• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.266-270
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• 2001

Objective : The purpose of this study was to compare the plasma amitriptyline and nortriptyline level between before and after fluoxetine addition with patients who were currently taking amitriptyline. Method : From the inpatient and outpatient unit of Soon Chun Hyang University Hospital, Chunan, fourteen subjects who were taking amitriptyline 25mg more than 1 week at least were given fluoxetine 20mg. Before and 2 weeks after fluoxetine addition, the plasma level of amitriptyline and nortriptyline are analyzed simultaneously by High Performance Liquid Chromatography(HPLC). At the same times, HAM-D(Hamilton Rating Scale for Depression) score and the UKU(Uldvalg for Klinske Unders${\Phi}$ gelser) side effect scale were checked. Results : After fluoxetine addition to the patients who were taking amitriptyline, the plasma level of amitriptyline, nortriptyline and sum of amitriptyline and nortriptyline had risen. The mean plasma amitriptyline level increased from $168.9{\pm}89.4ng/ml$ to $183.0{\pm}102.0ng/ml$ after fluoxetine addition(p=0.011), but the change was not statistically significant. The mean plasma nortriptyline level increased significantly from $114.3{\pm}70.2ng/ml$ to $168.0{\pm}86.2ng/ml$ after fluoxetine addition(p=0.011). In addition, the mean plasma level of total amitriptyline and nortriptyline increased significantly from $283.1{\pm}125.3ng/ml$ to $350.9{\pm}78.4ng/ml$ after fluoxetine addition(p=0.016). After fluoxetine addition, no significant change was noted in the UKU side effect scale score. Conclusion : As consequence of comparison of plasma amitriptyline and nortriptyline level before and after fluoxetine addition, mean amitriptyline, nortriptyline and total plasma level was increased after fluoxetine addition. This suggests that coadministration of amitriptyline and fluoxetine may induce improvement of depressive symptom in depressive patients by way of increased plasma level of amitriptyline.

• Korean Journal of Psychosomatic Medicine
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• v.3 no.1
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• pp.11-18
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• 1995

The efficacy of fluoxetine was evaluated in 32 patients with major depression in double-blind amitriptyline-controlled clinical trials. Patients were randomly assigned to 6 weeks of treatment with 20mg/day of fluoxetine and 25-100mg/day of amitriptyline. We used the Hamilton rating scale for depression(HAM-D) and the Clinical Global Improvement(CGI) to evaluate the improvement of depression. In addition, we also used the Covi Anxiety Scale and the Anxiety/Somatization subscale of HAM-D to investigate the relieving effect of anxiety. The improvement by fluoxetine in mean total score of HAM-D and CGI was comparable to amitriptyline. Fluoxetine also reduced anxiety significantly, but there was no difference between fluoxetine and amitriptyline in relieving anxiety symptoms. Fluoxetine showed considerably less adverse effects, especially anticholinergic effect and weight gain than amitriptyline. In conclusion, 20mg/day of fluoxetine was sufficiently effective in the treatment of depressive patients and was better tolerated than amitriptyline.

• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.515-522
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• 2004

The vasorelaxant effect of serotonin reuptake inhibitor fluoxetine was investigated in rat isolated thoracic aorta. Fluoxetine induced a concentration-dependent relaxation in aorta precontracted with phenylephrine (PE) and KCl. These relaxations were suppressed by removal of the endothelium (-E) or pretreatment of nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-Larginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue (MB) and 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ), and $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings. However, fluoxetine-induced relaxations were not suppressed by pretreatment of $K^{+}$ channel blockers, tetrabutylammonium and glibenclamide, in PE-precontracted endothelium intact (+E) rings. The fluoxetine-induced relaxations were not suppressed by removal of the endothelium or pretreatment of LNNA and MB in KCl-precontracted +E rings. Also, fluoxetine inhibited PE-induced sustained contraction in +E rings. These inhibitory effects of fluoxetine on contractions could be reversed by removal of the endothelium or pretreatment of L-NNA, L-NAME, MB, ODQ, nifedipine and verapamil, but not by pretreatment of etrabutylammonium and glibenclamide. These findings suggest that the vasorelaxant effect of fluoxetine is modulated by intracellular $Ca^{2+}$ with an involvement of endothelial NO-cGMP pathway and also may be related to the inhibition of $Ca^{2+}$ entry through voltage-gated channel.

• Archives of Pharmacal Research
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• v.28 no.6
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• pp.716-721
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• 2005

Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC ($\alpha$-MSH).

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.253-258
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• 1999

The fluoxetine is one of the most frequently prescribed drugs for the treatment of depression and obsessive-compulsive disorder(OCD). This has been known as one of the most safest medication. But since the advent of this drug, there have been several reports of side effects-the mania and suicidal ideation-encountered during coadministration of fluoxetine with or without other psychotropic drugs. We experienced a case of 20 years old male OCD patient who developed into abrupt manic state and also was preoccupied with intense suicidal ideation following fluoxetine use. He was a only child in his family and his father had a history of alcoholism about 15years ago. Our patient's obsessive-compulsive symptoms have been occured since puberty. His OCD symptoms and anxiety were aggravated since joining the army. Beside these facts, we could not find any other psychiatric history such as depressive disoder and bipolar disorder. We used the fluoxetine starting dosage of 20mg and increased to 40mg at second week. About 3 weeks after the treatment, he developed sudden manic symptom and more aggravated suicidal ideation without any OCD symptoms. He felt vitalized and energetic without having enough sleep and food. These symptoms were ceased over two weeks by stopping medication. Up to this point, the reason why fluoxetine induces mania and suicidal preoccupation is unclear. But somehow the fluoxetine has effects on serotonin receptor and serotonin-dopamine regulations, thus we could make an assumption that fluoxetine can induce mania, extrapyramidal symptoms(EPS) and suicidal ideation in some part of the serotonin unbalanced patients. We think this would be the first report to remark on fluoxetine's suicidal and manic side effects in Korea. So here we present the case with the summary of reviewed articles.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.6 no.1
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• pp.116-122
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• 1995

목적 : 다음과 같은 fluoxetine으로 유발된 조증 증례를 보고한다. 이와 함께 fluoxetine사용이후 보고된 조증 증례보고를 모아서 정리하고 함께 문헌고찰을 하였다. 증례요약 : 가족력상 기분장애의 병력이 없었으며, 다른 주요 정신과적 질환의 병력은 없었다. 환아는 개인력상 5세경에 주의력 결핍, 과잉행동의 양상을 보였던 병력이 있었고, 13세때에 피해 망상, 환청이 지속되어 haloperidol로 치료받기 시작하였다. 이후 피해 망상의 내용을 언급하거나 환청에 영향받는 행동은 없어졌고 간혹 우울감을 호소하였다. 이후 정신분열증의 진단 하에 haloperidol만으로 3년간 유지하였다. 1994년 환아는 18세때 고3이 되면서 대입에 대한 걱정과 신체적인 허약감을 자주 호소하며, 우울증상이 두드려져 fluoxetine 20mg를 3일간 투여하던 중 갑자기 조증의 임상적 양상을 보이기 시작하여 본원의 입원치료를 받게 되었는데, 입원당시 보인 임상양상은 앙양된 기분, 이자극성(irritability), 사고의 비약, 연상의 이완과 지리멸렬, 과대망상, 피해망상, 관계망상, 환청 등이었고 사람, 장소, 시간에 대한 지남력까지 일시적으로 상실되는 심헌 정신병적 조증상태였다. 토의 : fluoxetine 사용이후 현재까지 세계적으로 문헌상 보고된 14개의 증례보고를 모아서 정리하였다. fluoxetine-induced mania의 병태생리학적인 기전은 명확하지 않지만 가능한 기전에 대해 토론하였다. 이 약물의 중대한 부작용중의 하나인 조증을 예방하기 위해, 이 약물을 다루는 의사는 가능한 조증 발병의 위험인자들에 대하여 인식하고, 약물의 용량조절시에도 주의를 하여야 한다. 가능한 발병 위험인자들에 관해서도 검토하였다.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.121-126
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• 1997

Objectives : The authors have intended to know the drug interaction of fluoxetine and haloperidol when coadministering two drugs to the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms. Method : We selected 38 patients, the chronic schizophrenics with no physical problems. they are randomly assigned to placebo group and drug group. And then, placebo or fluoxetine 20mg were administered to the subjects of each group during 8 week period. We have assessed their psychopatholgy and extrapyramidal symptoms using Positive and Negative Syndrome Scale(PANSS), Clinical Global Impression(CGI), Simpson-Angus Scale at 0, 2, 4, 6, 8 week during the period. Results : 38 patients have completed the study during 8 weeks. 1) PANSS, CGI : no significant difference between groups and no significant change according to the times. 2) Simpson-Angus Scale : no significant changes. Conclusion : When co-administering fluoxetine and haloperidol, there were no significant changes of psychopathology and extrapyramidal symptoms. These results suggest that it is safe to coadminister fluoxetine to schizophrenic patients with haloperidol treatmemt.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.513-518
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• 1998

Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.27-41
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• 2004

This study was performed to evaluate the effects of Jowiseungchungtang and fluoxetine in the chronic mild stress(CMS) model of depression in rats. Chronic exposure to mild unpredictable stress was found to depress the consumption of sucrose solution in rats for 5 weeks. These CMS-treated rats were stratified into Jowiseungchungtang group, fluoxetine group and vehicle group. And control rats were also stratified into other CMS-treated group. The change of the consumption of sucrose solution was measured, and open field test were performed to investigate the anti-depression effect of Jowiseungchungtang and fluoxetine. The results were as follows : 1. The consumption of sucrose solution was significantly reversed in Jowiseungchungtang-treated group at 7 week, but there was no significant change in other groups. 2. CMS schedule decreased body weight. Jowiseungchungtang group and fluoxetine group showed significant decrease of body weight after 6 weeks. 3. In open field test, Jowiseungchungtang group and fluoxetine group showed no significant change of exploratory activity.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.202-210
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• 2020

Fluoxetine is used widely as an antidepressant for the treatment of cancer-related depression, but has been reported to also have anti-cancer activity. In this study, we investigated the cytotoxicity of fluoxetine to human gastric adenocarcinoma cells; as shown by the MTT assay, fluoxetine induced cell death. Subsequently, cells were treated with 10 or 20 µM fluoxetine for 24 h and analyzed. Apoptosis was confirmed by the increased number of early apoptotic cells, shown by Annexin V- propidium iodide staining. Nuclear condensation was visualized by DAPI staining. A significant increase in the expression of cleaved PARP was observed by western blotting. The pan-caspase inhibitor Z-VAD-FMK was used to detect the extent of caspase-dependent cell death. The induction of autophagy was determined by the formation of acidic vesicular organelles (AVOs), which was visualized by acridine orange staining, and the increased expression of autophagy markers, such as LC3B, Beclin 1, and p62/SQSTM 1, observed by western blotting. The expression of upstream proteins, such as p-Akt and p-mTOR, were decreased. Autophagic degradation was evaluated by using bafilomycin, an inhibitor of late-stage autophagy. Bafilomycin did not significantly enhance LC3B expression induced by fluoxetine, which suggested autophagic degradation was impaired. In addition, the co-administration of the autophagy inhibitor 3-methyladenine and fluoxetine significantly increased fluoxetine-induced apoptosis, with decreased p-Akt and markedly increased death receptor 4 and 5 expression. Our results suggested that fluoxetine simultaneously induced both protective autophagy and apoptosis and that the inhibition of autophagy enhanced fluoxetine-induced apoptosis through increased death receptor expression.