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Mind & Brain, the Journal of Psychiatry


evidence against it.8287 Hence, for Cotard’s syndrome, a two- factor hypothesis is proposed. Here, the first factor con- tributes to the total lack of autonomic response to anything (as in pure autonomic failure), the second to not being able to reject the hypothesis ‘‘I’m dead.’’84,86 In this hypothesis the loss of affect (first factor) is more pronounced and general- ized than in Capgras patients.90 On the other hand, the difference in attributional style could also be an explanation for the different hypothesis formation in the first factor.17


The importance of the right dorsolateral prefrontal cortex (RDLPFC) for hypothesis evaluating was demonstrated with fMRI.8789 It has also been observed that right frontal damage is commonly occurring in cases of delusional misidentifica- tions (including Cotard’s syndrome).84


PROGNOSIS AND TREATMENT Complete recovery may occur as spontaneously and as


suddenly as its onset, even in the most severe cases.12 Enoch and Trethowan12 link the prognosis to the underlying disorder.


If the nihilistic delusions are related to an acute psycho-organic syndrome, the prognosis is good and the condition tends to resolve. If, however, it is associated with a depressive illness, it may well persist even when the other symptoms of the depressive illness have cleared. Under this circumstance, and where the condition becomes chronic, the delusional state of negation usually waxes and wanes in intensity, depending on the periodic fluctua- tions of the depressive disorder. When the phenomenology is part of a schizophrenic illness, it usually improves when the other symptoms respond to therapy, but it can also persist for years as part of a chronic schizo- phrenic condition.12


In general, no further statements can be made about prognosis from the available literature. In most publications, prognosis is not discussed. It seems prognosis can widely vary from spontaneous recovery to a very severe chronic condition. An important exclusion for this is when Cotard’s syndrome is diagnosed under the age of 25 years. In these cases, there seems to be an association with bipolar disorder.19


Diagnostic work-up of the underlying disorders should therefore be a guide for treatment. Several reports are published about successful treatments. Pharmacological monotherapy such as amitriptyline,27 aripiprazole,32 dulox- etine,91 fluoxetine,17 olanzapine,21,92 sulpiride,55 and lithium26,27 has been reported as effective. However, usually combination strategies are used (clomipramine/ amitriptyline,12 pimozide/amitriptyline,24 haloperidol/clomi- pramine,22 cyamemazine/paroxetine,29 risperidone/fluoxe- tine,36 haloperidol/mirtazapine,44 risperidone/sertraline,46 risperidone citalopram,10 amisulpiride/clozapine,93 cloza-


M&B 2011; 2:(1). July 2011 70


pine/fluvoxamine/imipramine,33 paroxetine/pramipexole,43 quetiapine/venlafacine,94 and olanzapine/escitalopram/lora- zepam.95 Adding bromocriptine to clomipramine and lithium had a beneficial effect in a patient with bipolar disorder type I.47


is electroconvulsive therapy (ECT).1116,2325,29,31,34,3742,45, 48,50,58,59,93,9698 Based on the classification of Berrios and


The most reported treatment strategy for Cotard’s syndrome


Luque,8 a suggestion was made that ECT is indicated in patients with Cotard’s syndrome and psychotic depression, while antipsychotics exert better effects in Cotard’s syndrome type I.93 In one patient, spontaneous recovery after two grand mal seizures was reported illustrating the usefulness of seizure activity in the treatment of Cotard’s syndrome.99 Treatment should initially follow current treatment guidelines of the underlying conditions, since no randomized studies are performed on this Cotard’s syndrome. In depressive disorder with psychotic features, ECT (often in combination with farmacotherapy) seems to be the most supported strategy.


Enoch and Trethowan rightly argue that apart from these treatments, special measures can be needed. The severe distress may lead to important suicide risk, especially in patients suffering from major depressive disorder. This may be in contrast with the delusion of being already dead. During recovery this risk may even become more pronounced when the patient becomes more active.12 They also mention the importance of therapeutic support for these patients. They indeed suffer from severe fright and despair, making contact with caring professionals essential.12


DISCUSSION Despite that Cotard’s syndrome was first described more


than a century ago, literature on this topic remains restricted to case reports. Although the syndrome is rare, more larger scale research is needed to further clarify the pathophysiolo- gic underpinnings of the disease and its relation to other delusions of misidentification such as Capgras syndrome. Promising hypotheses have been formulated but evidence- based support is lacking. To elucidate uncertainties regarding epidemiology, course, associated diseases, treatment options, and prognosis, a careful registration of all cases could be of great value. In this regard, recognition of this condition is essential. The restriction of publications to case reports is a potential pitfall. Sometimes general conclusions on course, pathophysiology, or treatment are made, based on one or a few cases. On this topic, the literature has to be read carefully.


The syndrome as such is not catalogued in our current classification system. It has to be diagnosed as part of an underlying disorder. Also treatment is guided by this diagnosis. Although Cotard’s syndrome is more like a symptom of its underlying condition, in our opinion recognition of this phenomenological entity remains impor- tant. Its very specific presentation, in spite of the extensive list of etiologies indicating a shared pathological pathway, is intriguing. In the management of these patients, a better


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