Memantine as an Augmentation Treatment for Schizophrenia: Limitations of Meta-Analysis for Evidence-Based Evaluation of Research

Is Memantine Effective as an NMDA Receptor Antagonist in Adjunctive Therapy for Schizophrenia?

“…After the report by Parsons et al in 1999, it was reported that memantine has antagonist activity on 5-HT 3 receptors and that 5-HT 3 receptor antagonist activity might be related to improved negative symptoms in schizophrenia [ 90 ]. However, the IC 50 values of memantine for serotonin-induced inward currents in HEK-293 cells expressing 5-HT 3A receptors and in the N1E-115 cell line with native 5-HT 3 receptors were reported to be 2.2 and 2.29 μM, respectively [ 91 ].…”

“…The IC 50 values were approximately two-fold higher compared to the therapeutically relevant serum concentrations (around 1 μM), suggesting that the effects of adjunctive administration of memantine on negative symptoms does not seem to derive mainly from its 5-HT 3 receptor antagonist activity. Memantine has complex actions on α4β2, α7, and other nicotinic cholinergic receptors [ 90 ], and these actions may be related to the amelioration of cognitive impairments in schizophrenia [ 90 , 92 ]. However, it was reported that memantine inhibits α4β2 responses with an IC 50 of 6.6 or 11.3 μM; these concentrations are much higher than the therapeutic concentrations (around 1 μM) [ 55 ].…”

“…Memantine, at the concentrations between 200 and 2000 nM, directly acted on D 2 High receptors to decrease prolactin release from isolated anterior pituitary cells [ 94 ]. The stimulating effect could be associated with the positive symptoms of schizophrenia, but it may contribute to the amelioration of negative symptoms [ 90 ]. However, it was reported that memantine does not decrease serum prolactin levels in humans [ 95 ], which suggests that memantine could not exhibit dopamine D 2 receptor agonist activity in the human CNS.…”

Catatonic schizophrenia as a persistent therapeutic challenge – a case report

“…The positive aspect is the patient's good response to the added doses of me mantine. Despite the lack of registered indications for the use of memantine in schizophrenia and inconclu sive scientific reports on the drug's effectiveness in this illness, an attempt was made to initiate treatment with the hope of obtaining a beneficial effect on cognitive functions [14,15].…”

“…Pozytywnym aspektem jest jednak dość dobra odpowiedź pacjenta na dołączoną memantynę. Mimo braku zarejestrowanych wskazań do stosowania me mantyny w schizofrenii oraz niejednoznacznych doniesień naukowych o skuteczności leku w tym schorzeniu, podjęto próbę włączenia leczenia z nadzieją uzyskania korzystnego wpływu na funkcje poznawcze [14,15].…”