Thread by @markhoro

@joannamoncrieff and I reply to critics’ letters bit.ly/3wNOuwB regarding our analysis of esketamine bit.ly/3niISHH. There are now 6 short-terms studies published for esketamine vs pbo, 5 of which are negative, 1/8

and one which does not reach clinical significance from pbo.The FDA, which has shown itself not to have the distance from companies to make objective decision about #aducanumab, dropped the bar very low for Janssen on esketamine, re-writing the rules of what they would accept 2/8

Although the suicides in the study (3 in esk, 0 in placebo) were not purely from randomised sections of the trial so causal attributions cannot be established, it does fit with real world analysis finding disproportionately high suicides attributed to esketamine in the US 3/8

Ketamine bladder is still a concern with esketamine as it is dosed at doses that are similar to those used recreationally – a third of patients had non-minor bladder issues and one quarter had not resolved by the end of the observation period. 4/8

In one study the manufacturer reported withdrawal symptoms from esketamine which we reproduce here – they were common and numerous. In the discontinuation (relapse prevention) trial they did not report withdrawal symptoms 5/8

The pattern of relapse in the discon group has a pattern consistent with withdrawal, as Joanna et al outlined here: bit.ly/3CgJ1Qg but this was not considered in the study 6/8

Altho people refer to ‘rapid onset antidepressant effects’ for esketamine, difficult to distinguish this from the pleasurable high that recreational users of ketamine report –given effects were not sustained in the 4-week trials seems difficult to call this effect ‘sustained’ 7/8

It is worrying to see the Guardian covering ketamine (delivered intravenously, so somewhat different from nasal esketamine) so uncritically without regard to the lack of long-term evidence, withdrawal effects and uncertain long-term safety. bit.ly/30ykDg7 8/8

This is the article calling for 'urgent clarification' of esketamine's relationship to suicidality in light of the number of suicides linked to its use in the US: karger.com/Article/Abstra…