Memantine augmentation of escitalopram in treatment of executive function among patients with obsessive-compulsive disorder (OCD): a double-blind placebo-controlled randomized clinical trial

Abstract

Background

Obsessive-Compulsive Disorder (OCD) involves persistent, intrusive thoughts and repetitive behaviors. While SSRIs like escitalopram are common treatments, some patients do not respond adequately. This study aims to assess memantine’s effectiveness as an adjunct therapy to enhance executive function in OCD patients.

Methods

This study was a 16-week, randomized, double-blind, placebo-controlled clinical trial to evaluate if adding memantine to escitalopram helps treat OCD. A total of 60 participants were recruited from Namazi Hospital and Ibn Sina Polyclinic in Shiraz, Iran. Participants were randomly divided into two groups: the control group received escitalopram plus placebo, and the intervention group received escitalopram plus memantine. The main outcome, the severity of OCD symptoms, was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and executive function was assessed using the Barkley Deficits in Executive Functioning Scale (BDEFS). Safety was checked weekly using the Drug Adverse Event Questionnaire. Data were analyzed using SPSS, with a significance level set at p < 0.05.

Results

All sixty participants completed the 16 weeks of the study. Thirty participants per group (Placebo, Memantine) showed no significant differences in age, gender, or education (P > 0.05) at baseline. Both groups showed significant reductions in Y-BOCS scores (P < 0.001), with the Placebo group decreasing from 32.83 (SD = 4.04) to 5.30 (SD = 3.18) and the Memantine group from 31.60 (SD = 2.62) to 5.20 (SD = 2.62) without difference between groups (P = 0.12). Notebale Improvements in executive function were observed, particularly in time management, where Memantine outperformed Placebo (P = 0.03). Other domains showed no significant differences. Adverse events were minimal; gastrointestinal symptoms were rare, with Memantine showing a higher incidence but not statistically significant.

Conclusion

The study found that while both treatment regimens significantly alleviated OCD symptoms, memantine did not provide notable advantages over escitalopram alone, except in time management. Further research is needed to assess long-term effects and mechanisms of this combination therapy.

Trial registration

IRCT20211118053093N5, 25/06/2025.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12888-025-06856-7.

Introduction

Obsessive Compulsive Disorder (OCD) is one of the neuropsychiatric disorders that is stratified in anxiety disorders and is characterized by recurrent and persistent thoughts, impulses and images which are intrusive and inappropriate and cause anxiety and some repetitive behavior or mental acts for preventing or reducing the related anxiety and distress [1, 2]. The global prevalence of OCD is estimated to be about 2–3% [3]. Studies have shown that individuals with OCD exhibit significant cognitive deficits compared to unaffected individuals, particularly in areas such as verbal memory, psychomotor speed, global attention, and executive functions. Among these cognitive challenges, set shifting is frequently highlighted as a critical neuropsychological deficit, with executive dysfunction being one of the most significant impairments in OCD patients [4, 5]. The therapeutic approach to OCD patients is a combination of cognitive-behavioral therapy (CBT) and pharmacological therapies [6, 7]. Selective serotonin receptor inhibitors (SSRIs) are first-line pharmacological agents for this group of psychiatric disorders; however, 40% to 60% of patients do not respond clinically or functionally to SSRI monotherapy, even when combined with cognitive behavioral therapy (CBT) [8, 9].

Memantine, an NMDA receptor antagonist, shows promise as an adjunctive therapy in OCD, enhancing executive function and reducing compulsive behaviors. Studies highlight its efficacy in improving cognitive flexibility and safety when combined with SSRIs like sertraline. Memantine modulates glutamatergic neurotransmission, addressing cognitive deficits central to OCD pathology [10–12].

There are some hypotheses about pathophysiology of OCD. Some research has shown that oxidative stress and free radicals have a potential role in OCD, consistent with findings in other psychiatric conditions [13–15]. Free radicals damage cells and DNA, with 8-OHdG (a urine/blood biomarker) indicating oxidative DNA damage [16, 17]. While studies suggest oxidative stress in OCD, results conflict, and its role in inflammation or disease mechanisms remains unclear [18]. Another path for explaining OCD is the cortico-striato-thalamo-cortical (CSTC) circuits, driven by the neurotransmitter glutamate, which are linked to the pathophysiology of OCD [19, 20]. Glutamate is essential for memory, cognition, and learning, and its overactivity, along with elevated levels in cerebrospinal fluid and genetic variations in the NMDA receptor, may contribute to OCD development. Due to resistance to SSRIs, research has increasingly focused on glutamate’s role [21, 22]. The temporal lobe is also thought to play a significant role in OCD. Clinical trials of glutamatergic drugs have shown mixed results: while some studies on N-acetylcysteine and Riluzole have not confirmed efficacy, L-carnosine showed effectiveness as an adjunct therapy [23–26]. Initial studies on topiramate indicated positive effects, but more recent research did not demonstrate benefits [27, 28].

Therefore, the new therapeutic guidelines recommend pharmacological augmentation therapy with another agent which is added to SSRIs. One of the newest drugs which has investigated in the treatment of OCD is memantine that augments the effect of SSRIs. Several randomized clinical trials (RCTs) and reviews have shown the beneficial role of memantine in the management of OCD in combination with SSRIs [11, 29–31]. In this study, our objective was to examine the specific role of memantine in enhancing escitalopram for treating OCD symptoms and its impact on executive function in patients with OCD, employing a double-blind, placebo-controlled, randomized clinical trial approach.

Methods

Study design

The research achieved ethical clearance from the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1402.093) and the Iranian Registry of Clinical Trials - Bioregistry (IRCT) (IRCT20211118053093N5 as of June 2023). Each participant submitted signed informed consent before their enrollment in the study. The primary intent was to investigate the efficacy of memantine as an adjunctive treatment for patients with OCD, mainly its impact on executive function when taken in conjunction with escitalopram medication. The study adhered to the CONSORT criteria for executing and reporting clinical trials [32] and the CONSORT checklist is provided in the supplementary file.

Inclusion criteria

Individuals must meet the DSM-V criteria for OCD [33] and reach a score of 18 or higher on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [34], showing moderate to severe OCD symptoms, to be eligible for inclusion. The intensity of OCD symptoms was determined using the Y-BOCS, with a minimum score of 18 identified as acceptable for inclusion. In addition, participants were asked to submit written informed consent, demonstrate no noticeable allergies to memantine or escitalopram, have no history of psychosurgery for OCD, and no history of treatment-resistant OCD. Those included were forbidden from utilizing any psychotherapy during the study course.

Exclusion criteria

Exclusion criteria included any history of comorbid Axis I psychiatric disorders (e.g., depression or schizophrenia), critical psychiatric symptoms such as suicidal ideation or behavior, severe medical or neurological conditions, intellectual disability, or substance abuse (excluding nicotine). Pregnant or breastfeeding individuals, those with a prior complete response to escitalopram, and those who had used psychiatric medications within six weeks before the study initiation were excluded. Furthermore, participants with contraindications to the use of memantine or escitalopram, as per clinical judgment, were also excluded.

Sample size calculation

The sample size was calculated based on similar previous studies, aiming to detect a mean difference of 4 points on the BDEFS time management subscale, with a standard deviation of 6, a power of 80% (β = 0.2), and a significance level of 5% (α = 0.05). Based on these, a minimum of 26 participants per group was needed. To account for potential erosion, we enrolled 30 participants in each group, for a total of 60 participants.

Randomization and masking

Sixty patients got involved in the trial, divided into two groups of thirty each. The patients were randomly placed into one of two groups through a permuted block randomization technique including eight blocks of size five. This ensured to the balanced distribution of participants through the groups and both patients and investigators were blinded to group assignments, with identical capsules used for memantine and placebo. This double-blind design ensured that neither the participants nor the investigators knew which group the patients were assigned to.

As explained, the randomization process involved two groups, with Group A (Control) receiving escitalopram plus placebo, and Group B (Intervention) receiving escitalopram plus memantine. An independent research coordinator carried out randomization to ensure allocation concealment.

Intervention

The interventions were outlined as follows:

Group A (Control): Patients were given escitalopram (5 mg/day for the initial 4 weeks, then increased to 10 mg/day) combined with a placebo, following the same regimen as memantine. The titration schedule was established according to previous clinical trial experience [35]. Group B (Intervention): Patients received escitalopram (5 mg/day for the first 4 weeks, increased to 10 mg/day) alongside memantine (10 mg/day for an entire 16-week duration).

Outcomes

Yale-brown obsessive-compulsive scale (Y-BOCS)

The intensity of OCD was evaluated by calculating the overall Y-BOCS score, highlights the severity of obsessive-compulsive symptoms. Each item measures specific features of obsessions and compulsions, involving time period, interference, distress, resistance, and control. The primary outcome was evaluated using the Y-BOCS, a validated 10-item scale for measuring the intensity of OCD symptoms [36, 37]. Each question is scored from 0 to 4, providing a total score between 0 and 40. The severity levels were classified based on the overall score as follows: 8–15 = mild, 16–23 = moderate, 24–31 = severe, and ≥ 32 = very severe OCD symptoms.

The Y-BOCS was administered at weeks 0, 4, 8, 12, and 16 to track the progression of symptoms. The Persian version of the Y-BOCS has been validated in previous studies [38, 39].

Barkley deficits in executive functioning scale (BDEFS)

The secondary result included the evaluation of executive function in daily life by the Barkley Deficits in Executive Functioning Scale (BDEFS). This 89-item questionnaire measures five aspects: time management, organization, self-discipline, emotional regulation, and problem-solving. Increased scores suggest more executive function deficits [40, 41], which was validated in the Persian population by A. Mashhadi et al. [42]. The BDEFS was completed in weeks 0 and 16.

Adverse events

To monitor adverse events, a Drug Adverse Events Questionnaire was administered. This questionnaire assessed common adverse events such as dizziness, drowsiness, gastrointestinal disturbances, and skin issues.

The primary outcome was measured by changes in OCD symptom severity, assessed using the Y-BOCS scores at weeks 0, 4, 8, 12, and 16. The secondary outcome focused on executive functioning, assessed through the BDEFS scores at week 0 (baseline) and week 16. Finally, safety was evaluated by tracking adverse events, which were measured weekly using the Drug Adverse Events Questionnaire.

Statistical analysis

Data analysis was performed using SPSS version 23. To assess the normality of the dataset, we employed a Histogram, along with the Shapiro-Wilk Test and the Kolmogorov-Smirnov (KS) Test. Descriptive statistics were calculated, including means and standard deviations for continuous variables, as well as frequencies and percentages for categorical variables. To compare the BDEFS scores before and after the intervention between groups, we utilized both the paired t-test and the independent t-test. To analyze changes in Y-BOCS scores over time among participants, we applied a repeated-measures general linear model (GLM) using repeated measures ANOVA, with corrections made for sphericity assumptions. The Chi-square test was used to compare categorical variables (adverse events) between the two groups, and Fisher’s Exact Test was also included in our analysis. A p-value of less than 0.05 was deemed statistically significant for our hypothesis testing.

Results

A total of 192 participants were screened for eligibility, and 60 individuals (30 in the Placebo group and 30 in the Memantine group) met the inclusion criteria and were selected for the study. All participants completed the study with no missing data (Fig. 1).

Fig. 1.

CONSORT Flowchart of study participants

Baseline characteristics

Table 1 outlines the baseline characteristics of the individuals. There were 30 participants in each group (Placebo and Memantine). No significant differences were observed between the two groups in terms of age, gender, or educational status (P-values > 0.05). The majority of the population (46.7%) was between 29 and 39 years old, with no significant difference between the groups (P-value = 0.89). Gender distribution was equal, with 55% females in both groups (P-value = 0.80). 75% of the participants had no university degree, and no significant differences were observed in educational status between the groups (P-value = 0.55).

Table 1.

Baseline characteristics of participants by case (Escitalopram + Memantine) and control (Escitalopram + Placebo) groups

Variables	Subcategory	All (N = 60)	Escitalopram + Placebo (N = 30)	Escitalopram + Memantine (N = 30)	P-value
Age (years old)	28–28	11 (18.3%)	5 (16.7%)	6 (20%)	0.89
	29–39	28 (46.7%)	15 (50%)	13 (43.3%)
	40–50	21 (35%)	10 (33.3%)	11 (36.7%)
Gender	Female	33 (55%)	16 (53.3%)	17 (56.7%)	0.80
	Male	27 (45%)	14 (46.7%)	13 (43.3%)
Educational status	Without university degree	45 (75%)	21 (70%)	24 (80%)	0.55
	University degree	15 (25%)	9 (30%)	6 (20%)

P value < 0.05 is considered significant

Presented P values are based on Pearson’s Chi-Square

Clinical outcomes

The Friedman test revealed a substantial decrease in Y-BOCS scores over time within each group (P < 0.001), showing effective treatment improvement.

Both groups demonstrated significant reductions in their Y-BOCS scores during the study (P-value < 0.001). The Placebo group had a baseline mean score of 32.83 (SD = 4.04), which decreased to 5.30 (SD = 3.18) at the 16-week mark. In the Memantine group, the baseline mean score was 31.60 (SD = 2.62), which dropped to 5.20 (SD = 2.62) after 16 weeks. Between-group evaluations at each time point showed no statistically significant changes (all P > 0.05), except for week 4 (P = 0.03) when the Memantine group showed a: a statistically earlier response at week 4. (Table 2; Fig. 2).

Table 2.

Change in Yale-Brown obsessive compulsive scale (Y-BOCS) total score during the study period between case (Escitalopram + Memantine) and control (Escitalopram + Placebo) groups

Variable	Group	At baseline	4 weeks	8 weeks	12 weeks	16 weeks	P value time effect	Time effect (F, P value)	Time X Group (F, P value)
Y-BOCS total score	Escitalopram + Placebo	32.83 (4.04)	25.57 (4.64)	17.87 (4.46)	11.63 (4.51)	5.30 (3.18)	< 0.001	1.65, 0.18	2.44, 0.12
	Escitalopram + Memantine	31.60 (2.62)	23.13 (3.79)	16.50 (3.83)	11.17 (2.59)	5.20 (2.62)	< 0.001

Abbreviations: Y-BOCS: Yale-Brown Obsessive Compulsive Scale

P value < 0.05 is considered as significant

Presented P values are based on repeated measures GLM using Greenhouse-Geisser correction: Y-BOCS total score

Fig. 2.

Changes in Yale-brown obsessive compulsive scale (Y-BOCS) Total score throughout the study period for case (Escitalopram + Memantine) and Control (Escitalopram + Placebo) Groups (Data shown as mean with confidence intervals indicated by error bars)

Improvements in executive function were observed in both the Placebo and Memantine groups, with a significant reduction in time management, self-organization, and self-control (P-values < 0.01). However, significant baseline differences were observed in all subscales, prompting a focus on pre-to-post change scores for accurate between-group comparison. Based on these changes, a significant difference between groups was found only in the time management subscale, where the Memantine group demonstrated greater improvement than the Placebo group (mean change − 30.63 ± 6.08 vs. -26.66 ± 7.60; P = 0.03). No significant differences between the groups were found in other domains, including self-organization and problem-solving (P = 0.29), self-restraint (P = 0.80), self-motivation (P = 0.53), or self-regulation (P = 0.82). (Table 3).

Table 3.

Change in Barkley deficits in executive functioning scale (BDEFS) subscales during the study period between case (Escitalopram + Memantine) and control (Escitalopram + Placebo) groups

Variable	Group	At baseline	16 weeks	Change	P-value	P-value (between groups)
Self-Management of Time	Escitalopram + Placebo	66.7 (5.17)	40.03 (7.16)	-26.66 (7.6)	< 0.01	0.03
	Escitalopram + Memantine	59.87 (4.93)	29.23 (7.16)	-30.63 (6.08)	< 0.01
Self-Organization and Problem Solving	Escitalopram + Placebo	75.27 (6.65)	39.33 (9.93)	-35.93 (9.76)	< 0.01	0.29
	Escitalopram + Memantine	68.63 (7.27)	29.83 (3.8)	-38.8 (6.92)	< 0.01
Self-Restraint (Inhibition)	Escitalopram + Placebo	60.2 (5.58)	29.82 (8.2)	-30.36 (7.65)	< 0.01	0.80
	Escitalopram + Memantine	54.93 (5.66)	24.07 (4.71)	-30.86 (7.31)	< 0.01
Self-Motivation	Escitalopram + Placebo	37.77 (4.84)	20.03 (6.32)	-17.73 (6.14)	< 0.01	0.53
	Escitalopram + Memantine	34.00 (5.44)	15.27 (3.2)	-18.73 (6.05)	< 0.01
Self-Regulation of Emotion	Escitalopram + Placebo	41.17 (3.8)	21.67 (5.46)	-19.5 (4.86)	< 0.01	0.82
	Escitalopram + Memantine	35.07 (7.11)	16.77 (2.34)	-18.3 (7.3)	< 0.01

Abbreviations: BDEFS: Barkley Deficits in Executive Functioning Scale

Presented P values are based on paired t-test

Adverse events

The adverse effects were low across all groups. Regarding gastrointestinal (GI) issues, 3.3% of participants reported GI symptoms, while the Memantine group revealed a higher incidence (6.7%) than the Placebo group (0%). Yet, the difference was not statistically significant (P-value = 0.25). Furthermore, there were no cases of headache, vertigo, sleepiness, or dermatological complaints in either group, and the adverse event patterns were mostly comparable between the Placebo and Memantine groups. It is crucial to note that although the Memantine group had a greater incidence of gastrointestinal problems, these were few in both groups, reflecting that the treatment regimen was well tolerated. The lack of any prevalent adverse effects in both groups further supports the safety profile of the therapies (Table 4).

Table 4.

Adverse events reported in case (Escitalopram + Memantine) and control (Escitalopram + Placebo) groups during the study

Variables	All (N = 60)	Escitalopram + Placebo (N = 30)	Escitalopram + Memantine (N = 30)	P-value
Headache	0 (0%)	0 (0%)	0 (0%)	NA
Vertigo	0 (0%)	0 (0%)	0 (0%)	NA
Drowsiness	0 (0%)	0 (0%)	0 (0%)	NA
GI symptoms	2 (3.3%)	0 (0%)	2 (6.7%)	0.25
Skin symptoms	0 (0%)	0 (0%)	0 (0%)	NA

Abbreviations: GI: Gastrointestinal, NA: Not applicable

Presented P values are based on Fisher’s Exact Test

Discussion

In this 16-week double-blind, placebo-controlled study involving 60 patients with OCD, the effects of memantine as an augmentation to escitalopram on executive function were evaluated. Participants were divided into two groups: one receiving escitalopram plus placebo and the other receiving escitalopram plus memantine. Both groups demonstrated significant reductions in Y-BOCS scores, indicating substantial symptom relief. However, no significant difference in symptom reduction was observed between the two groups.

Improvements in executive function were noted, particularly in time management, where the memantine group showed greater gains and the difference between groups was significant. Adverse events were minimal, with slightly more gastrointestinal symptoms reported in the memantine group. This study is the first of its kind to evaluate memantine’s impact on executive function in OCD patients treated with escitalopram, contributing valuable insights amid mixed results from previous research.

In comparison to previous studies, similar to Askari et al. and Farnia et al. [10, 43], we showed no significant difference between memantine and placebo groups in Y-BOCS score, however in both groups the score had dropped. The results of Ghaleiha et al. which conducted a double-blind, randomized controlled trial involving thirty-eight patients with moderate to severe OCD to compare the efficacy of memantine combined with fluvoxamine against a placebo plus fluvoxamine was in contrast to our results. Their findings indicated that the combination treatment was significantly more effective than the placebo in terms of symptom severity and patient response rates over an 8-week period. However consistent with our own study, they reported no significant adverse effects associated with memantine when compared to the placebo group [44].

Modarresi et al. explored the effectiveness of memantine (10 mg taken twice daily) as an adjunct treatment for patients with OCD who were resistant to serotonin reuptake inhibitors (SRIs) in a 12-week study involving thirty-two participants. Their results showed a significant decrease in symptom severity, measured by the YBOCS, and a higher response rate in the memantine group compared to the placebo group. They also noted that memantine was well-tolerated and safe, aligning with our findings [30].

Also, Haghighi et al. in a 12-week placebo-controlled trial, assessed the efficacy of 5–10 mg daily memantine as an adjunct to either an SSRI or clomipramine, in 29 OCD patients. They found that memantine significantly reduced YBOCS scores in comparison to the placebo group [45]. Although, these two studies have outcomes different from ours, the population in which they studied was different from ours; They studied patients who were resistant to SSRIs for the treatment of OCD, but our study population did not include these patients. Our study had a different result to previous studies; we showed significant difference between two groups in time management.

A systematic review and meta-analysis by Kishi et al. examined the benefits of combining SRIs with memantine for treating OCD. The analysis included three double-blind, randomized, placebo-controlled trials, showing that memantine plus SRI was more effective than placebo plus SRI in terms of response rate and Y-BOCS scores for both obsessions and compulsions. No significant safety differences were found between the groups [46].

Additionally, rapastinel, a novel NMDA receptor modulator, has shown promise in treating OCD symptoms [47]. Given that about half of OCD patients do not respond to SRIs, the use of glutamate-modulating agents like memantine is expected to increase in clinical practice [48]. There are some hypotheses which consider the role of glutamatergic mechanisms in the pathophysiology of OCD [49]. There is mutual interaction between the direct and indirect pathways within the CSTC circuity. This interaction keeps these two pathways in balance and an overactivation in direct pathway or an underactive indirect pathway may lead to disinhibition in this circuitry, which can manifest as compulsions and obsessions [50, 51]. It has been considered that CSTC circuitryin OSD has a reversible impairment by glutamatergic mechanisms, based on several evidences [52]. The most likely cause of glutamatergic dysfunction in OCD seems to be related to post-synaptic issues in glutamate signaling [53].

As mentioned above, in several studies it has explained that oxidative stress has a potential role in the pathophysiology of OCD [13–18]; Also Kurhan et al. compared 35 OCD patients and 33 healthy controls, finding significantly lower total/native thiol levels and higher disulfide levels in patients, along with elevated 8-OHdG compared to controls. These results indicate disrupted thiol/disulfide homeostasis and increased oxidative stress in OCD, with 8-OHdG serving as a biomarker for oxidative DNA damage [54]. Also, it has been shown that memantine can protect neural health and improve brain functions in these patients by reducing oxidative stress [45]. These findings may be a field of research for future studies for investigating the potential role of memantine in reducing oxidative stress for treating OCD patients especially in time management.

Memantine, an NMDA receptor antagonist, is used as an adjunctive treatment for OCD, often alongside CBT and SRIs [55, 56]. Neurological studies suggest that it acts by blocking synaptic NMDA receptors, which can help reduce the activity of the direct pathway in the CSTC circuitry implicated in OCD’s pathophysiology. As a potent glutamatergic agent, memantine continues to demonstrate significant potential in relieving symptoms of OCD [57, 58]. Furthermore, memantine has an inhibitory effect on the glutamatergic system within the temporal lobes and associated brain areas, which may help alleviate symptoms of OCD [58]. This specific action of memantine in the temporal lobe could benefit patients who have cognitive deficits and maladaptive memory processes such as impairment in executive function [10, 59].

The study has notable limitations. The small sample size of 60 participants restricts the generalizability of findings to the broader OCD population. A longer duration than 16 weeks is needed to evaluate the long-term effects of memantine augmentation on executive functions. While validated scales like the Y-BOCS and BDEFS were used, reliance on self-reported measures may introduce bias; objective assessments could enhance evaluation. Additionally, excluding individuals with significant medical issues, substance abuse and whom were resistant to SSRIs may limit applicability to those with comorbid conditions. Despite a double-blind design, potential biases in reporting and assessments remain, highlighting the need for improved blinding techniques in future studies. Also, our study didn’t examine oxidative stress biomarkers due to lack of proper diagnostic kits so that the role of memantine in reducing oxidative wasn’t determined. However, this study has some strengths: the findings of this study highlight the potential of memantine as an effective adjunctive treatment for OCD, particularly in enhancing executive function, as evidenced by significant improvements in time management among participants. Despite the lack of notable differences in Y-BOCS scores between the memantine and placebo groups, the observed benefits on executive function suggest that memantine may provide specific advantages for patients with cognitive deficits.

Future research should focus on larger sample sizes and longer study durations to better assess the long-term effects and efficacy of memantine in diverse OCD populations, including those resistant to traditional SSRIs. Clinically, these insights underscore the importance of considering glutamate-modulating agents like memantine in treatment plans, particularly for patients who do not fully respond to standard therapies, thereby expanding therapeutic options and improving patient outcomes.

Conclusions

In conclusion, while both treatment regimens significantly reduced OCD symptoms and improved executive function overall, the addition of memantine did not yield substantial benefits over escitalopram alone in terms of Y-BOCS score changes or most executive function domains except for time management. The findings underscore the potential clinical implications of combining pharmacotherapies to address cognitive deficits in OCD, particularly in improving time management and daily functioning. Enhanced time management could significantly alleviate the burden of OCD symptoms, offering patients greater autonomy and efficiency in their routines. Future research should prioritize investigating the incorporation of oxidative stress biomarkers to better understand the mechanisms underlying these benefits and to establish robust, long-term efficacy. Future studies should aim to include larger sample sizes and longer follow-up periods to fully elucidate the benefits and risks associated with this combination therapy in diverse populations affected by OCD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

The article’s concept was developed by LRJ, YG, RM, and HM, who managed patient care and data collection. LRJ and YG facilitated patient enrollment and project management. RM, AMN, and MK reviewed the draft, with RM analyzing data. All authors contributed to content review and editing, providing their final approval for the article.

Funding

This study did not receive any funding.

Data availability

Data available from corresponding authors upon reasonable request.

Declarations

Ethical approval and consent to participate

The study received ethical approval from the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1402.093). All participants provided written informed consent prior to their inclusion in the study. The research was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.

Consent for publication

Not applicable.

Conflict of interest

The authors declare that they have no conflict of interest.