1023969 ANP ANZJP DebateMalhi et al.
Debate
What are the real costs of rTMS?
Gin S Malhi1,2 , Erica Bell1,2
Recently, the Australian government
has committed a significant amount of
funding to the provision of repetitive
transcranial magnetic stimulation
(rTMS) for the management of
patients with ‘treatment-resistant
depression’. A fundamental problem
is that the evidence for the efficacy of
this intervention is still very much in
its infancy. Indeed, as has been argued
in this journal, and illustrated through
a number of incisive articles published
in this journal in recent months, the
jury is very much out as to whether
there is a meaningful signal with rTMS
delivery in the treatment of depres-
sion (Malhi et al., 2021b, 2021c).
In line with the recommendations
of the recently published RANZCP
Clinical Practice Guidelines for mood
disorders, many others have raised
concerns regarding the use of TMS
(Amad et al., 2019), questioning its
antidepressant properties (Malhi et
al., 2021b) and in particular, the
extent to which any response to
rTMS is specific to the intervention –
as opposed to being the result of non-
specific and placebo effects, which
have been shown to be significant
(Malhi and Bell, 2021).
Notably, proponents of rTMS have
been unable to mount convincing sci-
entific responses to these questions
and have failed to identify the kind of
depression, if any, that is best suited
to rTMS, and what parameters ought
to be used to achieve meaningful
outcomes.
When the efficacy of rTMS is ques-
tioned, a common response is that
because rTMS is highly tolerable,
there is no harm in trying it. But, this
and Zola Mannie1,2,3
is not true. In addition to the financial
costs, which are considerable and
where it is clear that rTMS is
extremely expensive, its real costs
that are clinical have been overlooked
and remain unexplored. In this brief
article we outline the real costs of
rTMS, in other words, its direct and
indirect ‘hidden’ clinical costs and, in
particular, its potential harms.
The reality is that rTMS is being
offered to depressed patients with a
serious illness, one which confers
enormous disability and runs the risk
of suicide, and therefore prompt,
effective therapy is a must. In these
instances, offering treatment that
lacks proven efficacy means that
patients are likely to continue to suf-
fer. But in addition to the emotional
burden of the illness, it is important
to recognise that the disorder contin-
ues to negatively impact the brain. We
now know that depression leads to struc-
tural changes in the brain and that the
illness severely compromises its function-
ing (Moylan et al., 2013). Furthermore,
this is more pronounced during acute
episodes of depression. Therefore,
offering a therapy that is unlikely to be
of benefit comes at a significant cost to
the individual, as it allows the illness to
inflict further adverse impact on the
brain. This is the first hidden cost (see
Figure 1: Neural damage because of
depressive illness).
The second cost that is also ‘hid-
den’, because it is less obvious, is a
significant opportunity cost. The time
engaged in a treatment such as rTMS,
involving for example daily visits, is
extremely demanding and intensive. It
adds to the enormous burden that a
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depressed patient has to endure;
especially since this time could instead
have been used to undergo a more effec-
tive alternative. As mentioned above,
prompt treatment is essential, and
therefore, by not offering the best
treatment that is available, there is a
considerable cost of lost opportunity.
Drawing a parallel with cancer, it
would be unconscionable to sit back
and do nothing or offer a therapy with
little hope of therapeutic benefit sim-
ply because it is well-tolerated.
Furthermore, while tolerability is only
relevant while treatment is ongoing,
the adverse effects on the brain of not
treating depression are likely to be
more enduring and may even be irre-
versible and lifelong. In other words,
it is imperative that at every juncture
in the management of depression, the
best available therapy is prescribed
and that the fastest route to recovery
is pursued. Trialling treatments simply
because they are tolerable and
1
 cademic Department of Psychiatry, Kolling
A
Institute, Northern Clinical School, Faculty
of Medicine and Health, The University of
Sydney, Sydney, NSW, Australia
2
CADE Clinic, Department of Psychiatry,
Royal North Shore Hospital, Northern
Sydney Local Health District, St Leonards,
NSW, Australia
3
NSW Health, Northern Sydney Local Health
District, Royal North Shore Hospital, St
Leonards, NSW, Australia
Corresponding author:
Gin S Malhi, CADE Clinic, Department of
Psychiatry, Royal North Shore Hospital,
Northern Sydney Local Health District, Level
3, Main Hospital Building, St Leonards, NSW
2065, Australia.
Email: gin.malhi@sydney.edu.au
2 ANZJP Debate

Figure 1.  The hidden costs associated with rTMS in the management of depression.

For the management of depression, there are a number of effective therapies and treatment pathways. These include psychological and
pharmacotherapeutic options and electroconvulsive therapy (ECT). The particular treatment that is best suited to the management of depression
in an individual at a specific juncture in their life is determined by a number of factors including the nature of the illness and its causes. (For a more
comprehensive and detailed discussion, see the 2020 RANZCP Clinical Practice Guidelines for Mood Disorders; Malhi et al., 2021a.) The schematic
shows the likely trajectories of response with ECT typically achieving remission and recovery sooner than other interventions such as psychological
therapies and pharmacotherapy. As discussed in the text, a response to rTMS is yet to be determined but by in addition to not achieving recovery and/
or remission of symptoms the institution of rTMS (orange trajectory), incurs the hidden cost of neural damage because of depression (1) shown in red.
This neural damage is cumulative, and it occurs with prolonged periods of acute illness, as well as across several episodes of illness (see Chapter
68, Primary prevention of mood disorders: building a target for prevention strategies; Geddes and Andreasen, 2020, and Kaltenboeck and Harmer,
2018). The damage to the brain caused by depression affects several neural networks – including in particular the hippocampus, which is reduced in
size – and it may scar brain function, and impact upon key cognitive reserves and resilience. The second hidden cost of rTMS is that of being denied
effective alternatives ((2) shown in Green). Psychological interventions and/or pharmacotherapy (blue trajectory) and electroconvulsive therapy
(ECT; green trajectory) have all been shown to have significant therapeutic benefits including sustained remission and recovery from depression.
By denying the individual effective treatment alternatives, a person with depression is having to bear a significant opportunity cost; namely, that of
getting better sooner and remaining well for longer.

therefore incorrectly thought to be
safe is not acceptable practice.
Therefore, it can be seen that
naïvely arguing that an intervention or
therapy is tolerable, while not demon-
strating its efficacy, does actually have a
significant cost. This indirect cost is
twofold and the first of these is liter-
ally hidden from view as it concerns
the pathophysiological toll that
depression inflicts on the brain
because of not adequately treating
the illness and leaving it unchecked.
The second hidden cost is the fact
that an alternative effective therapy
could have been administered instead
of rTMS and this may well have pro-
duced a clinically meaningful response
and alleviated the burden of the acute
episode of depression.
In addition to these clinically impor-
tant indirect costs, the direct financial
cost is a separate consideration, but
one which again falls in favour of not
providing an expensive treatment for
which a clinical phenotype is not read-
ily apparent. This is because without a
clinical phenotype, a treatment can be
administered indiscriminately to all
manner of presentations.
Thus, the real costs of rTMS are
very significant and the issue should
be of grave concern to all. A failure to
address this issue is likely to lead to a
loss of trust in the therapeutic rela-
tionship that is core to psychiatry and
threaten the integrity of the profes-
sion as a whole.
Declaration of Conflicting
Interests
The author(s) declared the following poten-
tial conflicts of interest with respect to the
research, authorship, and/or publication of
this article: G.S.M. has received grant or
research support from National Health and
Medical Research Council, Australian Rotary
Health, NSW Health, American Foundation
for Suicide Prevention, Ramsay Research and
Teaching Fund, Elsevier, AstraZeneca,
Janssen-Cilag, Lundbeck, Otsuka and
Servier; and has been a consultant for
AstraZeneca, Janssen-Cilag, Lundbeck,
Otsuka and Servier. E.B. and Z.M. declared
no potential conflicts of interest with
respect to the research, authorship and/or
publication of this article.
Funding
The author(s) received no financial sup-
port for the research, authorship, and/or
publication of this article.
ORCID iDs
Gin S Malhi https://orcid.org/0000-
0002-4524-9091
Erica Bell https://orcid.org/0000-
0002-8483-8497
Zola Mannie https://orcid.org/0000-
0001-6407-9115

Australian & New Zealand Journal of Psychiatry, 00(0)

Malhi et al. 3
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