● Original Antidepressive Effect of Nicergoline on Patients with Mild Post-stroke Depression Yasuhiro Nishiyama1）, Yuichi Komaba1） Sunao Mizumura2） and Yasuo Katayama1） Abstract Background and Purpose : Post-stroke depression（PSD）is considered the most frequent and important neu- ropsychiatric complication in stroke patients. Antidepressants are commonly used in the treatment of severe PSD, but these drugs are not necessarily administered to patients with mild PSD. Nicergoline is an ergoloid mesylate derivative currently used for the treatment of cognitive and behavioral disorders of older people or neuropsychological impairments in cerebrovascular disorders, though antidepressive effects of nicergoline is unknown. We investigated whether nicergoline is effective on patients with mild PSD instead of antidepres- sants. Methods : We selected 6 patients with mild PSD defined by the Zung’s self-rating depression scale（SDS）1 month after the onset of stroke. Nicergoline（15 mg!day）was administered for four weeks to the patients one month after the onset of cerebral infarction. Depression was also evaluated using SDS after administration of nicergoline. Furthermore, we evaluated the effect of nicergoline on three subscales of SDS, i.e., cognitive, affec- tive and somatic symptoms. Results : The SDS score improved significantly in all patients after treatment（p＝0.0042）. The analysis of three subscales revealed that the cognitive symptom in the SDS scores is a significant improved（p＝0.026）. Conclusions : Our findings suggest that niceijoke nicergoline has antidepressive effect on patients with mild PSD instead of antidepressants and diagnosis of PSD should be performed in early period of stroke. （Cerebral Blood Flow and Metabolism 17 : 11―16, 2005） Key words : nicergoline, depression, cerebrovascular disease adverse impact on functional recovery2） and sur- Introduction vival3）. It has previously been reported that PSD is an independent predictor of poor long-term func- Symptoms of depression, such as deteriorated mo- tional outcome4,5）. Recent reports underlined the im- tivation and apathy, after stroke are collectively portance of early treatment for PSD that can have a called poststroke depression（PSD）, and the concept positive effect on rehabilitation and functional recov- of PSD has been established in recent years. Post- ery of the patients6,7）. stroke depression（PSD）is considered as the most Nicergoline is an ergoloid mesylate derivative with frequent and important neuropsychiatric complica- pharmacological actions such as cerebral metabo- tion in stroke patients, since 12％ to 64％ of stroke lism-improving action8） and cerebral neurotransmi- survivors experience depression both early and late ssion-improving action9）. Nicergoline is also effective after stroke1） and since this condition can have an from the clinical view point in improving decreased motivation and initiative10）. However, effect of nicer- 1）The Second Department of Internal Medicine, 2）Depart- goline for PSD is unclear. In the treatment of PSD, ment of the Radiology, Nippon Medical School tricyclic, tetracyclic antidepressants, or selective ―11― 脳循環代謝 第 17 巻 第 1 号 Table 1. Background SDS 1 Age Diagnosis Atrial Case Sex month after Hypertension Hyperlipidemia Diabetes Smoking （yr） （lesion location） fibrillation onset 1 81 F Atherothrombotic infarction 52 ＋ ＋ － － － （left putamen to radio corporis callosi） 2 76 M Atherothrombotic infarction 51 ＋ － － － ＋ （left arteria cerebri media area） 3 55 M Atherothrombotic infarction 46 － － － － ＋ （left pons） 4 68 M Cardiogenic cerebral embolism 46 － － － ＋ ＋ （left arteria cerebri anterior area） 5 67 M Lacunar infarction 44 ＋ － ＋ － － （left medulla oblongata） 6 77 F Cardiogenic cerebral embolism 41 ＋ － － ＋ － （right arteria cerebri posterior area） serotonin reuptake inhibitors（SSRI）is commonly ad- ministered, but cannot be administered to some pa- tients, especially elderly patients, because of their side effects. As a result, these antidepressants are not often administerd to patients with mild PSD. Here we investigate whether nicergoline has antide- presseive effect on mild PSD. Subjects and Methods Fig. 1. Changes in Zung self-rating depression scale The present study included 30 of 36 consecutive （SDS）scores after treatment with nicergoline. All pa- patients with their first significant acute-ischemic tients treated with nicergoline had significantly better stroke admitted to the Department of Neurology, scores after treatment with nicergoline（p＝0.0042 ; paired t-test）. The scores changed from 47.17±4.26 to Nippon Medical School between June and Septem- 40.33±4.96. There was a significant reduction of the ber 2002. Diagnosis of stroke was made clinically by scores after treatment with nicergoline. stroke with experienced stroke neurologists using the Trial of ORG 10172 in Acute Stroke Treatrment （TOAST）criteria11）. All patients was underwent CT Of these patients, 4 were male, and 2 were female ; and!or MRI scanning. We selected the 30 patients their mean age±SD was 70.6±9.4 years（range, 55 who met the following criteria（I）no : severe apha- to 81）. The patients’clinical backgrounds data are sia（II）no ; reduced level of consciousness（III）no ; summarized in Table 1. One tablet（5 mg）of nicer- dementia（IV）no ; alcohol abuse（V）no ; psychosis goline was administered three times daily for four or current antidepressant treatment. Six of 36 pa- consecutive weeks. PSD was also evaluated by SDS tients were excluded. All 30 patients were evaluated after the administration of nicergoline. The 20 items using the Zung SDS12） one month after the onset. of SDS were divided into the following three The 20 items of SDS are scored according to a stan- subscales according to the report of Sakamoto et dard 4-point scale（1 to 4）for each item, with a poten- al14）. 1）cognitive symptoms, 2）affective symptoms, tial range of 20 to 80. Mild PSD was defined be- and 3）somatic symptoms. SDS item Nos. 11, 12, 14, tween 40 and 59 points according to the the report 16, 17, 18, and 20, Nos. 1, 3, 10, 13, and 15, and Nos. 4, of Herrmann2） and Ohira13）. From among patients, six 5, 7, and 9 were considered to represent cognitive, patients were remained, meeting mild PSD criteria. affective and somatic symptoms, respectively. Cere- All six patients were administerd with nicergoline. bral blood flow was also quantified in one patient be- ―12― Nicergoline for Depression after Stroke Fig. 2. Changes in three subscales of SDS after treatment with nicergoline. After treatment with nicergoline, cognitive symptoms were significantly improved（p＝ 0.026 ; paired t-test）. However, no statistically significant differences were found regarding affective symptoms（p＝0.091 ; paired t-test）or somatic symptoms（p＝ 0.095 ; paired t-test）. Fig. 3. Cerebral blood flow and images obtained by single photon emission com- puted tomography（SPECT）with N-idopropil-p-［123I］-iodoamphetamine（123I-IMP） before and after treatment with nicergoline in Case 1. A. Cerebral blood flow was quantified before and after treatment with nicergoline in relation to the location of the lesions. B . Imaging of cerebral blood flow by SPECT before and after treat- ment．（before : before nicergoline treatment ; after : after nicergoline treatment） Little increases of the cerebral blood flow in the occipital cortex and in the thala- mus on the left side, as well as approximately 10％ increases in the bilateral striata were noticed, but no other clear changes were observed. ―13― 脳循環代謝 第 17 巻 第 1 号 fore and after nicergoline treatment using on recovery of functions, some authors4,5） have con- N-idopropil-p-［123I］-iodoamphetamine（123I-IMP）single firmed that PSD is an independent predictor of poor photon emission computed tomography（SPECT）. long-term functional outcome. The influence of PSD The location of the lesion detected by SPECT was on post-stroke outcome has been confirmed by a re- as follows : frontal lobe, temporal lobe, parietal lobe, cent study18）, which has shown that the presence of occipital lobe, white matter, striatum, thalamus, PSD 1 month after stroke increases the risk of mor- brainstem and cerebellum, as previously reported15,16）. tality 12 and 24 months later. Gonzalez-Torrecillas et Changes in SDS scores after nicergoline administra- al6） and, recently Miyai and Reding7） and Chemerin- tion were statistically assessed using a paired t-test. ski et al.19） underlined the importance of early treat- ment for PSD that can have a positive effect on the Results outcome of the patients. Depression itself is responsi- ble for the delay in rehabilitation and the prevention As illustrated in Figure 1, SDS scores after treat- of functional recovery. Therefore, diagnosis of PSD ment with nicergoline were significantly improved in should be performed in early period of stroke. all the patients（p＝0.0042 ; paired t-test）.Theim- Moreover, we divided the 20 items of SDS into provement shown by the three subscales was statis- three subscales, that is cognitive, affective and so- tically analyzed. As shown in Figure 2, cognitive matic symptoms, and then compared the scores of symptoms showed a significant improvement after these subscales obtained before and after treatment treatment（p＝0.026 ; paired t-test）. No statistically with nicergoline. Our results revealed a significantly significant differences were found regarding affec- better improvement of cognitive symptoms, while tive symptoms（p＝0.091 ; paired t-test）or somatic there was no significant improvement in affective or symptoms（p＝0.095 ; paired t-test）. Cerebral blood somatic symptoms. In a previous study, nicergoline flow in Case 1 is shown in Figure 3. Apart from a lit- was found to inhibit the activity of brain acetyl- tle increases of the cerebral blood flow in the occipi- cholineesteraseinmiceandrats20）. The central tal cortex and the thalamus on the left side and ap- cholinergic system is known to play a fundamental proximately 10％ increases of blood flow in the bilat- role in cognitive function, and extensive evidence in- eral striae, no other noticeable changes were ob- dicates that a disruption of the cholinergic function served. leads to characterisic signs of aging and Alzheimer’s disease.