Effects of dextromethorphan on electroconvulsive therapy.

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revealed (block 1 comprised rs917251 and rs3763463; block 2
consisted of rs10235968 and rs6967368). However, we did
not detect significant associations between the haplotypes
in block 1 or 2 and schizophrenia. The result indicates
that NRCAM do not contribute to a genetic susceptibility to
schizophrenia.
ACKNOWLEDGEMENTS
This study was supported by grants from the SRC program of
KOSEF (R11-2005-014), Republic of Korea.
REFERENCES
1Dirks P, Thomas U, Montag D. The cytoplasmic domain of
nrCAM binds to PDZ domains of synapse-associated proteins
sap90/psd95 and sap97. Eur. J. Neurosci. 2006; 24: 25–31.
2Hutcheson HB, Olson LM, Bradford Y et al. Examination of
NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate
genes. BMC Med. Genet. 2004; 5: 12.
3Sakurai T, Ramoz N, Reichert JG et al. Association analysis of the
NrCAM gene in autism and in subsets of families with severe
obsessive-compulsive or self-stimulatory behaviors. Psychiatr.
Genet. 2006; 16: 251–257.
4Ishiguro H, Liu QR, Gong JP et al. NrCAM in addiction vulner-
ability: Positional cloning, drug-regulation, haplotype-specific
expression, and altered drug reward in knockout mice. Neurop-
sychopharmacology 2006; 31: 572–584.
Hak-Jae Kim, PhD1
Hyoun Geun Kim, MS2
Min-Ho Kim, MS2
Kyu Bum Kwack, PhD2
Jin Kyung Park, MD, PhD3
Tae Kim, MD3
Jong Woo Kim, MD, PhD3
Ju Yeon Ban, PhD1
Joo-Ho Chung, MD, PhD1
1Kohwang Medical Research Institute, School of Medicine, Kyung
Hee University,3Department of Neuropsychiatry, School of
Medicine, Kyung Hee University, Seoul,2Medical Genomics Lab.
School of Biological Sciences, Pochon CHA University,
Sungnam-si, Gyeonggi-Do, Korea
Email: jhchung@khu.ac.kr
Received 28 March 2008; revised 7 August 2008; accepted
12 August 2008.
Effects of dextromethorphan on
electroconvulsive therapy
doi:10.1111/j.1440-1819.2008.01895.x
D
N-methyl-D-aspartate (NMDA) antagonist. Animal studies
have shown evidence that dextromethorphan can protect
EXTROMETHORPHAN is prescribed as an antitussive
agent due to its cough-suppressant activity. It is also an
against NMDA-induced convulsions.1However, there are no
published reports regarding the effects of dextromethorphan
on electroconvulsive therapy (ECT) in humans. We report a
case of a chronic schizophrenic who took dextromethorphan
because of the symptom of coughing during an ECT course and
this agent remarkably influenced the therapeutic quality of
the ECT.
A 40-year-old male schizophrenic has been hospitalized in
our chronic ward for more than 15 years. He has been con-
tinuously treated with clozapine 400 mg/day. However, addi-
tional ECTs are required each year when his psychosis gets
exacerbated. On 19 April 2004 the patient was admitted to the
acute ward because of acute exacerbation of psychotic symp-
toms. Bilateral ECT three times a week were arranged. The ECT
procedure was performed based on the American Psychiatric
Association’s ECT Task Force.2
On 21 April 2004 we administered his first ECT. The ECT
device was Thymatron System IV (Somatics, Inc., IL). We used
maximum sustained power (MSP) and postictal suppression
index (PSI) as the ECT therapeutic markers. MSP is used to
measure the highest average ictal amplitude, and the PSI
reports the decrease percentage in ictal EEG amplitude imme-
diately following seizure termination.3These two indexes
have been reported to be related to ECT clinical efficacy.3,4The
patient’s concomitant medication was clozapine 400 mg per
day. His initial four ECTs were performed smoothly. The MSPs
of these four ECTs were all above 100 000 uV2(range: 102 600
to 126 430 uV2) and the PSIs of these four ECTs ranged from
95.7% to 99.4 %. However, the patient was given dex-
tromethorphan (30 mg) four times on 29 April 2004 because
of the symptom of coughing. On the following day, we found
that his fifth ECT MSP dropped down to 76598 uV2, his PSI
was reduced to 95.2 %, and his seizure tonic and clonic motor
responses were decreased. Therefore, we discontinued his dex-
tromethorphan immediately. Interestingly, his sixth ECT MSP
returned to 112 510 uV2, his sixth PSI was normalized up to
99.2%, and his seizure motor intensity was restored. After we
stopped dextromethorphan, the patient received four more
ECTs. Each ECT response was adequate. The MSPs of the latter
four ECTs were all above 100 000 uV2(range: 100 620 to
123 480 uV2), and the latter four PSIs ranged from 95.5% to
99.8%. His psychosis improved with the ECT.
Our case suggests that dextromethorphan can influence the
therapeutic quality of ECT, as indicated by the indexes of MSP
and PSI, in schizophrenics. This is consistent with the findings
from animal studies that dextromethorphan possesses an anti-
convulsant effect.1The mechanism underlying the anticonvul-
sant effect of dextromethorphan has been suggested to be
its antagonizing effect on glutamate,1which is an excitatory
amino acid neurotransmitter and can lead to seizures. If we
had not discontinued the patient’s dextromethorphan, he
might not have had the following adequate therapeutic sei-
zures. Physicians should be aware that dextromethorphan is a
potential anticonvulsant and it should not be used during the
course of ECT.
ACKNOWLEDGEMENT
The report was presented at the XIII World Congress of
Psychiatry, Cairo, Egypt, 10–15 September 2005.
124
Letters to the Editor
Psychiatry and Clinical Neurosciences 2009; 63: 122–128
© 2009 The Authors
Journal compilation © 2009 Japanese Society of Psychiatry and Neurology

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REFERENCES
1Kim HC, Ko KH, Kim WK et al. Effects of dextromethorphan on
the seizures induced by kainate and the calcium channel agonist
BAY k-8644: Comparison with the effects of dextrorphan. Behav.
Brain Res. 2001; 120: 169–175.
2Weiner RD, Coffey CE, Fochtman LJ, Greenberg RM, Isenberg KE,
Kellner CM. The Practice of Electroconvulsive Therapy. American
Psychiatric Press, Washington, DC, 2001.
3Abrams R, Swartz CM. ECT Instruction Manual for the Thymatron
System IV. 13th edn. Somatics Inc., Lake Bluff, 2006.
4Perera TD, Luber B, Nobler MS, Prudic J, Anderson C, Sackeim
HA. Seizure expression during electroconvulsive therapy: Rela-
tionships with clinical outcome and cognitive side effects. Neu-
ropsychopharmacology 2004; 29: 813–825.
Wen-Kuei Lee, MD1
I-Shin Shiah, MD, PhD2,3
Chun-Wei Chang, MD1
Tzu-Yun Wang, MD2
Shih-Mao Lo, MD1
Lih-Jong Shen, MD, MPH1
1Department of Psychiatry, Armed Forces Beitou Hospital,
2Department of Psychiatry, Tri-Service General Hospital and
3National Defense Medical Center, Taipei, Taiwan
Email: ishiah@ms45.hinet.net
Received 20 June 2008; revised 2 September 2008; accepted
9 September 2008.
Case report: Effective Treatment of
Cotard’s Syndrome: Quetiapine in
Combination with Venlafaxine
doi:10.1111/j.1440-1819.2008.01891.x
CASE REPORT
T
bipolar disorder,3and schizophrenia.4,5We report a case of a
68-year-old woman with Cotard’s syndrome successfully
treated with quetiapine and venlafaxine. The woman for-
merly worked in a public institution as a clerk. In 1999, she
experienced depressed mood, poor concentration, auditory
hallucinations (transient voices with insulting contents) and
inability to do her job properly. She was admitted to a
general hospital for 1 month. The next three years were
characterized by severalmajor
major depression with psychotic features was impressed
due to major depressive episodes and coexisting auditory
hallucinations.
In June 2004 she was admitted to our acute psychiatric ward
due to depressed mood, social withdrawal, poor appetite,
guilty feelings and delusions of reference. Initially, sulpiride
(600 mg/day) and fluoxetine (40 mg/day) were prescribed. Six
weeks later, her depressive symptoms and psychotic symptoms
still persisted. Risperidone (4 mg/day) was later substituted for
HE PRIMARY SYMPTOM of Cotard’s syndrome is a nihil-
istic delusion. It has been associated with depression,1,2
depressiveepisodes.A
sulpiride. About four weeks later, her psychotic symptoms
improved. She was transferred to a rehabilitation ward and
held a part-time job.
In October 2006, she developed insomnia, guilty feelings,
auditory hallucinations and a suicide attempt by tongue
biting. She was transferred to an acute ward in December
2006. Fluoxetine (40 mg/day) and haloperidol (15 mg/day)
were prescribed for treating the depressive symptoms and
auditory hallucinations. Four weeks later, the depressive and
psychotic symptoms did not improve. Moreover, she revealed
nihilistic delusions (she stated that her buttocks and nose
had disappeared) and persistent memory impairment. She
scored 16 out 30 on the Mini-Mental State Examination
(MMSE). Laboratory test results, including serum electrolytes,
chemistry profile, liver and renal function, thyroid function
tests, rapid plasma reagin screening test, serum B12, folate
levels, HIV screening, chest radiograph and electrocardiogram
were within normal limits. Computed tomography of the
brain (to exclude an organic cause) showed no essential
abnormality. Fluoxetine and haloperidol were discontinued
due to unsatisfactory effects. Venlafaxine (150 mg/day) and
quetiapine (400 mg/day) were prescribed for four weeks.
Initially, the medications did not relieve her depression
and delusion. For the purpose of treating depression
and psychotic symptoms simultaneously, the venlafaxine and
quetiapine dosages were increased to 225 mg/day and
600 mg/day, respectively. Two weeks later, the depressive
symptomsand nihilisticdelusions
March 2007, she was transferred to a rehabilitation ward.
Following this her cognitive function improved markedly
and her MMSE score increased to 26. Her mood has been
euthymic and she has been free from positive symptoms of
psychosis.
This is the first report demonstrating a combination of
quetiapine and venlafaxine in the treatment of Cotard’s Syn-
drome. In this case, the subject displayed miscellaneous
psychiatric symptoms in addition to the typical nihilistic
delusions. The diagnoses of schizophrenia and schizoaffective
disorder were not justified because the hallucinations and
delusions occurred only during major depressive episodes.
She experienced memory impairment but the results of labo-
ratory tests were within normal limits. The memory impair-
ment subsided when the patient recovered from depression.
The memory impairment may have been due to the depres-
sion condition (pseudodementia). In previous reports,4,6
patients with Cotard’s syndrome were treated with antipsy-
chotics and there was only a partial response. Our patient
had a good response while using quetiapine and venlafaxine.
Her psychotic and depressive symptoms almost completely
disappeared. Clinical studies revealed that quetiapine was
effective asaugmentationof
take inhibitor/venlafaxine therapy in patients with major
depression.7Some researchers proposed a possible mecha-
nism for quetiapine in treating depression when com-
bined with venlafaxine.8The effects may be due to the
synergetic action of combined treatment to increase neuro-
genesis and brain-derived neurotrophic factors expression in
the hippocampus, which is reduced in volume among
patients with depression or schizophrenia. It is necessary to
further study the treatment and underlying mechanisms of
this disorder.
were alleviated.In
selective serotoninreup-
Psychiatry and Clinical Neurosciences 2009; 63: 122–128 Letters to the Editor
125
© 2009 The Authors
Journal compilation © 2009 Japanese Society of Psychiatry and Neurology