Treatment strategy in depression. I. Non-tricyclic and selective reuptake inhibitors in resistant depression: a double-blind partial crossover study on the effects of oxaprotiline and fluvoxamine

Antidepressants are ineffective in about 30% of patients with major depression. Some authors then advise treatment of non-responders with (non-tricyclic) more selective reuptake inhibitors. In a double-blind, partial crossover study, 71 patients were selected for treatment during 4 weeks with oxaprotiline and/or fluvoxamine, two non-tricyclic antidepressants that are selective reuptake inhibitors or noradrenaline and serotonin respectively. All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode. Only 13% of the patients responded, with 27% of them responding to oxaprotiline and none to fluvoxamine. Moreover, a low response of 27% was also obtained in the crossover phase, which included all non-responders to the first treatment, oxaprotiline being effective in 39% and fluvoxamine in 10% of the patients. The results indicate that selective reuptake inhibitors are not an effective alternative for non-responders to other cyclic antidepressants and that non-responders to "noradrenergic" antidepressants do not appear to have much chance of responding to "serotonergic" antidepressants and vice versa.     

In vitro interactions between fluoxetine or fluvoxamine and methadone or buprenorphine

Summary— Methadone and buprenorphine, widely used in the treatment of opioid abuse, are metabolized by cytochrome P450 3A4, while fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors, are known to be P450 2D6 and 3A4 inhibitors in vitro. This study deals with the in vitro interactions between methadone or buprenorphine and fluoxetine or fluvoxamine. Fluoxetine inhibited methadone N -demethylation (K i = 55 μM), but conversely did not inhibit buprenorphine dealkylation. Norfluoxetine inhibited the metabolism of both methadone and buprenorphine metabolisms (K i 13 and 100 μM, respectively). Fluvoxamine inhibited methadone N -demethylation with a K i of 7 μM and buprenorphine dealkylation, uncompetitively, with a K i of 260 μM. Finally, these results suggest that care should be taken when selective serotonin reuptake inhibitors are administered in the treatment of drug craving. This is particularly true in the case of fluvoxamine which is more potent than fluoxetine in inhibiting methadone and buprenorphine metabolism.     

氟伏沙明与帕罗西汀治疗强迫症对照研究

目的探讨氟伏沙明与帕罗西汀治疗强迫症的临床疗效及安全性。方法将56例强迫症患者随机分为研究组和对照组各28例,分别给予氟伏沙明、帕罗西汀治疗。观察8周。于治疗前及治疗4周、8周末采用Yale-Brown强迫量表,副反应量表评定临床疗效和不良反应。结果治疗后两组Yale-Brown强迫量表评分均较治疗前有显著下降（P〈0．01）;治疗8周末研究组有效率为75％,对照组为78．5％,两组差异无显著性（P〉0．05）;两组不良反应均轻微,发生率无显著性差（P〉0．05）。结论氟伏沙明治疗强迫症疗效显著,与帕罗西汀相当,安全性高,依从性好。     

Selective serotonin reuptake inhibitors and withdrawal symptoms: a review of the literature

There are accumulating reports of withdrawal symptoms emerging following the discontinuation of selective serotonin reuptake inhibitor antidepressants. This report summarizes published reports, characterizes the withdrawal syndrome, discusses potential mechanisms of withdrawal, and makes recommendations for prevention and management. A computerized search was conducted using MEDLINE (1985–1996) to retrieve all case reports and pertinent studies of antidepressant withdrawal. A total of 46 case reports and two drug discontinuation studies were retrieved. All of the selective serotonin reuptake inhibitors were implicated in withdrawal reactions with paroxetine most often cited in case reports. Withdrawal reactions were characterized most commonly by dizziness, fatigue/weakness, nausea, headache, myalgias and paresthesias. The occurrence of withdrawal did not appear to be related to dose or treatment duration. Symptoms generally appeared 1–4 days after drug discontinuation, and persisted for up to 25 days. Time of onset and duration of symptoms differed little among the agents. The pathophysiology/pharmacology of withdrawal is unclear but may involve multiple neurotransmitter systems. It is concluded that all of the SSRIs can produce withdrawal symptoms and if discontinued, they should be tapered over 1–2 weeks to minimize this possibility. Some patients may require a more extended tapering period. No specific treatment for severe withdrawal symptoms is recommended beyond reinstitution of the antidepressant with subsequent gradual tapering as tolerated. © 1997 John Wiley & Sons, Ltd.     

齐拉西酮联用氟伏沙明治疗难治性抑郁症的临床对照研究

目的：观察齐拉西酮联用氟伏沙明治疗难治性抑郁症的疗效。方法：将符合条件的60例难治性抑郁症患者随机分成两组,分别给与齐拉西酮联用氟伏沙明（联用组）和单用氟伏沙明（对照组）,进行12周的系统治疗,使用HAMD（汉密尔顿抑郁量表）和HAMA（汉密尔顿焦虑量表）评估其疗效;以TESS（副反应量表）和有关的实验室检查评定副反应。结果：治疗以后两组患者的HAMD评分均明显下降,联用组的治疗效果较好,两组之间差异存在显著性（P〈0.01）,并且联用组起效快;而两组HAMA量表的评分明显下降,联用组的治疗效果较好,两组之间差异存在显著性（P〈0.01）,联用组起效快,联用组的副反应发生率高于对照组,但差异无显著性;两组药物引起的副反应均为轻度或中度,表现有所不同,患者耐受性好。结论：齐拉西酮联用氟伏沙明治疗难治性抑郁症的疗效优于单独使用氟伏沙明组,且联用组起效较快,并且对于焦虑症状的改善好于对照组;两组副反应较轻,副反应的表现有所不同。联用这两种药物对于治疗难治性抑郁症具有良好的疗效,且安全性高。     

氟伏沙明与氟汀治疗强迫症对照研究

目的探讨氟伏沙明与氟西汀治疗强迫症的临床疗效及安全性。方法将48例强迫症患者随机分为研究组25例,对照组23例,研究组口服氟伏沙明治疗,对照组口服氟西汀治疗,观察8w。于治疗前及治疗2w、4w、8w末采用Yale—Brown强迫量表、汉密顿抑郁量表、副反应量表评定临床疗效和不良反应。结果治疗8w末研究组有效率为84％,对照组为82．6％;Yale-Brown强迫量表、汉密顿抑郁量表评分,研究组治疗2w末起,对照组治疗4w末起较治疗前均有显著下降（P〈0．05或0．01）;研究组治疗2w末均较对照组下降显著（P〈0．05）,其它时点评分均无显著性差异（P〉O．05）;两组不良反应发生率较低,程度较轻微,经对症处置后可消失或缓解。结论氟伏沙明治疗强迫症疗效与氟西汀相当,安全性高,服药依从性好,但氟伏沙明治疗起效更快。     

氟伏沙明联合氯米帕明治疗强迫症对照研究

目的探讨氟伏沙明联合氯米帕明治疗强迫症的临床疗效及安全性。方法将45例强迫症患者随机分为两组,研究组25例,口服氟伏沙明联合氯米帕明治疗;对照组20例,单用氯米帕明治疗。观察8w。于治疗前及治疗8w末采用Yale-Brown强迫量表,汉密顿焦虑量表、汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果治疗8w末研究组显效率为80%,对照组为50%,研究组显效率显著高于对照组（χ^2=4.09,P〈0.05）。Yale-Brown强迫量表,汉密顿焦虑量表、汉密顿抑郁量表评分,治疗8w末两组均较治疗前有显著下降（P均〈0.01）,但研究组均较对照组下降显著（P均〈0.05）。研究组不良反应多在联用氯米帕明治疗的第1w出现,且程度及发生率显著低于对照组。结论氟伏沙明联合氯米帕明治疗强迫症疗效显著,且安全性高。