Memantine as an augmentation therapy in obsessive–Compulsive disorder

Parul Gupta; Shazia Anjum; Leezu Bhusri; Angad Harshbir Singh

doi:10.4103/jmhhb.jmhhb_20_19

CASE REPORT

Year : 2019 | Volume : 24 | Issue : 1 | Page : 60-62

Memantine as an augmentation therapy in obsessive–Compulsive disorder

Parul Gupta, Shazia Anjum, Leezu Bhusri, Angad Harshbir Singh
Department of Psychiatry, Maharishi Markandeshwar Institute of Medical Sciences and Research, Ambala, Haryana, India

Date of Web Publication

4-Jun-2020

Correspondence Address:
Shazia Anjum
Block-H Flat No. 11 MMU, Mullana, Ambala - 133 207, Haryana
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/jmhhb.jmhhb_20_19

Abstract

Obsessive Compulsive Disorders a mental illness, which is long lasting and the person has recurrent thoughts or mental images and compulsive acts, which the person is unable to resist. SSRI and TCA are primarily used drugs for obsessive-compulsive disorder (OCD), but in few patients these lead to less response and some other augmenting drugs have to be added along with them. A role for glutamatergic dysfunction in the pathophysiology of OCD has been found. We report 2 cases with a diagnosis of OCD where the patients did not show good response on YBOCS with SSRI and other adjunctive drugs like venlafaxine, resperidone in adequate dose and duration. When memantine was added (20 mg) the patient showed improvement on YBOCS where score reduced within the 6 weeks of augmentation.

Keywords: Memantine, OCD, Residual symptoms, YBOCS

How to cite this article:
Gupta P, Anjum S, Bhusri L, Singh AH. Memantine as an augmentation therapy in obsessive–Compulsive disorder. J Mental Health Hum Behav 2019;24:60-2

How to cite this URL:
Gupta P, Anjum S, Bhusri L, Singh AH. Memantine as an augmentation therapy in obsessive–Compulsive disorder. J Mental Health Hum Behav [serial online] 2019 [cited 2023 Jun 4];24:60-2. Available from: https://www.jmhhb.org/text.asp?2019/24/1/60/285988

Introduction

Obsessive–compulsive disorder (OCD) is a mental illness, in which the person has obsessions as well as compulsions. Obsessions are ideas, images, or impulses that enter the individual's mind again and again in a stereotyped manner. Compulsive acts or rituals are the stereotyped behaviors that are repeated again and again.^[1] Selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant are the first-line drugs in most cases; treatment should be initiated with a SSRI because of the superior safety, tolerability, and equivalent efficacy of this class of drugs compared with clomipramine.^[2] When dealing with patients who do not respond to one SSRI even after adequate dose and time duration, then augmentation with other drugs such as venlafaxine, risperidone, lithium, buspirone, and memantine is recommended. Initial relief is observed in 4–6 weeks and maximum result in about 8–16 weeks.^[3] Risperidone was found to increase the obsessions but at a higher dose of more than 3 mg/day. At lower dose, it helps as an augmenting agent in case of OCD.^[4] Unfortunately, a significant proportion of patients are refractory to these treatment modalities as well. Memantine, which is an N-methyl-D-aspartate (NMDA) antagonist, is also found to be a good agent as an augmentation therapy for OCD. The frontostriatal circuits implicated in compulsivity and impulsivity are notable for their relatively rich glutamatergic receptor density. Moreover, glutamate modulates the metabolism and function of the frontostriatal circuits. Glutaminergic projections to and from the various frontal subregions (orbitofrontal cortex, infralimbic cortex, and prelimbic cortex) to the striatum play a key role in the regulation of various compulsive behaviors in humans including (1) the feeling of loss of control (OCD), (2) repetitive motor behaviors (stereotypy in autistic spectrum disorder), and (3) a maladaptive habitual pattern (addiction). Neuroimaging studies have confirmed that glutamatergic projections between the various frontal subregions and the striatum play a key role in the regulation of compulsive behaviors in humans. Compulsivity has been associated with increased glutamatergic activity in the striatum and the anterior cingulate cortex in clinical magnetic resonance spectroscopy studies.^[5] Glutamate, the predominant excitatory neurotransmitter in the central nervous system, is thought to play an important role in the pathophysiology of anxiety. Memantine partially inhibits NMDA glutamate receptors, thus dampening synaptic glutamate availability. The authors feel that memantine, given its ability to manipulate the gamma-aminobutyric acid–glutamate balance by lowering glutamate without major side effects (weight gain and sexual problems, i.e., SSRI/serotonin-norepinephrine reuptake inhibitor [SNRI]) or addiction (i.e., sedatives) may be a reasonable add-on or augmentation strategy to better alleviate anxiety in SNRI or SSRI partial responders.^[6] Memantine, although is beneficial as an augmenting agent in OCD, is not used frequently. Therefore, we report these cases where its addition improved the clinical outcome of the disease.

Case Reports

Case 1

A 38-year-old female, educated till 12^th class, married, homemaker, Hindu, with premorbid condition of introvert, calm, and responsible, with no significant past history and family history, presented with complaints of fear of contamination, repetitive hand washing for the past 9 months, and low mood for the past 3 months. She had repeated urges to wash hands, clothes, and home. The same activity and chores were done multiple times in a day, despite her hands, clothes, and home being clean. These led to disturbance in her daily activities and sleep disturbances and also made her restless. On mental status examination, mood was sad, affect was anxious, obsession of cleanliness and compulsions of washing were present. The severity of symptoms was assessed by Yale–Brown Obsessive–Compulsive Scale (YBOCS) [Table 1].

Table 1: Treatment change; dosage and the corresponding YBOCS Score (Case 1)

Click here to view

The patient is maintaining well on this dose and session of cognitive behavioral therapy every 3 weeks. A written informed consent was obtained from the patient.

Case 2

A 26-year-old male, graduate, unmarried, doing private job, with premorbid condition of extrovert, short tempered, and organized, with no significant past history and family history of OCD in mother, presented with complaints of repetitive thoughts for the past 3 months and irritability for 1 month. This led to a lot of distress in his daily routine activities; he had a lot of trouble at his workplace also. He always tried to control those thoughts by trying to engage in recreational activities by diverting his attention to some other work but was not able to do so. On mental status examination, affect was anxious and rumination of thought was present. YBOCS was used to assess the symptoms [Table 2]. A written informed consent was obtained from the patient.

Table 2: Treatment change; dosage and the corresponding YBOCS Score (Case 2)

Click here to view

Discussion

In our study, full trials of SSRI were given, but not much improvement was reported; still, the patients had the symptoms with the same intensity as seen by the YBOCS score. Then, augmentation was thought of with the atypical antipsychotics which were given for an adequate period of time, but again, the patents did not report much improvement. Therefore, memantine was added, which was found to have good results according to the above-mentioned studies. It was observed that patients showed much improvement with the memantine at the dose of 20 mg/day in about 8 weeks. In case 1, it was added with fluoxetine and risperidone, whereas in case 2 with fluvoxamine and risperidone.

A significant response is seen with SSRI monotherapy when given for <2 weeks, and a greater improvement is seen when given in maximum doses.^[7]

However, in our case, there was an inadequate response observed with SSRIs even in maximum doses given for adequate duration. It was observed that glutaminergic drugs do not have any additional effect on OCD not responding to other first-line drugs; in fact, side effects were seen;^[8] clomipramine has been found to be significantly more effective than placebo in multiple randomized control trials and meta-analysis of RCTs.^[9] No doubt SSRI is effective at higher doses in OCD, but the increased efficacy comes at the cost of poor tolerability as evidenced by increased dropouts due to adverse effects according to a study by Bloch et al.^[10] Memantine has been reported as an effective add – on in an open-label trial of memantine in treatment-resistant OCD by Aboujaoude et al.^[11] Furthermore, a study conducted in Iran showed that memantine is an effective and well-tolerated augmentation in patients with severe OCD refractory to SSRI monotherapy showing reduction in the YBOCS score.^[12] Accordingly, both the cases have responded to memantine. Thus, memantine plays an important role in OCD cases not showing improvement with the first-line drugs when given in adequate dose and duration. Addition of memantine maintains the compliance of the patient without any significant side effect.

Conclusion

Memantine can be used as an effective drug for augmentation in patients of OCD showing less response with other augmenting agents.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostics Guidelines. Geneva: World Health Organization; 2002. p. 142-5.
2.	Goodman WK. Obsessive-compulsive disorder: Diagnosis and treatment. J Clin Psychiatry 1999;60 Suppl 18:27-32.
3.	Sadock BJ, Sadock VA, Ruiz P. Obsessive-compulsive and related disorders. In: Sadock BJ, Sadock VA, Ruiz P, editors. Kaplan and Sadocks's Synopsis of Psychiatry. 11^th ed. Philadelphia, PA, USA: Lippincott, Williams and Wilkins; 2016. p. 418-36.
4.	Collantes C. Antipsychotic-induced obsessive-compulsive disorder. Rho Chi Post 2015;5:6-8.
5.	Häge A, Banaschewski T, Buitelaar JK, Dijkhuizen RM, Franke B, Lythgoe DJ, et al. Glutamatergic medication in the treatment of obsessive compulsive disorder (OCD) and autism spectrum disorder (ASD) – Study protocol for a randomised controlled trial. Trials 2016;17:141.
6.	Schwartz TL, Siddiqui UA, Raza S. Memantine as an augmentation therapy for anxiety disorders. Case Rep Psychiatry 2012;2012:749796.
7.	Issari Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: A meta-analysis. J Clin Psychiatry 2016;77:e605-11.
8.	Farnia V, Gharehbaghi H, Alikhani M, Almasi A, Golshani S, Tatari F, et al. Efficacy and tolerability of adjunctive gabapentin and memantine in obsessive compulsive disorder: Double-blind, randomized, placebo-controlled trial. J Psychiatr Res 2018;104:137-43.
9.	Skapinakis P, Caldwell DM, Hollingworth W, Bryden P, Fineberg NA, Salkovskis P, et al. Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: A systematic review and network meta-analysis. Lancet Psychiatry 2016;3:730-9.
10.	Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry 2010;15:850-5.
11.	Aboujaoude E, Barry JJ, Gamel N. Memantine augmentation in treatment-resistant obsessive-compulsive disorder: An open-label trial. J Clin Psychopharmacol 2009;29:51-5.
12.	Modarresi A, Sayyah M, Razooghi S, Eslami K, Javadi M, Kouti L. Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder: A randomized controlled trial. Pharmacopsychiatry 2018;51:263-9.