suspected association between psychiatric symptoms and HCQ for COVID-19, in all Americas (Table 1 in the cited study). Additionally, the authors found only 751 reports of psychiatric side effects “associated” with HCQ, throughout the world, before 2020.  Since more than one hundred million patients have been treated with HCQ, 751 cases is consistent with the definition of “anecdotal evidence” (Table 3 in the cited study).

The “suicidal behavior” mentioned by the Newsweek article likely arose form 48 reported suicides and 44 other self-injuries, out of the total 751 adverse reports. 48 cases of suicides, out of over one hundred million patients, is not a factor. But there are reasons to suspect that most of these reports are phony. The majority of these self-harm cases lack information about the time and the diagnosis for which HCQ was supposedly prescribed. Less then 5 out of the 92 reports include the time since beginning of taking HCQ to the self-harm incident. On the other hand, most of these patients (up to 68 out of 92) received psychotropic drugs.

This study makes an allegation of four suicides of COVID-19 patients, “linked” to HCQ, but the referenced documents do not confirm this claim.

The reporting odds ratios (RORs), used in the study, are unsuitable statistics for the claimed purpose. Many citations do not support or even contradict the study’s claims. Despite all the efforts, the authors concluded with a noon-statement:

“Our findings imply that during the COVID-19 pandemic, some patients may have experienced psychiatric symptoms associated with the use of hydroxychloroquine.”

Considering the complete lack of any evidence provided by PRAC and the subsequent lack of evidence throughout peer review literature to support their conclusions, the media is yet again engaging on unsubstantiated HCQ attacks.