Death delusion
BMJ 2007; 335 doi: https://doi.org/10.1136/bmj.39408.393137.BE (Published 20 December 2007) Cite this as: BMJ 2007;335:1305
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Authors’ response
EDITOR. We highly appreciate the interest and comments to our report
by Drs Mehdi, Subramaniam, Gupta, Stanhope and Meagher, as expressed in
the rapid responses section of this journal. Despite its rarity, the
unusual features of Cotard’s syndrome are very intriguing, which also
these comments reflect. Dr Mehdi suggests that the symptoms we describe
are merely an expression of confusion. While some of these patients at
some time-points well might fulfil the criteria for confusion, the very
specific characteristics of Cotard’s syndrome, a steadfastly conviction
that he or she is dead, or variations of it, as belief in having lost
one’s blood, soul or internal organs or having ceased to exist, is really
not part of the confusion syndrome. Further, dr Subramaniam puts forward
the resemblance of our observations to near-death-experiences (NDE). We
disagree. In NDE, the person is clinically dead or dying but feels alive.
In Cotard’s syndrome, the person is not at all dead or dying but yet
persistent in the belief of being dead or variations of it. Drs
Gupta/Stanhope/Meagher suggest that what we report is an expression of
deep depression with a death wish, which we also disagree to. While
Cotard’s syndrome has been reported in depression, it has also been
associated with psychiatric disorders without depression and furthermore
not infrequently with severe somatic disease without signs of psychiatric
disturbances altogether. Consistently, patients have been reported to be
disturbed, anxious or terrified over the knowledge of being dead, which
rather precludes a depressive death wish. This is illustrated in our first
case report. The patient was very frightened when she came to the dialysis
unit. The following day, when she was back in her normal state, she had no
death wish but a strong wish of receiving a new transplant. We suggest
that adverse drug reaction to (val-)acyclovir (ACV) is the probable cause,
since we have seen several cases of similar, neuropsychiatric disturbances
in patients with high plasma concentrations of ACV and/or its metabolite
CMMG, since ACV treatment was a common characteristic in these patients,
and the symptoms reversed as ACV and CMMG concentrations decreased. Our
report might not be the final evidence of the association, but at least a
reasonable hypothesis for others to elaborate further.
Competing interests:
None declared
Competing interests: No competing interests
Hellden et al (1) report two cases of Cotard’s syndrome as an adverse
drug reaction (ADR) to aciclovir and its prodrug valaciclovir. We,
however, we do not agree with their interpretation of the reported
phenomena.
Firstly, in relation to proposed aetiology, the patients were also
receiving prednisolone and ciclosporin, both of which can be associated
with neuropsychiatric disturbances (including psychotic phenomena). While
we acknowledge that the neuropsychiatric disturbance developed after
administration of aciclovir or valaciclovir, the degree of association is
debatable in terms of causality. Using the Naranjo Adverse Drug Reaction
Probability Scale (2), there was, at best, a probable relationship between
the ‘Cotard’s Syndrome’ and aciclovir/varaciclovir therapy in the
patients. Due to the presence of other factors (medications, renal
impairment, diarrhoea), which are known to lead onto neuropsychiatric
disturbances, it may be more prudent to term the ADR as an adverse event
that can occur in people who are predisposed due to their compromised
physical health and use of certain specific medications until the authors’
assertion of a specific ADR can be established in other non/less
confounded populations (and/or settings).
Secondly, in relation to form and content, the authors’ report the
patients belief that they were dead (Cases one, two) and ‘asking if they
were dead (Case two)’. There is no evidence, from the description
provided, that these patients were experiencing major depressive symptoms.
Moreover, the conviction concerning death does not resemble the nihilistic
delusion in Cotard’s classical description of delire de negation, where
the patient has a markedly negative affect and all things are seen as
without value (3). The brief presence of a ‘belief (delusion) about being
dead’ is a phenomenon that can occur in a variety of states, but with
depression reported in 89% of 100 patients studied (4). We query whether
it is appropriate to label these cases as having suffered from Cotard’s
Syndrome and propose that this symptom may, at best, be labelled as
Cotard’s state (or symptom).
Finally, Case 1 developed this symptom with associated features of
anxiety, visual and auditory hallucinations that were fluctuating in
nature, sudden in onset and remitted over a short period. Case 2 presented
with anxiety, fear, confusion, and altered mental state. The context of
both cases described (acute onset, fluctuating course, physical insult as
etiology) is highly characteristic of delirium as a clinical syndrome
rather than anything else. Formal testing of cognitive functioning is not
reported and although Case 1 may well have been orientated, disorientation
is an unreliable marker of delirium such that orientation can often appear
unaffected in delirious patients who have difficulties with attention,
memory, executive function and comprehension (5). Delirium classically
presents with impairment of consciousness along with disorganised
thinking, delusions, hallucinations, affective and psychomotor
disturbances. Psychotic symptoms (including delusions) can occur
frequently in delirium, though persecutory type tends to be the commonest
(5) and themes of death or dying are common (6). The ‘preoccupation with
theme of death/Cotard’s symptom’ may thus be a clinical manifestation of
the syndrome of delirium. Also, etiological/risk factors like medications,
metabolic disturbances, systemic illnesses (as present in these cases) can
all be intuitively linked with the development of delirium.
To conclude, we propose that these two cases suffered with the
clinical syndrome of delirium (with prominent psychotic symptoms
presenting as Cotard’s phenomena); this being a probable ADR due to use of
aciclovir/varaciclovir in combination with other neuropsychiatric symptom
producing drugs (ciclosporine, steroids). Hence, clinicians treating
patients with chronic physical illnesses and using drugs with
neuropsychiatric adverse effects should have a heightened index of
suspicion of ruling out development of delirium. We agree with the authors
in principle that, if delirium (with concomitant psychotic phenomena)
develops then, the immediate management should be at treating the
underlying causes rather than a referral only to psychiatrists.
REFERENCES
[1] Hellden A, Odar-Cederlöf I, Larsson K, Fehrman-Ekholm I, Lindén
T. Death Delusion. BMJ 2007; 335: 1305.
[2] Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA et
al. A method for estimating the probability of adverse drug reactions.
Clin Pharmacol Ther 1981; 30: 239-45.
[3] Greenberg DB, Hochberg FH, Murray GB. The theme of death in
complex partial seizures. Am J Psychiatry 1984; 141: 1587-9.
[4] Berrios GE, Luque R. Cotard’s syndrome: analysis of 100 cases.
Acta Psychiatr Scand 1995; 91: 185-8.
[5] Trzepacz P, Meagher D. Neuropsychiatric aspects of delirium. In:
The American Psychiatric Publishing Textbook of Neuropsychiatry and
Behavioral Neurosciences, Fifth Edition. Yudofsky SC, Hales RE (Eds.).
American Psychiatric Publishing Inc, Arlington, 2007: 445-518.
[6] Cutting J. The phenomenology of acute organic psychosis:
comparison with acute schizophrenia. Br J Psychiatry 1987; 151: 324–32.
Nitin Gupta, MD (e-mail: nitingupta659@yahoo.co.in) & David
Meagher, MRCPsych
Competing interests:
Nitin Gupta is Member of European Delirium Association. David Meagher is Vice Chairman of European Delirium Association.
Competing interests: No competing interests
Anders Hellden and colleagues described Cotard syndrome as an adverse
reaction to use of val(acyclovir) 1. It is important to be aware of the
exact psychiatric phenomenon to be able to treat it properly; cotard
syndrome in the described cases appeared more like a part of a bigger
clinical picture, delirium.
The fluctuating course, confusion, auditory and visual
hallucinations, delusions (in this case, cotard’s syndrome), physical
tiredness and emotional disturbances fulfil the criteria for a diagnosis
of Delirium, not induced by alcohol and other psychoactive substances 2.
The diurnal variation of death delusions particularly in the case 2 also
favours a diagnosis of delirium. Delirium or acute confusional state is
under-recognised by the health care workers and is exhibited by
approximately 10 to 30 % of the medically ill patients who are
hospitalised.3. Cotard’s syndrome has been observed in confusional states
4.
Cotard syndrome could be a novel adverse reaction to (val)acyclovir,
however, early recognition of delirium cannot be overemphasised in order
to start treatment of the underlying cause. Clinicians should be alert to
delirium as a potential adverse reaction to (val)acyclovir treatment. I
completely agree with the authors that the treatment recommendation in
such cases would not be a referral to psychiatry department, instead,
active management to lower the blood concentration of the culprit drug to
improve patient’s physical condition thus improving the mental state, as
described in the reported cases.
1. BMJ 2007;335:1305 (22 December)
2. The ICD-10 Classification of Mental and Behavioural Disorders.
World Health Organisation Geneva; 1992: 57-59
3. Sadock BJ, Sadock VA, eds Kaplan and Sadock’s Synopsis of
Psychiatry .10th ed. Lippincott Williams and Wilkins; 2007: 322-323.
4. Hansen E, Bolwig T. 1998. Cotard syndrome: An important
manifestation of melancholia. Nordic Journal of Psychiatry 52(6):459-464
Competing interests:
None declared
Competing interests: No competing interests
Dear Sir
I read with interest the above article.
The authors claim that this perception of 'death delusion' is specific to
the above two reported antiviral drugs.
I have however some doubts about the specificity, I rather suspect this is
a reflection of heightened anxiety states that often accompany delirious
episodes.
There are few points that I wish to make to support my statement.
1. Such feelings are not specifically related to drug related delirious
episodes but are also reported in other situations. For example 'Near
Death Experiences(1)' have been variously reported in literature including
vivid descriptions reported by survivors of cardiopulmonary resusciations.
The descriptions would seem to suggest that these people were 'dead' at
the time and seemingly attempting to 'interact' with the adjacent humans
but only to be 'revived' later. Surivors strongly believe that they were
'dead' then and the terminology of being labelled as 'delusions' in such
scenarios is questionable.
2. Depressive symtoms and depressive disorders have been reported with
anti-viral drug use. Similarly, increasing anxiety and confusion have also
been reported. In the two above scenarios patients have been physically
unwell and the combination of physical(medical illness), the depressive
symptoms/disorders and the associated iatrogenic side effects of the
antiviral drug use increase the propensity to develop delirious states
that are well known to be associated with heightened anxiety levels. In
the presence of such confounding factors it is difficult to attribute the
symptoms in their entirety as an adverse drug reaction, rather it is one
of the several factors that might predispose to increasing confusion and
delirious states that accompany morbid illnesses.
Thanks
Dr Hari Subramaniam
Consultant Psychaitrist for the Elderly
(1) Near-death experience in survivors of cardiac arrest: a
prospective study in the Netherlands: Lancet 2001; 358: 2039-45
Competing interests:
None declared
Competing interests: No competing interests
correlation does not imply causation
In both the above cases it seems the association of Cotard’s state
and administration of valciclovir could be explained by the delirious
state. There are too many confounding factors (namely infection, metabolic
disturbances, renal failure, medications )to attribute this finding as a
causal relationship between the drug and Cotard’s state.
‘Our findings add adverse response to an antiviral drug as another
cause and provide clues to the syndrome’s possible neuropsychiatry
origin.’(Author)
It is important to remember that correlation per se does not imply
causation.
Competing interests:
None declared
Competing interests: No competing interests