 |
|
|
EFFECTS OF SULPIRIDE OR FLUVOXAMINE ON CATECHOLAMINE METABOLITES
IN PLASMA
N. Ueda, R. Yoshimura, K. Shinkai, J. Nakamura
Department of Psychiatry, School of Medicine, University of
Occupational and Environmental Health, Fukuoka, Japan.
<Introduction> Sulpiride, a dopamine (D2)
receptor antagonist, has a dual dose-dependent profile; it is
an antipsychotic drug at high doses and antidepressant at low
doses. On the other hand, fluvoxamine, a selective serotonin
reuptake inhibitor (SSRI), has a selective potent effect on
serotonin transporters. In the present study, we investigated
the effects of sulpiride and fluvoxamine on plasma monoamine
metabolites and the clinical improvement of depressive symptoms.
<Subjects and Methods> Fifty patients who met DSM-IV
criteria for major depressive disorder and scored at least 15
on the 17-item Hamilton Depression Rating Scale (Ham-D) entered
this study. Patients were randomly assigned to either the sulpiride
or fluvoxamine treatment group. There were 25 cases in the sulpiride
group and 25 in the fluvoxamine group. Each subject was evaluated
the clinical response using Ham-D at three times; before administration
(baseline), 2 weeks and 4 weeks after drugs had reached a stable
dosage (endpoint) and blood samples were drawn twice; baseline
and endpoint. Patients with an at least 50 % decrease in baseline
Ham-D scores were defined as responders, whereas the others
as nonresponders. This study was approved by the Ethics Committee
of our university.
<Results> (1) There were no significant differences
in sex, age, baseline Ham-D scores, and baseline pMHPG and pHVA
levels between the sulpiride and fluvoxamine group. A significant
difference was found between both drugs only with regard to
the daily dosage. (2) The decreases in Ham-D scores with regard
to psychomotor retardation (sulpiride group: 1.76±0.75, fluvoxamine
group: 0.93±0.77, P<0.05) were higher in the sulpiride group
than in the fluvoxamine group, whereas the decreases in Ham-D
scores with regard to anxiety (psychic) (sulpiride group: 1.00±0.70,
fluvoxamine group: 1.75±0.77, P<0.05) and hypochondriasis
(sulpiride group: 0.88±0.69, fluvoxamine group: 1.50±0.81,
P<0.05) were greater in the fluvoxamine group than in the
sulpiride group. (3) There were significant differences between
the sulpiride and fluvoxamine groups in the Ham-D scores at
2 weeks after the administration of each drug, the differences
disappeared, however, at the endpoint. (4) Responders to sulpiride
had significantly lower pHVA levels before administration of
sulpiride than nonresponders (responders: 4.2±2.8ng/ml, nonresponders:
9.9±5.8ng/ml, P<0.05). (5) Significant positive correlations
were found between the changes of pHVA levels and the percent
improvement of Ham-D with regard to the sulpiride group (rho=0.54,
P<0.01). (6) Responders to fluvoxamine had significantly
higher pMHPG levels before administration of fluvoxamine than
nonresponders (responders: 8.2±2.2ng/ml, nonresponders: 5.9±2.6ng/ml,
P<0.05). (7) Significant negative correlations were found
between the changes of pMHPG levels and the percent improvement
of Ham-D with regard to the fluvoxamine group (rho=-0.61, P<0.01).
<Conclusion> These results suggest that sulpiride
improves depressive symptoms affecting dopaminergic neurons,
whereas, fluvoxamine improves those influencing noradrenergic
neurons as well as serotonergic neurons. |
|
|
|
sulpirideおよびfluvoxamineの血中カテコールアミン代謝産物に及ぼす影響
上田展久、吉村玲児、新開浩二、中村 純
産業医科大学精神医学教室、福岡県
＜緒言＞強いD2受容体阻害作用を持つsulpirideは、少量
投与では抗うつ効果を有するユニークな薬剤である。一方fluvoxamineは、本邦にはじめて導入された選択的セロトニン再取り込み阻害薬(SSRI)であり、sulpirideと同様軽症うつ病の治療に対してよく使用される。今回演者らはfluvoxamineとsulpirideの抗うつ効果
に関して、臨床精神薬理学的見地から比較検討した。
＜対象と方法＞DSM-IVの大うつ病性障害の診断基準を満たし､ハミルトンうつ病評価尺度17項目の合計点(Ham-D)が15点以上である50症例を対象とした。sulpirideか
fluvoxamineのどちらかを無作為に選択し､臨床症状に応じて至適量
まで増量した。sulpiride群が25例、fluvoxamine群が25例であった。臨床症状は、投薬前（baseline）、至適量
投与2週間後および4週間後(endpoint)の合計3回、Ham-Dを用いて評価した。採血はbaselineおよびendpointの2回行った。Ham-Dが50%以上改善した群をresponder､改善しなかった群をnonresponderとした。なお本研究は、産業医科大学倫理委員会の承諾を得て行った。
＜結果＞(1) fluvoxamine群およびsulpiride群で、年齢､性別
､baselineのHam-D、baselineのpMHPGおよびpHVAに有意差はなかった。至適投与量
はsulpiride群の方が有意に高かった。(2)endpointにおけるHam-Dの下位
項目のうち、sulpiride群では精神運動制止(sulpiride group: 1.76±0.75,
fluvoxamine group: 0.93±0.77, P<0.05)が、fluvoxamine群では精神的不安(sulpiride群:
1.00±0.70, fluvoxamine群: 1.75±0.77, P<0.05)および心気(sulpiride群:
0.88±0.69, fluvoxamine群: 1.50±0.81, P<0.05)が有意に改善していた。（3）至適量
投与2週間後ではsulpiride群のほうがfluvoxamine群に比べてHam-Dが有意に低かった。しかしその差はendpointでは消失していた。(4)
sulpiride群では、responder群の方がnonresponder群と比べてbaselineのpHVA濃度が有意に低かった(responder群:
4.2±2.8ng/ml, nonresponder群: 9.9±5.8ng/ml, P<0.05)。(5)
sulpiride群ではpHVA濃度の変化とHam-Dの改善率には正の相関が認められた(rho=0.54,
P<0.01)。(6) fluvoxamine群では、responder群の方がnonresponder群と比べてbaselineのpMHPG濃度が有意に高かった(responder群:
8.2±2.2ng/ml, nonresponder群: 5.9±2.6ng/ml, P<0.05)。(7)
fluvoxamine群ではpMHPG濃度の変化とHam-Dの改善率には負の相関が認められた(rho=-0.61,
P<0.01)。
＜結語＞sulpirideはドパミン神経系に影響を及ぼすことによって抑うつ症状を改善し、fluvoxamineはノルアドレナリン神経系へも影響を及ぼすことによって抑うつ症状を改善している可能性が示唆された。
|
|
previous