氟西汀早期干预卒中后抑郁的临床及实验研究
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摘要
目的：1．观察卒中后抑郁的发生率以及氟西汀早期治疗对卒中后抑郁的干预作用及对神经功能康复的影响。2．探讨血小板和血浆中5-羟色胺的含量与卒中后抑郁的关系及氟西汀治疗对其影响。
方法：选取2003年9月-2004年2月住院的脑卒中患者66例，随机分为氟西汀治疗组和常规治疗组，常规治疗组仅给神经内科常规治疗，氟西汀治疗组在常规治疗一周后加用氟西汀口服四周。对两组病人均在病程的一周及五周时采用汉密尔顿抑郁量表(HAMD)、日常生活能力量表(ADL)、神经功能缺损评分标准(SSS)进行评定，同时采用高效液相色谱-荧光法检测血小板和血浆中5-羟色胺的含量。
结果：卒中后抑郁发生率为38.24％，治疗后氟西汀治疗组HAMD抑郁评分低于常规治疗组(P＜0.05)，两组患者SSS、ADL分值均有好转，在好转程度上，氟西汀治疗较常规治疗明显(P＜0.05)，卒中后抑郁患者血小板5-羟色胺的含量正常，氟西汀治疗四周后血小板5-羟色胺的含量较治疗前明显减低(P＜0.05)，常规治疗前后血小板5-羟色胺的含量无明显差异(P＞0.05)，两组治疗前后血浆5 -羟色胺无差异。
氟西汀早期干预卒中后抑郁的临床及实验研究中文提要
结论:卒中急性期卒中后抑郁发生率高;早期应用氟西汀治疗可
减轻PSD症状、促进神经功能康复;血浆5轻色胺检测结果无显著
意义，PSD患者血小板5经色胺含量正常，氟西汀治疗可引起脑卒
中患者血小板5轻色胺含量降低。
Objective
(1) Observing the prevalence of post-stroke depression (PSD) to find out whether or not early anti-depression treatment by fluoxetine can either intervene PSD or be any beneficial to the rehabilitation after stroke.
(2) Researching the relationship between blood 5-HT concentration and PSD to find out the influence of fluoxetine on plasma and platelet 5-HT concentration.
Methods
66 patients who were stroke (2003.09-2004.02) were chosen and divided into fluoxetine treatment group and regular treatment group. The regular treatment group only received regular treatment, while the fluoxetine treatment group received four-week fluoxetine treatment after one week regular treatment. Patients were evaluated by HAMD, ADL and SSS at the 1st week and the 5th week after stroke. Meanwhile, plasma and platelet 5-HT concentrations were measured by high performance liquid chromatography fluorescence detector.
Results
The prevalence of PSD after stroke is 38.24%. The fluoxetine treatment group is scored lower than regular treatment group in the HAMD scale after treatment (P<0.05). Although rehabilitation evaluated by SSS and ADL is found in both groups after 4-week treatment (P<0.05 ) , advantages of fluoxetine treatment can be observed (P<0.05 ) .Generally, the platelet 5-HT concentration of PSD patients is normal, fluoxetine reduced platelet 5-HT concentration after 4-week treatment (P<0.05 ) . No notable difference in platelet 5-HT value can be observed before and after regular treatment (P>0.05) . No notable change in plasma 5-HT concentration can be observed in both groups before and after treatment (P>0.05) . Conclusion
Prevalence of PSD is often after acute stroke. Early treatment by fluoxetine can release the symptom of PSD and promote rehabilitation of PSD patients. The effect of plasma 5HT value is not clear. The platelet 5-HT concentration of PSD patients is normal; however, fluoxetine treatment can reduce the platelet 5-HT concentration of stroke patients.
方法：选取2003年9月-2004年2月住院的脑卒中患者66例，随机分为氟西汀治疗组和常规治疗组，常规治疗组仅给神经内科常规治疗，氟西汀治疗组在常规治疗一周后加用氟西汀口服四周。对两组病人均在病程的一周及五周时采用汉密尔顿抑郁量表(HAMD)、日常生活能力量表(ADL)、神经功能缺损评分标准(SSS)进行评定，同时采用高效液相色谱-荧光法检测血小板和血浆中5-羟色胺的含量。
结果：卒中后抑郁发生率为38.24％，治疗后氟西汀治疗组HAMD抑郁评分低于常规治疗组(P＜0.05)，两组患者SSS、ADL分值均有好转，在好转程度上，氟西汀治疗较常规治疗明显(P＜0.05)，卒中后抑郁患者血小板5-羟色胺的含量正常，氟西汀治疗四周后血小板5-羟色胺的含量较治疗前明显减低(P＜0.05)，常规治疗前后血小板5-羟色胺的含量无明显差异(P＞0.05)，两组治疗前后血浆5 -羟色胺无差异。
氟西汀早期干预卒中后抑郁的临床及实验研究中文提要
结论:卒中急性期卒中后抑郁发生率高;早期应用氟西汀治疗可
减轻PSD症状、促进神经功能康复;血浆5轻色胺检测结果无显著
意义，PSD患者血小板5经色胺含量正常，氟西汀治疗可引起脑卒
中患者血小板5轻色胺含量降低。
Objective
(1) Observing the prevalence of post-stroke depression (PSD) to find out whether or not early anti-depression treatment by fluoxetine can either intervene PSD or be any beneficial to the rehabilitation after stroke.
(2) Researching the relationship between blood 5-HT concentration and PSD to find out the influence of fluoxetine on plasma and platelet 5-HT concentration.
Methods
66 patients who were stroke (2003.09-2004.02) were chosen and divided into fluoxetine treatment group and regular treatment group. The regular treatment group only received regular treatment, while the fluoxetine treatment group received four-week fluoxetine treatment after one week regular treatment. Patients were evaluated by HAMD, ADL and SSS at the 1st week and the 5th week after stroke. Meanwhile, plasma and platelet 5-HT concentrations were measured by high performance liquid chromatography fluorescence detector.
Results
The prevalence of PSD after stroke is 38.24%. The fluoxetine treatment group is scored lower than regular treatment group in the HAMD scale after treatment (P<0.05). Although rehabilitation evaluated by SSS and ADL is found in both groups after 4-week treatment (P<0.05 ) , advantages of fluoxetine treatment can be observed (P<0.05 ) .Generally, the platelet 5-HT concentration of PSD patients is normal, fluoxetine reduced platelet 5-HT concentration after 4-week treatment (P<0.05 ) . No notable difference in platelet 5-HT value can be observed before and after regular treatment (P>0.05) . No notable change in plasma 5-HT concentration can be observed in both groups before and after treatment (P>0.05) . Conclusion
Prevalence of PSD is often after acute stroke. Early treatment by fluoxetine can release the symptom of PSD and promote rehabilitation of PSD patients. The effect of plasma 5HT value is not clear. The platelet 5-HT concentration of PSD patients is normal; however, fluoxetine treatment can reduce the platelet 5-HT concentration of stroke patients.
引文
1. Fuh JL, Liu HC,Wang SJ, et al. Poststroke depression among the Chinese elderly in a rural community. Stroke. 1997,28:1126-1129
2. Robinson RG. Morris PL. Raphael B. Prevalence and course of depressive disorders in hospitalized stroke patients. [J] International Journal of Psychiatry in Medicine. 1990, 20(4): 349-364.
3. Kotila M, Numminen H, Waltimo O, et al. Depression after stroke: results of the FINNSTROKE Study. Stroke. 1998, 29:368-372
4. Gongaleg T, Mendlewicg J, Lobe A. Analysis of intensity of post-stroke depression and its relationship with the cerebral lesion location. Med Clin Barc, 1997;109(7):241-244
5. Vogel CH. Assessment and approach to treatment in post-stroke depression. Am Acad Narse Pract, 1995,7:493-497
6. Hermann M, Bartels C, Schnmasher M, et al. Poststroke depression: is there a pathoanatomic correlate for depression in the postacute stage of stroke. Stroke, 1995;26(5):850-856
7．张通，孟家眉，项曼君．脑卒中后抑郁症的前瞻性研究[J]．中华精神科杂志，1996，29(2)：73-76
8. Starkstein SE. Robinson RG. Affective disorders and cerebral vascular disease[J]. Br J Psychiatry, 1989. 15(4): 170-182
9. Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatr. 1960, 23, 56-62
10. Robinson RG, Murata Y, Shimoda K. Dimensions of social impairment and their effect on depression and recovery following stroke. International Psychogeriatrics. 1999, 11(4): 375-384
11. Paolucci S. Antonucci G, Pratesi L, et al. Poststroke depression and
its role in rehabiliation of inpatients. Archives of Physical Medicine &Rehabiliation, 1999,80(9): 985-989
12. Paradiso S, Robinson RG. Gender differences in poststroke depression. Journal of Neuropsychiatry &Clinical Neurosciences, 1998, 10(1): 41-47
13．龙洁，刘永珍，蔡焯基，等．卒中及抑郁状态的发生率及相关因素研究[J]．中华神经科杂志，2001,34(3)：145-148
14．张庆臣等，脑血管意外伴发抑郁症状群的多因素相关研究．中华神经精神疾病杂志，1993，19(2)：73-75
15．贾艳滨，周迁玲．首发脑卒中后抑郁相关因素的临床研究[J]．中华神经精神疾病杂志．1998，24：66-69
16．苏占清，邵伟波，翟毅．脑卒中后抑郁障碍相关因素及症状特点的研究．现代康复．2001，5(11)：34-35
17．卢伟，蒋波，宋兴旺，谭利明．黛安神与阿米替林治疗脑卒中后抑郁对照研究．现代康复．2000,4(11)：1632
18. Cheer SM,Gon KL. Fluoxetine, a review of its therapeutic potential in the treatment of depression associated with physical illness[J].Drugs, 2001,61:81-110
19. Li C, Ji Z, Nan F, et al. Liquid chromatography/tandem mass spectrometry for the determination of fluoxetine and its main active metabolite norfluoxetine in human plasma with deuterated fluoxetine as internal standard.Rapid Commun[J]. Mass Spectrom , 2002, 16:1844-1850
20. Waswani M, Linda FK,Ramesh S. Role of SSRIs in psychiatry disorders: a comprehensive review. Prog Neuropsychopharmzol. Biol Psychiatry,2003, 27(2):85-102
21. Anderson G, Vestergaard K, Lauritzen LU. Effective treatment of
depression following apoplexy with citalopram [J]. Ugeskr Laeger, 1995,157(14):200
22. Glanzman DL. Postsynaptic regulation of the development and long term plasticity of aplysia sensorimotor synapses in cell culture [J]. J of Neurobiology. 1994,25(6):666-693
23. Hrdina P, Yuu T. Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 rechptors in rat brain: an autoradiographic study [J]. Synapse, 1993, 14:324-331
24. Cole MG, Elic LM, Mcusker J, et al. Feasibility and effectiveness of treatment for post-stroke depression in elderly inpatients: systemstic review[J]. J Geriatr psychiatry Neurol, 2001,14(1):37-41
25. Eran Chemerinski, Robert G, Robinson, et al. Improved recovery in activities of daily living associated with remission of post-stroke depression. Stroke,2001, 32:113-117
26. Gainotti Antonucci G. Marra C. Paolucci S. Relation between depression after stroke, antidepressant therapy, and functional recovery. [J] J Neurosurg Psychiatry,2001, 71(2):258-261
27. Rasmussen A. Lunde M. Poulsen DL.,et al. A double-blind, placebocontrolled study of sertraline in the prevention of depression in stroke patients. Psychosomatics, 2003,44 (3):216-221
28．韩济生主编．神经科学原理．第二版．北京大学出版社，505-522
29. Lloyd KG, Farley IJ, Deck JH, et al. Serotonin and 5-hydroxyindo -leacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 1974; 11:387-397.
30. Asberg M, Eriksson B, Martensson B, et al. Therapeutic effects of serotonin uptake inhibitors in depression. J Clin Psychiatry 1986; 47:23-35.
31. Perez V, Bel N, Celada P, et al. Relationship between blood serotoninergic variables, melancholic traits and response to antidepressant treatments. J Clin Psychopharm 1998;18(2)22-30.
32．吕路线，宋景贵，卢红，等，卒中后抑郁状态患者的血浆、脑脊液单胺类神经递质测定．中华精神科杂志2000：33(1)29-30
33. Camacho, A., Dimsdale, J.E. Platelets and psychiatry: lesions learned from old and new studies. Psychosom. Med. 1997, 62,326-336
34. Pfeffer CR, McBride PA, Anderson GM,Kakuma T, Fensterheim L, Khait V. Peripheral serotonin measures in prepubertal psychiatric inpatients and normal children; association with suicidal behaviour and its risk factors. Biol Psychiatry,1998, 44:568-577
35. Blardi, P., De Lalla, A.,Leo,A. Serotonin and fluoxetine levels in plasma and platelets after fluoxetine treatment in depressive patients. [J] Clin Psychopharmacology. 2002, 22(2): 132-136
36. Maes, M., Meltzer, H.Y. The serotonin hypothesis of major depresssion. In: Bloom, EE, Kupfer, D.J.(EDS).),Psychopharmacology: The Fourth Generation of Progess. Raven Press, New York, 1995, 933-934
37. Muck-Seler, D., Jakovljevic, M., Pivac, N. Platelet 5-HT concentrations and suicidal behavior in recurrent major depression. J. Affect. Disord. 1996, 39, 73-80
38. Pivac,n., Jakovljevic, M, Muck-Seler, D. Hypothalamic-pituitary -adrenal axis function and platelet serotonin concentrations in depressed patients. Psychiatry Res. 1997, 73, 123-132
39. Karege, E, Widmer, J., Bovier, P., Gaillard, J.M. Platelet serotonin and plasma tryptophan in depressed patients: Effects of drug treatment and clinical outcome. Neuropsychopharmacology 1994, 10,207-214
40. Guicheney, P., Leger, D., Barrat, J., Trevoux, R. Platelet serotonin
content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms. Eur. J. Clin. Invest. 1988,18, 297-304
41. Muck-Seler, D., Bujas, M., Ljubic-Thiebal, V. Effect of age on platelet 5-HT concentrations in healthy controls, depressed and schizophrenic patients. Neuropsychobiology 1996b,34, 201-203
42. Mann JJ, McBride PA, Anderson GM. Platelet and whole blood serotonin content in depressed inpatients: Correlations with acute and life-time psychopathology. Biol Psychiatry 1992; 32:243-257
43. Wirz-Justice, A., Puhringer, W. Seasonal incidence of an altered diurnal rhythm of platelet serotonin in unipolar depression. J. Neural Transm. 1988a,42, 45-53
44. Jakovljevic, M., Muck-Seler, D., Pivac, N. Seasonal influence on platelet 5-HT levels in patients with recurrent major depression and Schizophrenia. Biol. Psychiatry. 1997, 41,1028-1034
45. Rausch, J.L, Hobby, H.M., Shendarkar, Johnson, M.E, Li,J. Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically mediated anxiolysis. J. Clin. Psychopharmacol. 2001, 21,139-142
46. Hervas I, Bel N, Fermandez GA, Palacios JM, Artigas F.In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat brain areas differentially innervated by the dorsal and median raphe nuclei. Naunyn Schmiedebergs Arch Pharmacol. 1998, 358;315-322
47. Briley M, Moret C. 5-HT and antidepressants: in vitro and in vivo release studies. Trends Pharmacol Sci 1993, 14:396-397
48. Blier P, de Montigny C. Current advances in trends in the treatment of depression. Trends Pharmacol Sci 1994,15:220-226
2. Robinson RG. Morris PL. Raphael B. Prevalence and course of depressive disorders in hospitalized stroke patients. [J] International Journal of Psychiatry in Medicine. 1990, 20(4): 349-364.
3. Kotila M, Numminen H, Waltimo O, et al. Depression after stroke: results of the FINNSTROKE Study. Stroke. 1998, 29:368-372
4. Gongaleg T, Mendlewicg J, Lobe A. Analysis of intensity of post-stroke depression and its relationship with the cerebral lesion location. Med Clin Barc, 1997;109(7):241-244
5. Vogel CH. Assessment and approach to treatment in post-stroke depression. Am Acad Narse Pract, 1995,7:493-497
6. Hermann M, Bartels C, Schnmasher M, et al. Poststroke depression: is there a pathoanatomic correlate for depression in the postacute stage of stroke. Stroke, 1995;26(5):850-856
7．张通，孟家眉，项曼君．脑卒中后抑郁症的前瞻性研究[J]．中华精神科杂志，1996，29(2)：73-76
8. Starkstein SE. Robinson RG. Affective disorders and cerebral vascular disease[J]. Br J Psychiatry, 1989. 15(4): 170-182
9. Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatr. 1960, 23, 56-62
10. Robinson RG, Murata Y, Shimoda K. Dimensions of social impairment and their effect on depression and recovery following stroke. International Psychogeriatrics. 1999, 11(4): 375-384
11. Paolucci S. Antonucci G, Pratesi L, et al. Poststroke depression and
its role in rehabiliation of inpatients. Archives of Physical Medicine &Rehabiliation, 1999,80(9): 985-989
12. Paradiso S, Robinson RG. Gender differences in poststroke depression. Journal of Neuropsychiatry &Clinical Neurosciences, 1998, 10(1): 41-47
13．龙洁，刘永珍，蔡焯基，等．卒中及抑郁状态的发生率及相关因素研究[J]．中华神经科杂志，2001,34(3)：145-148
14．张庆臣等，脑血管意外伴发抑郁症状群的多因素相关研究．中华神经精神疾病杂志，1993，19(2)：73-75
15．贾艳滨，周迁玲．首发脑卒中后抑郁相关因素的临床研究[J]．中华神经精神疾病杂志．1998，24：66-69
16．苏占清，邵伟波，翟毅．脑卒中后抑郁障碍相关因素及症状特点的研究．现代康复．2001，5(11)：34-35
17．卢伟，蒋波，宋兴旺，谭利明．黛安神与阿米替林治疗脑卒中后抑郁对照研究．现代康复．2000,4(11)：1632
18. Cheer SM,Gon KL. Fluoxetine, a review of its therapeutic potential in the treatment of depression associated with physical illness[J].Drugs, 2001,61:81-110
19. Li C, Ji Z, Nan F, et al. Liquid chromatography/tandem mass spectrometry for the determination of fluoxetine and its main active metabolite norfluoxetine in human plasma with deuterated fluoxetine as internal standard.Rapid Commun[J]. Mass Spectrom , 2002, 16:1844-1850
20. Waswani M, Linda FK,Ramesh S. Role of SSRIs in psychiatry disorders: a comprehensive review. Prog Neuropsychopharmzol. Biol Psychiatry,2003, 27(2):85-102
21. Anderson G, Vestergaard K, Lauritzen LU. Effective treatment of
depression following apoplexy with citalopram [J]. Ugeskr Laeger, 1995,157(14):200
22. Glanzman DL. Postsynaptic regulation of the development and long term plasticity of aplysia sensorimotor synapses in cell culture [J]. J of Neurobiology. 1994,25(6):666-693
23. Hrdina P, Yuu T. Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 rechptors in rat brain: an autoradiographic study [J]. Synapse, 1993, 14:324-331
24. Cole MG, Elic LM, Mcusker J, et al. Feasibility and effectiveness of treatment for post-stroke depression in elderly inpatients: systemstic review[J]. J Geriatr psychiatry Neurol, 2001,14(1):37-41
25. Eran Chemerinski, Robert G, Robinson, et al. Improved recovery in activities of daily living associated with remission of post-stroke depression. Stroke,2001, 32:113-117
26. Gainotti Antonucci G. Marra C. Paolucci S. Relation between depression after stroke, antidepressant therapy, and functional recovery. [J] J Neurosurg Psychiatry,2001, 71(2):258-261
27. Rasmussen A. Lunde M. Poulsen DL.,et al. A double-blind, placebocontrolled study of sertraline in the prevention of depression in stroke patients. Psychosomatics, 2003,44 (3):216-221
28．韩济生主编．神经科学原理．第二版．北京大学出版社，505-522
29. Lloyd KG, Farley IJ, Deck JH, et al. Serotonin and 5-hydroxyindo -leacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 1974; 11:387-397.
30. Asberg M, Eriksson B, Martensson B, et al. Therapeutic effects of serotonin uptake inhibitors in depression. J Clin Psychiatry 1986; 47:23-35.
31. Perez V, Bel N, Celada P, et al. Relationship between blood serotoninergic variables, melancholic traits and response to antidepressant treatments. J Clin Psychopharm 1998;18(2)22-30.
32．吕路线，宋景贵，卢红，等，卒中后抑郁状态患者的血浆、脑脊液单胺类神经递质测定．中华精神科杂志2000：33(1)29-30
33. Camacho, A., Dimsdale, J.E. Platelets and psychiatry: lesions learned from old and new studies. Psychosom. Med. 1997, 62,326-336
34. Pfeffer CR, McBride PA, Anderson GM,Kakuma T, Fensterheim L, Khait V. Peripheral serotonin measures in prepubertal psychiatric inpatients and normal children; association with suicidal behaviour and its risk factors. Biol Psychiatry,1998, 44:568-577
35. Blardi, P., De Lalla, A.,Leo,A. Serotonin and fluoxetine levels in plasma and platelets after fluoxetine treatment in depressive patients. [J] Clin Psychopharmacology. 2002, 22(2): 132-136
36. Maes, M., Meltzer, H.Y. The serotonin hypothesis of major depresssion. In: Bloom, EE, Kupfer, D.J.(EDS).),Psychopharmacology: The Fourth Generation of Progess. Raven Press, New York, 1995, 933-934
37. Muck-Seler, D., Jakovljevic, M., Pivac, N. Platelet 5-HT concentrations and suicidal behavior in recurrent major depression. J. Affect. Disord. 1996, 39, 73-80
38. Pivac,n., Jakovljevic, M, Muck-Seler, D. Hypothalamic-pituitary -adrenal axis function and platelet serotonin concentrations in depressed patients. Psychiatry Res. 1997, 73, 123-132
39. Karege, E, Widmer, J., Bovier, P., Gaillard, J.M. Platelet serotonin and plasma tryptophan in depressed patients: Effects of drug treatment and clinical outcome. Neuropsychopharmacology 1994, 10,207-214
40. Guicheney, P., Leger, D., Barrat, J., Trevoux, R. Platelet serotonin
content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms. Eur. J. Clin. Invest. 1988,18, 297-304
41. Muck-Seler, D., Bujas, M., Ljubic-Thiebal, V. Effect of age on platelet 5-HT concentrations in healthy controls, depressed and schizophrenic patients. Neuropsychobiology 1996b,34, 201-203
42. Mann JJ, McBride PA, Anderson GM. Platelet and whole blood serotonin content in depressed inpatients: Correlations with acute and life-time psychopathology. Biol Psychiatry 1992; 32:243-257
43. Wirz-Justice, A., Puhringer, W. Seasonal incidence of an altered diurnal rhythm of platelet serotonin in unipolar depression. J. Neural Transm. 1988a,42, 45-53
44. Jakovljevic, M., Muck-Seler, D., Pivac, N. Seasonal influence on platelet 5-HT levels in patients with recurrent major depression and Schizophrenia. Biol. Psychiatry. 1997, 41,1028-1034
45. Rausch, J.L, Hobby, H.M., Shendarkar, Johnson, M.E, Li,J. Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically mediated anxiolysis. J. Clin. Psychopharmacol. 2001, 21,139-142
46. Hervas I, Bel N, Fermandez GA, Palacios JM, Artigas F.In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat brain areas differentially innervated by the dorsal and median raphe nuclei. Naunyn Schmiedebergs Arch Pharmacol. 1998, 358;315-322
47. Briley M, Moret C. 5-HT and antidepressants: in vitro and in vivo release studies. Trends Pharmacol Sci 1993, 14:396-397
48. Blier P, de Montigny C. Current advances in trends in the treatment of depression. Trends Pharmacol Sci 1994,15:220-226