Shahin Akhondzadeh

According to his ResearchGate profile, Shahin Akhondzadeh's main research interest is repositioning psychopharmacology in the treatment of Psychiatric Disorders.

2023 RCT studies

L-carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors (Aug 7 2023)

Results: L-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD.

Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo (P = 0.033 and P < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD.

https://doi.org/10.1097/yic.0000000000000496

Celecoxib monotherapy for treatment of moderate depressive symptoms following COVID-19 infection (Aug 1 2023)

Results: A total of 62 patients were included. GLM repeated-measures showed a significant effect of time × treatment (F = 12.95, df = 1.98, p < 0.001) for celecoxib, suggesting superior improvement of depressive symptoms in celecoxib compared to placebo from baseline to the study endpoint. HDRS scores in the celecoxib group showed a greater decline from baseline to both week 3 (t = 4.12, p < 0.001, Cohen's d = 1.10) and week 6 (t = 4.76, p < 0.001, Cohen's d = 1.27), compared to the placebo group. Rate of response to treatment (70% vs 9%, p < 0.001) and remission (67% vs 0%, p < 0.001) was significantly higher in celecoxib compared to the placebo group at week 6. Adverse event frequencies were not significantly different between the two groups.
Conclusion: We demonstrated that treatment with celecoxib significantly improved depression scores of patients with depressive symptoms following COVID-19 infection. Further trials with larger sample sizes and longer study periods should assess our findings before any suggestion for clinical use. The trial was prospectively registered at the Iranian registry of clinical trials (www.irct.ir; registration number: IRCT20090117001556N142).

https://doi.org/10.1016/j.jpsychores.2023.111471

Reboxetine Combination Therapy With Fluoxetine in Moderate to Severe Obsessive-Compulsive Disorder (July 18 2023)

Results: A total of 76 patients completed the trial. There was no significant difference between the 2 groups in baseline Y-BOCS scores. General linear model repeated-measures showed significant effects on time-treatment interaction on total Y-BOCS (F = 6.33, df = 1.42, P = 0.006) and obsession subscale scores (F = 10.39, df = 1.48, P < 0.001), and insignificance on compulsion subscale scores (F = 1.86, df = 1.24, P = 0.173). Reboxetine combination therapy demonstrated a higher partial and complete treatment response rate (P < 0.01) according to the Y-BOCS total scores. There was no significant difference between the 2 groups in the frequency of adverse effects.
Conclusions: Reboxetine combination therapy with fluoxetine can effectively improve symptoms in patients with OCD in a short period of treatment. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings.This trial was registered with the Iranian Registry of Clinical Trials (www.irct.ir; No IRCT20090117001556N129).

https://doi.org/10.1097/wnf.0000000000000564

L‐theanine combination therapy with fluvoxamine in moderate‐to‐severe obsessive–compulsive disorder (May 11 2023)

Results

From a total of 95 evaluated patients, 50 completed our study; 30 were randomly assigned to each group. Multivariate analysis (ANOVA) showed a significant effect of time treatment for L-theanine in obsession subscale (F = 5.51, P = 0.008) of the Y-BOCS score but not in the total and compulsion scores. Our results showed significantly more improvement in obsession subscale scores in L-theanine compared to placebo group (P = 0.007, Cohen's d = 0.82). Also, total Y-BOCS scores were lower in L-theanine compared to placebo group at week 5 (P = 0.039, Cohen's d = 0.60) and 10 (P = 0.008, Cohen's d = 0.80). However, there was no significant between-group differences in compulsion subscale scores. Complete response was also more frequent in the L-theanine group (P = 0.0001).

Conclusion

Findings in this study suggest L-theanine as a relatively safe and effective adjuvant therapy for moderate to severe OCD.

https://doi.org/10.1111/pcn.13565

Famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection (May 1 2023)

Results: At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects.

Conclusion: Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19.

Trial registration: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

https://doi.org/10.1016/j.jpsychores.2023.111389

Celecoxib for treatment of mild to moderate postpartum depression (Apr 25 2023)

Results: Patients in the celecoxib group showed a greater decline in HDRS scores from baseline to all three study time points compared to the placebo group (p = 0.12 for week 2, p = 0.001 for week 4, p < 0.001 for week 6). Rate of response to treatment was significantly higher in the celecoxib group compared to the placebo group at week 4 (60 vs 24%, p = 0.010) and week 6 (96 vs 44%, p < 0.001). Rate of remission was significantly higher in the celecoxib group compared to the placebo group at week 4 (52 vs 20%, p = 0.018) and week 6 (96 vs 36%, p < 0.001). Levels of most inflammatory markers were significantly lower in the celecoxib group compared to the placebo group at week 6. Levels of BDNF were significantly higher in the celecoxib group compared to the placebo group at week 6 (p < 0.001).
Conclusions: Findings suggest adjunctive celecoxib is an effective treatment for the improvement of postpartum depressive symptoms.

https://doi.org/10.1007/s00404-023-07042-4

L-theanine adjunct to sertraline for major depressive disorder (April 19 2023)

Results: Twenty-five participants in each group, a total of 50 patients, completed the study. All baseline characteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p-value = 0.014), indicating more remarkable symptom improvement in the l-theanine group. A greater reduction in HDRS scores was observed in the l-theanine group from baseline to weeks 2, 4, and 6 (p-values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus l-theanine until week 6. l-theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p-values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups.

Limitations: The small sample size and short study period were the limitations.

Conclusions: l-theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence.

https://doi.org/10.1016/j.jad.2023.04.029

Adjunctive therapy with fingolimod in patients with schizophrenia (April 2023)

Risperidone versus fingolimod plus risperidone.

Results

Seventy participants completed the trial (35 in each arm). The baseline characteristics of the groups were comparable (P-value > 0.05). There were significant time-treatment interaction effects on negative symptoms (P-value = 0.003), general symptoms (P-value = 0.037), and the PANSS total score (P-value = 0.035), suggesting greater improvement in symptoms following the fingolimod adjuvant therapy. In contrast, the longitudinal changes in positive and depressive symptoms were similar between the groups (P-values > 0.05). Regarding the safety of treatments, there were no differences in extrapyramidal symptoms [assessed by the extrapyramidal symptom rating scale (ESRS)] or frequency of other complications between the fingolimod and the placebo groups (P-values > 0.05).

Conclusions

This study indicated that fingolimod is a safe and effective adjuvant agent for schizophrenia treatment. However, further clinical trials are required to suggest extensive clinical application.

https://doi.org/10.1016/j.schres.2023.02.020

2022 RCT studies

Cilostazol as adjunctive therapy in treatment of children with autism spectrum disorders (Sept 14 2022)

This trial was an exception and only found statistically significant benefits in a subgroup.

We aimed to evaluate cilostazol therapeutic effects on aberrant behaviors of autism spectrum disorder (ASD) children and its safety profile in a double-blind, randomized clinical trial. Sixty-six children with confirmed ASD were allocated to receive either daily 50-mg cilostazol (increased to 100 mg/day after 2 weeks) or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and a checklist of probable adverse effects were used to assess the behavioral outcomes and safety profile at weeks 0, 5, and 10 of the study.

Sixty-one participants, with comparable baseline characteristics, completed the trial.

Unlike other ABC-C subscales, repeated-measures analysis showed significant effect for time × treatment interaction in the hyperactivity subscale (P = 0.047; partial eta squared = 0.06). We used the median value for the baseline score hyperactivity subscale [median (interquartile range) = 31 (24–37)] to stratify participants to higher hyperactivity and lower hyperactivity subgroups and found that only participants with higher hyperactivity benefit from cilostazol adjunctive therapy (P = 0.028; partial eta squared = 0.14). Cilostazol could be considered as a safe agent with beneficial effects on hyperactivity in children with ASD and higher levels of hyperactivity.

https://doi.org/10.1097/YIC.0000000000000431

Evidence for Anti-inflammatory Effects of Adalimumab in Treatment of Patients With Major Depressive Disorder (Sept 7 2022)

Results Fifteen patients in each group completed the trial course. All baseline characteristics of participants were similar between the groups. Adalimumab adjunct to sertraline resulted in a greater improvement in HAM-D score compared with placebo over the trial period (P < 0.001). Participants receiving adalimumab significantly experienced greater response to treatment (≥50% reduction in the HAM-D score) than those receiving placebo (P = 0.042). Furthermore, after 6 weeks of adalimumab combination therapy with sertraline, inflammatory biomarkers significantly decreased (P ≤ 0.001), whereas no significant alteration was found in the placebo group. No serious adverse event was documented in the treatment arms.

Conclusions

Adalimumab adjunctive therapy remarkably improves depressive symptoms of patients with MDD. Further investigations with larger sample sizes and longer follow-up periods are required to confirm the findings.

https://doi.org/10.1097/WNF.0000000000000518

Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia (Oct 2022)

Results A total of 50 participants completed the trial (25 in each group). Baseline characteristics of the groups were comparable (p>0.05). There was significant effect from time-treatment interaction on negative symptoms (p = 0.012) suggesting greater symptom improvement in the PEA group. In contrast, the longitudinal changes in positive symptoms and depressive symptoms were similar between groups (p values>0.05). Safety assessments showed no significant difference regarding extrapyramidal symptoms, measured by ESRS, and also frequency of other complications between PEA and placebo groups (p values>0.05).

Conclusions

Adjunctive therapy with PEA and risperidone alleviates schizophrenia-related primary negative symptoms in a safe manner.

https://doi.org/10.1016/j.psychres.2022.114737

Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania (June 23 2022)

Results A total of 63 patients (32 in palmitoylethanolamide and 31 in placebo groups) completed the trial. We found a significant effect for time×treatment interaction on the YMRS score (F = 5.22, d.f. = 2.34, P= 0.004) from baseline to study end point. Results from independent t test showed a significantly greater decrease in YMRS scores in the palmitoylethanolamide group, compared with the placebo group, from baseline to weeks 4 and 6 (P= 0.018 and P= 0.002, respectively). There was no significant difference between palmitoylethanolamide and placebo groups based on ESRS scores or ESRS changes in scores (P>0.05).

Conclusions

Our findings provide preliminary evidence that palmitoylethanolamide is an effective adjunctive medication that improves manic symptoms and overall clinical status in acute episodes of mania. However, larger sample sizes and more extended follow-up therapy are needed in future studies to confirm our findings.

https://doi.org/10.1111/pcn.13441

Melatonin Effects in Women With Comorbidities of Overweight, Depression, and Sleep Disturbance (May 17 2022)

Not surprisingly, this study did not find that melatonin (an OTC supplement in most countries) was significantly effective for weight loss. it did find that melatonin significantly reduced depression symptoms and significantly improved sleep quality in this patient group.

Results

Melatonin significantly reduced depression symptoms compared with the placebo, F = (1, 34) = 6.2, p = 0.017. Also, melatonin significantly improved sleep quality, F = (1, 33) = 8.0, p = 0.008. Besides, subjects on the melatonin reduced more weight compared with the placebo but difference between groups was not significant, F = (1, 41) = 0.2, p = 0.650. Patients in the melatonin group did not show significantly more side effects compared to placebo.

Conclusions

Based on our findings, melatonin was not able to significantly reduce the body weight more than placebo, but as a safe over-the-counter supplement, it may be helpful in patients with co-morbidities of sleep disturbance, mild and moderate depression, and obesity in reducing the symptoms of depression and insomnia.

https://doi.org/10.17241/smr.2021.01130

Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia (Mar 7 2022)

This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients’ positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P < 0.001), negative (t = 2.88, df = 38, P = 0.006), and general psychopathology (t = 4.06, df = 38, P < 0.001) scores demonstrated a significantly greater decline in adalimumab compared with the placebo group from baseline study endpoint. However, improvement of PANSS positive subscale scores showed no significant difference from the baseline study endpoint. There was no significant between-group difference regarding levels of C-reactive protein, interleukin (IL)-1β, TNF-α, IL-6, and IL-8 at baseline and also at the week 8 visit (P > 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.

https://doi.org/10.1097/YIC.0000000000000399

Oxcarbazepine versus sodium valproate in treatment of acute mania (Feb 2 2022)

Oxcarbazepine as an anticonvulsant has been suggested as an effective drug in affective disorders. The present study was designed to compare the efficacy of oxcarbazepine and sodium valproate in the treatment of acute mania in the Iranian population. In a double-blind, randomized clinical trial, hospitalized bipolar patients in the acute manic phase who were admitted to Ibn-e-Sina psychiatric hospital in Mashhad city (north-eastern part of Iran) were enrolled. The diagnosis was confirmed using Structured Clinical Interview for DSM-IV-TR. Patients were then randomly allocated into two groups taking oxcarbazepine (900–2400 mg/day) and sodium valproate (about 20 mg/kg/day) for 6 weeks. Young Mania Rating Scale (YMRS), Clinical Global Impression Scale (CGI-S), and adverse effects of drugs were assessed at baseline and after 3 and 6 weeks. Mania symptoms based on mean scores of YMRS and CGI-S significantly decreased from baseline to endpoint in both treatments (P < 0.01). However, there was no significant difference between the two groups in terms of reduction of symptoms during times (P = 0.715 and P = 0.446, respectively) and adverse events (P > 0.05). This study confirmed the previous findings that indicate the efficacy of oxcarbazepine as same as sodium valproate. Moreover, its adverse effects resemble sodium valproate in the treatment of acutely manic patients.

https://doi.org/10.1097/YIC.0000000000000394

Possible effects of Saffron (Crocus sativus) in the treatment of erectile dysfunction (Feb 1 2022)

Results

Sixty-two participants were equally randomized into two groups, and 29 participants in each group completed the trial. Participants had a mean age of 41 years, and the majority suffered from mild erectile dysfunction. Positive changes in erectile function scores reached 6.14 (95% CI [4.97, 7.30]) points in the saffron group, which was superior to the placebo. The confidence interval excluded the minimal clinically important difference of the scale. The adverse events were similar between the two groups and saffron showed a clinically acceptable profile.

Conclusion

Our findings suggest saffron might be an effective and safe option to ameliorate erectile dysfunction among ED patients, especially those who decline or are unwilling to use phosphodiesterase type 5 inhibitors.

DOI

Cilostazol as an adjunctive treatment in major depressive disorder (Jan 24 2022)

Results At week 6, patients in the cilostazol group had significantly lower HAM-D score (p value= 0.015). General linear model repeated-measure analysis showed significant effect for treatment in improving MDD severity (p value <0.001). The remission rate at the study endpoint and number of responders at week 4 were significantly higher in the cilostazol group (p value= 0.047, p value= 0.032, respectively). The cilostazol group demonstrated a significantly shorter time to response. No significant difference was observed in treatment response at the study endpoint, and there were no serious adverse effects.

Conclusion Our study supports safety and efficacy of cilostazol in treating MDD patients.

Trial registration

This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N130)

https://doi.org/10.1007/s00213-021-06041-0

Efficacy and safety of saffron as adjunctive therapy in adults with attention-deficit/hyperactivity disorder (Jan 1 2022)

The study found statistically significant results for one endpoint (ASRS) but not the other (CAARS).

Results Forty-four patients completed the trial. GLM repeated-measure analysis demonstrated significant time × treatment interaction effect for ASRS (df=2, F=3.455, and P-value=0.036) and CAARS (df=1.584, F=3.939, and P-value=0.033) score from baseline to the study endpoint. We found a significantly greater reduction in ASRS scores in the saffron group compared with the placebo group from baseline to the study endpoint (week 6) (P-value=0.024). However, the change score from baseline to week 3 was not significantly different between trial groups (P-value=0.269). There was no significant difference in the improvement of CAARS scores between saffron and placebo from baseline to week 3 or 6 (P-value=0.564 and 0.089, respectively). There was no significant difference between the two groups in baseline parameters and frequency of side effects.

Conclusions

Saffron combination therapy with Ritalin can effectively improve symptoms of patients with ADHD. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.

Results Forty-four patients completed the trial. GLM repeated-measure analysis demonstrated significant time × treatment interaction effect for ASRS (df=2, F=3.455, and P-value=0.036) and CAARS (df=1.584, F=3.939, and P-value=0.033) score from baseline to the study endpoint. We found a significantly greater reduction in ASRS scores in the saffron group compared with the placebo group from baseline to the study endpoint (week 6) (P-value=0.024). However, the change score from baseline to week 3 was not significantly different between trial groups (P-value=0.269). There was no significant difference in the improvement of CAARS scores between saffron and placebo from baseline to week 3 or 6 (P-value=0.564 and 0.089, respectively). There was no significant difference between the two groups in baseline parameters and frequency of side effects.

Conclusions Saffron combination therapy with Ritalin can effectively improve symptoms of patients with ADHD. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.

Crocus sativus (saffron) in the treatment of female sexual dysfunction (Jan 31 2022)

Results: Seventy-four patients were equally randomized to each group, and 34 in each group completed the trial. Participants in both groups experienced improved total scores at each visit. However, a repeated-measures ANOVA revealed that time treatment differed between groups in favor of the saffron group (p=0.050). During the 6th week follow-up, the saffron group had a 62% score improvement from baseline. Desire, lubrication, and satisfaction were female sexual function index domains in which saffron demonstrated superiority over placebo. The adverse event profile was similar for the groups, and no participant discontinued treatment.

Conclusion: Findings of this study suggest that saffron might be a safe and effective option to ameliorate female sexual dysfunction. Further robust research is warranted.

https://dx.doi.org/10.22038/AJP.2022.19714 | https://pdfs.semanticscholar.org/6abd/02d0b1a76506db13dfe4cd42b39881dbf901.pdf?_gl=1*177rt77*_ga*MTUwMTAzMDMwOS4xNjkxMjkxNTA2*_ga_H7P4ZT52H5*MTY5NDA1MzYyNS44LjEuMTY5NDA1NTE2NC4xNi4wLjA.

Notable papers

Clinical trial of adjunctive celecoxib treatment in patients with major depression (July 2009)

Results: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti‐inflammatory therapies should be further investigated.