Scientists have linked semaglutide use to suicidal ideation.
A new study finds a significant correlation between the use of semaglutide drugs such as Ozempic, antidepressant, or benzodiazepine use, and suicidal ideation.
- No such link was found between liraglutide
GLP-1 drugs and suicidal ideation.
- National health authorities have so far found
no connection between GLP-1 medications and suicidal thoughts, but
research is continuing.
A new
study adds to the conversation regarding the possible effect of GLP-1
diabetes/weight loss drugs on suicide ideation, although its message is a
subtle one.
The study finds a
disproportionality in the number of people who take semaglutide-based GLP-1
drugs and antidepressants or benzodiazepines and who report
suicidal ideation.
Glucagon-like
peptide 1 (GLP-1) receptor agonist medications were originally developed to
help people with diabetes maintain blood sugar levels and a healthy weight.
They have since become popular as weight loss drugs, with Wegovy officially
being approved by the U.S. Food and Drug Administration (FDA) for this use, as
well as Zepbound (tirzepatide) receiving approval from the FDA for weight management in November
2023.
Many
of these drugs are based on semaglutide, which was first made available to
patients in 2017. These include Wegovy, Ozempic, and Rybelsus, all manufactured
by Novo Nordisk.
Among
the early GLP-1 drugs still in use is liraglutide. Drugs based on liraglutide
include Saxenda and Victoza.
The
researchers found no indication of increased suicidal ideation in people who
took liraglutide GLP-1 drugs alongside antidepressants.
Experts’
concerns regarding GLP-1 drugs and suicidal ideation stem from three patients
reported in Iceland, and 201 similar reports received by the FDA. Since that
time, the European Medicines Agency (EMA) and the FDA have investigated the
issue. On January 11, 2024, the FDA released a statement saying
it had found no connection between the drugs and suicidal thoughts. In April
2024, EMA did the same.
In
fact, in January 2024, the U.S. National Institutes of Health reported on
a study finding people on GLP-1 drugs had less suicidal
ideation than other people.
What
is unusual about the new study, and what it adds to the discussion, is that it
found a disproportionality “signal” specifically among people who were taking
both semaglutide medications and antidepressants and benzodiazepines.
In
arriving at their findings, the authors of the new study analyzed the World
Health Organization’s global database of adverse drug reactions that were
suspected to be attributable to semaglutide or liraglutide.
The
study is published in the JAMA Network Open.
A possible
connection between GLP-1 drugs and suicidal ideation
To begin with, lead author Georgios Schoretsanitis, MD, PhD, pointed
out to Medical News Today, “The
disproportionality signal is a hint and cannot be interpreted as a proxy of
severity.”
It is
not clear how strong the association is, nor does the study in any way
demonstrate a causal relationship.
Mir Ali, MD,
board certified bariatric surgeon and medical director of MemorialCare Surgical
Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who
was not involved in the study, said:
“As
far as I know, no definite mechanism to link GLP-1 medications and suicidal
ideation [has been described].” He also said, “There is disagreement because
the incidence [of suicidal ideation] is so rare that it is difficult to
accurately assess and try to delineate a possible reason for this.”
Separating
existing psychological stressors from those possibly caused by GLP-1 is also
difficult.
Ian Douglas,
PhD, BSc, professor of pharmacoepidemiology at the London School of
Hygiene & Tropical Medicine, who was also not involved in the study,
pointed out:
“The
time at which someone starts a treatment for obesity can itself be correlated
with mental health difficulties, and the effects of the medication on weight,
whether this is a dramatic reduction in weight, or a disappointing lack of
weight reduction, can also trigger changes in mental health.”
“If we want to know whether GLP-1 agonists cause
changes in mental health status, either through their direct pharmacological
action or indirectly through their action on weight, we ideally need studies
that compare people treated with GLP-1 agonists with similar people not
receiving them to see if there are differences in their risk of mental health
outcomes.”— Ian Douglas, PhD, BSc
Of
the NIH study, Douglas said, “I wouldn’t go so far as to say GLP-1 agonists
prevent mental health problems based on these findings, but the results are
certainly not consistent with a harm.”
Douglas
questioned the methodology used in the new study, saying, “Individual
spontaneous reports of suspected adverse drug reactions… such as those used in
the new study are not an appropriate resource in which to test this hypothesis
about GLP-1 agonists.”
Ali
expressed a similar concern. “A disproportionality analysis is a quick and
inexpensive way to assess whether a certain group is overrepresented or
underrepresented in a particular outcome.”
Keeping
semaglutide users safe
Schoretsanitis
said they suggest “that physicians prescribing semaglutide should inform their
patients about the medications’ risks, assess their psychiatric history, and
evaluate the mental state of patients before starting treatment with
semaglutide.”
“If needed, such as in cases of persisting suicidal
ideation or in cases of other relevant mental disorders, the treating physician
should involve different specialists, including a psychiatrist and/or clinical
psychologists for a psychological and psychiatric evaluation.”— Georgios
Schoretsanitis, MD, PhD
Of particular concern with GLP-1
drugs is that some people obtain online prescriptions and receive them by home
delivery. “We highly discourage off-label
use of semaglutide and without any medical supervision,” said
Schoretsanitis.
“One
of the reasons most medications are only available by prescription is to make
sure they are used appropriately, and this includes potential monitoring for
emerging side effects,” added Douglas.
“There
is a world of difference,” Douglas said, “in terms of follow-up between being
prescribed a medication by a known family physician and a relatively anonymous
online operator. There is a vital duty of care for all prescribers to ensure
they are available and accessible for follow-up and monitoring.”
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