Giulia Serra, Department of Psychiatry, Harvard Medical School, Boston, MA 02115, United States.
World J Psychiatry. 2014 Dec 22;4(4):80-90. doi: 10.5498/wjp.v4.i4.80.
We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar.
A randomized controlled clinical trial is needed to confirm our naturalistic observations.
We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.
我们回顾了大量临床前和临床证据，这些证据强烈表明，美金刚，一种目前被批准用于治疗老年痴呆症的老药，对于治疗急性躁狂症以及预防躁狂症、双相情感障碍和抑郁发作具有显著疗效。在治疗和预防双相情感障碍方面，锂仍是首选药物，但目前针对锂抵抗患者的替代治疗方法疗效有限，且存在争议。因此，开发更有效的情绪稳定剂药物是现代精神药理学面临的主要挑战。我们已经证明，21 天的丙咪嗪给药会导致大鼠出现类似于双相情感障碍周期的行为综合征，即躁狂后出现抑郁。事实上，这种治疗会导致多巴胺 D2 受体激动剂的行为超敏反应，与性欲增加和攻击性（躁狂）有关。在停止使用丙咪嗪后，多巴胺受体脱敏会导致相反的现象（多巴胺受体脱敏），并在强迫游泳试验中增加不动时间（抑郁）。美金刚可阻断超敏反应的发展以及随之而来的与类似抑郁行为相关的脱敏反应。基于这些观察结果，我们建议将美金刚用于治疗躁狂症和预防双相情感障碍。为了验证这一假设，我们进行了几项自然主义研究，结果表明美金刚具有急性抗躁狂作用和长期且渐进的情绪稳定作用（至少 3 年），且无明显临床副作用。为了证实我们的自然主义试验观察结果，我们目前正在进行一项随机对照临床试验。最后，我们描述了报道美金刚对双相情感障碍以外的精神障碍中出现的躁狂样症状有效作用的研究。
需要进行随机对照临床试验来证实我们的自然主义观察结果。
我们认为，这篇综述提供了足够的药理学和临床信息，可考虑将美金刚用于治疗对标准情绪稳定剂无反应的双相情感障碍。
