Effects of desmopressin (DDAVP) on memory impairment following ...

Blackwell Munksgaard 2004: 16: 130–137 Copyright # Blackwell Munksgaard 2004
Printed in Denmark. All rights reserved ACTA NEUROPSYCHIATRICA
ORIGINAL ARTICLE
<strong>Effects</strong> <strong>of</strong> <strong>desmopressin</strong> (<strong>DDAVP</strong>) on memory
impairment following electroconvulsive
therapy (ECT)
Abdollahian E, Sargolzaee MR, Hajzade M, Mohebbi MD,
Javanbakht A. <strong>Effects</strong> <strong>of</strong> <strong>desmopressin</strong> (<strong>DDAVP</strong>) on memory
impairment following electroconvulsive therapy (ECT).
Acta Neuropsychiatrica 2004: 16:130–137. # Blackwell Munksgaard
2004
Background: Memory impairment is a common adverse effect <strong>of</strong>
electroconvulsive therapy (ECT). Studies on animals and humans
suggest that vasopressin improves the cognitive function, and positive
effects <strong>of</strong> <strong>desmopressin</strong> on memory and learning have been reported.
This research was performed for evaluation <strong>of</strong> the effects <strong>of</strong> <strong>desmopressin</strong>
in the prevention <strong>of</strong> memory impairment following ECT.
Methods: This randomized, double-blind controlled clinical trial with
placeboadministrationwasperformedon50patientswithpsychiatric
disorders who were candidates for ECT. Subjects in the case group
received 60 mm <strong>of</strong> intranasal <strong>desmopressin</strong> daily (in three doses <strong>of</strong>
20 mm). For the control group 0.9% saline solution was administered in
the same way. Memory function was evaluated using Wechsler’s
Memory Scale three times a week (the first time before the start <strong>of</strong>
ECTandthesecondandthirdtimesafterthethirdandsixthsessions,
respectively). Results were analyzed by t-test and Paired t-test.
Results: The mean age <strong>of</strong> patients was 29 years (range 20–40). During
the course <strong>of</strong> ECT, patients in the control group demonstrated a
meaningful decrease in memory scores (from a base score <strong>of</strong>
80.15–75.45 in the second test and 72.60 in the third test). Despite this,
a meaningful increase in memory scores was observed during the
treatment with <strong>desmopressin</strong> in the case group (from a base score <strong>of</strong>
73.27–75.70 and 79.13 in the second and the third tests, respectively).
There was a meaningful difference between the two groups
(P < 0.0001).
Conclusion: This study confirms the protective effect <strong>of</strong> <strong>desmopressin</strong>
against memory impairment. The results confirm that memory
impairment is a common side-effect <strong>of</strong> ECT and suggest that
<strong>desmopressin</strong> may prevent ECT-induced memory impairment by
its effects on memory and the learning process.
Introduction
Electroconvulsive therapy (ECT) is a common and
effective psychiatric treatment for disorders such
asmajordepressivedisorder(MDD),mania,and
catatonia. By controlled induction <strong>of</strong> seizure, ECT
prepares the therapeutic effects by changes in brain
neurons, neurotransmitters, and receptors (1).
130
Ebrahim Abdollahian 1 , Mohammad R.
Sargolzaee 1 , Moosareza Hajzade 2 ,
Mohammad D. Mohebbi 1 , Arash
Javanbakht 3
1 Ibn E Sina Hospital <strong>of</strong> Psychiatry, 2 Physiology Department, Qaem
Hospital, and 3 Department <strong>of</strong> Vice President for Research,
Mashhad University <strong>of</strong> Medical Sciences, Mashhad, Iran
Key words: <strong>desmopressin</strong>; ECT; memory
Correspondence: Arash Javanbakht MD, 180 Banafsheh St,
Sajjad Blvd, Mashhad, Iran. PC: 91876. Tel: þ98 511 7610403;
Fax: þ98 511 8430249. E-mail: Javanbakht@mums.ac.ir
Although the exact mechanism <strong>of</strong> ECT effects
is still unknown, some findings have shown that
the changes following ECT are somewhat similar
to those that occur during treatment with antidepressive
agents (1). ECT may result in changes
in brain endogenous opioids. These factors have
anticonvulsive effects and may be inhibited by
# Blackwell Munksgaard, Acta Neuropsychiatrica, 16, 130–137

naloxone. Findings have also shown that memory
impairment following ECT is related to the high
level <strong>of</strong> some modulator molecules such as betaendorphins
and certain other endogenous opioids.
It is believed that ECT and endogenous endorphins
exert their effects through the regulatory
memory systems (2). In addition to its effects on
cerebral neurotransmitters or brain metabolism,
ECT may also bring about changes in the endocrine
system. On the other hand, the neuroendocrine
response to ECT includes increased levels
<strong>of</strong> stress hormones like adrenocorticotropic
hormone (ACTH), cortisol, arginin, vasopressin,
prolactin, and growth hormone. Immediately
following ECT, epinephrine and norepinephrine
levels are elevated, but the epinephrine level falls
to normal more quickly. Changes in the autonomous
system following ECT are mainly due to
these changes in the levels <strong>of</strong> catecholamines (3).
Some studies demonstrate an increased level <strong>of</strong>
plasma vasopressin in both the short and the
long term, which continues for 8 days after the
ECT session. This increase is not significant and
its relation to memory loss is unknown (4). A
relationship between the increase in vasopressin
level and the amount <strong>of</strong> electricity received has
not yet been found, but it is clear that there is no
relationship with electrode positioning method
(unilateral or bilateral) (5). Several previous studies
support the effect <strong>of</strong> vasopressin on memory
and learning enhancement. The effect may be
through the V1 subcategories <strong>of</strong> receptors but
the exact vasopressin central effect on memory
is not known (6). Intraseptal administration <strong>of</strong>
the V1 receptor subgroup antagonist (AAVP)
impairs social memory. Endogenous vasopressin
may affect V1 receptor subgroups in this part <strong>of</strong>
the brain. Previous studies do not confirm a
hormonal basis for vasopressin effects on memory.
But recent research has shown that vasopressin
increases intracellular NO (nitric oxide) production.
Despite this, NO synthesis inhibition by
angiotensin II decreases vasodilation following
vasopressin administration and inhibits memory
and learning enhancement, although other studies
do not confirm the correlation between vasopressin
effects and nitric oxide (NO) concentration in
the brain (7). According to other findings,
NMDA non-competitive antagonists and competitive
glycin antagonists may decrease vasopressin
effects on memory. This may help to
conclude that an NMDA receptor may be necessary
for the vasopressin to act on memory (8).
Neuropeptides do not only affect attention, concentration,
and drive, but they are also effective
in situations such as fear, anxiety, and memory
<strong>Effects</strong> <strong>of</strong> <strong>DDAVP</strong> on memory post-ECT
and learning processes. Neuropeptides such as
corticotropin-releasing factor (CRF) and AVP
modulate the secretion <strong>of</strong> stress hormones such
as epinephrine. CRF and AVP may be found in
paraventricular nuclei cells. Their output enters
the midbrain and modulates the autonomous
system. AVP and CRF both affect behavior,
learning, memory, and stress responses (catecholamine
and ACTH release) in the same way.
These neuropeptides may act synergistically or
separately in the process <strong>of</strong> learning and organism
compatibility with the environment (9).
Finally, the facilitating effect <strong>of</strong> vasopressin on
memory may be due to some unknown neuromediators.
The effects <strong>of</strong> endogenous neuropeptides
such as vasopressin, ACTH, and opioids on memory
and cognition are demonstrated by the use <strong>of</strong>
new methods <strong>of</strong> molecular biology such as gene
cloning and electrophysiology such as the patch
clamp. There are hopes for future drugs containing
these molecules in the treatment <strong>of</strong> dementia (10).
In line with many previous studies on humans or
animals supporting the vasopressin-positive effects
on memory processes, this research was performed
to evaluate the efficacy <strong>of</strong> this molecule as a
protective agent or probable treatment for cognitive
side-effects and memory impairment in patients
receiving ECT.
In this study we attempted to evaluate the effect
<strong>of</strong> vasopressin (<strong>DDAVP</strong>) on memory impairment
following ECT.
Methods
This was a double-blind clinical trial in which
memory impairment following ECT and the effect
<strong>of</strong> <strong>desmopressin</strong> on this impairment were analyzed.
In addition, we tried to investigate interfering
factors such as age, number <strong>of</strong> ECT sessions,
and ECT type (unilateral or bilateral).
During the memory scaling tests, interviewers
did not know if patients belonged to the case or
control group. Moreover, nurses did not know
whether they were giving patients drug or placebo.
This study covered 50 patients who where candidates
for ECT because <strong>of</strong> psychiatric disorders;
<strong>of</strong> these 50, 30 (60%) were chosen at random as
cases and 20 (40%) as controls. Among the
patients, 28 were male (56%) and 22 (44%) were
female. The case group included 17 men (57% <strong>of</strong>
the group and 34% <strong>of</strong> all patients) and 13 women
(43% <strong>of</strong> the group and 26% <strong>of</strong> all patients). In the
control group comprised 11 men (55% <strong>of</strong> the
group and 22% <strong>of</strong> all patients) and nine women
(45% <strong>of</strong> the group and 18% <strong>of</strong> all patients).
131

Abdollahian et al.
We tried to choose people <strong>of</strong> the same age, ECT
type, and number <strong>of</strong> ECT sessions to limit the
interfering factors. All subjects were between the
ages <strong>of</strong> 20 and 40 years (mean ¼ 29) and the type
<strong>of</strong> ECT was unilateral dominant for all and
covered six sessions.
For evaluation <strong>of</strong> memory impairment, we chose
Wechsler’s Memory Scale (WMS), which includes
subscales for all aspects <strong>of</strong> immediate, short, long
and visual memory. The most important subscales
include mental control, logical memory, memory
span for digits forwards and backwards, visual
reproduction, knowing personal and current information,
time and place orientation, and associate
learning. This scale gives the corrected score for
patients’ specific age as well as the gross score.
Evaluation using WMS was performed three
times for all patients. The first time was before
receiving ECT as a base, and the second and
third times were after the third and sixth sessions,
respectively, <strong>of</strong> ECT (WMS was evaluated after
patients left the ECT room and their consciousness
was stabilised, a mean time <strong>of</strong> around 2 h post-ECT).
Desmopressin was administered to 30 people in
the case group in the form <strong>of</strong> an intranasal spray;
they were given 60 mg daily in three doses (20 mg
each). Administration <strong>of</strong> the drug was started the
day before the beginning <strong>of</strong> ECT courses and was
continued for 2 weeks (a total <strong>of</strong> 15 days). In the
same way, normal saline solution 0.9% in the form
<strong>of</strong> spray was administered to the control group for
the same period <strong>of</strong> time as a placebo. Both patients
and the nurses who gave the drugs to them were
blind as to the content <strong>of</strong> the sprays.
For those in the case group, electrolytes were
assessed before and after the courses to evaluate
possible adverse electrolytic effects.
Results <strong>of</strong> WMS assessments <strong>of</strong> the two groups
were analyzed both separately by paired t-test and
comparatively by t-test. The primary related variablesinbothgroupswerethechangesinWMS
subscores and gross memory score at the second
and third evaluations. Correlation between <strong>desmopressin</strong>
administration and the changes in scores in
the case group, and also the difference between the
changes in both groups were analyzed. The other
important variable was the effect <strong>of</strong> gender in both
groups. The accepted reliability for the changes in
memory subscores was 95% (P < 0.05).
This study had certain limitations, as follows:
* At first, the study was scheduled to be performed
on 60 patients, but because <strong>of</strong> a lack
<strong>of</strong> ECT candidates, it was decreased to 50.
* The basic psychiatric disorder was not considered,
which may have interfered with the results.
132
* According to different levels <strong>of</strong> convulsion
threshold for different people, the amount <strong>of</strong>
electricity administered was not the same for
all patients, which may have interfered with the
results.
Results
The main results <strong>of</strong> the memory assessment
following ECT in both groups are described below.
Case group
Statistical comparison <strong>of</strong> the WMS subscores for
knowing personal and current information by
paired t-test showed no significant difference
between evaluation times 1 and 2, 1 and 3, and 2
and 3 (Table 1).
For time and place orientation there was no
significant difference between evaluation times.
The results <strong>of</strong> comparison <strong>of</strong> evaluation times 1
and 2, 1 and 3, and 2 and 3 for mental control
revealed no significant difference.
There was also significant difference between
evaluation times 1 and 3, and 2 and 3 for logical
memory. For memory span for digits forwards
and backwards there was no significant difference.
Visual reproduction scores, however, were significantly
different between the three times.
The result <strong>of</strong> comparison <strong>of</strong> evaluation times 1
and 2, 1 and 3, and 2 and 3 for associate learning
was significant for times 1 and 3.
A comparison <strong>of</strong> mean WMS gross scales
demonstrated significant statistical differences
between the three scores. A comparison <strong>of</strong> WMS
memory quality also demonstrated significant statistical
difference between the three scores.
Control group
Comparison <strong>of</strong> the subscores for knowing personal
and current information by paired t-test showed
no significant difference between the three evaluation
times (Table 1).
Results <strong>of</strong> the comparison <strong>of</strong> time and place
orientation scores showed significant difference
for evaluation times 1 and 3. Comparison <strong>of</strong>
evaluation times 1 and 2, 1 and 3, and 2 and 3
for mental control did not demonstrate any
significant difference.
Comparison <strong>of</strong> logical memory scores showed
significant statistical difference between the three
evaluation times and a decrease in logical memory
in the control group.
Comparison <strong>of</strong> memory span for digits forwards
and backwards demonstrated significant difference

Table 1. Results <strong>of</strong> the memory subscores in the case and control groups
between the three scores and showed a decrease
in the score in the control group.
For visual reproduction there was significant
statistical difference between the three evaluation
times, and a decrease in the ability <strong>of</strong> visual reproduction
through the ECT period was demonstrated.
Comparison <strong>of</strong> associate learning scores revealed
significant statistical difference and demonstrated
a decrease in associate learning through the ECT
period.
Results <strong>of</strong> comparison <strong>of</strong> the mean WMS gross
scales showed statistically significant differences
between the three scores (P ¼ 0.0001) and demonstrated
a decrease in WMS gross scale in the
control group during the course <strong>of</strong> ECT.
WMS memory quality mean scores for the first,
second, and third evaluation times were significantly
different, demonstrating a decrease in the
mean memory quality in the control group during
the course <strong>of</strong> ECT.
Results <strong>of</strong> the comparison <strong>of</strong> changes in
subscores between the case and control groups
The main results <strong>of</strong> this research with regard to the
difference between changes in memory subscores
were as follows.
Knowing personal and current information. Results
<strong>of</strong> a comparison <strong>of</strong> changes in scores in the two
groups for the different evaluation times were as
follows:
First time Second time Third time Paired t-test
Mean SD Mean SD Mean SD Times 1 and 2 Times 1 and 3 Times 2 and 3
Case group
Personal and current information memory 4.10 1.71 4.00 1.64 4.13 1.68 0.476 0.845 0.293
Time and place orientation 3.63 1.40 3.67 1.47 3.80 1.40 0.831 0.169 0.293
Mental control 4.77 3.05 4.97 2.86 4.93 2.77 0.363 0.517 0.801
Logical memory 5.48 3.43 5.90 3.79 6.45 3.63 0.138 0.002* 0.018*
Span for digits forwards and backwards 6.83 2.39 7.00 2.15 7.13 2.27 0.465 0.071 0.403
Visual memory 6.30 3.72 7.53 3.88 9.17 3.96 0.001* 0.001* 0.001*
Associate learning 9.10 5.18 9.68 4.70 10.15 4.99 0.266 0.019* 0.062
Gross WMS 40.38 16.24 42.78 16.31 45.40 16.77 0.003 0.0001* 0.0001*
Memory quality 73.27 17.62 75.70 18.55 79.13 19.32 0.005 0.0001* 0.0001*
Control group
Personal and current information memory 4.05 1.15 4.15 1.09 4.15 1.04 0.330 0.163 0.999
Time and place orientation 3.85 1.14 3.70 1.17 3.55 1.19 0.186 0.010* 0.267
Mental control 5.65 2.40 4.80 2.40 4.55 2.48 0.0001* 0.0001* 0.056
Logical memory 8.20 3.99 7.70 3.99 7.35 3.86 0.004* 0.0001* 0.015*
Span for digits forwards and backwards 7.60 2.86 7.05 2.86 6.60 3.12 0.001* 0.0001* 0.009*
Visual memory 7.90 2.80 6.80 2.80 5.90 2.59 0.0001* 0.0001* 0.0001*
Associate learning 10.15 3.79 9.15 3.79 8.60 3.68 0.0001* 0.0001* 0.004*
Gross WMS 47.50 14.84 43.55 14.84 40.80 14.89 0.0001* 0.0001* 0.0001*
Memory quality 80.15 16.32 75.45 16.32 72.60 15.40 0.0005* 0.0001* 0.0001*
WMS, Wechsler’s Memory Scale.
*Statistically significant (P < 0.05).
<strong>Effects</strong> <strong>of</strong> <strong>DDAVP</strong> on memory post-ECT
* For times 1 and 2 statistical comparison
between the two groups by t-test did not
show any statistically significant difference
(P ¼ 0.112).
* For times 1 and 3, the comparison <strong>of</strong> the two
groups revealed a statistically significant
difference (P < 0.0001).
* For times 2 and 3, the difference was statistically
significant (Table 2).
Time and place orientation. Results <strong>of</strong> a comparison
<strong>of</strong> the changes in time and place orientation
subscores in the two groups for the different
evaluation times were as follows:
* For times 1 and 2, statistical comparison
between the two groups by t-test showed
statistically significant difference (P < 0.0001),
with a decrease in the mean scores in the
control group compared with the case group
after ECT.
* For times 1 and 3, there was a statistically
significant difference.
* For times 2 and 3, the result was statistically
significant (Table 2).
Mental control. A comparison <strong>of</strong> the changes
in mental control scores in the two groups for
the different evaluation times revealed the
following:
133

Abdollahian et al.
Table 2. Comparison <strong>of</strong> the changes in subscores in the case and control groups for the different
subscales
Times 1 and 2 Times 1 and 3 Times 2 and 3
Group Mean SD Mean SD Mean SD
Knowing personal and current information
Case (30 people) 1.44 4.09 0.73 1.75 3.25 2.44
Control (20 people) 1.47 5.22 2.47 9.57 0.0 4.59
Paired t-test P ¼ 0.112 P < 0.0001 P < 0.0001
Time and place orientation
Case (30 people) 1.1 5.0 4.68 3.78 3.54 4.76
Control (20 people) 3.90 2.63 7.79 4.39 4.05 1.71
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
Mental control
Case (30 people) 4.19 6.23 3.35 9.18 0.8 3.15
Control (20 people) 15.04 8.41 19.47 12.09 5.21 3.33
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
Logical memory
Case (30 people) 7.66 10.5 17.7 5.83 9.32 4.22
Control (20 people) 6.10 2.44 10.37 5.62 4.55 3.26
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
Numbers repeats memory
Case (30 people) 2.49 10.04 4.39 5.02 1.68 5.58
Control (20 people) 7.24 6.84 13.16 1.63 6.38 9.09
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
Visual memory
Case (30 people) 19.52 4.3 45.56 6.45 21.78 2.06
Control (20 people) 13.92 3.45 25.32 10.69 13.24 7.5
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
Associate learning
Case (30 people) 6.37 9.27 11.54 3.67 4.86 6.17
Control (20 people) 9.85 9.76 15.27 12.38 6.1 2.9
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
* For times 1 and 2 the comparison showed significant
difference, with a decrease in the mean
scores <strong>of</strong> mental control in the control group
compared with the case group after ECT.
* For times 1 and 3, there was a significant
difference.
* For times 2 and 3, there was a significant
decrease in the mean score for the control
group (Table 2).
Logical memory. Results <strong>of</strong> a comparison <strong>of</strong> the
changes in logical memory scores in the two
groups for the different evaluation times were as
follows:
* For times 1 and 2, the comparison between the
two groups showed significant difference, with
a decrease in the mean scores <strong>of</strong> logical memory
in the control group compared with the
case group after ECT.
* For times 1 and 3, we found a significant statistical
difference.
* For times 2 and 3, the comparison showed a
significant decease in the mean score <strong>of</strong> the
control group (P < 0.0001) (Table 2).
134
Memory span for digits forwards and backwards.
Comparison <strong>of</strong> the changes in these scores in the
two groups for the different evaluation times
revealed the following:
* For times 1 and 2 statistical comparison
between these two groups by t-test showed a
statistically significant difference (P < 0.0001),
with a decrease <strong>of</strong> the mean scores in the
control group compared with the case group
after ECT.
* For times 1 and 3, the comparison <strong>of</strong> the two
groups revealed a significant decrease <strong>of</strong> the
scores in the control group (P < 0.0001).
* For times 2 and 3, the comparison showed a
significant decease in the mean score for the
control group (P < 0.0001) (Table 2).
Visual reproduction. Results <strong>of</strong> the comparison <strong>of</strong>
the changes in these scores in the two groups for
the different evaluation times were as follows:
* For times 1 and 2, statistical comparison
between these two groups by t-test showed a
significant statistical difference (P < 0.0001)
with a decrease in the mean scores <strong>of</strong> visual
reproduction in the control group compared
with the case group after ECT.
* For times 1 and 3, there was a significant
statistical difference.
* For times 2 and 3, the comparison showed a
significant decease in the mean score for the
control group (P < 0.0001) (Table 2).
Associate learning. Results <strong>of</strong> a comparison <strong>of</strong> the
changes in these scores in the two groups for the
different evaluation times were as follows:
* For times 1 and 2 statistical comparison showed
a significant difference, with a decrease in the
mean scores <strong>of</strong> associate learning in the control
group compared with the case group after
ECT.
* For times 1 and 3, there was a significant
statistical difference.
* For times 2 and 3, the comparison showed a
significant decease in the mean score <strong>of</strong> the
control group (Table 2).
Gross WMS. Comparison <strong>of</strong> the changes in gross
Wechsler’s scores in the two groups for the different
evaluation times revealed the following:
* For times 1 and 2 statistical comparison
between these two groups by t-test showed a
significant statistical difference (P < 0.0001)

with a decrease in the gross WMS in the control
group after ECT.
* For times 1 and 3, there was a significant statistical
difference, with a decrease in the control
group and an increase in the case group.
* For times 2 and 3, the comparison showed a
significant decease in the mean score <strong>of</strong> the
control group and an increase in the case
group (P < 0.0001) (Table 3).
Memory quality. Results <strong>of</strong> the comparison <strong>of</strong>
changes in Wechsler’s memory quality scores in
the two groups for the different evaluation times
were as follows:
* For times 1 and 2, comparison by t-test showed
a statistically significant difference (P < 0.0001),
with a decrease in the mean memory quality
score in the control group compared with the
case group after ECT.
* For times 1 and 3, comparison between the
two groups revealed a significant statistical
difference (P < 0.0001).
* For times 2 and 3, there was significant decease
in the mean score <strong>of</strong> the control group and an
increase in <strong>of</strong> the case group (Table 4)
Comparison <strong>of</strong> the memory quality changes
between the two sexes
Case group. Results <strong>of</strong> the comparison <strong>of</strong> the
changes in Wechsler’s memory quality between
men and women for the different evaluation
times were as follows:
* For times 1 and 2 there was no significant
difference.
* For times 1 and 3, comparison between the
two groups showed no significant statistical
difference (P ¼ 0.114).
* For times 2 and 3, comparison between the
groups showed no significant statistical difference
(P ¼ 0.225) (Table 5).
Control group. Results <strong>of</strong> the comparison <strong>of</strong>
changes in Wechsler’s memory quality between
Table 3. Comparison <strong>of</strong> the changes in gross Wechsler’s Memory Scale scores in the case and
control groups
Times 1 and 2 Times 1 and 3 Times 2 and 3
Group Mean SD Mean SD Mean SD
Case (30 people) 5.49 4.62 12.43 3.26 6.12 2.63
Control (20 people) 8.32 3.78 14.11 3.44 6.31 2.34
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
<strong>Effects</strong> <strong>of</strong> <strong>DDAVP</strong> on memory post-ECT
Table 4. Comparison <strong>of</strong> the changes in memory quality score in the case and control groups
Times 1 and 2 Times 1 and 3 Times 2 and 3
Group Mean SD Mean SD Mean SD
Case (30 people) 3.32 5.28 8.00 9.65 4.53 4.15
Control (20 people) 5.86 9.63 9.42 4.73 3.78 5.64
Paired t-test P < 0.0001 P < 0.0001 P < 0.0001
men and women for the different evaluation
timeswereasfollows:
* For times 1 and 2 there was no significant
statistical difference.
* For times 1 and 3, comparison between the
two groups showed no significant statistical
difference (P ¼ 0.866).
* For times 2 and 3, there was no significant
statistical difference (P ¼ 0.945) (Table 5).
Discussion
This study did not reveal memory impairments in
thecontrolgroupwithregardtoknowingpersonal
and current information such as birthplace, historical
events, or names <strong>of</strong> important places. According
to previous studies, common knowledge and
word memory are both very resistant to neurological
and psychological damage and are among
the most stable WMS subscores. As is shown in
Table 1, this score was decreased for evaluation
times 1 and 2 in the case group (from the score <strong>of</strong>
4.10–4.00), but the change was not statistically
significant (P ¼ 0.476). This decrease may be due
to tiredness or anxiety. As Wechsler has mentioned,
although these subscores are permanent,
they may become impaired if one is tired or
anxious.
Other subscores in the control group in fields
such as time and place orientation showed significant
decreases only between evaluation times 1
and 3, while for mental control significant
Table 5. Comparison <strong>of</strong> the changes in memory quality score according to gender in the case and
control groups
Times 1 and 2 Times 1 and 3 Times 2 and 3
Group Mean SD Mean SD Mean SD
Cases
Male (17 people) 3.67 6.54 9.71 6.24 5.80 6.43
Female (9 people) 2.70 6.61 5.30 8.63 2.50 8.21
t-test P ¼ 0.692 P ¼ 0.114 P ¼ 0.225
Controls
Male (11 people) 5.55 4.12 9.40 8.19 3.70 7.39
Female (13 people) 6.27 5.40 9.90 3.51 3.88 2.78
t-test P ¼ 0.738 P ¼ 0.866 P ¼ 0.945
135

Abdollahian et al.
differences between evaluation times 1 and 2, and
1 and 3 were seen. We may conclude that ECT is
more effective for the mental control process.
Although changes in these two subscores in the
case group did not reveal any significant difference,
comparison <strong>of</strong> the two groups showed a
statistically significant difference and confirmed
the effect <strong>of</strong> <strong>desmopressin</strong> on these two aspects <strong>of</strong>
memory (Table 2).
Long-term memory, which may be constructed
by physical, chemical, and structural changes in
neurons and their connections, seems to be stabilized
by different hormones and neurotransmitters.
In the process <strong>of</strong> stabilization, long-term data
become stable by neuronal plasticity, LTD, and
LTP, which makes them resistant to neurological
damage. However, as was seen in this study, shortterm
memory seems not to be based on structural
changes in neurons and is not well stabilized and
may be more affected by ECT (Table 1). This
vulnerability was more prominent with regard to
visual memory. In the control group, the visual
memory score was decreased by 13.95% after
three sessions <strong>of</strong> ECT and 25.32% after six
sessions. However, as shown in Table 2, while no
visual memory impairment was seen in the case
group following ECT, an increase (about 45%)
wasobservedincomparisonbetweentimes1and3
after 15 days <strong>of</strong> <strong>desmopressin</strong> administration.
This means there is a special effect for <strong>desmopressin</strong>
on visual memory. These results confirm
Laczi et al.’s (11) report on the effects <strong>of</strong> <strong>desmopressin</strong>
on patients with memory impairment but
with no impairment in attention or concentration.
According to previous studies, a function <strong>of</strong> the
hippocampus may to help with orientation learning
in the environment and the hippocampus is
able to code the data according to time, place,
and order.
This study shows the effects <strong>of</strong> <strong>desmopressin</strong> in
the prevention <strong>of</strong> memory impairment following
ECT and supports the results <strong>of</strong> previous studies
suggesting the use <strong>of</strong> <strong>desmopressin</strong> in the treatment
<strong>of</strong> memory impairment and its effects on normal
memory. Beckwith and Till (12) found that
<strong>desmopressin</strong> facilitates memory recall. Tiller et al.
(13) also reported positive effects on immediate
memory in the first week <strong>of</strong> treatment. Weingartner
et al. (14), in their study on patients with memory
defects, found that <strong>desmopressin</strong> facilitates
learning processes like completing sentences,
organization, and retrograde memory after ECT.
As noted before, in the comparison <strong>of</strong> all WMS
subscores between the case and control groups,
except for knowing personal and current information
(in the comparison between evaluation times 1
136
and 2), in all other subscores and all evaluation
times, there were significant differences, with
decreases in the subscores in the control group,
while such decreases were not seen in the case
group receiving the same ECT. There was even
an increase in some subscores (about 19% for
evaluation times 1 and 2, 21% for times 2 and 3,
and 45% for times 1 and 3). All these data support
the hypothesis <strong>of</strong> this study concerning the diminishing
effects <strong>of</strong> <strong>desmopressin</strong> on memory impairments
following ECT.
Comparison <strong>of</strong> the changes in memory quality
between men and women in the control group
revealed no significant differences between evaluation
times 1 and 2, 2 and 3, and 1 and 3 (Table 5),
showing that ECT results in a manifest decrease
in memory quality in both men and women.
Although the decrease in memory quality in
women seems higher than in men ( 6.27% for
women and 5.55% for men for times 1 and 2,
and 3.88% for women and 3.70 for men for
times 1 and 3), these differences are not statistically
significant. This means that ECT results in
memory impairment in both men and women
and that the degree <strong>of</strong> impairment is not different
in men and women. This contrasts with the results
<strong>of</strong> previous studies which claimed that memory
impairment following ECT was more dominant
in women than in men. This may be because all
the women in this study were similar in age and in
other characteristics (all were between the ages 20
and 40 and all were fertile). Since cognitive defects
in women are probably affected by other factors,
such as menopause, old age, or hormonal changes
during pregnancy, we tried to select women with
similar characteristics. They also had similar characteristics
to the male group in order to eliminate
probable interfering factors.
We found that <strong>desmopressin</strong> was effective in
the inhibition <strong>of</strong> memory impairment following
ECT in both men and women (Table 5). We even
observed some increases in memory quality: 9% in
men and 5% in women. Although this increase is
higher in men, the difference is not statistically
significant. This finding is in disagreement with
the results <strong>of</strong> Beckwith and Till (13), who found
that <strong>desmopressin</strong> had positive effects in men but
not in women. They suggested different effects for
<strong>desmopressin</strong> in men and women. As mentioned
above, this difference may be due to the elimination
<strong>of</strong> interfering factors in this study, such as
age and differences in fertility or menopause, and
similarities in other areas between the women and
between the women and the men.
With regard to the permanence <strong>of</strong> the effects <strong>of</strong>
<strong>desmopressin</strong> on memory function for the case

group, all subscores showed an increase between
evaluation times 1 and 2, 1 and 3, and 2 and 3.
(Table 1) This confirms that effects <strong>of</strong> <strong>desmopressin</strong>
on ECT-induced memory impairment persist
with the continuing administration. This result
supports the research by Dons et al. (15), which
revealed that effects <strong>of</strong> <strong>desmopressin</strong> continue with
continued administration but will be decreased
within a week after discontinuation <strong>of</strong> drug. In
this study we only evaluated the effects <strong>of</strong> the
drug until the last day <strong>of</strong> administration. An
evaluation after the discontinuation <strong>of</strong> drug is
needed to know how long the effects remain.
As Couk et al. (16) noted, <strong>desmopressin</strong> facilitates
memory processes but this effect is short
and is not permanent after the discontinuation
<strong>of</strong> drug.
Conclusions
This study has shown that ECT results in cognitive
impairment. Cognitive side-effects indicated in this
study were in the fields <strong>of</strong> immediate memory,
short-term memory, visual memory, and associate
learning and overall decrease in memory quality
score. The main result <strong>of</strong> the study was the finding
that <strong>desmopressin</strong> is effective in the prevention <strong>of</strong>
these adverse effects <strong>of</strong> ECT. This study also
revealed that <strong>desmopressin</strong> facilitates learned
memory recall, stabilizes memory against adverse
ECT effects and also prevents memory impairment
following ECT.
Although the exact mechanism <strong>of</strong> <strong>desmopressin</strong>
action is still not clear, it is known that <strong>desmopressin</strong>
causes biological or physiological changes in
certain brain structures such as the hippocampus
or cortex, and also increases certain gene expressions
in these structures (17). Other changes
caused by <strong>desmopressin</strong> include induction <strong>of</strong>
secondary messengers, changes in the function
<strong>of</strong> calcium channels, activation <strong>of</strong> cholinergic
mechanisms (such as increasing acetylcholine
esterase level in the frontal cortex, and induction
<strong>of</strong> acetylcholine release), and induction <strong>of</strong> hippocampal
metabolism <strong>of</strong> inositol phospholipid (6).
In the light <strong>of</strong> these data, we conclude that <strong>desmopressin</strong>
administration can be a proper pharmacological
means for prevention for adverse effects
<strong>of</strong> ECT on memory. In addition, this drug has no
<strong>Effects</strong> <strong>of</strong> <strong>DDAVP</strong> on memory post-ECT
severe side-effects and no contraindication during
pregnancy and breast-feeding.
References
1. LARRY R, KEN A. Biology <strong>of</strong> memory. In: KAPLAN HI,
SADOCK S, eds. Comprehensive Textbook <strong>of</strong> Psychiatry,
7th edn. Philadelphia: Lippincott William and Wilkins,
2000: 426–429.
2. IZQUIERDO I, MEDINA JH. Systemic administration <strong>of</strong>
ACTH or vasopressin reverses the amnestic effect <strong>of</strong> posttraining
beta-endorphin or electroconvulsive shock but
not that <strong>of</strong> intrahippocampal infusion <strong>of</strong> protein kinase
inhibitors. Neurobiol Learn Mem 1997;68:197–202.
3. MILLER RD. Anesthesia, 5th edn. Philadelphia: Churchill
Livingstone, 2000.
4. CAR H, BORAWSKA M, WISNIEWSKI K. The effect <strong>of</strong>
<strong>DDAVP</strong> on memory process in rats with ‘experimental
amnesia’. Acta Neurobiol Exp 1997;55:221.
5. DEVANAND DP, LISANBY S, LO ES et al. <strong>Effects</strong> on ECT
on plasma VP and oxytocin. Biol Psychiatr 1998;44:
610–616.
6. ENGELMANN M, BURES J, LANDGRAF R. AVP adminstration
via microdialysis into the septom interferes
with the aquistion <strong>of</strong> spatial memory in rats. Neurosci
Lett 1992;142:69–72.
7. JACHIMOWICZ A, HOLY Z, WISNIEWSKI K. The participation
<strong>of</strong> no in the facilitatory effect <strong>of</strong> AVP on memory.
Acta Neurobiol Exp Warsz 1998;58:37–45.
8. ARTEMOWICZ B, WISNIEWSKI K. Role <strong>of</strong> NMDA receptor
in the effect <strong>of</strong> AVP on memory processess. Pol S
Pharmacol 1998;50:5–14.
9. CROISET G, NIJSEN MJ, KAMPHUIS PJ. Role <strong>of</strong> CRF, VP
and antonomin nervous system in learning and memory.
Eur J Pharmacol 2000;405:225–234.
10. SHEN Y, LI R. The role <strong>of</strong> neuropeptides in learning and
memory. Med Hypotheses 1995;45:529–538.
11. LACZI F, VALKUSZ Z, LASZLO FA et al. <strong>Effects</strong> <strong>of</strong> AVP
and <strong>DDAVP</strong> on memory healthy individuals and
diabetes incipidus patients. Psychoendocrinology
1982;7:185–193.
12. BECKWITH BE, TILL RE. Sentence memory affected
by AVP analog (<strong>DDAVP</strong>) in cross-over experiment.
Peptides 1985;6:397–402.
13. TILL RE, BECKWITH BE. Sentence memory affected
by <strong>DDAVP</strong> in cross-over experiment. Peptides 1985;6:
397–402.
14. WEINGARTNER H, GOLD P, BALLENGER JC et al. Effect
<strong>of</strong> AVP on human memory function. Science 1981;
211:601–603.
15. DONS RF, HOUSE JF, HOOD D, KREHBIEL M. Assessment
<strong>of</strong> <strong>DDAVP</strong>-enhanced cognitive function in a neurosurgical
patient. Mil Med 1989;154:83–85.
16. COUK DI, BECKWITH BE. Effect <strong>of</strong> <strong>DDAVP</strong> on learning
<strong>of</strong> brightness discrimination. Peptides 1982;3:627–630.
17. TANAKA T, YAMADA K, SENZAKI K et al. NC-1900, an
active fragment analog <strong>of</strong> arginine vasopressin, improves
learning and memory deficits induced by beta-amyloid
protein in rats. Eur J Pharmacol 1998;352:135–142.
137