Agomelatine augmentation of sertraline in the treatment of moderate to severe obsessive-compulsive disorder: a randomized double-blinded placebo-controlled clinical trial.

BACKGROUND: As 40-60% of the patients with obsessive-compulsive disorder (OCD) do not adequately respond to the first-line treatment, finding an effective second-line treatment is required. Our aim was to assess the efficacy and safety of agomelatine (a selective melatonin receptor agonist and a 5-hydroxytryptamine (HT)2 C antagonist) augmentation of sertraline in the treatment of patients with moderate to severe OCD. METHODS: In this 12-week randomized, double-blinded, placebo-controlled, parallel-group clinical trial, 65 patients with moderate to severe OCD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5) criteria and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of over 21, were included. They were assigned with sertraline (100 mg/day for the first 4 weeks and 200 mg/day for the next 8 weeks) and either agomelatine (25 mg/day) or placebo. The primary outcome was OCD symptoms measured by the Y-BOCS. RESULTS: Fifty patients (24 in agomelatine group and 26 in placebo group) completed the trial. The Y-BOCS scores in total (MD (95% CI) = 12.25 (11.00, 13.49) (P < 0.001) vs. MD (95% CI) = 12.46 (6.65, 15.74) (P < 0.001)), the obsession subscale (MD (95% CI) = 5.04 (4.19, 5.88) (P < 0.001) vs. MD (95% CI) = 5.00 (3.84, 6.16) (P = 0.0001)), and compulsion subscale (MD (95% CI) = 7.21 (6.34, 8.07) (P < 0.001) vs. MD (95% CI) = 7.460 (6.50, 8.42) (P < 0.001)) significantly decreased in both groups. Although, at the end of the trial, no significant difference was observed between the scores of the two groups in total (MD (95% CI) = 0.480 (-1.23, 2.19) (P = 0.78)), the obsession subscale (MD (95% CI) = 1.020 (-0.15, 2.19) (P = 0.38)), and the compulsion subscale (MD (95% CI) = 0.540 (-0.34, 1.42) (P = 0.54)). No major adverse effects were recorded, and the frequency of side effects was not significantly different between the groups. CONCLUSION: Agomelatine in augmentation with sertraline is safe and tolerable in patients with moderate to severe OCD. However, our study does not support its efficacy in improving OCD symptoms, compared to placebo. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials on 14/07/2020 ( www.irct.ir ; IRCT ID: IRCT20170123032145N5).

The effectiveness of pregabalin with or without agomelatine in the treatment of chronic low back pain: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Although various pharmacological and nonpharmacological treatments are available for the chronic low back pain (CLBP), there is no consensus on the best optimal treatment for this condition. This study aimed to investigate the efficacy of co-administration of pregabalin and agomelatine versus pregabalin with placebo to treat CLBP. METHODS: Forty-six CLBP patients without the surgical indication referred to the outpatient orthopedic clinic of Rasoul-e-Akram Hospital, Tehran, Iran, were randomly divided into two study groups: Group A [pregabalin (75 mg twice per day) + placebo] and Group B [pregabalin (75 mg twice per day) + agomelatine (25 mg per night)]. Patients were evaluated at weeks 0, 4, and 8. Outcome measures were the Persian versions of the Brief Pain Inventory (BPI) interference scale, Roland-Morris Disability Questionnaire (RMDQ), The Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Survey (SF-36), and General Health Questionnaire-28 (GHQ-28) were used. RESULTS: At weeks 4 and 8 after the intervention, all evaluated measures showed significant improvement in both study groups (P < 0.01). The mean improvement of GHQ-28 was 3.7 ± 1.22 in group A and 13.1 ± 4.71 in group B. This difference was statistically significant (P = 0.003). Other outcomes did not vary substantially between the two research groups. Agomelatine treatment was well tolerated, with no significant adverse effects seen in patients. Liver tests of all patients were routine during the study period. Major adverse effect was not seen in any patient. The prevalence of Minor side effects was not significantly different between two study groups. CONCLUSION: Compared with the pregabalin and placebo, co-administration of pregabalin and agomelatine had no added effect on improving pain scores in CLBP patients. However, the patients' general health was significantly improved after the combined administration of pregabalin and agomelatine. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials before starting the study (NO.IRCT20200620047852N1, Registration date: 23/06/2020).

Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20-30%, and satisfactory treatment is obtained in 40-60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients' function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms. In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. METHODS: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS. RESULTS: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron plus sertraline and 27.5 to 19.3 for placebo plus sertraline group with a slightly greater drop for granisetron plus sertraline group), while the granisetron plus sertraline group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57) = 4.52,p-value = 0.01). Moreover, in comparison with the placebo plus sertraline group, the proportion of the patients showing complete response was considerably higher among the granisetron plus sertraline group (P-value < 0.01). No major adverse effects were observed in any of the groups. CONCLUSION: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.

Memantine augmentation of sertraline in the treatment of symptoms and executive function among patients with obsessive-compulsive disorder: A double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually decrease the severity of the symptoms by 20-30%; however, 40-60% of OCD patients do not achieve a satisfactory response. Our main objective was to investigate the effectiveness of memantine, a non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist, as an adjunct therapy to sertraline, a selective serotonin reuptake inhibitor (SSRI), to improve severity of symptoms and executive function among patients with obsessive-compulsive disorder. METHODS: Seventy patients with OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of more than 21 were recruited to the study. They received sertraline (100 mg daily initially followed by 200 mg daily after week 4) and either memantine (10 mg twice daily) or placebo in a placebo controlled, double-blinded, parallel-group, clinical trial of 12 weeks. The primary outcome was OCD symptoms measured by the Y-BOCS. Moreover, executive function of participants was measured by the Wisconsin Card Sorting Test (WCST). RESULTS: The total score, and obsession and compulsion subscales of Y-BOCS significantly dropped in both groups with no significant difference between the two groups. However, memantine group showed a greater response in the number of completed categories subscale of the WCST (p value<0.001). We did not observe any major adverse effects in any of the groups. CONCLUSION: Memantine has an acceptable safety and tolerability in patients with OCD and might have a positive effect on their executive function. Nevertheless, the current results don`t support the efficacy of memantine as an adjunctive agent to sertraline for symptoms in patients with OCD. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials on 04/10/2019 ( www.irct.ir ; IRCT ID: IRCT20170123032145N4).

Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Tipepidine, a synthetic, non-opioid expectorant, has been shown to improve depressive-like behavior in animal models of depression. In this study, we assessed the efficacy and tolerability of tipepidine combination therapy with citalopram in treatment of major depressive disorder (MDD). METHODS: In a randomized, double-blinded, placebo-controlled clinical trial, 62 patients with MDD were assigned into two parallel groups to receive citalopram (up to 40 mg/day) plus placebo or citalopram plus tipepidine (30 mg twice daily) for 6 weeks. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D) at baseline and Weeks 2, 4, and 6. RESULTS: Fifty-six patients completed the trial. The tipepidine group showed greater improvement in HAM-D scores from baseline to all three study time points (P = 0.048 for all). The remission and response-to-treatment rates were significantly higher in the tipepidine group (53.6% and 100%) compared to the placebo group (25.0% and 75%) at the study end-point (P = 0.029 and 0.005, respectively). The remission and response times in patients in the tipepidine group were also shorter compared with the placebo group (log-rank P = 0.020 and 0.004). There was no significant difference between the two groups in baseline parameters or frequency of side-effects. CONCLUSION: Tipepidine combination therapy with citalopram can effectively improve symptoms of patients with MDD in a shorter period of treatment. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.