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On-line version ISSN 1809-452X
Rev. Bras. Psiquiatr. vol.28 no.3 São Paulo Sept. 2006
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Memantine may acutely improve cognition and have a mood stabilizing effect in treatment-resistant bipolar disorder
Memantina pode melhorar acentuadamente a cognição e possui efeito estabilizador do humor no transtorno bipolar resistente ao tratamento
Bipolar patients can often show cognitive deficits, which are sometimes not associated with acute affective episodes.1 In the most severe cases, cognitive deficits are disabling and may interfere with treatment adherence.
Cholinesterase inhibitors are used in patients with Alzheimer Disease in order to delay cognitive impairment. Donepezil was reported as a useful add-on medication in treatment-resistant bipolar patients in a case series report.2 However, there have also been reports of mania, induced by donepezil and galantamine.3-4
Memantine is an effective drug for the treatment of moderate-to-severe cognitive impairment related to Alzheimer Disease.5 We are reporting two cases of treatment-resistant bipolar disorder patients who showed substantial cognitive and mood symptom improvements.
Case 1 (Table 1): a 29-year-old female fashion stylist with bipolar disorder type II and bulimia nervosa, who used to read and had been able to write short stories, was suffering from severe depression over the last 2 years, having spent most of her time in bed. She was unable to read a newspaper or to write a single letter. Lamotrigine and lithium were useful for 2 years, but they lost their efficacy. Other mood stabilizers (divalproex, carbamazepine, oxcarbazepine) were tried with no success. She did not tolerate some atypical antipsychotics, such as aripiprazol, olanzapine, quetiapine, risperidone and ziprasidone, due to severe tachycardia or reported lack of effect of these medications. In August 2005 she received memantine as an add-on treatment up to 20 mg/day. During the first week following treatment with memantine, she could go to the computer and wrote a short story, spending most of the time out of bed. After one month's treatment, she showed a moderate improvement in psychomotricity and depressive mood, along with cognitive gains.
Case 2 (Table 2): a 32-year-old male judge (retired), with bipolar disorder type I, who had recently suffered from treatment-resistant mixed states, mostly with depressive symptoms. He reported mental incapacity, difficulty in concentrating and in performing abstract reasoning. He also reported hypomanic episodes characterized by compulsive shopping, binge eating and lack of insight. Previous unsuccessful treatments had included divalproex, oxcarbazepine, olanzapine, ziprasidone and haloperidol. The introduction of memantine up to 10 mg/day, in November 2005, promoted a rapid improvement in depressive symptoms, concentration and performance of tasks that were hitherto considered impossible, such as reading. Despite the maintenance of impulsivity, his insight into the compulsive shopping behavior and binge eating improved.
There are similarities in the mechanism of action of memantine, an anti-glutamatergic drug, and lamotrigine, the latest drug associated with antidepressant and mood stabilizing effects in bipolar depressive patients. This mechanism of action could explain the positive effects of memantine in these treatment-resistant patients.
The patients described in this report used medications that could cause cognitive impairment. Memantine could have antagonized these effects, through unclear mechanisms.
To our knowledge, this is the first report on the usefulness of memantine in the treatment of cognitive impairment in bipolar disorder patients. Randomized double-blind controlled studies are needed to validate these preliminary observations.
Chei Tung Teng
Clinical Hospital, Medical School, Group of Affective Diseases and Liaison Psychiatry Group, Institute of Psychiatry, Universidade de São Paulo (USP), São Paulo (SP), Brazil
Frederico Navas Demetrio
Clinical Hospital, Medical School and ambulatory of the Group of Affective Diseases, Universidade de São Paulo (USP), São Paulo (SP), Brazil
1. Osuji IJ, Cullum CM. Cognition in bipolar disorder. Psychiatr Clin North Am. 2005;28(2):427-41.
2. Burt T, Sachs GS, Demopulos C. Donepezil in treatment-resistant bipolar disorder. Biol Psychiatry. 1999;45(8):959-64.
3. Benazzi F. Mania associated with donepezil. J Psychiatry Neurosci. 1999;24(5):468-9.
4. Snorrason E, Stefansson JG. Galanthamine hydrobromide in mania. Lancet. 1991;337(8740):557.
5. Lipton SA. Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurological disorders. J Alzheimers Dis. 2004; 6(6 Suppl):S61-74.
Conflict of interests: None