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Ind Psychiatry J. 2013 Jul-Dec; 22(2): 149–152.
doi: 10.4103/0972-6748.132930
PMCID: PMC4085808
An open-label trial of memantine in
treatment-resistant obsessive-compulsive
disorder
Ajay Kumar Bakhla, Vijay Verma, Subhas Soren,1 Sujit Sarkhel,2 and Suprakash Chaudhury3
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Abstract
Background:
Obsessive-compulsive disorder (OCD) is often refractory to treatment. Glutamatergic
neurotransmission modulating agents like memantine, an N-methyl-D-aspartate receptor open
channel blocker (antagonist), has been reported to be beneficial in OCD.
Materials and Methods:
Twelve subjects of OCD who had been on various medications for over 5 years, but were poor
responders, were enrolled for a 12-week open-label trial with fixed dose trial of memantine as an
augmenting agent. The OCD symptoms and adverse effects of the drug were monitored.
Results:
Out of 12 subjects, eight had clear benefit, with reduction of 25% or more on Yale-Brown
Obsessive-Compulsive Scale, and there were no side-effects with the medication,
Conclusion:
Memantine may be beneficial for treatment-resistant OCD as an augmenting agent.
Keywords: Glutamatergic modulation, memantine, obsessive compulsive disorder
Recent literature strongly implicate disrupted neurotransmission of glutamate within the corticostriato-thalamocortical circuitry in the pathogenesis of obsessive-compulsive disorder
(OCD).[1,2] Based on this, drugs modulating glutaminergic neurotransmission like Riluzole[3] –
a glutamatergic neurotransmission modulating agent and memantine[4,5,6,7,8] are being used in
treatment of OCD. These case reports and open-label studies have shown the beneficial effect of
memantine in case of OCD even in refractory and pediatric OCD. In view of available literature,
we planned this open-label trial using fixed dose memantine in few OCD patients as augmenting
agent, who were not responding to standard routine pharmacotherapy.
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MATERIALS AND METHODS
The study was conducted at Ranchi Institute of Neuropsychiatry and Allied Sciences, Ranchi.
The Institutional Review Board of the institute approved the protocol. The sample consisted of a
total of 13 patients, who gave informed consent for participation in the study. All subjects had at
least moderately severe symptoms of OCD with Yale-Brown Obsessive-Compulsive Scale (YBOCS)[9] scores above 25. There was persistence of symptoms for at least 5 years, despite
having been put on at least two adequate trials (both in terms of dose and duration) of different
Serotonin Reuptake Inhibitors or anti-obsessional medications with or without augmentation by
any antipsychotic medications or exposure and response prevention therapy. The exclusion
criteria were presence of any medical or psychiatric co-morbid conditions. Memantine was
started at 5 mg/day, hiked up to 10 mg/day at the end of 4 weeks and this dose was kept constant
throughout the study period [Table 1]. The subjects continued previously prescribed medications
throughout the study period, but did not initiate new medications, nor did they engage in any new
psychotherapy. The severity of OCD was assessed with Y-BOCS at baseline and after that every
week until completion of 12 weeks of memantine use. Subjects were also assessed weekly for
adverse effects with the Udvalg for Kliniske Undersøgelser (UKU) side-effect rating scale.
Memantine was continued after the end of the 12 weeks if desired by subjects.
Table 1
Demographic characteristics Y-BOCS scores of treatment resistant obsessive-compulsive
disorder patients
Data were analyzed using SPSS version 16.0. Normality of distribution of the data was assessed
using Shapiro Wilk test, which revealed that the data were normally distributed. Descriptive
statistics was used for socio-demographic and clinical variables. Independent samples t-test was
used to compare treatment responders with non-responders across various socio-demographic
and clinical variables. Wilcoxon signed-rank test was used to compare the Y-BOCS scores at
baseline and 12 weeks after treatment.
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RESULTS
One patient was dropped from the study for stopping her medications in between; rest 12 patients
participated in the augmentation for 12 weeks. Mean age of the sample was 30.33 years (SD =
6.84) and the mean duration of illness was 94.5 months (SD = 22.17). Response was defined as
25% or more reduction in Y-BOCS scores within 12 weeks. There were eight responders and
four non-responders. Among responders, mean baseline Y-BOCS score was 29.25 (SD = 3.37),
which reduced to a mean of 16.37(SD = 3.07) at the end of 12 weeks, i.e., 44% improvement
from baseline. When the responder group was compared with the non-responder group in terms
of age, duration of illness and baseline Y-BOCS scores, no significant difference was found
between the two groups (P>0.05).
Wilcoxon signed-rank test revealed a significant difference in Y-BOCS total scores between
baseline and week 12 (P<0.002). Similarly, the mean Y-BOCS obsession and Y-BOCS
compulsion scores at baseline and at week 12, are showed a significant difference (P<0.003 and
0.002) [Table 2]. There were no significant side-effects reported for the study period as measured
with UKU side-effects rating scale.
Table 2
Characteristics of non-responders and responders to memantine augmentation and change in YBOCS ratings at 12 weeks compared to baseline
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DISCUSSION
The response to currently available treatments in OCD is about 40% to 60% in terms of
reduction in Y-BOCS scores,[10] which remains a major concern for clinicians and morbidity for
patients in our day-to-day clinical practice. Based on earlier reports about the mechanism and
improvement reported by memantine, we carried out this open-label trial. This study, though of
small sample size, supported the role of NMDA receptor and Glutamate in OCD and showed
significant improvement with memantine. This is in accordance with a few previous
studies.[4,5,6,7,8] We found good result in eight patients with mean Y-BOCS reduction of 44%
in good responders as compared to 14% in non- responders and for the total sample, it was
37.4% improvement. This is in accordance to previously reported rates of 40.6%[6] and 27%.[5]
Although the duration of 12 weeks was the same as of our study, previous studies used higher
dose (20 mg/day) of memantine in comparison to 10 mg/day in our study [Table 3]. This may be
attributable to specific profile of Indian population, and we also plan a higher dose up to 20
mg/day in non-responders of this study. There was no significant side-effect found in this study,
which may again be attributed to a lower dose selection. Thus, if equal efficacy can be
established in further studies with a lower dose of memantine, it would help in reducing the
potential for adverse effects in the patient population.
Table 3
Comparison with earlier studies using memantine as augmenting agent in treatment-resistant
obsessive-compulsive disorder patients
One of the patients stopped all her previous medications on her own and continued with
memantine alone, and she found good response at 5th week, but her obsessive compulsive (OC)
symptoms reappeared by 9th week, we dropped this case from the final analysis. Almost all of the
patients were satisfied with the inclusion of memantine and were willing to continue with it
beyond the study period.
Future studies should involve randomized controlled trials for more definitive evidence of the
efficacy of memantine as an adjunctive treatment in resistant OCD as well as looking for clinical
predictors for response with adequate sample size.
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CONCLUSION
Memantine augmentation was beneficial in resistant OCD and was well-tolerated in this openlabel trial.
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Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
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