|Year : 2021 | Volume
| Issue : 3 | Page : 356-364
Ondansetron in combination with fluoxetine for obsessive–compulsive disorder: A randomized, double-blind, placebo-controlled study from North India
Jamshed Ahmad1, Anuradha Nischal2, Anil Nischal3, Bandna Gupta3, Manu Agarwal3, Adarsh Tripathi3
1 Private Practice, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Pharmacology, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Submission||18-Feb-2021|
|Date of Acceptance||03-May-2021|
|Date of Web Publication||30-Sep-2021|
Dr. Bandna Gupta
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
BACKGROUND: A large percentage of patients with obsessive–compulsive disorder (OCD) do not respond to first-line medications. Ondansetron, a 5-HT3 receptor antagonist, has been shown to be effective in the treatment of OCD as an augmentation agent to selective serotonin reuptake inhibitors. However, scientific evidence in this regard is limited.
AIMS: This study aimed to study the effect of ondansetron in combination with fluoxetine on psychopathology, functioning, and quality of life in patients with obsessive–compulsive disorder and to compare these parameters with patients treated with fluoxetine alone.
METHODS: This was a 12-week prospective, randomized, double-blind, placebo-controlled study. Patients fulfilling diagnostic criteria for OCD on the basis of the International Classification of Diseases 10-DCR and having a score of ≥4 clinical global impression-severity (CGI-S) were enrolled in the study. The patients received either fluoxetine with Ondansetron (4 mg/day in two divided doses) or fluoxetine with placebo randomly for a period of 12 weeks. The patients were assessed using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), Social and Occupational Functioning Assessment Scale, CGI, WHO Quality of Life-BREF, and an adverse event checklist at baseline and at weeks 4, 8, and 12. Seventy patients completed the study.
Results: The Y-BOCS total score, obsession subscale score, and compulsion subscale score showed a significantly greater reduction in the ondansetron group than in the placebo group. Improvement in functioning and quality of life was significantly higher in ondansetron group than in placebo group. There was no statistically significant difference between the two groups in terms of side effects.
Conclusion: A significant beneficial effect of combining ondansetron to fluoxetine in patients with OCD was observed.
Keywords: Fluoxetine, obsessive–compulsive disorder, ondansetron
|How to cite this article:|
Ahmad J, Nischal A, Nischal A, Gupta B, Agarwal M, Tripathi A. Ondansetron in combination with fluoxetine for obsessive–compulsive disorder: A randomized, double-blind, placebo-controlled study from North India. Indian J Health Sci Biomed Res 2021;14:356-64
|How to cite this URL:|
Ahmad J, Nischal A, Nischal A, Gupta B, Agarwal M, Tripathi A. Ondansetron in combination with fluoxetine for obsessive–compulsive disorder: A randomized, double-blind, placebo-controlled study from North India. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2022 Aug 14];14:356-64. Available from: https://www.ijournalhs.org/text.asp?2021/14/3/356/327257
| Introduction|| |
Obsessive–compulsive disorder (OCD) is the fourth most common psychiatric illness after phobias, substance-related disorders, and major depressive disorders. The lifetime prevalence of OCD in the general population is estimated to be around 2%–3%., The quality of life of patients with OCD as well as the quality of life of relatives of patients with OCD is severely affected. As the mainstay of pharmacological treatment for OCD includes serotonin reuptake inhibiting medications, it is apparent that dysfunction within the serotonin system is the major pathophysiology underlying this disorder. However, 20% of OCD patients do not respond to adequate trial and another 20%–30% show only partial response to first-line treatment. Hence, the overall response to medication is far from satisfactory. Various augmentation strategies to first-line medications, for example, low-dose antipsychotics (risperidone, olanzapine, haloperidol, quetiapine), memantine, glycine, riluzole, topiramate, amantadine, pregabaline, N-acetylcysteine, D-cycloserine, sodium valproate, lithium, carbamazepine, pindolol, venlafaxine, and buspirone have been suggested, with variable effects. With existing studies showing that only one-third of treatment-resistant OCD patients show a positive response to antipsychotic augmentation, there is a need to study other pharmacological strategies involving the serotonergic and dopaminergic neurotransmission., Since 5HT-dopamine interacts both at cortical and sub-cortical levels, 5HT-recepor-modulating agents were used in the treatment of OCD., 5-HT3 receptors effect reward circuitry indirectly by attenuating cortico-mesolimbic dopamine release.,, Ondansetron, a 5-HT3 receptor antagonist, has been used successfully in the treatment of OCD both as monotherapy as well as an augmentation agent to selective serotonin reuptake inhibitor (SSRI).,,,, Low-dose ondansetron studies by Pallanti et al., as an augmentation agent to SSRI for treatment of OCD and treatment-resistant patients of OCD, reported that ondansetron is effective as an augmentation agent in both the groups., Two randomized controlled trials (RCTs) by Soltani et al. 2010, an 8-week trial conducted on 42 patients randomized to ondansetron plus fluoxetine group and placebo plus fluoxetine group and Heidari et al. 2014, another 8-week trial conducted on 46 patients randomized to ondansetron plus fluvoxamine group and placebo plus fluvoxamine group, reported that ondansetron augmentation to SSRI was associated with striking benefit in patients with OCD., Both the trials revealed that ondansetron group showed a significant reduction in Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) score as compared to placebo group, thereby implicating superior efficacy of ondansetron combination with SRIs over SRIs alone. In another study of ondansetron augmentation of treatment-resistant OCD by Pallanti et al., 2009, treatment response was shown by 64% patients as compared to around 86% treatment response by other two studies., Thus, it can be postulated that combining ondansetron to SRIs in the initial phase of treatment of milder forms of OCD shows promising results.
Hence, this study was designed to see the efficacy and tolerability of ondansetron in combination with fluoxetine, a SSRI in patients with obsessive–compulsive disorder and compare results with a control group receiving placebo with fluoxetine. The study has compared psychopathology, functioning, and quality of life of patients in both the groups.
| Methods|| |
This was a 12-week prospective, randomized double-blind placebo-controlled study conducted at the department of psychiatry of a tertiary care center in North India from September 2015 to September 2016. The study was approved by the Institutional Ethics Committee and registered under Clinical Trial Registry-(CTR I/2017/09/009896). The study was approved by the Institutional Ethics Committee of King George's Medical University, Lucknow, U.P. with Reference number 9366/ Ethics / R.Cell-16, dated on 27/01/2016.
The sample was drawn from the outpatient service of the department of psychiatry and those fulfilling selection criteria were included. A total of 70 patients completed the study with study group having 34 patients (ondansetron with fluoxetine) and control group having 36 patients (placebo with fluoxetine) [Figure 1]. The selection criteria were (a) patients aged between 18 and 50 years, (b) written informed consent from the patient, and (c) diagnosis of OCD as per the International Classification of Diseases (ICD)-10, DCR. Clinical global impression severity (CGI-S) score was ≥4 (moderately ill). Patients were excluded if they had (a) any other comorbid psychiatric disorders except depression and nicotine dependence, (b) treatment-resistant OCD (≥2 adequate SSRI trials), (c) history of intolerance to fluoxetine, (d) history of nonresponse to prior trial of fluoxetine with ondansetron, (e) use of psychotropic medications within 8 weeks of the screening visit, (f) patients having clinically significant medical comorbidity or taking treatment for the same, (g) any clinically significant abnormality in baseline investigations (Hb, TLC, DLC, RBS, serum urea, serum creatinine, and LFT), and (h) pregnant and lactating females. Patients were dropped out from the study if they (a) were nonadherent to treatment. (i.e., missing >20% of the prescribed dose), (b) missed any appointments beyond window period (±3 days), (c) had intolerable side effects, (d) had worsening of symptoms, (e) developed any emergent safety condition, and (f) withdrew consent. There are multiple factors responsible for treatment resistance which could have confounded the assessment of efficacy of ondansetron in our study, so to have more homogenous sample, treatment-resistant OCD patients were not included. Resistance was defined as a YBOCS score >20 after >12 weeks of treatment with an established effective dose of an SSSI or clomipramine, and after >10 weeks of augmentation treatment with antipsychotics. Treatment nonresponse was suggested by a CGI-I score of 4 and <25% reduction in YBOCS total score; however, no patient was found to have a history of past or current intake of ondansetron along with fluoxetine. An age range of 18–50 years was chosen, as child and adolescent OCD may have different characteristics in domains of symptomatology and etiopathogenesis than adult OCD. Depression is commonly associated with OCD and nicotine dependence is very common in this part of the country, so to maintain sample size, we included depression and nicotine dependence. Diagnosis of OCD was confirmed on ICD-10 DCR, which does not classify hoarding as an independent disorder; however, none of the patients in our sample reported hoarding as part of their symptomatology. We ruled out patients with a CGI-S <3 as these patients usually have low level of symptomatology and identifying clinically meaningful change during the study period may be difficult. Pregnant females were excluded as fluoxetine is a Group C drug (i.e., the risk of adverse effects cannot be ruled out) as per the Food and Drug Administration (FDA) pregnancy classification. Lactating females were excluded as fluoxetine is L2 category (i.e., limited studies about safety) as per the FDA classification.
Sample size calculation and statistical analysis
The sample size was calculated using the following formula by Charan and Biswas, 2013, N = 2SD2 (Zα/2 + Zβ/2) 2/d2. In a study (Mahnaz et al., 2014), changes in YBOCS total score from baseline in ondansetron and placebo group were 5.2 ± 4.9 and 3.2 ± 3.2, respectively, thereby pooled standard deviation (SD) being 4 and differences in mean (d) being 2. Assuming 80% power of the study and 5% significance level with 95% confidence interval, the required sample size came out to be around 63 and adding a margin of 10% attrition rate, it converted to a figure of 70, which was divided into two groups. Thus, a sample size of 70 patients was calculated and effort was made to enroll more than this figure. The results are presented as mean ± SD and percentages. The continuous score variables were tested for normalcy by using the Kolmogorov–Smirnov Z-test and data were found to be not normally distributed thereby implicating use of nonparameteric test. Thus, Mann–Whitney U-test (nonparametric test) was used to compare the scores between the two groups at different time periods. The Chi-square/Fisher's exact test was used to compare the categorical variables/dichotomous variables. P < 0.05 was considered significant. Friedman analysis (nonparametric equivalent of repeated measure analysis of variance) was used to see the effect of two treatments with time on the clinical variables (Y-BOCS, CGI-S, Social and Occupational Functioning Assessment Scale (SOFAS) and WHOQOL-BREF). All the analyses were carried out using SPSS 16.0 version (IBM Corporations, Somers, New York, USA).
All symptomatic patients (old and new) of OCD attending the adult psychiatry outpatient department (OPD) on specified OPD days were screened and the first two patients fulfilling the selection criteria were recruited after obtaining written informed consent. Diagnosis of OCD as per the ICD-10 DCR was confirmed and patients were assessed on CGI-S for inclusion in the study. MINI v 6.0.0 was applied and clinical evaluation was conducted to rule out any psychiatric comorbidity. For patients who had taken treatment for OCD in the past, a period of 8-week of medications was set considering that 5 half-lives are required to completely washout the drugs from the body and 6 weeks period of medication was used in previous studies., Majority of the patients were receiving SSRI, clomipramine, other augmenting agents, and benzodiazepines. None of the patients receiving any nonpharmacological treatment were included in the study. Following enrollment, the sociodemographic and clinical details of the patients were recorded in a semi-structured pro forma. Baseline routine investigations were done. Baseline clinical variables were assessed using the following scales: Y-BOCS-II for assessing the severity of OCD, HAM-D for the severity of depression, SOFAS for occupational and social functioning, and WHOQOL-BREF for quality of life.
Allocation, randomization, and blinding
The patients were randomized into two groups, A and B based on a computer-generated randomization table, and allocation concealment was maintained by the use of sequentially numbered opaque and sealed envelopes. Identical capsules of ondansetron and placebo were prepared and prelabelled as Group A/Group B by one of the cosupervisors. Both patients and clinical investigator (s) were blind to this random allocation and the clinical investigator assessing the outcome measures was a resident of psychiatry trained enough to apply the assessment tools.
Both the groups received fluoxetine starting at a dose of 20 mg/day from baseline which was increased to 40 mg/day at week 1. At week 4/week, 8 doses were up titrated or down titrated, in steps of 20 mg, based on clinical judgment and tolerability (target dose range: 40–80 mg/day). One of the treatment groups (study Group A) received ondansetron 2 mg twice a day for duration of the study starting from day 1, while the other group received similar placebo capsules twice a day for the study duration (control Group B). Rescue medications allowed in the study such as clonazepam (up to 2 mg/day for anxiety) and zolpidem (up to 10 mg/day for insomnia) were used as per need and proper documentation of the same was kept. Patients were instructed to take their medication at the same time each day. All the patients were provided phone number of the investigator for management of any emergent condition. All the patients were followed up at weeks 4, 8, and 12 (±3 days). Y-BOCS, CGI-S, SOFAS, and WHOQOL-BREF scales were applied by the investigator on each visit to assess and monitor the response. The primary outcome measure was to compare the difference in the YBOCS total score and subscale scores from baseline to the end of the study between the ondansetron and placebo group. Secondary outcome measures were to compare differences in functioning, quality of life, and side effect profile from baseline to the end of the study between the two groups. Adherence was assessed by verbal inquiry and by pill count on each visit.
| Results|| |
Sociodemographic and clinical details
Both the groups were comparable at baseline on all the sociodemographic parameters. Most of the patients were in the age group of 18–30 years. The mean age of the patients was 31.47 ± 9.25 and 28.22 ± 8.21 years in study and control groups, respectively. Gender distribution was approximately similar in both the groups. Most of the patients were Hindus (88.9% for control group and 79.4% for the study group), married (61.8% for control group and 44.4% for study group), most (32.4%) in the study group were educated up to high school, and in control group, most (33.3%) had received education up to graduation. Most of the patients in both the groups were housewives (35.3% in the study groups and 38.9% in the control groups). Majority of patients in both the groups were from urban background (70.6% for study group and 63.9% for control groups) and belonged to nuclear families (55.9% for study groups and 63.9% for control groups). Most of the patients had family income up to Rs. 10,000 per month (41.2% for the study group and 47.2% for the control group).
Both the groups were comparable at baseline on all the clinical variables including duration of illness in years, type of OCD, family history of psychiatric illness, Y-BOCS total score as well as obsession and compulsion subscale, SOFAS, quality of life (WHOQOL-BREF), and Clinical Global Impression Scale (severity) [Table 1].
The difference in mean score of each clinical variable at weeks 4, 8, and 12 from the baseline score (week 0) was calculated and compared between the ondansetron group and placebo group using the Mann–Whitney U-test [Table 2].
|Table 2: Comparison of Yale-Brown Obsessive-Compulsive Scale total and subscales scores at different visits 4, 8, and 12 and difference in score from week 0 to week 12 between the ondansetron group and the placebo group|
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Yale–Brown Obsessive–Compulsive Scale, clinical global impression severity, Social and Occupational Functioning Assessment Scale, and WHO Quality of Life-BREF
The ondansetron group showed 16.97 point reduction as compared to 11.72 point reduction in the placebo group in the total Y-BOCS score at week 12 and the mean change in the total Y-BOCS score was significantly higher in the ondansetron group from 0 week to 12 weeks (P = 0.001) [Table 2]. Friedman's analysis showed a significant effect for time. By 8 weeks, there was no difference in score reduction between the two groups but showed significant difference at the completion of the study (week 12) [Figure 2].
|Figure 2: Friedman analysis for the effect of two treatments on the Yale–Brown Obsessive–Compulsive Scale total score. Friedman Test Result: Gr A – Chi-square = 99.25, P < 0.001 (highly significant), Gr B – Chi-square = 105.03, P < 0.001 (highly significant)|
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On the CGI, the outcomes were significantly better in the study group at week 8 (P = 0.034) and week 12 (P = 0.009) [Table 2]. Friedman analysis showed a significant effect for time starting from 8 weeks and continuing till the end of the study (week 12) [Figure 3].
|Figure 3: Friedman analysis for the effect of two treatments on the CGI-S Scale total score. Friedman Test Result: Gr A – Chi-square = 88.24, P < 0.001 (highly significant), Gr B – Chi-square = 68.24, P < 0.001 (highly significant)|
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The comparison on SOFAS revealed a significantly higher difference in the mean change in the study group at week 4 (P = 0.001), week 8 (P < 0.001), and week 12 (P = 0.015) [Table 2]. The Friedman analysis for time showed a significant effect starting from week 4 and continuing till the end (week 12) [Figure 4].
|Figure 4: Friedman analysis for the effect of two treatments on the SOFAS Scale total score. Friedman Test Result: Gr A – Chi-square = 95.90, P < 0.001 (highly significant), Gr B – Chi-square = 36.63, P < 0.001 (highly significant)|
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The comparison on SOFAS and WHOQOL-BREF revealed a significantly higher difference in the mean change in WHOQOL-BREF at week 12 (P = 0.0001) and (P = 0.009) respectively [Table 3] and [Table 4]. All the domains of WHOQOL-BREF, i.e., physical health, psychological, social relationship, and environment, showed significant improvement in the ondansetron group from week 0 to week12 as compared to placebo group. The Friedman analysis for time showed improvement in QOL-BREF in the study group starting after week 8 and becoming significant at week 12 [Figure 5].
|Table 3: Comparison of Social and Occupational Functioning Assessment Scale and quality of life (world health organization quality of life-BREF ) total score at weeks 4, 8, and 12 and mean change from week 0 to weeks 12 between the ondansetron and placebo group|
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|Table 4: Comparison of clinical global impression scale score at week 4, 8, and 12 and mean change from week 0 to week 12 between the ondansetron and placebo group|
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|Figure 5: Friedman analysis for the effect of two treatments on the WHO quality of life-BREF Scale total score. Friedman Test Result: Gr A – Chi-square = 95.19, P < 0.001 (highly significant), Gr B – Chi-square = 89.75, P < 0.001 (highly significant)|
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The mean daily dose (in mg/day) of fluoxetine, clonazepam, and zolpidem used in the study did not differ significantly between the groups. The daily dose of fluoxetine was 20.00 ± 0.00 mg/day in the study and control group at the baseline that increased to 58.29 ± 10.14 mg/day in the study group and 60.57 ± 11.36 mg per day in the control group, at week 12. The daily dose of clonazepam was 0.64 ± 0.27 mg/day in the study group and 0.59 ± 0.27 in the control group at the baseline that increased to 0.70 ± 0.24 mg/day in the study group and 0.66 ± 0.21 mg per day in the control group at week 12. The daily dose of zolpidem was 2.57 ± 4.08 mg/day in the study group and 2.57 ± 3.90 in the control group at the baseline that increased to 3.71 ± 4.75 mg/day in the study group and 3.14 ± 4.71 mg per day in the control group at week 12. However, the difference in use of clonazepam and zolpidem at the end of the study in both the groups was not statistically significant. [Table 5] shows the mean scores for the UKU side effect scale used to monitor and measure the side effects of psychotropic medications given. There was no significant difference in the incidence or severity of side effects between the groups [Table 3].
|Table 5: Comparison of UKU side effects (means±standard deviation) at week 4, 8, and 12 between the ondansetron and placebo group|
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| Discussion|| |
The results of our study showed that ondansetron group had a significantly higher reduction in the total Y-BOCS score at week 12 and the mean change in the total Y-BOCS score of week 12 from baseline was significantly higher. These findings were similar to Soltani et al., in an 8 week double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive–compulsive disorder reporting beneficial effects of ondansetron on obsessions and compulsions. Similar finding was reported in an 8-week RCT conducted by Heidari et al. and Pallanti et al., 2009. An open-label pilot trial (n = 8) conducted by Hewlett et al. 2003 showed that ondansetron monotherapy (1 mg TDS) was effective in the treatment of OCD. In addition to this, in a study by Askari et al., using granisetron, another 5HT-3 antagonist in combination with fluvoxamine reported beneficial effects in the treatment of OCD patient. The mean change in the SOFAS was significantly better in the ondansetron group denoting a good functional recovery and overall, a better functional outcome in these patients. The comparison on WHOQOL-BREF revealed significantly higher scores in the ondansetron group at week 12, hence a better outcome in the study group. All earlier studies have indicated impairment in quality of life among OCD patients. Another study by Pallanti et al., 2014, replicated similar results as in accordance to our study showing improvement in the ondansetron group. On the CGI, the outcomes were significantly better in the ondansetron group. The fact that a significant effect was observed not only in Y-BOCS score but also in CGI points to a convincing effect.
The dose of the administered medications, i.e., fluoxetine, clonazepam, and zolpidem, did not differ significantly between the groups as reported in previous studies.,, This finding indicates that the differences in the outcomes between the groups cannot be attributed to the differences in medications used and thus are in all probabilities caused due to the use of ondansetron. The side effects of the psychotropic medications used were measured using two scales, the UKU side effects scale for psychotropic medications and ondansetron side effects checklist. On both the scales, there were no significant differences among the groups at any stage of the therapy. Other studies also did not find any significant differences in the incidence or severity of side effects in the patients treated with ondansetron.,
Neurobiology of OCD implicates different pathophysiological mechanisms including serotonergic, dopaminergic, and glutamatergic systems. Ondansetron, a potent 5HT-3 antagonist, is recently gaining attention for the treatment of OCD; however, studies in this area are few and a systematic review by Serata et al., 2015, quotes around six studies till now exploring the role of 5HT-3 as monotherapy as well as an adjunctive treatment for OCD and its treatment-resistant counterpart. There is co-localization of serotonin-3 receptors with gamma-amino-butyric acid inter-neurons in the ventral tegmental area and thus indirectly inhibiting cortico-mesolimbic dopaminergic release., A low dose of ondansetron, 5-HT3 serotonin blocking agent, regulates dopamine turnover in the nucleus accumbens in the mesolimbic reward pathway. The result is a reduction in striatal dopamine-induced repetitive behavior and has been used effectively in different psychiatric disorders such as schizophrenia, Tourette syndrome, and Tic disorder, including OCD and reported improvement in their symptoms., Uncertain risk perception, one of the OCD symptomatologies, was found to improve in an animal study with intake of a selective 5HT-3 receptor antagonist.
There are other mechanisms responsible for the therapeutic effect of ondansetron in OCD. Ondansetron is FDA approved for the treatment of chemotherapy-induced nausea and vomiting and is also an agonist at opioid μ-receptors. There are studies favoring the effects of opioid agonists in improving symptoms of OCD., Ondansetron, an agonist at opioid μ-receptor, can explain to some extent its augmentative effect in OCD. In addition, glutamatergic modulating agents through N-methyl-D-aspartate (NMDA)-receptors have shown beneficial effects in OCD., NMDA-mediated response in pre-frontal cortex of rats is found to be directly inhibited by serotonin through 5HT-3 receptors, thus illustrating another mechanism by which 5HT-3 antagonists play a therapeutic role in OCD by attenuating of NMDA receptors. Ondansetron may be tried as an experimental treatment to treat OCD patients as is evident that the combination is more effective than the fluoxetine alone and the drug can also be tried in drug-naive patients in combination with SSRI to expedite the treatment response.
Limitations of the study
There are few limitations of the study. In various studies, dose of ondansetron augmentation in OCD was different, some studies use 1 mg/day, and some used up to 8 mg/day. Hence, we plan to study with median dose, i.e., 4 mg/day. Our study was a single-center study with small sample size, thereby limiting the generalizability of the results. Furthermore, the effect on treatment-resistant OCD cannot be commented upon. The study had a short duration (12 weeks of follow-up), so it is difficult to comment, how long the beneficial effects of ondansetron would last. Serum fluoxetine levels could not be done due to limited availability of resources and time constraints. Serum fluoxetine levels are important to exclude any differences in fluoxetine metabolism and plasma levels in both the groups. There is a future need to plan more number of such studies with extended follow-up, large sample size, and including treatment resistant group and other subtypes of OCD to explore further in this area.
| Conclusion|| |
This 12-week, double-blind, RCT of ondansetron in combination with fluoxetine therapy shows beneficial effects of adding ondansetron to therapy in patients with OCDs. There was an improvement in total Y-BOCS score, obsession subscale, compulsion subscale, and CGI scores as well as beneficial effects on social and occupational functioning and quality of life of the patients. The addition of ondansetron enhances the rate of improvement of symptoms, functioning, and quality of life of patients. The present study indicates that ondansetron holds promise as a potential add-on treatment strategy in OCDs.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]