Disseminated tuberculosis with myelofibrosis presentation: a case report.

BACKGROUND: Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow fibrosis because, in reactive fibrosis, treatment approaches depend on the underlying etiology. CASE PRESENTATION: Here we report the case of a middle-aged Iranian man who was diagnosed and treated as primary myelofibrosis at presentation, and whose final diagnosis was disseminated tuberculosis with reactive bone marrow fibrosis. CONCLUSIONS: It is prudent to evaluate the potential causes of myelofibrosis in any patient with the diagnosis primary myelofibrosis. Tuberculosis can be an important etiology of bone marrow fibrosis, especially in endemic areas.

The effects of pioglitazone adjuvant therapy on negative symptoms of patients with chronic schizophrenia: a double-blind and placebo-controlled trial.

OBJECTIVE: The evident central role of inflammation, oxidative stress, and metabolic derangement in pathophysiology of negative symptoms of schizophrenia has opened new insights into probable pharmacological options for these symptoms. Pioglitazone is an antidiabetic agent with anti-inflammatory and antioxidant properties. In this study, we evaluated the efficacy of pioglitazone as an adjunct to risperidone for reduction of negative symptoms in schizophrenia. METHODS: In this randomized, double-blind, placebo-controlled trial, 40 patients with chronic schizophrenia and a minimum score of 20 on the negative subscale of Positive and Negative Syndrome Scale (PANSS) were randomly allocated to receive risperidone plus either pioglitazone (30 mg/day) or placebo for 8 weeks. Patients' symptoms and adverse events were rated at baseline and weeks 2, 4, 6, and 8. The difference between the two groups in decline of PANSS negative subscale scores was considered as the primary outcome of this study. RESULTS: At the study endpoint, patients in the pioglitazone group showed significantly more improvement in PANSS negative subscale scores (p < 0.001) as well as PANSS total scores (p = 0.01) compared with the placebo group. CONCLUSION: These findings suggest the probable efficacy of pioglitazone as an augmentation therapy in reducing the negative symptoms of schizophrenia.

Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial.

Statins have been shown to decrease depressive symptoms in certain groups of patients, an effect that is mostly attributed to their anti-inflammatory and neurotransmitter modulatory potentials. We aimed to investigate the antidepressant effects of simvastatin as an adjuvant therapy in patients with moderate to severe depression. In this double-blind placebo-controlled clinical trial, 48 patients were randomly allocated to receive simvastatin or placebo as an adjunct to fluoxetine for six weeks. Patients were evaluated with the Hamilton Depression Rating Scale (HDRS) at baseline and weeks 2, 4 and 6. Probable clinical and laboratory adverse events were also monitored and compared between the two groups. Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36). No serious adverse event was reported during this trial. In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder. However, more confirmatory studies are warranted.

Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: a double-blind randomized clinical trial.

OBJECTIVES: Limited pharmacological options are available for the management of Alzheimer's disease (AD) in severe stages. Cognitive-enhancing properties of saffron, the dried stigma of Crocus sativus L., have been evidenced in different studies. We aimed to compare the efficacy and safety of saffron extract versus memantine in reducing cognitive deterioration of patients with moderate to severe AD. METHODS: In this randomized double-blind parallel-group study, 68 patients with moderate to severe AD (Mini-Mental State Examination score of 8-14) received memantine (20 mg/day) or saffron extract (30 mg/day) capsules for 12 months. Participants were evaluated every month by Severe Cognitive Impairment Rating Scale (SCIRS) and Functional Assessment Staging (FAST) in addition to recording the probable adverse events. RESULTS: Both treatment groups showed similar outcomes as demonstrated by insignificant effect for time × treatment interaction on SCIRS scores [F(2.95, 194.78) = 2.25, p = 0.08]. There was no significant difference between the two groups in the scores changes from baseline to the endpoint on SCIRS (p = 0.38) and FAST (p = 0.87). The frequency of adverse events was not significantly different between the two groups as well. CONCLUSIONS: In addition to its favorable safety profile, 1-year administration of saffron extract capsules showed to be comparable with memantine in reducing cognitive decline in patients with moderate to severe AD. Confirmatory studies with larger sample sizes and longer follow-up periods are warranted.

Low-dose human chorionic gonadotropin adjunct to an antagonist protocol in assisted reproductive technology: a randomized trial study.

The aim of this study was to evaluate the outcomes of adding low-dose hCG (human chorionic gonadotropin), as an LH active supplement, to a GnRH antagonist protocol in patients undergoing assisted reproduction techniques. In this parallel-group randomized clinical trial, 137 infertile female outpatients aged 20 - 39 years were randomized into two groups: hCG group and non-hCG group. All patients received r-FSH (150-300 IU) and then a GnRH-antagonist, Cetrorelix (0.25 mg/day). Concomitantly with Cetrorelix, patients in the hCG group received low-dose hCG (200 IU daily), but the patients in the non-hCG group did not. 10,000 IU Urinary hCG (10,000 IU) was injected to all patients, and ICSI was performed after oocyte retrieval. The primary outcome of this study was comparing the pregnancy rates between two study groups. Other differences between two groups such as serum estradiol concentration, fertilization rate, etc. were considered as secondary outcomes. A total of 130 patients completed this trial. No significant difference was detected between pregnancy rates of the two groups (P=0.52) as well as the fertilization, implantation and ongoing pregnancy rates (P=0.11, P=0.75 and P=0.06 respectively). The only significant difference between two groups was a higher concentration of estradiol in the hCG-treated patients (P<0.05). HCG-treated patients experienced a shorter treatment duration and a lower r-FSH required dose than the non-hCG group, but none of these differences were statistically significant (P=0.19 and P=0.10, respectively). The findings of the current study did not support advantages of adding low-dose hCG to GnRH antagonist plus r-FSH protocol in an unselected population of patients. Well-designed trials with a larger sample size for specific patients' subgroups are warranted.

Intranasal desmopressin as an adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled, clinical trial.

Considering the role of neurohypophyseal peptides in normal development and function of higher cortical processes along with their proven abnormalities in schizophrenic patients, these pathways have recently attracted greater attention as treatment targets for schizophrenia. Desmopressin (DDAVP) is a synthetic analog of vasopressin. This study aimed to evaluate the efficacy and safety of DDAVP nasal spray as an adjunct to risperidone in improving negative symptoms of schizophrenia. In this randomized double-blind placebo-controlled clinical trial, forty patients aged 18-50 years with a DSM IV-TR diagnosis of chronic schizophrenia and a minimum score of 60 on positive and negative syndrome scale (PANSS) were equally randomized to receive DDAVP nasal spray (20mcg/day) or placebo in addition to risperidone for 8 weeks. Patients were partially stabilized and treated with a stable dose of risperidone (5 or 6mg/day) for at least four weeks prior to entry. Participants were rated by PANSS every two weeks and decrease in the PANSS negative subscale score was considered as our primary outcome. By the study endpoint, DDAVP-treated patients showed significantly greater improvement in the negative symptoms (P=0.001) as well as the PANSS total and general psychopathology subscale scores (P=0.005 and P=0.003; respectively) compared to the placebo group. Treatment group was the strongest predictor of changes in negative symptoms (ß=-0.48, t=-3.67, P=001). No serious adverse event or fluid/electrolyte imbalance was reported in this trial. In conclusion, DDAVP nasal spray showed to be an effective and safe medication for improving negative symptoms in patients with chronic schizophrenia.

Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P<0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P<0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (ß=-0.94, t=-10.59, P<0.001) followed by the change in PANSS positive subscale (ß=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia.

A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia.

RATIONALE: Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies. OBJECTIVES: We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia. METHODS: In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups. RESULTS: By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P < 0.001) as well as the PANSS total and general psychopathology subscale scores (P = 0.001 and P < 0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (ß = -0.56, P < 0.001). No significant difference was observed between two groups in the frequency of side effects. CONCLUSION: These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted. Clinical trial registry name and registration number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26

Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial.

The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms.

A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients.

OBJECTIVE: A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). METHODS: In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. RESULTS: By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial. LIMITATIONS: Relatively small sample size and short observational period were the major limitations of this study. CONCLUSION: Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression.

N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Despite the burden of negative symptoms on quality of life in schizophrenic patients, no completely effective treatment has been developed to address such symptoms yet. Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia, and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia. N-Acetylcysteine (NAC) is a potent antioxidant with neuroprotective properties. This study aimed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. The participants were equally randomized to receive NAC (up to 2 g/d) or placebo, in addition to risperidone (up to 6 mg/d) for 8 weeks. The participants were rated using PANSS every 2 weeks, and the decrease of PANSS negative subscale score was considered as our primary outcome. RESULTS: By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total (P = 0.006) and negative subscale (P < 0.001) scores than that in the placebo group, but this difference was not significant for positive and general psychopathology subscales. There was no significant difference between the 2 groups in the frequency of adverse effects. CONCLUSIONS: NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia.

Double-blind, placebo-controlled trial of risperidone plus amantadine in children with autism: a 10-week randomized study.

OBJECTIVE: This study aimed to investigate the effect of adding amantadine to risperidone for treatment of autism. METHODS: Forty outpatients aged 4 to12 years, who were diagnosed with autism spectrum disorders based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, were assigned to this double-blind clinical trial. The subjects were divided randomly into 2 groups. One group received risperidone plus amantadine, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of amantadine was 100 or 150 mg/d for patients less than 30 kg or more than 30 kg, respectively. The patients were assessed using the Aberrant Behavioral Checklist-Community (ABC-C) and adverse effects checklist as well as clinical global impression-improvement (CGI-I) at2 checkpoints of 5-week intervals after the baseline. Informed consentwas obtained from the parents of each participant. RESULTS: Among ABC-C subscales, Hyperactivity and Irritability showed significantly greater reduction in the amantadine group than the placebo group. There was no significant difference in adverse effects between the 2 groups. The CGI-I scores show significant improvement in the amantadine group compared to the placebo group. CONCLUSIONS: The present study suggests that amantadine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated.

Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications. STUDY DESIGN: This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial. PARTICIPANTS: The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy. INTERVENTIONS: Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks. OUTCOME: Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups. RESULTS: Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech subscale (P = 0.20) than patients in the placebo group. Eleven patients in the riluzole group and five patients in the placebo group were classified as responders based on their CGI-I scores [χ(2)(1) = 3.750, P = 0.05]. Children in the riluzole group experienced significantly more increases in their appetite and bodyweight than children in the placebo group by the end of the study. CONCLUSION: Riluzole add-on therapy shows several therapeutic outcomes, particularly for improving irritability, in children with autism. However, its add-on to risperidone also results in significantly increased appetite and weight gain.

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia.

RATIONAL: A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia. METHODS: In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8. RESULTS: Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699) = 37.366, p < 0.001] as well as negative scores [F(2.439,92.675) = 16.623, p < 0.001] and general psychopathology [F(1.767,67.158) = 4.602, p = 0.017], but not positive subscale scores [F(1.348, 51.218) = 0.048, p = 0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized ß = -0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups. CONCLUSION: Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.

Cardiovascular considerations in antidepressant therapy: an evidence-based review.

There is a definite correlation between cardiovascular diseases and depressive disorders. Nevertheless, many aspects of this association have yet to be fully elucidated. Up to half of coronary artery disease patients are liable to suffer from some depressive symptoms, with approximately 20% receiving a diagnosis of major depressive disorders. Pharmacotherapy is a key factor in the management of major depression, not least in patients with chronic diseases who are likely to fail to show proper compliance and response to non-pharmacological interventions. Antidepressants are not deemed completely safe. Indeed, numerous side effects have been reported with the administration of antidepressants, among which cardiovascular adverse events are of paramount importance owing to their disabling and life-threatening nature. We aimed to re-examine some of the salient issues in antidepressant therapy vis-à-vis cardiovascular considerations, which should be taken into account when prescribing such medications.