Trazodone as an Alternative Treatment for Neuroleptic-Associated Akathisia: A Placebo-Controlled, Double-Blind, Clinical Trial.

BACKGROUND: Akathisia is a distressing extrapyramidal complication that follows the use of antipsychotic medications. Early treatment of neuroleptic-associated akathisia (NAA) is of great importance because it may lead to poor therapeutic response and ultimately treatment noncompliance. Considering the lack of adequate response of some patients to conventional treatments and the assumption that serotonin might be involved in the pathophysiology of the disease in addition to dopaminergic mechanisms, we aimed to evaluate the effectiveness of trazodone as an antidepressant agent with strong antagonistic effects on serotonin receptors in the treatment of akathisia. METHODS: In a double-blind clinical trial, 52 patients receiving antipsychotic medications who were diagnosed to have mild to severe NAA using Barnes Akathisia Rating Scale were treated with trazodone 50 mg daily for 5 days and compared with the placebo control group. RESULTS: Patients receiving trazodone did not show a significant difference compared with the control group in terms of the severity of akathisia symptoms until the third day of the study. In contrast, at the end of the fifth day, there was a significant improvement in objective (P = 0.01) and subjective (P = 0.001) symptoms of akathisia and the global clinical assessment of akathisia scale (P = 0.001). Moreover, there was no clear difference between trazodone and placebo group in terms of adverse effects. CONCLUSIONS: Considering the antagonistic effect of trazodone on postsynaptic 5-hydroxytryptamine2A receptors as a possible mechanism of efficacy of this agent in the treatment of NAA, this study suggests that trazodone might be an effective and relatively safe drug.

Prevalence and quality of anxiety in patients with epilepsy.

BACKGROUND: Depression and anxiety are the most frequent psychiatric disorders identified in patients with epilepsy. We aimed to determine the prevalence of state and trait anxiety in patients with epilepsy compared with people without epilepsy. METHODS: We recruited patients and healthy controls in the outpatient neurology clinic of Kurdistan University of Medical Sciences, Iran, during 2011. Eighty-four patients with epilepsy and 168 healthy persons from relatives of the patients in the case group were recruited and filled out the inventory. The State-Trait Anxiety Inventory (STAI) was used to measure anxiety. After selection of participants and neurological evaluation, all subjects were clinically interviewed at the outpatient clinic of neurology. Data were analyzed using SPSS software, version 16. Fisher's exact and chi-square tests were used for nominal variables, and the t-test was used for anxiety scores. RESULTS: The average ages of the patients in the case and control groups were 28 and 27.5 years, respectively. State anxiety was significantly higher in patients with epilepsy than in the control group (p=0.042). Also, a higher trait anxiety score was reported in the case group compared with the control group (p=0.009). CONCLUSION: The rates of both state and trait anxiety were higher in patients in the case group. It appears that anxiety in epilepsy is not just a reaction to a stressful situation, and there may be genetic or temperamental factors that contribute to the relationship between epilepsy and anxiety.

Association between postictal suppression and the therapeutic effects of electroconvulsive therapy: A systematic review.

Electroconvulsive therapy (ECT) is an effective and safe medical treatment for patients with severe mood and neuropsychiatric disorders. Since the advent of ECT, extensive research has been performed to identify the predictive factors for response to ECT. In recent decades, postictal suppression on an electroencephalogram (EEG) has been considered a potential predictor of response to ECT. We aimed to investigate the direct association between postictal suppression and the therapeutic effects of ECT. In this systematic review, all articles in the field of the association between postictal suppression and the therapeutic effects of ECT published between 1990 and 2021 were identified. The full texts of these articles, which include clinical trials and retrospective and cross-sectional studies, are available in scholarly research databases and search engines, including PubMed, Google Scholar, OVID, Web of Science, and Scopus. Of all retrieved articles, eight studies, including four retrospective cohort articles and four clinical trials, met the inclusion criteria for further analyses. The findings of this study showed a significant association between postictal suppression and the therapeutic efficacy of ECT. Factors such as electrode placement, tachycardia, type of anesthetic agent, and EEG amplitude were also directly related to postictal suppression and the efficacy of ECT. Postictal suppression on EEG can be considered a predictor of response to ECT. To increase the effectiveness of treatment with ECT and increase postictal suppression, factors including electrode placement, tachycardia, type of anesthesia, and EEG amplitude should be considered, which highlights the need for further research.

Effects of remifentanil on convulsion duration and hemodynamic responses during electroconvulsive therapy: a double-blind, randomized clinical trial.

BACKGROUND: Among the drugs used for the induction of anesthesia for electroconvulsive therapy (ECT), thiopental induces a greater degree of cardiovascular alteration than other agents. Remifentanil has been found to reduce blood pressure and heart rate when administered as an adjuvant during general anesthesia, with unknown effects on the duration of motor or electroencephalographic seizure activity during ECT. The purpose of this prospective, randomized, double-blind, placebo-controlled, crossover study was to evaluate the effects of supplementing thiopental anesthesia with remifentanil on convulsion duration and cardiovascular response during ECT. METHODS: Twenty-four American Society of Anesthesiologists I and II patients receiving 6 sessions of ECT were randomly allocated to 2 groups. All patients were premedicated with atropine (0.4 mg, intravenously), then anesthesia was induced by thiopental (1.0 mg/kg), succinylcholine (0.5 mg/kg), and remifentanil (1.0 microg/kg) in the case group or normal saline (3 mL) in the control group in a crossover format. Stimulus amplitude for applying ECT was kept constant during the sessions of treatment in the course of study for each patient. Hemodynamic parameters, convulsion duration, and recovery parameters were recorded. Statistical analysis was done using paired t tests. RESULTS: There was no statistically significant difference between the groups regarding convulsion duration, recovery times to eye opening, obeying specific commands, and walking without help. Remifentanil significantly attenuated the increase in heart rate and arterial blood pressure (P < 0.05). CONCLUSIONS: Remifentanil (1 microg/kg) administered before thiopental (1 mg/kg) has no adverse effect on the duration of ECT-induced convulsion and recovery time, but it can attenuate the increase in heart rate and arterial blood pressure.

Effect of Donepezil on Cognitive Deficits Associated With Electroconvulsive Therapy: A Randomized Triple-blind Clinical Trial.

OBJECTIVES: Despite the effectiveness of electroconvulsive therapy (ECT) in a wide range of psychiatric disorders, the role of memory-enhancing agents in post-ECT cognitive disturbances has remained controversial. In this study, we aimed to assess the effect of donepezil on improving the cognitive performance of patients undergoing ECT. METHODS: In a psychiatry hospital, patients who were admitted for ECT underwent a triple-blind randomized controlled trial. After randomizing the participants into 2 groups, 1 group received ECT with placebo, whereas the other group received ECT plus 5 mg/d donepezil during the ECT period. The patients in both groups were cognitively assessed using the Mini Mental Status Evaluation and Wechsler Memory Scale, 24 hours before ECT and 48 hours after the end of the ECT sessions. RESULTS: The results of Mini Mental Status Evaluation scores did not show any significant difference in memory performance between the 2 groups before and after ECT (F = 0.108, P = 0.743). Moreover, the intervention and placebo groups did not have any significant difference in the scores of the 7 subscales of the Wechsler Memory Scale after ECT (P = 0.07). In addition, the patients on donepezil group tolerated the drug well and did not differ significantly compared with the control group in this regard. CONCLUSIONS: Despite a few evidence confirming the effect of acetylcholinesterase inhibitors in improving cognitive defects related to ECT, this study did not find such an effect in patients under ECT. Further studies are required to reach a clear conclusion.

Sleep Architecture in Patients With Primary Snoring and Obstructive Sleep Apnea.

INTRODUCTION: This study aimed to investigate sleep architecture in patients with primary snoring and obstructive sleep apnea. METHODS: In this study, we analyzed polysomnographic data of 391 clients who referred to Sleep Disorders Research Center (SDRS). These people were classified into three groups based on their Apnea-Hypopnea Index (AHI) and snoring; control, Primary Snoring (PS), and Obstructive Sleep Apnea (OSA) group. Sleep architecture variables were then assessed in all groups. RESULTS: The results of this study indicated a decrease in deep sleep or Slow Waves Sleep (SWS) and increase in light sleep or stage 1 of non-REM sleep (N1) in OSA patients compared with the control and PS groups. After controlling the effects of confounding factors, i.e. age and Body Mass Index (BMI) (which was performed through multiple regression analysis) significant differences were observed among the three groups with regard to N1. However, with regard to SWS, after controlling confounding variables (age and BMI), no significant difference was found among the groups. CONCLUSION: The results indicated that OSA, regardless of age and BMI, may increase light (N1) sleep possibly via a decline in blood oxygen saturation (SpO2 ). Such increase in N1 may be responsible for brain arousal. In addition, by controlling confounding factors (age and BMI), OSA did not affect SWS in OSA patients. However, further research is necessary to determine sleep architecture in more detail in the patients with OSA.

Premenstrual dysphoric disorder and suicide attempts as a correlation among women in reproductive age.

AIM: Women likely attempt suicide more than men and sex hormones or menstrual cycle may be associated with female suicide attempts. There are debates regarding the correlation of premenstrual dysphoric disorder (PMDD) and suicidal behaviors. The objective of this study was to examine if PMDD was associated with suicidal attempts as sex hormones are contributed in its pathogenesis. METHODS: As a case-control study 120 fertile woman with regular menstrual cycles attempting suicide and admitted to a general hospital were compared with a matched control group of 120 women selected among those accompanying other patients in other wards. Psychiatric interview based on DSM-5 criteria was conducted for diagnosing PMDD. RESULTS: There was a significantly higher frequency of PMDD in suicide attempters than in the controls (P = 0.001); while no remarkable difference was seen in frequency of premenstrual syndrome (PMS) between the two groups (P = 0.294) and attempting suicide was not related to the menstrual cycle (P = 0.52). CONCLUSIONS: This study suggests that PMDD may be associated with suicidal attempts, however it is not related to menstrual cycle. No relationship was found between PMS and suicidal acts.

Effect of Memantine on Cognitive Performance in Patients Under Electroconvulsive Therapy: A Double-Blind Randomized Clinical Trial.

OBJECTIVES: Various strategies such as adding cholinesterase inhibitors are used to reduce cognitive impairments during electroconvulsive therapy. In this study, we aimed to assess the effectiveness and safety of memantine as an N-methyl-D-aspartate receptor antagonist in the prevention of cognitive deficits due to ECT. METHODS: Thirty-eight adult patients with various mental disorders were randomized to memantine (10 mg/day initially and 20 mg/day at the end of the first week) or placebo during the ECT period. Mini Mental Status Examination, Digit Span Subtest, and backward memory span of Wechsler Adult Intelligence Scale were used to assess the cognitive functions 24 hours before and after ECT. Subjective ratings of side effects were obtained in the first, second, and fourth week of the treatment. RESULTS: The mean Mini Mental Status Examination score relatively increased in the intervention group showing a significant improvement with memantine (P < 0.001). The direct digit span had decreased in the control group, whereas no significant change was observed in the intervention group (P < 0.001). Backward memory span test showed a decrease in the control group after the ECT sessions, whereas a relative increase was observed in the intervention group (P = 0.001). The most frequently reported side effects in the intervention group did not differ significantly from the control group. CONCLUSIONS: This initial study showed that cognitive performance was enhanced in patients receiving memantine during ECT, indicating the possible role of the glutamatergic system in creating ECT-induced deficits. Larger long-term studies are necessary for understanding the role of the glutamatergic system in these disorders.

Antidepressant Effect of Combined Ketamine and Electroconvulsive Therapy on Patients With Major Depressive Disorder: A Randomized Trial.

BACKGROUND: One of the shortcomings of the available treatments for major depressive disorder (MDD) is the time delay between starting the treatment and achieving an antidepressant response. OBJECTIVES: We aimed to determine the effect of Ketamine as a synergistic antidepressant and anesthetic agent on MDD in electroconvulsive therapy (ECT). PATIENTS AND METHODS: Twenty-two patients with MDD received Ketamine and Propofol as anesthetic agents compared with 20 patients as the control group who received Propofol in a double-blind randomized clinical trial. The Hamilton rating scale for depression was used to determine the changes in symptoms severity during ECT and a 2-week follow-up. RESULTS: Both groups showed a reduction in depression severity, but there was no significant difference between the groups in the recovery process (P = 0.92). However, the cognitive performance recovery time in the Ketamine group was lower than that in the control group (P = 0.042). CONCLUSIONS: This study could not show the effect of Ketamine on depression recovery in a 2-week follow-up period. Nevertheless, Ketamine may provide a better cognitive performance in patients under ECT.

Evaluation of sleep problems in preeclamptic, healthy pregnant and non-pregnant women.

OBJECTIVE: Sleep problems are common complaints among pregnant women. This study was designed to compare subjective sleep problems in non-pregnancy condition, healthy and preeclamptic pregnancy as a major complication of pregnancy. We hypothesized that some sleep problems are more prevalent in females with preeclampsia. METHODS: In this cross-sectional study, 102 women with preeclampsia, 106 healthy pregnant women in the third trimester and 103 healthy non-pregnant women were selected through random sampling. Age and parity were matched in the three groups. We used Global sleep assessment questionnaire (GSAQ) to check the subjective sleep problems, and then we performed statistical analysis using Analysis of variance (ANOVA) and Pearson Chi-square tests. RESULTS: Our findings revealed significant differences in initial insomnia (p = 0.034), fragmented sleep (p = 0.022), snoring (p<0.001), non-idiopathic insomnia (p = 0.045) and sadness and anxiety (p = 0.001) between the three groups. Some sleep problems were more common in preeclampctic compared to healthy pregnant women including initial insomnia, fragmented sleep, snoring, sleep apnea and non-idiopathic insomnia. Moreover, the subjects with preeclampsia revealed more fragmented sleep, snoring, sadness and anxiety and lack of getting enough sleep due to other activities compared to non-pregnant women. CONCLUSION: Different kinds of sleep problems can occur in subjects with preeclampsia in comparison with the non-pregnant and healthy pregnant subjects. Sleep problems should be evaluated during pregnancy, particularly in pregnant women with preeclampsia, and suitable treatment should be provided for any specific sleep problem.

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial.

RATIONAL: It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia. OBJECTIVE: This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial. METHODS: Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS). RESULTS: Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively). CONCLUSION: Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania.

BACKGROUND: Considerable amount of biochemical data supports the potential involvement of protein kinase C in the pathophysiology and treatment of bipolar disorder. The aim of this double-blind, placebo-controlled study was to investigate the efficacy and tolerability of tamoxifen as an adjunct to lithium for the treatment of acute mania in hospitalized bipolar patients. METHODS: Eligible participants were 40 inpatients, between the ages of 19 and 49 years with current manic episode. Patients were randomly allocated to lithium (1-1.2 mEq/L) + tamoxifen 80 mg/day (group A) or lithium (1-1.2 mEq/L) + placebo (group B) for a 6-week, double-blind, placebo-controlled study. The principal measure of outcome was the Young Mania Rating Scale. The raters used standardized instructions for Young Mania Rating Scale. RESULTS: Young Mania Rating Scale scores improved with tamoxifen. The difference between the two protocols was significant as indicated by the effect of the group, the between-subjects factor (F=5.41, df=1, p=0.02). A significant difference was observed on the Positive and Negative Syndrome Scale total score at week 6 in the two groups. The difference between the two groups in the frequency of side effects was not significant except for fatigue that occurred more often in the tamoxifen group. LIMITATIONS: Tamoxifen is an antagonist of estrogen receptor as well. CONCLUSION: The results demonstrate that the combination of tamoxifen with lithium was superior to lithium alone for the rapid reduction of manic symptoms. The combined use of tamoxifen with lithium was well tolerated in these acutely manic patients.