İkinci Öğretim Öğrencilerinin Dikkatine

Klinik Psikofarm akoloji B ü lten i / Cilt 8: Sayı 3, 1998
Effects of 5hort and Long-Term
Lithium Treatment on 5erum Cortiso
Levels in Patients With Bipolar
Affective Disorder
Dr. Mustafa 6AŞTÜRK, Prof. Dr. Seher SOFUOGLU, Doç. Dr. Fatih KARASLAN,
Dr. A.TUTUŞ, Dr. İ.YAEANOGLU, Dr. Ali Saffet GÖNÜL
ÖZET
Both basic and clinical studies have shown that lithium can affect the pituitary-adrenocortical axis. In this study, we sougl
test the hypothesis that prophylactic lithium (Li) treatment can induce alterations in cortisol secretion in euthym ic bipolar ]
ents and the length of Li administration can affect the degree of alterations. 2İ euthymic bipolar patients (m ean±SD
34.90±10.05) on long-term lithium carbonate treatment for more than 6 months and 15 euthymic bipolar patients (m ean±SD
29.53±8.76) on short-term Li therapy for shorter than 6 months who met DSM-IV criteria for bipolar affective disorder were
luded in the study. 17 healthy control subjects (mean±SD age: 33.88±1.72) were chosen among the hospital staff. Serum t
cortisol values were within the normal limits in all study groups but they were significantly lower in the Li-treated patients
those of the controls. However, there was no difference between the two patient groups in plasma basal cortisol values,
study documents that Li administration induces a significant reduction in cortisol release in bipolar patients com pared tc
normal control subjects, but cortisol secretion remains quite stable during the prolonged Li treatment. However, since basal
tisol concentrations show considerable intraindividual and interindividual variations further studies are needed .
A n ahtar K elim eler: Bipolar affective disorder, lithium, cortisol
BulI.Clin.Psychopharmacol. 8:3 (160-162), 1998
SUM M ARY
BIPOLAR AFFEKTİF HASTALARDA KISA VE UZUN SÜRELİ LİTYUM TEDAVİSİNİN SERUM KORTİZOL
SEVİYELERİNE ETKİSİ
Tem el ve klinik çalışm alar lityum un pitüiter-adrenal kortikal ekseni etkileyebildiğini göstermiştir. Biz bu çalışm ada profili
lityum tedavisinin ötimik bipolar hastalarda kortizol sekresyonunda değişiklik oluşturabileceği ve lityum tedavi süresini
değişiklikleri etkileyebileceği hipotezini araştırdık. Çalışmaya DSM-IV teşhis kriterlerini karşılayan ve 6 aydan uzun süre
yum tedavisi altında olan 20 ötimik bipolar hasta (ort±SD yaş: 34.90+10.05) ile 6 aydan kısa süredir lityum tedavisi altında
15 ötim ik bipolar hasta (ort.±SD yaş: 29.53+8.76) dahil edildi. 17 sağlıklı kontrol şahıs (ort.±SD yaş: 33.88±1.72) hastahane
söneli arasından seçildi. Serum bazal kortizol değerleri bütün çalşma gruplarında normal sınırlar içinde olmakla beraber, lit
ile tedavi edilen hastalarda kontrollerinkinden önemli şekilde düşük bulundu. Bununla beraber, iki hasta grubu arasınd
rum kortizol değerleri bakım dan önemli fark mevcut değildi. Bizim çalışmamız lityumun bipolar hastalarda kortizol salını
normal kontrol şahıslardakine nazaran önemli şekilde azalttığını ortaya koymaktadır, fakat kortizol sekresyonu uzun süre
yum tedavisi esnasında oldukça sabit bir şekilde kalabilmektedir. Yine de, bazal kortizol seviyeleri aynı şahısda ve şahı
şahısa önem li değişiklikler gösterdiği için bulgularımızı teyid etmek üzere başka çalışmalara ihtiyaç vardır.
K ey W ords: Bipolar affektif bozukluk, lityum, kortizol.
BulI.Clin.Psychopharm acol. 8:3 (160-162), 1998
he im portance of lithium (Li) salts as prophy
lactic therapeutic agents in bipolar affective di
sorder is now well-known. However, both basic
and clinical studies have shown that lithium treat
m ent can be associated with a wide range of adver
se effects on m etabolic and endocrine functions. It
T
has also been suggested that Li can affect the f
itary-adrenal axis (1). In this study, we sougl
test the hypothesis that prophylactic lithium ti
ment can induce alterations in cortisol secretio
euthymic bipolar patients and .the length of Li ac
nistration can affect the degree of alterations.
Erciyes Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı-KAYSERİ
160
Effects of Sh o rt and Long-Term Lithium T reatm en t... / Mustafa Baştürk ve ark.
Table 1. Clinical Variables of the Li-treated Bipolar Patients and the Controls
Clinical variables
Age
Lenghf of illness
Number of episodes
Duration of li-treatment (mont
Patients on short-term
Li
(n=15)
M ean
SD
Patient on long-term
Li
(n=20)
Mean
SD
Control subjects
(n=17)
M e an
SD
2 9 .5 3
7 .1 3
4 .3 3
4 .0 0
3 4 .9 0
11.95
7 .4 0
6 8 .0 0
3 3 .8 8
Nil
Nil
Nil
1.72
8 .7 6
5 .8 7
2 .4 9
3 .4 2
METHODS
Subjects and procedure
Twenty euthym ic bipolar patients (4 remales, 16
males; m ean±SD age: 34.90±10.05) on long-term lit
hium carbonate treatment for more than 6 months
(range: 18-18İ months) and 15 euthymic bipolar pa
tients (II fem ales, 5 m ales; m ean±SD age:
29.53±8.76) on short-term Li therapy for shorter
than 6 months (range: 2-6 months) who met DSMIV criteria for bipolar affective disorder (2) were inc
luded in the study. The investigations were carried
out mostly on an outpatient basis. Seventeen he
althy control subjects (7 females, 10 males; mean±SD age: 33.88±1.72) were chosen among the hos
pital staff. The subjects participated in the study wrere free of any physical disorder and were drug- free
for at least 3 weeks. Before enrollment, each subject
underwent a physical examination and a laboratory
evaluation that included a multichannel serum che
mistry analysis and complete blood count and a ba
sal PRL level. Informed w'ritten consent was obta
ined from each subject before participation. This
study was approved by the local ethics committee.
A single fasting m orning blood specimen was
obtained at 07.00-08.00 a.m. from all the subjects af
ter 10-12 h after the previous lithium dose from the
patients. Venous blood was drawn into ice-cold heparinized tube and centrifugated at 4oC. Serum Li
was measured by atomic absorption spectroscopy.
i 0 .0 5
5 .5 6
7 .3 5
4 6.3 1
The remaining serum was frozen and stored at 70oC untilthe analysis of basal cortisol. Serum basal
cortisol wras determined using the standard RIA
(ICN Biomedicals, Inc. US. Cortisol 1251 kits). The
lowest sensitivity limit wras 0.5 pg/dl; intra-assay
and inter-assay coefficient of variation were 5.8%
and 6.5% at cortisol concentration of 22.3 and 23.1
pg/dl, respectively; normal range was 7-24 p g / d l).
Data analysis
The hormone values were compared across the
patient and control groups by one-way ANOVA
followed by Bonferoni's multiple comparison. P va
lues less than 0.05 were considered statistically sig
nificant. We performed m ultiple regression analysis
using plasma cortisol values as a dependent variab
le and serum and red blood cell Li values as an in
dependent variable each.
RESULTS
As shown in Table 1, there was no significant
difference in mean age among the three study gro
ups. The m ean±SD duration of Li use was
68.93±46.31 months in the long-term group and
4±3.42 months in the short-term group. Serum basal
cortisol values were within the normal limits in all
study groups but they were significantly lower in
the Li-treated patients than those of the controls.
However, there was no difference between the two
Table 2. Serum cortisol and Li levels of the Patients and the Controls
Biochemical variab le s
Plasma Li level (mmol/L)
Li le v e l (mmol/L)
Red B lo o d c e ll
Serum c o rfis o l le v e l ( ( g / d l j
Patients on short-term
Li
(n=15)
M ean
SD
0 .7 2
0 .3 2
1 1.37a
a - b. S ig n ific a n tly d iffe r e n t fro m th e c o n tro l s u b je c ts
0 .1 9
0 .0 9
3 .8 8
Patient on long-term
Li
Control subjects
(n=17)
(n=20)
M ean
SD
M ean
SD
0 .7 6
0 .3 7
1 2 .8 6 b
0 .1 8
0 .1 0
4 .3 3
Nil
Nil
2 1 .5 0
5 .7 2
(F=22.52 p c O .O O l)
161
Klinik Psikofarm akoloji B ü lten i / Cilt 8: Sayı 3, 1998
patient groups in serum basal cortisol values (Table
2). There was no significant correlation between the
serum or red blood cell Li levels and serum cortisol
values in the Li-treated groups.
DISCUSSION
The effects of Li treatm ent on cortisol secretion
are much less studied, and the data reported are
conflicting. Indeed, there have been reports of either
increases (3, 4) or no change (5, 6) or decreases (7, 8)
in plasm a cortisol during Li treatment. Most of the
studies exam ining the effects of starting Li have be
en confused by the effects of acute illness on hormo
ne levels. Therefore, we studied basal cortisol levels
in Li-treated patients who have euthymic mood sta
te in both short and long-term treatment.
Our findings indicated that administration of
both short and long-term Li treatment induced sig
nificant changes in basal cortisol values in bipolar
patients compared to those of the healthy control
subjects although cortisol values were not different
in the short-term and long-term Li-treated groups.
It has been known that exogenous or endogenous
steroid excess m ay precipitate affective illness (1)
and based on this idea, one may speculate that Liinduced cortisol decrease contributes to mood stabi
lisation in bipolar patients. Our finding that Li dec
reases cortisol secretion which is concordant with
those of two previous studies (7, 8 ) supports this
speculation. But since we did not have the pre-Li
cortisol values of the Li-treated patients, it is not
possible to determ ine whether those patients had an
absolutely increased cortisol secretion prior to the
Li treatm ent or not. Cristie et al (9) reported that gi
ving Li for 14-22 days significantly reduced evening
cortisol levels compared both to the pre-Li levels
and the control values, but that giving Li for 7-14
days did not. Cristie et al (9) also suggested that lo
wering of cortisol concentrations appears to be asso
ciated w ith recovery from manic illness, irrespecti
ve of the type of treatm ent given either lithium or
sulpiride. We consider that our short-term Li study
group corresponds to the Cristie's 14-22 day's Litreated group.
162
We did not find that either plasma or red bloo<
cell Li concentrations were correlated with the coi
tisol values. Furthermore, lenght of Li-treatmer
did not affect the reduction in cortisol secretion dil
ferently and the modest decrease in cortisol secret
on induced by short-term Li treatm ent did not sho^
a significant change with the prolonged Li trea
ment. Thus, cortisol levels rem ained quite stable di
ring the long-term Li treatment.
In conclusion, our study docum ents that Li ac
ministration induces a significant reduction in cort
sol release in bipolar patients com pared to the no
mal control subjects. But cortisol secretion remaii
quite stable during the prolonged Li treatment. H
wever, since basal cortisol concentrations sho
considerable intraindividual and interindividu
variations, further studies are needed.
KAYNAKLAR
1.
2.
3.
4.
5.
6.
7.
8.
9.
_
Souza FGM., Mander AJ., Foggo M., et al.: The effects
lithium discontinuation and the non-effect of oral inosi
upon thyroid hormones and cortisol in patients with
polar affective disorder. J Affective Dis 1991, 22:165-17
Am erican Psychiatric Association.: Diagnostic and Sta
tical Manual of Mental Disorders (4th Ed). Washing!
DC, 1994
Platman SR., Fieve RR.,: Lithium carbonate in healthy
ung volunteers. Acta Endocrinol 1968, 106:203-208.
Noyes R., Ringdahl IC., Andreasen NJC.: Effect of lithi
citrate on adrenocortical activity in manic depressive
ness. Comp Psychiatry 1971,12:337-347.
Brooksbank BWL., Coppen A.: Plasma 11-hydroxycc
costeroids in affective disorders. Br J Psychiatry IS
113:395-404.
Sachar EJ., Heilman L., Kream J., et al.: Lithium carbc
te and plasma cortisol response in affective disord
Arch Gen Psychiatry 1970, 18:591-594.
Smigan L, Perris C.: Cortisol changes in long term lithi
therapy. Neuropsychobiology 1984, 11:219-223.
M uehlbauer HD., M ueller-Oerlinghausen B.: Fenflurs
ne stimulation of serum cortisol in patients with majo:
fective disorders and healthy controls: further evide
for a central serotonergic action of lithium in man. J
ural Trans , 1985, 61:81-94.
Cristie JE., W halley LJ., H unter J., et al.: Sulpiride ti
ment of acute mania with a com parison of the effect
plasma hormone concentrations of lithium and sulpi
treatment. J Affective Dis 1989, 16:115-120.

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