How are poor sleepers with other clinical conditions affected by maladaptive personality traits? A neural network-based analysis.

Background: Psychopathology research mainly focused on the cross-sectional and longitudinal associations between personality and psychiatric disorders without considering the moment-to-moment dynamics of personality in response to environmental situations. The present study aimed to both cluster a young sample according to three mixed clinical conditions (poor sleep quality, depression, and somatization) and to predict the derived clusters by maladaptive personality traits and sex differences using a deep machine learning approach. Methods: A sample of 839 adults aged 18-40 years (64% female) from the west of Iran were clustered according to the mixed clinical conditions using the cluster analysis techniques. An Artificial Neural Network (ANN) modeling is used to predict the derived clusters by maladaptive personality traits and biological gender. A receiver operating characteristic (ROC) curve was used to identify independent variables with high sensitivity specific to the derived clusters. Results: The cluster analysis techniques suggested a fully stable and acceptable four-cluster solution for Depressed Poor Sleepers, Nonclinical Good Sleepers, Subclinical Poor Sleepers, and Clinical Poor Sleepers. The ANN model led to the identification of one hidden layer with two hidden units. The results of Area under the ROC Curve were relatively to completely acceptable, ranging from.726 to.855. Anhedonia, perceptual dysregulation, depressivity, anxiousness, and unusual beliefs are the most valuable traits with importance higher than 70%. Conclusion: The machine learning approach can be well used to predict mixed clinical conditions by maladaptive personality traits. Future research can test the complexity of normal personality traits connected to mixed clinical conditions.

The sensitivity of the ICD-11 trait model to the symptoms of clinical disorders in young adults.

Hierarchical psychopathology contributes to providing a broader picture of the links between emerging personality structures such as the DSM-5/ICD-11 trait models and clinical disorders. The present study aimed to predict the specific and general clinical symptoms by the less studied constructs of the ICD-11 model (negative affectivity, detachment, dissociality, disinhibition, and anankastia). Data from 642 young adults from Iran (63% female, 18-34 years) were collected by three mental symptom scales and the Personality Inventory for DSM-5 (PID-5), which was recently used to harmonize the constructs of the DSM-5 and ICD-11 trait models. Multiple linear regressions showed that the ICD-11 model significantly predicted both the specific clinical symptoms (ranging from R2 = 0.15 to 0.40) and the general factor of clinical symptoms extracted by exploratory factor analysis (R2 = 0.40, all p < 0.001). Negative affectivity was the strongest construct correlated with both the specific symptoms (ranging from ß = 0.36 to 0.69) and the general symptom factor (ß = 0.59, all p < 0.001). Because the ICD-11 trait model is a practical structure related to the clinical psychopathology in young adults, screening for maladaptive traits can help clinicians in case formulation for diagnosis and treatment.

Meta-Analytic Review of Temperamental Correlates of the Five-Factor Model and Hierarchical Taxonomy of Psychopathology Domains.

Background: There is little and heterogeneous knowledge on the links between the temperamental predispositions of psychopathology and the contemporary dimensional models of psychopathology, such as the Hierarchical Taxonomy of Psychopathology (HiTOP) classification system, which can be aligned with the five-factor model (FFM) of personality. This meta-analysis seeks to expand the temperamental theoretical basis of the HiTOP model by incorporating associations of temperament traits of two temperamental theories measured, respectively, by the Temperament and Character Inventory (TCI) and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) with (a) the FFM's personality domains and (b) HiTOP's five psychopathological spectra. Methods: A systematic search was done on Web of Science, Scopus, PubMed, ProQuest, Cochrane Database, and Google Scholar for all articles published in English from January 1990 to August 2020. Because of heterogeneity in the results of almost 70% of studies, pooled estimates of correlation coefficients were calculated using the random-effects method. Risk of bias (low-quality studies) and publication bias are reported. Results: The pooled correlations obtained from the analysis of 35 studies showed that the temperamental profile associated with each FFM domain and HiTOP spectra is distinct. Specifically, TCI-harm avoidance (HA) and all TEMPS temperaments were more strongly related to neuroticism/internalizing, extraversion/low detachment, and conscientiousness/disinhibition. In contrast, TCI-novelty seeking was more strongly related to both disinhibited/antagonistic externalizing and thought disorder. Conclusions: A large body of research supports maladaptive variants of all FFM domains and some psychopathological spectra of HiTOP related to the abnormal-range temperaments.

Clinical cut scores for the Persian version of the personality inventory for DSM-5.

BACKGROUND: The cut points of psychological tools to diagnose clinical conditions are not universal and depend on the region and prevalence of the disorder. Thus, we aimed to identify the cutoff points of the Persian original version of the personality inventory for DSM-5 (PID-5; 220 items) that would optimally distinguish nonclinical from clinical groups. METHODS: Both nonclinical (N = 634, 73% female, 34.0 ± 10.8 years) and clinical (N = 454, 29% female, 29.5 ± 7.4 years) samples from the West of Iran participated in the study. Data were analyzed using receiver operating characteristic (ROC) and Youden's index was used to determine the cutoff scores across the PID-5 domains and facets. The means and standard deviations of both the clinical male and female were compared with the nonclinical group using Cohen's d and independent t-tests. RESULTS: All the PID-5 algorithms and facets significantly distinguished clinical from nonclinical samples with some unique findings for male and female samples. The mean score of all the PID-5 algorithms and facets in the clinical male and female samples were respectively 1.0-2.0 SD and 0.5-1.0 SD above the mean for the nonclinical counterparts. A score higher than 1.5 on ranging from 0 to 3 in each domain or facet indicated clinical status. CONCLUSION: Raw cutting scores throughout the PID-5 algorithms can be well used to diagnose any pathology of personality and the severity of the disorder in clinical patients. The cut scores provide a useful tool for the clinical use of the original version of PID-5 in Iran.

A head-to-head comparison of eight unique personality systems in predicting somatization phenomenon.

BACKGROUND: If somatization is an independent personality trait, it is not clear whether it is specific to the temperament or maladaptive spectrum of personality. We aimed at the head-to-head comparison of temperament and maladaptive systems and spectra of personality to predict both somatization and somatic symptom and related disorders (SSRD). METHODS: The samples included 257 cases with SSRD (70.8% female) and 1007 non-SSRD (64.3% female) from Western Iran. The Personality Inventory for DSM-5 (PID-5), Personality Diagnostic Questionnaire-4 (PDQ-4), Temperament and Character Inventory (TCI), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), Affective and Emotional Composite Temperament Scale (AFECTS), and Positive Affect and Negative Affect Model (PANAS) was used to data collection. A somatization factor plus temperament and maladaptive spectra of personality were extracted using exploratory factor analysis. Several hierarchical linear and logistic regressions were used to test the predictive systems and spectra. RESULTS: All personality systems jointly predict both somatization and SSRD with a slightly higher contribution for temperament systems. When the temperament and maladaptive spectra were compared, both spectra above each other significantly predicted both somatization (R2 = .407 versus .263) and SSRD (R2 = .280 versus .211). The temperament spectrum explained more variance beyond the maladaptive spectrum when predicting both the somatization factor (change in R2 = .156 versus .012) and SSRD (change in R2 = .079 versus .010). CONCLUSION: All temperament and maladaptive frameworks of personality are complementary to predicting both somatization and SSRD. However, the somatization is more related to the temperament than the maladaptive spectrum of personality.

Construct and criterion validity of the HiTOP spectra to predict dimensional and categorical somatization in a large non-western sample.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a phenotypic data-driven framework for the classification of psychopathology. We tested the construct and criterion validity of the HiTOP spectra measured by the Personality Inventory for DSM-5 (PID-5) using exploratory structural equation modeling (ESEM) and hierarchical regressions both to predict somatic symptom and related disorders (SSRD) and a somatization factor. The case-control study used hierarchical logistic regressions to distinguish 257 cases with SSRD from 1007 healthy controls by both the maladaptive and the temperament factors. The extracted factors were also used in hierarchical linear regressions to predict the dimensional somatization factor. The seven temperament factors explained more variance above and beyond the five maladaptive factors when predicting SSRD (pseudo R2 = 0.169 to 0.266 versus 0.125 to 0.196; change in pseudo R2 = 0.055 to 0.087 versus 0.011 to 0.017). The temperament factors also explained more variance above and beyond the maladaptive factors when predicting the somatization factor (R2 = 0.392 versus 0.269; change in R2 = 0.146 versus 0.023). Although the HiTOP spectra measured by PID-5 are significant structures related to the categorical and dimensional measurements of somatoform, our findings highlight potential problems with both the construct and criterion validity of the HiTOP spectra.

Comparison of the relative sensitivity of two dimensional personality models to the psychopathological symptoms: the section III DSM-5 maladaptive traits versus affective temperaments.

BACKGROUND: The Personality Inventory for DSM-5 (PID-5) and Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) are tools designed for personality dispositions for mental health symptoms. The present study was conducted to compare these models in terms of their relative sensitivity to the symptoms of personality disorders (PDs) and non-personality disorders (NPDs). METHODS: Subjects in this cross-sectional study were 1232 (805 female; 63.5%) community samples in western Iran. Data were collected using the PID-5, the TEMPS-A, the Symptom Checklist-90 (SCL-90-R), and the Personality Diagnostic Questionnaire (PDQ-4). Correlations and Regression models were used to examine associations between traits and symptoms. RESULTS: Maladaptive traits assessed by the PID-5 were more strongly associated with PD symptoms, whereas affective temperaments measured by the TEMPS-A were more strongly associated with NPD symptoms. CONCLUSION: The present findings highlighted the practical utility of both the PID-5 and TEMPS-A indicating risk for psychopathology, but also suggest a distinction between PDs and NPDs in terms of underlying personality dispositions.

Comprehensive meta-analysis of associations between temperament and character traits in Cloninger's psychobiological theory and mental disorders.

OBJECTIVE: To explore the relationship between temperament and character traits in Cloninger's psychobiological theory and mental disorders.Methods: A systematic literature search was conducted of five international databases for all articles published in English between January 1990 and April 2019 (PROSPERO-CRD42019133214). Owing to heterogeneity, pooled estimates of correlations for personality disorders and standardized mean differences for case-control studies related to other mental disorders were calculated using the random-effects method. RESULTS: The pooled effect sizes obtained from 149 studies showed that high harm avoidance (related to 22/24 diagnostic categories), low self-directedness (21/23), low cooperativeness (17/23), high self-transcendence (14/23), low reward dependence (11/24), high novelty-seeking (10/24), low novelty-seeking (7/24), high persistence (2/23), low persistence (2/23) and high reward dependence (2/24) were related to psychopathology. CONCLUSIONS: All traits provided unique psychobiological tools for differential diagnosis of mental disorders. However, high harm avoidance and low self-directedness played a canonical role in psychopathology. Despite the study limitations, additional studies are warranted to evaluate the differential diagnoses suggested by the present model.

Changes in neuroticism-related constructs over the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in patients on an optimal dose of SSRI.

Recent advances in clinical practice emphasize the utility of Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) as an effective intervention for targeting core processes underlying comorbid disorders. This study aimed to evaluate changes in psychopathological risk factors associated with the construct of neuroticism (i.e., negative affect, anxiety sensitivity, experiential avoidance, intolerance of uncertainty) within the UP to adults already on an optimal and stable dose of SSRIs. In a randomized controlled trial, a total of 39 adults (Mage = 27.51 [±8.43]; 56.4% female) on SSRIs with a diagnosis of comorbid anxiety and depressive disorder were randomly assigned to either UP + SSRI (n = 18) or continued SSRI-only (n = 21). Neuroticism dimensions were assessed at baseline, posttreatment, and 1-month follow-up. UP + SSRI condition demonstrated medium to large effect sizes for changes over time on facets of neuroticism including negative affect (Cohen's d = 1.12, 95% confidence interval [CI; 0.44, 1.80]), anxiety sensitivity (Cohen's d = 1.21, 95% CI [0.53, 1.90]), experiential avoidance (Cohen's d = 0.74, 95% CI [0.09, 1.04]), and intolerance of uncertainty (Cohen's d = 1.66, 95% CI [0.93, 2.39]). Post hoc analyses showed reductions in variables that were maintained at follow-up. Results adds to the growing body of literature and provide cross-cultural support for the utility of UP in targeting pathological risk factors as adjuncts to SSRI. Implications for future studies and limitations are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Construct Validity of the ICD-11 Severity of Personality Dysfunction Under Scrutiny of Object-Relations Theory.

The current classification of personality disorder in ICD-11 includes a description of personality functioning, derived from a number of theoretical paradigms, but most notably consistent with the psychodynamic approach. Concurrently, an object-relations model of personality functioning in a dimensional assessment of severity is provided in the Structured Interview of Personality Organization-Revised (STIPO-R). To date, there are no published measures of International Classification of Diseases-11 (ICD-11) personality severity, though the construct is very comparable to the concepts assessed in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) levels of personality functioning concept, which is measured by the Level of Personality Functioning Scale-Self-Report (LPFS-SR). This study examined the validity of ICD-11 personality functioning, as measured by the LPFS-SR, by evaluating its associations with the STIPO-R in Kurdistan region. The samples included 231 University students and 419 inpatient participants across four hospitals (267 with a diagnosed personality disorder). All the components of LPFS-SR and STIPO-R were positively and significantly intercorrelated. The components of each measure discriminated PD and non-PD patients from a University, non-clinical group adequately. Despite slightly better performance of the STIPO-R in this discrimination, the measures had a high congruence in predicting personality dysfunction. Overall, the findings of the present study support the validity of ICD-11 construct for evaluating personality functioning.

Temperaments and characters: incompatible or complementary components for criterion B of the alternative model in predicting DSM-5 section II personality disorders?

BACKGROUND: Many studies have found clear correspondence among the domains of the five-factor model of personality (FFM) and the alternative model of personality disorders (AMPD) in DSM-5-III, which is assessed with the Personality Inventory for DSM-5 (PID-5). However, very few studies have compared the PID-5 with the other well-known established dimensional models of personality such as Cloninger's model. The present study examined whether the Temperament and Character Inventory (TCI-125) dimensions, PID-5 dimensions, or a combination would represent PD-scale scores more accurately. PARTICIPANTS AND PROCEDURE: In this regard, 437 college students completed the Persian version of the PID-5, TCI-125 and SCID-II Screening Questionnaire.RESULTS The results indicated that cooperativeness (low), self-directedness (low), and self-transcendence (high) characters of the TCI-125 and the psychoticism (high) domain of the PID-5 are the most consistent predictors of all PD-scale scores. CONCLUSIONS: Overall, the findings showed that an integrative model, combining dimensions of the TCI-125 and PID-5, represented the features of PD-scale scores most effectively.

Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial.

BACKGROUND: Patients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia. METHODS: In a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms. RESULTS: A total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups. CONCLUSION: Adding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.

The Clinical Effect of Electroconvulsive Therapy and Its Relationship with Serum Levels of MMP-9 and CXCL12 in Patients with Mania.

INTRODUCTION: Electroconvulsive therapy (ECT) is a non-pharmacological method for the treatment of psychiatric disorders. The precise biochemical mechanism of the effects of ECT is not clear, and since the two factors including matrix metalloproteinase-9 (MMP-9) and stromal cell-derived factor-1 alpha (CXCL12) play an important role in improving nerve damage, the effects of ECT and its relation with serum levels of MMP-9 and CXCL12 in patients with mania were investigated in this study. METHODS: In this before and after intervention study, the patients with mania, referring to the Qods Hospital in Sanandaj, were selected by the census method during the years 2015-2018. Young's test was performed 24 hrs before and after the first, third, and sixth sessions of ECT. For biochemical analysis, 3 mL of peripheral blood were taken prior to any anesthesia and 6 hrs after the first, third, and sixth sessions. Data were analyzed by two-way ANOVA and Pearson correlation coefficient by using the SPSS16 software. RESULTS: The results showed a significant decrease in Young's test scores during the first to the sixth session of ECT (P≤0.05). Although the levels of CXCL12 were slightly increased after the sixth course of ECT, they were not significant. Moreover, there were no significant relationship between the Young's test score and the serum levels of both MMP-9 and CXCL12 (P≥0.05). CONCLUSION: ECT improved patients clinically, but this effect was independent of serum levels of MMP-9 and CXCL12, and possibly other biochemical factors are involved in this pathway.

Examining the Contribution of Perfectionistic Traits to the Construct Validity of the DSM-5 Alternative Model of Personality Disorder.

Scholars of perfectionism have proposed significant modifications to DSM-5's alternative model of personality disorders (AMPD), such that (1) perfectionism be expanded beyond the inclusion of a singular trait-rigid perfectionism-and (2) perfectionistic traits be specified as trait descriptors of personality disorders (PDs) other than obsessive-compulsive PD. In this study, we evaluate these proposals by examining the degree to which (a) perfectionistic traits are already instantiated in Section II and Section III models of personality pathology; and (b) perfectionistic traits meaningfully augment the construct validity of AMPD PDs. We conducted these approaches in a large sample (N =3D 435) from an Iranian undergraduate population that is atypically found in the literature. Results showed that perfectionistic traits are already fairly well instantiated in Section III Criterion B. Perfectionistic traits minimally improved the construct validity of OCPD, but did not meaningfully do so for other PDs. Future investigation into the clinical utility of perfectionistic traits is needed.

Vortioxetine as adjunctive therapy to risperidone for treatment of patients with chronic schizophrenia: A randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION AND OBJECTIVES: Vortioxetine, a novel antidepressant, may be an interesting candidate for adjunctive therapy of schizophrenia. Our primary objective was to investigate the effect of vortioxetine on negative symptoms, with the assessment of positive, general psychopathology and total symptoms as our secondary goal. METHODS: This was an eight-week randomised, double-blind, placebo-controlled, parallel-group clinical trial, in which 78 inpatients with chronic schizophrenia were stabilised with risperidone (4-6 mg/day) for two months before being assigned to adjunctive vortioxetine (10 mg b.i.d.) or placebo. The patients were assessed using the Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Symptom Rating Scale and Hamilton Depression Rating Scale during the study course. All participants had a PANSS negative symptoms subscale score of ⩾16 at baseline. Sixty-eight patients completed the trial. RESULTS: Vortioxetine improved the negative symptoms score as the primary outcome and total PANSS score as a secondary outcome significantly better than placebo from baseline to end point at week 8, accompanied by significant time × treatment interactions and effect sizes (negative symptoms: mean difference (95% confidence interval (CI)) = -1.82 (-2.73 to -0.92); total scores: mean difference (95% CI) = -2.09 (-3.16 to -1.01). No significant difference was detected for changes in positive symptoms score or PANSS general psychopathology score as the other secondary outcomes from baseline to end point between the two treatment arms. The incidence of adverse events was comparable between groups. CONCLUSIONS: This is the first study to provide evidence for the therapeutic effect of vortioxetine on negative symptoms as an adjunctive to treatment with antipsychotics in patients with schizophrenia.

A systematic review of personality temperament models related to somatoform disorder with main focus on meta-analysis of Cloninger's theory components.

The systematic review aims to identify four personality temperament models related to somatoform disorder with the main focus on the meta-analysis of temperaments and characters in Cloninger's theory. The literature search was performed on PubMed (Medline), Scopus, Web of Science, Cochrane, and ProQuest for all articles published in English from January 1990 to April 2019. Due to heterogeneity, pooled estimates of the standard mean difference between cases and controls were calculated using the random-effects model. Based on our inclusion criteria, 14 studies were identified, 7 of which were included in the meta-analysis. The results show that there is a significant difference between cases and controls with regard to harm avoidance (HA) (z = 5.322, P < 0.001), self-directedness (z = -4.719, P < 0.001), and self-transcendence (z = 2.848, P = 0.004). Compared to controls, HA and self-transcendence were higher and self-directedness was lower in cases. With regard to other subscales, there was no difference between the two groups (P > 0.05). The publication bias was not seen (P > 0.05 for Egger statistics). Up to now, very few studies have been focused on the relationship between personality temperament models and somatoform disorder. Among the components of the Cloninger's model, the poor self-directedness along with the abnormally high self-transcendence and HA is the personality component related to the somatoform disorder. Thus, Cloninger's model may potentially draw a personality profile for vulnerability to somatoform disorder. Given the limited number of studies available, future studies may challenge the results of the present study.

Resveratrol as adjunctive therapy in treatment of irritability in children with autism: A double-blind and placebo-controlled randomized trial.

WHAT IS KNOWN AND OBJECTIVE: The underlying pathophysiology of autism spectrum disorder (ASD) has been linked to immune dysregulation, oxidative stress and excitation-inhibition imbalance. Among associated symptoms of ASD, management of irritability has gained considerable attention as it complicates adjustment of ASD patients and thus necessitates its pharmacological treatment. Resveratrol is a plant phytoalexin, which has been demonstrated to have neuroprotective effects through its anti-inflammatory and antioxidant properties. This double-blind, placebo-controlled randomized trial was designed to assess the potential therapeutic effects of resveratrol plus risperidone on irritability of ASD patients. METHODS: Sixty-two patients were assigned randomly into two groups of resveratrol and placebo. Both groups were treated with risperidone twice daily starting at a dose of 0.5 mg with a dose increase of 0.5 mg per week (for the first 3 weeks). Resveratrol dosage was 250 mg twice per day from the beginning of the study. Using the Aberrant Behavior Checklist-Community (ABC-C), patients were assessed for ASD-related behavioural symptoms at baseline, week 5 and week 10. The frequency of adverse events was recorded using a checklist containing 25 possible side effects, including general, gastrointestinal, neurological and cardiovascular complications. RESULTS AND DISCUSSION: Improvements in primary outcome measure (irritability) and three secondary outcome measures (lethargy/social withdrawal, stereotypic behaviour and inappropriate speech subscales) in the resveratrol group were statistically similar to those in the placebo group. The repeated measures analysis showed no time × treatment interaction on these subscale scores. In contrast, patients in the resveratrol group showed greater decline in hyperactivity/non-compliance score as a secondary outcome measure (mean difference [CI = 95%] = 4.51 [0.10-8.92], t = 2.04; P = .04), and repeated measures analysis showed significant effect for time × treatment effect on this subscale score (F = 3.81; df = 1.30; P = .043). There was no significant difference in number and severity of adverse events between the two groups. WHAT IS NEW AND CONCLUSION: This clinical trial demonstrated no significant effect for adjunctive treatment with resveratrol on irritability of patients with ASD. However, it provided preliminary evidence indicating that resveratrol could improve hyperactivity/non-compliance of ASD patients.

Efficacy of melatonin as an adjunct in the treatment of acute mania: a double-blind and placebo-controlled trial.

This is a double-blind, placebo-controlled, parallel-grouped clinical trial, which was designed to investigate the potential effects of melatonin add-on treatment with lithium and risperidone on acute manic episodes in patients with bipolar disorder (BD). A total of 54 patients were included and randomly assigned into two groups of melatonin and placebo. The trial group received 3 mg/day risperidone, 900 mg/day lithium, and 6 mg/day melatonin. The placebo group received the same dose of risperidone and lithium plus placebo. The participants were evaluated at four sessions, consisting of baseline, weeks 1, 4, and 6. The manic symptoms and overall clinical improvement of the patients were assessed using the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I), respectively. Two trial groups were matched based on all baseline characteristics. The patients in two trial groups had comparable serum lithium levels at weeks 1, 4, and 6. Our results from the general linear model repeated measures analysis showed a significant effect for time × treatment interaction on YMRS scores (P = 0.021 and F-value = 3.7). Furthermore, outcomes of the CGI-I rating scale demonstrated that patients in the melatonin group had better clinical improvements compared to the placebo group (P = 0.018). Our results provided preliminary evidence supporting melatonin as an effective adjunctive treatment leading to significant improvements in manic symptoms and overall clinical status in acute episodes of mania.