The Characteristics, Reliability and Validity of the Persian Version of Simplified Nutritional Appetite Questionnaire (SNAQ).

BACKGROUND/AIMS: Using a reliable and valid instrument to measure appetite is highly important in clinical practice and research. We aimed to evaluate characteristics, reliability and validity of the Persian version of simplified nutritional appetite questionnaire (SNAQ). MATERIAL AND METHODS: After face and content validation of the SNAQ by a panel of experts, the reliability and validity of the Persian form of this questionnaire were assessed among 213 weight-reduction seeking women referring to a nutrition clinic. Furthermore, the factor analysis was performed by varimax rotation method. RESULTS: Confirmatory factor analysis shows that all items of the questionnaire are unified and loaded on one factor of "appetite". Internal consistency of the test was approved by Cronbach's alpha coefficient of 0.7. The test-retest reliability of the questionnaire was performed within a two weeks interval. The Pearson correlation showed a consistency of 0.85 between the two administrations (p<0.0001). Concurrent Validity of SNAQ with other eating questionnaires and visual analogue rating scale for appetite (r=0.7, p<0.001)) shows strong correlation. The SNAQ was positively correlated with total dietary calorie intake (r=0.23, p=0.018) Also convergent validity with body composition measurements shows positive weak correlation with body weight, waist circumference, and total body fat percentage, and negative correlation with muscle mass (divergent validity). CONCLUSION: The current study provides sufficient supports in favor of the reliability and validity of the Persian version of the SNAQ. This questionnaire is a simple and valid instrument to assess the patient's increased appetite in practice and research.

Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial.

Introduction: Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. Methods: 66 patients with major depressive disorder accompanied by anxious distress were randomly assigned to receive either saffron (30 mg/day) or citalopram (40 mg/day) for 6 weeks. Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) were used to assess treatment effect during the trial. Results: 60 participants finished the study. Patients who received either saffron or citalopram showed significant improvement in scores of the Hamilton Rating Scale for Depression (P-value<0.001 in both groups) and Hamilton Rating Scale for Anxiety (P-value<0.001 in both groups). Comparison of score changes between the 2 trial arms showed no significant difference (P-value=0.984). Frequency of side effects was not significantly different between the 2 groups. Discussion: The present study indicates saffron as a potential efficacious and tolerable treatment for major depressive disorder with anxious distress.

Comparison of Saffron versus Fluoxetine in Treatment of Mild to Moderate Postpartum Depression: A Double-Blind, Randomized Clinical Trial.

Introduction: Postpartum depression is a common mental health problem that is associated with maternal suffering. The aim of this double-blind clinical trial was to compare safety and efficacy of saffron and fluoxetine in treatment of mild to moderate postpartum depression. Methods: This was a 6-week, double-blind, randomized clinical trial. Subjects were women aged 18-45 years with mild to moderate postpartum depression who had Hamilton Depression Rating Scale (HDRS 17-item) score≤18. Eligible participants were randomized to receive either a capsule of saffron (15 mg capsule) or fluoxetine (20 mg capsule) twice daily for 6 weeks. The primary outcome measure was to evaluate efficacy of saffron compared to fluoxetine in improving depressive symptoms (HDRS score). Results: There was no significant effect for time×treatment interaction on HDRS score [F (4.90, 292.50)=1.04, p=0.37] between the 2 groups. 13 (40.60%) patients in the saffron group experienced complete response (≥50% reduction in HDRS score) compared with 16 (50%) in the fluoxetine group and the difference between the 2 groups was not significant in this regard (p=0.61). Frequency of adverse events was not significantly different between the treatment groups. Discussion: The results of this study may suggest that saffron is a safe alternative medication for improving depressive symptoms of postpartum depression. Nevertheless, it should be mentioned that the trial is not well powered and should be considered a preliminary study. Therefore, large clinical trials with longer treatment periods and comparison with placebo group would be appropriate for future studies.

Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

WHAT IS KNOWN AND OBJECTIVE: Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. METHODS: Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. RESULTS AND DISCUSSION: A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. WHAT IS NEW AND CONCLUSION: A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing.

N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: N-acetylcysteine (NAC) has been proposed as a potential therapy for obsessive-compulsive disorder (OCD) as it may regulate the exchange of glutamate and prevent its pre-oxidant effects. The aim of the present double-blind, placebo-controlled trial was to assess the efficacy and tolerability of NAC augmentation in moderate-to-severe (OCD) treatment. METHODS: In this randomized, double-blind, two-centre, placebo-controlled, 10-week trial, patients with moderate-to-severe OCD were enrolled. Patients were randomized into two parallel groups to receive fluvoxamine (200 mg daily) plus placebo or fluvoxamine (200 mg daily) plus NAC (2000 mg daily). A total of 44 patients (22 in each group) were visited to evaluate response to therapy using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at baseline, and at weeks 4, 8 and 10. Side effects were recorded using predesigned checklists upon each visit. RESULTS AND DISCUSSION: Repeated-measures ANOVA showed a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5·14, d.f. = 1·64, P = 0·012) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5·44, d.f. = 1·54, P = 0·011) in the Y-BOCS obsession subscale between the two groups. WHAT IS NEW AND CONCLUSION: Our results showed that NAC might be effective as an augmentative agent in the treatment of moderate-to-severe OCD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (www.irct.ir): IRCT201405271556N60.

Duloxetine Add-On to Risperidone for Treatment of Negative Symptoms in Patients with Stable Schizophrenia: Randomized Double-Blind Placebo-Controlled Study.

INTRODUCTION: Although the pathogenesis of symptoms of schizophrenia is largely unknown, a variety of neurotransmitters are implicated, including serotonin and norepinephrine. Here we investigate the effectiveness of duloxetine as a serotonin-norepinephrine inhibitor in the treatment of negative symptoms. METHODS: We performed a double-blind clinical trial on 64 patients with stable schizophrenia and no prominent symptoms of depression. Patients received risperidone (up to 6 mg/day) plus either duloxetine (60 mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6 and 8 weeks of therapy. RESULTS: Compared to the placebo group, the duloxetine group showed significantly higher improvement in negative symptoms (p<0.001), PANSS total (p<0.001), and the general psychopathology subscale scores (p=0.001), but no significant difference in positive symptoms (p=0.13). The side effect profiles of the 2 treatment regimens were not significantly different. DISCUSSION: Duloxetine adjuvant to risperidone seems to be a tolerable and efficacious treatment for primary negative symptoms of schizophrenia.

Effect of Adjunctive Celecoxib on BDNF in Manic Patients Undergoing Electroconvulsive Therapy: a Randomized Double Blind Controlled Trial.

INTRODUCTION: The possible effect of inflammatory factors on decreasing BDNF has been proposed in the literature. There is conflicting evidence regarding association between BDNF level alteration and treatment response in depressive patients undergoing electroconvulsive therapy (ECT). This study investigated the effects of celecoxib in manic patients undergoing ECT on treatment response and BDNF levels. METHODS: This randomized, double-blind, clinical trial included 35 manic patients who received either celecoxib (200 mg twice daily) or placebo, from one day before the 1(st) ECT session throughout the 6(th) session. BDNF levels were measured at baseline, 1(st), 3(rd) and 6(th) ECT sessions. Young mania rating scale was used to assess treatment response. RESULTS: Adding celecoxib was not associated with a significant rise in BDNF levels following ECT. No difference was noted between groups in terms of treatment response. No significant association was found between changes in BDNF levels and patients' responses. DISCUSSION: Adjuvant celecoxib did not significantly affect the BDNF level or the treatment response following ECT in manic patients.

Celecoxib for the treatment of mild-to-moderate depression due to acute brucellosis: a double-blind, placebo-controlled, randomized trial.

WHAT IS KNOWN AND OBJECTIVE: Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate. Inflammatory processes are involved in the pathogenesis of both brucellosis and depression. Therefore, we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis. METHODS: Forty outpatients with depression due to brucellosis with a Hamilton Depression Rating Scale score (HDRS) <19 participated in a randomized, double-blind, placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib (200 mg bid) or placebo as an adjunctive to antibiotic therapy. Patients were evaluated using HDRS at baseline and weeks 4 and 8. RESULT AND DISCUSSION: Repeated-measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [F (1·43, 57·41) = 37·22, P < 0·001]. Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [10 patients (50%) vs. no patient (0%), respectively, P < 0·001]. No serious adverse event was observed. WHAT IS NEW AND CONCLUSION: Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo.

Celecoxib as an Adjuvant to Fluvoxamine in Moderate to Severe Obsessive-compulsive Disorder: A Double-blind, Placebo-controlled, Randomized Trial.

INTRODUCTION: A growing body of evidence implicates inflammatory cascades in the pathophysiology of obsessive-compulsive disorder (OCD), making this pathway a target for development of novel treatments. METHODS: 50 outpatients with moderate to severe OCD participated in the trial, and underwent 10 weeks of treatment with either celecoxib (200 mg twice daily) or placebo as an adjuvant to fluvoxamine. Participants were investigated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the efficacy of celecoxib in improving the OCD symptoms. RESULTS: General linear model repeated measures demonstrated significant effect for time × treatment interaction on the Y-BOCS total scores [F (1.38, 66.34)=6.91, p=0.005]. Kaplan-Meier estimation with log-rank test demonstrated significantly more rapid response in the celecoxib group than the placebo group (p<0.001). There was no significant difference in adverse event frequencies between the groups. DISCUSSION: The results of the current study suggest that celecoxib could be a tolerable and effective adjunctive treatment for more rapid and more satisfying improvements in OCD symptoms.

Nitric oxide and peroxynitrite serum levels in Parkinson's disease: correlation of oxidative stress and the severity of the disease.

BACKGROUND: Nitric oxide (NO) and its toxic product peroxynitrite contribute to oxidative stress and neurodegeneration in Parkinson's disease (PD). The relationship of serum levels of these oxidants with the severity of the disease [evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS)] is not established. AIM: This study was designed to evaluate whether patients with PD had higher NO and peroxynitrite serum level or not. PATIENTS AND METHODS: Fifty eight patients with PD and 15 healthy volunteers entered this study. The concentrations of serum NO and peroxynitrite were assayed and their correlation with the UPDRS score was assessed. RESULTS: Mean serum NO levels in patient group was 29.8 ± 21.631 versus 7.49 ± 2.573 in control group, which was significantly higher in patients (p ≤ 0.0001). Peroxynitrite levels in patient and control groups were 7.37±3.501 µmol/L and 3.94 ±1.389 µmol/L respectively. Patients had a significantly higher peroxynitrite level (p = 0.0004). CONCLUSIONS: Higher levels of NO and peroxynitrite leads to higher UPDRS scores. It seems since current PD treatments do not affect the pathology of the disease, using drugs that exert neuroprotective properties should be considered for the treatment of PD in order to prevent further neuronal cell loss.  

Glutathione-related factors and oxidative stress in autism, a review.

Autism spectrum disorders are complex neuro-developmental disorders whose neurobiology is proposed to be associated with oxidative stress which is induced by reactive oxygen species. The process of oxidative stress can be a target for therapeutic interventions. In this study, we aimed to review the role of oxidative stress, plasma glutathione (GSH), and related factors as the potential sources of damage to the brain as well as the possible related factors which reduce the oxidative stress. Methylation capacity, sulfates level, and the total glutathione level are decreased in autism. On the other hand, both oxidized glutathione and the ratio of oxidized to reduced glutathione are increased in autism. In addition, the activity of glutathione peroxidase, superoxide dismutase, and catalase, as a part of the antioxidative stress system are decreased. The current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing the oxidative stress might be a potential treatment for autism.

Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.

WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid ß in the human brain and may therefore be useful in Alzheimer's disease (AD). OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events. WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for.

Major depressive disorder in children and adolescents after renal transplantation.

This cross-sectional study evaluated the prevalence of major depressive disorder and depressive symptoms in children and adolescents after renal transplantation. A total of 71 patients who had undergone renal transplantation were interviewed in person using the Farsi (Persian) version of the Kiddie Schedule for Affective Disorders and Schizophrenia and Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria. Major depressive disorder, depressive symptoms, and suicidal behaviors were assessed. The rate of major depressive disorder was 2.8%; two-thirds of the patients had irritability; and approximately 40% had recurrent thoughts of death and suicidal ideation. The rate of major depressive disorder was lower than in other chronic diseases such as thallasemia or hemophilia; however, the rate of suicidal behaviors was high.

Variations in thyroidal activity during estrous cycle and natural breeding season in Markhoz goat breeds.

The aim of this study was to determine the profile of changes in T3, T4 and TSH levels during breeding season and estrous cycle in Markhoz (Angora) Goats. Whereas the peaks of T3 were recorded in January, concentrations of T4 and TSH were highest in October. Variations in T3 and TSH concentrations among the different months of experiments period were not significant, although T4 concentration was significantly higher during September, October and November in comparison to December and January. Weekly variations in serum T4 and TSH concentrations were directly correlated to the changes in photoperiod and temperature. Monthly variation in serum T3 and TSH did not have a significant (p>0.05) relationship with the changes in photoperiod and temperature, but there was a highly significant positive relationship between serum T4 and temperature. This study showed that T4 concentration was high in the early phase but decreased in the late phase of the breeding season, but T3 and TSH concentrations varied markedly from week to week. However, it appears that weekly rhythms are controlled by photoperiod and temperature because, changes in these factors resulted in different profiles of both T4 and TSH, but there was not any correlation between T3 and those factors.

Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial.

OBJECTIVE: The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). DESIGN: Double-blind, randomised and placebo-controlled trial. SETTING: Departments of Gynaecology/Obstetrics and Psychiatry, Tehran and Zanjan University of Medical Sciences. POPULATION: Women aged 20-45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. METHOD: Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) (group A) or capsule placebo (twice a day) for a two menstrual cycles (cycles 3 and 4). MAIN OUTCOME MEASURES: The primary outcome measure was the Daily Symptom Report, and secondary outcome measure was the Hamilton Depression Rating Scale. RESULTS: In this trial, saffron was found to be effective in relieving symptoms of PMS. A significant difference was observed in efficacy of saffron in cycles 3 and 4 in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. CONCLUSION: The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS. However, a tolerable adverse effects profile of saffron may well confirm the application of saffron as an alternative treatment for PMS. These results deserved further investigations.

Artificial neural networks in prediction of bone density among post-menopausal women.

Artificial neural networks (ANN) are promising tools in learning complex interplay of factors on a particular outcome. We performed this study to compare the predictive power of ANN and conventional methods in prediction of bone mineral density (BMD) in Iranian post-menopausal women. A database of 10 input variables from 2158 participants was randomly divided into training (1400), validation (150) and test (608) groups. Multivariate linear regression and ANN models were developed and validated on the training, and validation sets and outcomes (femoral neck and lumbar T-scores) were predicted and compared on the test group using different numbers of input variables. Results were evaluated by comparing the mean square of differences between predicted and reference values (non-central chi-square test) and by measuring area under the receiver operating characteristic curve (AUROC) around cut-off value of -2.5 for T-scores. For models with less than 3 input variables in femoral neck and 4 variables in spinal column, performance of regression and ANN models was almost the same. As more variables imported into models, ANN outperformed linear regression models. AUROC varied in 2 to 10 variable models as follows: for ANN in spine, from 0.709 to 0.774; linear models in spine, from 0.709 to 0.744; ANN in femoral neck, from 0.801 to 0.867; linear models in femoral neck, from 0.799 to 0.834. The ANN model performed better than five established patient selection tools in the test group. Superior performance of neural networks than linear models demonstrate their advantage especially in mass screening applications, when even a slight enhancement in performance results in significant decrease in number of misclassifications.

Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.

BACKGROUND: Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder. METHODS: Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6. RESULTS: Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant. CONCLUSION: In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.

Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial.

Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.

Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial.

Attention-deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3-6% of school children. Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative, safe and effective medications in the treatment of this disorder. Theophylline is a psychomotor stimulant most widely used as a broncodilator. Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders. We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylphenidate for the treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were randomized to theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2) for a 6-week double-blind and randomized clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist, at baseline and at 14, 28 and 42 days after start of the medication. No significant differences were observed between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores over the trial (t = 0.49, d.f. = 24 P = 0.62 and t = 0.19, d.f. = 24 P = 0.54 respectively). Although the number of dropouts in the methylphenidate group was higher than the theophylline group, there was no significant difference between the two protocols in terms of the dropouts. In addition, headaches were observed more often in the methylphenidate group. The results suggest that theophylline may be a useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD. Nevertheless, our study is small and our results would need to be confirmed in a larger study.

Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial.

OBJECTIVE: Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. METHODS: Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. RESULTS: The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant. CONCLUSION: The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial.