In my view this is not a significant or noteworthy paper, and it has major limitations.  This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction.  These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting.  The evidence is extremely weak for a genuine effect in this instance 

A useful remark in the accompanying editorial is “Khouri et al showed a wide variability of results coming from disproportionality analyses, depending both on the method and model specifications, thus opening the door for a selective reporting of results”. 

Spontaneous report databases are especially prone to biases in relation to suicidal effects.  Reference 5 in the editorial analysing only US data did not find an adverse effect. 

Reference 3 in the editorial, Wang et al, is a much more reliable type of study, and not only does not show an effect but suggested protection: “semaglutide compared with non-GLP1R agonist anti-obesity medications was associated with lower risk for incident (HR = 0.27, 95% CI = 0.200.32–0.600.36) and recurrent (HR = 0.44, 95% CI = 0.32–0.60) suicidal ideation, consistent across sex, age and ethnicity stratification”.

We can’t conclude from the study by Schoretsanitis et al that semaglutide itself is responsible for suicidality. 

There are other grounds, based on previous evidence and with other drugs, for being cautious cautious in the use of semaglutide, and being aware of patients’ mental health when prescribing it is sensible, even though semagutide itself seems not to increase mental health problems.

I am concerned that these analyses combine and conflate on-target effects of GLP-1R agonists with the broader consequences of weight loss.  There are biological effects of the mechanism of action of these drugs.  And there is the wider impact of losing as much as 20% of one’s bodyweight, as has been seen in trials of these drugs.  This is a life-changing intervention that will have largely positive consequences for many.  But for others, the impact of losing a large amount of weight could have negative emotional consequences.  If an individual thinks that losing weight is the key to happiness, but losing weight does not bring happiness, could this lead to depression and suicidal ideation?  And if it did, would we say that GLP-1R agonists caused suicidal thoughts?  While any mechanism that increases suicide risk demands action, these two potential causal pathways require different management.  We need to understand whether these results represent a specific side-effect of these drugs, or an uncommon but tragic consequence of some individuals’ weight loss journey.