Alterations in plasma endocannabinoid concentrations among individuals with major depression treated with electroconvulsive therapy.

The role of the endocannabinoid system (ECS) in depression and suicidality has recently emerged. The purpose of the study was to identify changes in plasma endocannabinoid concentrations of several endocannabinoids and correlate them with depressive symptoms and suicidality in patients with severe major depression undergoing electroconvulsive therapy (ECT). The study included 17 patients that were evaluated in four visits at different stages of therapy. At each visit depression, anxiety and suicidality symptoms were assessed and blood samples collected. Several endocannabinoid concentrations increased following six sessions of ECT, as 2-AG (p < 0.05) and LEA (p < 0.01), and following twelve sessions of ECT, as 2-AG (p < 0.05), AEA (p < 0.05), LEA (p < 0.05) and DH-Gly (p < 0.05). Endocannabinoids also correlated with symptoms of depression, anxiety and suicidality at baseline and at the sixth ECT session. Finally, we found one endocannabinoid, l-Gly, that differentiated between remitted and not-remitted patients at the seventh and thirteenth ECT sessions (p < 0.05). Our findings suggest that depression is markedly related to imbalance of the endocannabinoid system, and further regulated by ECT. Plasma endocannabinoids could be promising biomarkers for detection of depression response and remission.

Short-term chloral hydrate as an add-on treatment may improve sleep and alleviate agitation in inpatients with treatment resistant schizophrenia: a retrospective case series study.

Introduction: Chloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile. Methods: This study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders. Results: CH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition. Discussion: CH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep.

Inflammation Markers Among Schizophrenia Patients Who Use Cannabis.

OBJECTIVES: The mechanism of inflammation of the immune system, for example, such circulatory markers as the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV), has been shown in many studies to be associated with schizophrenia. In addition, it has been shown that the cannabidiol component reduces the activation of the acquired immune system. This study examined the differences in the levels of NLR and MPV among schizophrenia patients with cannabis use versus those without. METHODS: In 2019 to 2020, a retrospective cross-sectional study was conducted based on digital medical records. Demographic, clinical, and complete blood cell count data were collected from records of rehospitalization of active psychotic schizophrenia inpatients. Data on NLR, MPV values, and demographic and clinical characteristics were compared between the groups and according to the degree of prevalence of cannabis use. RESULTS: No differences were found in the NLR and MPV values between the groups. CONCLUSION: The results were contrary to our expectations. These results may be explained by the presentation of a "pseudo-balanced" picture created when multiple processes affect inflammatory indices.

Olanzapine intramuscular shows better efficacy than zuclopenthixol acetate intramuscular in reducing the need for restraint, but not in comparison to haloperidol intramuscular.

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

A Double-Blind, Placebo-Controlled Trial of Bupropion Add-on to Olanzapine or Risperidone in Overweight Individuals With Schizophrenia.

BACKGROUND: Weight gain due to antipsychotics is a challenging clinical problem because, to date, no effective pharmacological strategies have been found. Bupropion is often used in people with schizophrenia for smoking cessation and is well tolerated. However, studies on its use as weight loss treatment are scarce. The aim of the study was to examine the effectiveness of bupropion as a single weight loss treatment in overweight individuals maintained on long-term olanzapine or risperidone. METHODS: This randomized, double-blind, placebo-controlled, 8-week study included 26 overweight (body mass index ≥27 kg/m2) individuals with schizophrenia maintained on olanzapine (10-20 mg/d) or risperidone (2-4 mg/d). Participants were randomly allocated to a study group that received bupropion (150-300 mg/d) or to a placebo group. The positive and Negative Syndrome Scale and the Clinical Global Impression-Severity Scale were used to assess severity of psychosis at baseline and end of study (8 weeks). RESULTS: Bupropion addition, but not placebo, was associated with a significant reduction in body weight. Severity of psychotic symptoms was not altered in either group. CONCLUSIONS: The results demonstrate the efficacy of bupropion, compared with placebo, in patients maintained on chronic treatment with olanzapine or risperidone, both known to be major contributors to significant weight gain.

Cognitive enhancement drug use among resident physicians: Prevalence and motivations for use - results from a survey.

Background: Non-medical use of prescription drugs for the enhancement of cognitive functioning has gained popularity in recent years, especially among young educated adults. To our knowledge, no previous study investigated this phenomenon among resident physicians.Objective: To analyze cognitive enhancement drugs use motivations and patterns among resident physicians.Methods: A survey and statistical analysis regarding the use of drugs traditionally prescribed for the treatment of Attention Deficit Hyperactivity Disorder: stimulants, amphetamines and modafinil.Participants: 1,453 residents who took their written residency exam in the summer of 2017. The response rate was 32.3%.Results: 28.1% of responders reported past use, with 73.67% of them reporting use without a related medical diagnosis. Almost half of the users (47.1%) acquired the drug with a prescription, but without a diagnosis of a related medical disorder. The first use was predominantly during residency (54.3%), with 45% reporting it as related to the residency exam.Factors found to positively impact non-medical use include: declaring undiagnosed Attention Deficit Hyperactivity Disorder, fear of failing the exam, a belief that more than 30% of other examinees take cognitive enhancements drugs, and a learning disability diagnosis. Self-reports of being a competitive person and being a parent, were negatively correlated with non-medical use.Conclusions: The use of drugs that are taken traditionally for the treatment of Attention Deficit Hyperactivity Disorder is common among resident physicians, both with and without related medical indication. Interestingly, factors associated with the fear of being "left behind" increase non-medical use and not the desire to succeed.

The effectiveness of high-dose escitalopram in the treatment of patients suffering from schizophrenia with comorbid obsessive-compulsive disorder: an open-label study.

Obsessive-compulsive disorder frequently co-occur with schizophrenia causing a significant impairment. There is a paucity of published data on the treatment of such complicated patients. It has been suggested that the combination of antipsychotics and antiobsessive agents is the best treatment for schizophrenia with obsessive-compulsive disorder; however, there is no published data regarding the use of high dose (up to 40 mg/day) escitalopram. This open-label, prospective study was designed to investigate the efficacy, short-term safety and tolerability of escitalopram in doses up to 40 mg in patients with schizophrenia and obsessive-compulsive disorder. Patients were treated with increasing doses of escitalopram for 13 weeks. Thirteen patients (86.67%) completed the study. A significant improvement was observed in the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of Y-BOCS-Obsession and Y-BOCS-Compulsion subscales. Furthermore, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and Clinical Global Impression-severity scale. Escitalopram, up to 40 mg/day was well tolerated and may be beneficial in the management of patients with schizophrenia and obsessive-compulsive disorder. Further studies are needed to confirm this finding and to assess long-term safety.

Equine Assisted Therapy for Patients with Post Traumatic Stress Disorder: A Case Series Study.

INTRODUCTION: Equine assisted therapy (EAT) which includes therapeutic horseback riding (THR), grooming, horsemanship and ground level work with horses, has been studied as treatment for children with special needs and/or autistic spectrum disorder. Preliminary evidence indicates that EAT is also effective for improving self-efficacy and self-esteem in adults with psychiatric disorders. Empowerment, bonding and building trust with the horses, may promote functioning of patients struggling with post traumatic stress disorder (PTSD).The authors performed a prospective, pilot open case series study to assess the effect of EAT on patients with PTSD in terms of symptoms and functioning in work, family and social interaction. METHODS: Patients with PTSD received EAT once a week for 3 consecutive hours for 6 months. The Short Post Traumatic Stress Disorder Rating Interview (SPRINT) and the Sheehan Disability Scale (SDS) were assessed at baseline, the SDS after 1 and 6 months, and the SPRINT after 6 months. RESULTS: Thirteen of 23 participants completed the study. Ten participants withdrew from the study for various reasons including discomfort from horses. Total SPRINT scores showed a statistically significant improvement in PTSD symptoms (baseline vs. 6 months: 24.38 ± 6.4 vs. 21.54 ± 7.94 points; p < 0.05). SPRINT scores indicated improvement in the ability to work and perform daily tasks (p < 0.05). A statistically significant improvement in the total SDS score was revealed following 1 month (p < 0.03) and after 6 months (p < 0.02) of EAT. There was also a significant decline in the days of inefficiency (baseline vs. 6 months: 4.15 ± 2.73 vs, 1.88 ± 2.18 days per week, p < 0.02). CONCLUSION: This preliminary pilot open case series study suggests that EAT may be a beneficial treatment for patients suffering from PTSD. The study demonstrated improved ability to work and perform daily tasks and reduction in the number of days of inefficiency. Further large-scale long-term studies are warranted to substantiate our observation.

Add-on benzodiazepines for psychosis-induced aggression.

In severely psychotic, violent patients, add-on benzodiazepines are often prescribed with antipsychotic agents. We examined aggression, suicidality, and self-harm among psychotic patients treated with antipsychotic monotherapy, compared with those treated with add-on benzodiazepines, during the first 2 weeks of psychiatric hospitalization to clarify the association of add-on benzodiazepines and aggression. Electronic medical records of 400 patients consecutively admitted to Abarbanel Mental Health Center from 2012 to 2014 for psychosis, and remained hospitalized for at least 2 weeks were evaluated. Violence toward staff, patients, and property, physical restraints, seclusion, self-harm, and suicidal thoughts, were examined. Falls and referrals to general hospital indicated adverse medication effects, and were recorded. No significant between-group differences were found for sex, age, psychiatric diagnosis, compulsory admissions, antipsychotic dosages, number of previous hospitalizations, or hospitalization days were detected. Maximum dosage for antipsychotics in the monotherapy group did not reveal a statistically significant difference from the add-on benzodiazepine group (2.2 ± 1.4 vs. 2.2 ± 1.3, respectively), expressed in defined daily dose. There were no between-group differences in frequency of any violent event, incidence of self-harm, suicidal thoughts, frequency of falls, and/or referrals to a general hospital. Addition of benzodiazepines might be unnecessary. Benzodiazepine addition to antipsychotic drugs for patients with severe psychosis should be with caution.

[NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS].

INTRODUCTION: This review deals with the neuropsychiatric disorders resulting from systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease that impacts all systems in the human body, including the central nervous system. Neuropsychiatric symptoms in SLE are a common complication of the disease. This complication has significant implications for the severity of the illness. In most cases no thorough psychiatric assessment is performed during initial evaluation of the disease and no protocol or clear guidelines for treating the psychiatric symptoms in SLE are available. Early diagnosis of the psychiatric symptoms in SLE is critical since absence of treatment may result in severe psychiatric complications. Clinical pharmacological studies are needed in order to develop guidelines for treating psychiatric symptoms in SLE.

Magnetic resonance brain imaging in patients with visual vertigo.

INTRODUCTION: Patients with visual vertigo (VV) report dizziness provoked by moving visual surroundings. It has been suggested that these subjects develop a compensation strategy for a vestibulo-proprioceptive deficit and rely excessively on visual input. We have postulated that patients with VV might have brain abnormalities that interfere with appropriate processing of visual stimulation and performed a brain MRI study to verify this hypothesis. MATERIALS AND METHODS: Patients with VV of more than 3 months duration were included. They were asked to complete the Situational Characteristic Questionnaire (SCQ) that scores for the symptoms of VV. Dizzy patients without VV served as controls. A brain MRI was performed with a Siemens 1.5 Tesla scanner in patients and controls. RESULTS: Twenty-four patients with VV were included. Their mean SCQ score was 1.45 ± 0.9 (normal 0.16 ± 0.28). In 50% of patients, abnormalities in MRI imaging were found. Thirty-three percent of 27 controls demonstrated an abnormal brain MRI. The two groups were similar in respect to the prevalence of a localized hemispheric or posterior fossa lesion (P = 0.13), but VV patients had more unspecific white matter brain changes than controls (P = 0.009). Patients and controls did not differ in age and gender distribution (P = 0.9) or the history of a neurotological event preceding their symptoms (P = 0.3). CONCLUSIONS: Our study suggests that multiple white matter lesions might contribute to occurrence of the phenomenon of VV. Future prospective large-scale studies by specific MR techniques are indicated to validate our preliminary findings and elucidate the pathological mechanism of VV.

Social Anxiety Disorder Comorbid with Schizophrenia: The Importance of Screening for This Under recognized and Under treated Condition.

BACKGROUND: While the presence of comorbid anxiety disorders such as obsessive-compulsive disorder and panic disorder have been well described in schizophrenia, comorbid social anxiety disorder (SAD) has been less emphasized. The goal of this study was to examine the prevalence of SAD in our ambulatory population of patients with schizophrenia. METHODS: A group of 50 outpatients with schizophrenia randomly selected from our public mental health outpatient population was evaluated with the Structured Clinical Interview for DSM-IV (SCID)-schizophrenia section, the Positive and Negative Syndrome Scale (PANSS), the Schizophrenia Quality of Life Scale (SQLS), the Liebowitz Social Anxiety Scale (LSAS) and the Global Assessment of Functioning Scale (GAF). After completion of assessments, a retrospective chart review was conducted on all study patients who met criteria for a diagnosis of SAD in order to determine how many of these patients had been previously given a diagnosis of SAD. RESULTS: Based on a cutoff score of 29/30 on the total LSAS score, 38% of our sample had a comorbid diagnosis of SAD. Compared to patients who did not suffer from comorbid SAD, patients with schizophrenia and comorbid SAD had lower ratings of quality of life, but similar GAF and PANSS scores. According to the results of the chart review, none of the affected patients had been previously diagnosed with SAD. CONCLUSIONS: According to the results of our study, SAD as a comorbid condition is highly prevalent in schizophrenia and may be under-detected in the outpatient mental health care setting. Furthermore, the presence of SAD may lead to a decreased quality of life for patients with schizophrenia. Further studies should evaluate whether the diagnosis and treatment of comorbid SAD would improve the treatment and quality of life of patients with schizophrenia.

Fatigue during an episode of benign paroxysmal positional vertigo.

Fatigue is characterized by weariness unrelated to exertion levels. It has been reported in chronic neurological diseases such as multiple sclerosis, Parkinson disease and stroke. Patients with benign paroxysmal positional vertigo (BPPV) often complain about fatigue during a vertigo attack. No attention has been paid to this symptom in the literature so far. We were interested to evaluate the frequency and factors influencing fatigue in BPPV. Patients treated for idiopathic BPPV during the years 2011-2012 were prospectively evaluated for the presence of fatigue. During the first visit, patients were asked to complete two questionnaires based on their experience during the last week: the Fatigue severity scale and the Hospital anxiety and depression scale. Patients' demographic data and BPPV characteristics were registered. Among 172 patients treated for BPPV, 40 (23.2 %) reported fatigue. The mean fatigue score was 4.73 ± 1.98 indicating moderate fatigue. No correlation was found between fatigue and anxiety or fatigue and depression. Fatigue scores were inversely related to age (r = -0.36, p = 0.020) and were not dependent on the type of BPPV, its recurrence, background diseases, gender, duration of vertigo or the presence of autonomic symptoms. Moderate fatigue is quite common during an attack of BPPV. It seems to be a genuine symptom of the entity that might worsen patients' distress. For severe or persistent fatigue treatment with fatigue relieving drugs such as amantadine, methylphenidate or modafinil could be tried in the future.

Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study.

BACKGROUND: It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. METHODS: Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. RESULTS: Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. CONCLUSIONS: AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.

Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

The current data suggest that up to 50% of patients with schizophrenia have obsessive-compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive-compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks' duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21-61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

Rivastigmine treatment for the prevention of electroconvulsive therapy-induced memory deficits in patients with schizophrenia.

Electroconvulsive therapy (ECT) is an effective strategy in some treatment-resistant patients with schizophrenia. However, ECT is associated with cognitive adverse effects, most notably, memory loss. This study examined the effects of rivastigmine, a selective central nervous system acetylcholinesterase inhibitor, with benefits on cognition in Alzheimer disease, on memory performance in patients with schizophrenia treated with ECT. Thirty inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia treated with ECT were coadministered rivastigmine (3-4.5 mg/d) or placebo in a prospective, randomized, double-blind, placebo-controlled trial (maximum period of 4 weeks). Over the ECT course, scores on the cognitive subscale of the Alzheimer's Disease Assessment in subjects receiving placebo showed no significant change, whereas subjects receiving rivastigmine displayed decreased cognitive subscale of the Alzheimer's Disease Assessment scores, indicating cognitive improvement (P < 0.05). Findings suggest possible involvement of the acetylcholinergic system in mediation of cognitive deficits after ECT and indicate possible beneficial effects of rivastigmine coadministration in minimizing some of these ECT-induced cognitive impairments.

Beliefs and emotional reactions in patients with benign paroxysmal positional vertigo: a longitudinal study.

OBJECTIVE: Psychologic studies in patients with benign paroxysmal positional vertigo (BPPV) are scarce, considering the high frequency of the disorder. We performed a repeated-measures design questionnaire study in a cohort of patients with BPPV before and after treatment to investigate the dynamics of the psychologic findings and possible treatment consequences. METHODS: Thirty-seven consecutive patients with idiopathic BPPV participated in the study. During the first visit and 2 to 3 months after therapy, the patients completed 4 questionnaires: the Dizziness Handicap Inventory, the Illness Perception Questionnaire-Revised, the Intolerance of Uncertainty Scale, and the State-Trait Anxiety Inventory. RESULTS: The scores for all questioned items did not change before and after treatment except for the physical handicap scores. Correlation was found between the grade of functional and emotional impact of the disease and belief in consequences as well as anxiety levels of the patients. Moreover, uncertainty scores were in correlation with emotional impact, anxiety levels, and perceived consequences of the disease. The belief in personal control of the condition was correlated with the belief in treatment control and understanding of the disease. CONCLUSION: The main finding in this study is the lack of a significant change in beliefs and emotional reactions in patients with BPPV after treatment of their condition. Physicians dealing with BPPV should be aware that the disease is not solely a somatic condition but has a serious impact on the patient's mental state. Selected patients might benefit from anxiolytic medication.

Response to deep TMS in depressive patients with previous electroconvulsive treatment.

BACKGROUND: The efficacy of transcranial magnetic stimulation (TMS) in the treatment of major depression has already been shown. Novel TMS coils allowing stimulation of deeper brain regions have recently been developed and studied. OBJECTIVE: Our study is aimed at exploring the possible efficacy of deep TMS in patients with resistant depression, who previously underwent electroconvalsive therapy (ECT). METHODS: Using Brainsway's deep TMS H1 coil, six patients who previously underwent ECT, were treated with 120% power of the motor threshold at a frequency of 20 Hz. Patients underwent five sessions per week, up to 4 weeks. Before the study, patients were evaluated using the Hamilton depression rating scale (HDRS, 24 items), the Hamilton anxiety scale, and the Beck depression inventory and were again evaluated after 5, 10, 15, and 20 daily treatments. Response to treatment was considered a reduction in the HDRS of at least 50%, and remission was considered a reduction of the HDRS-24 below 10 points. RESULTS: Two of six patients responded to the treatment with deep TMS, including one who achieved full remission. CONCLUSIONS: Our results suggest the possibility of a subpopulation of depressed patients who may benefit from deep TMS treatment, including patients who did not respond to ECT previously. However, the power of the study is small and similar larger samples are needed.

Trazodone for the treatment of neuroleptic-induced acute akathisia: a placebo-controlled, double-blind, crossover study.

INTRODUCTION: Neuroleptic-induced acute akathisia (NIA) is a common and distressing extrapyramidal symptom usually resulting from the use of antipsychotic medication.Despite its high incidence (20%-45%), the underlying mechanism of NIA has not yet been adequately explained. Although treatment strategies for NIA have traditionally included anticholinergic agents, γ-aminobutyric acid agents, dopamine enhancers, and the ß-adrenergic antagonists, many patients fail to respond. Trazodone (Trz) is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. In a recent pilot open-label trial, Trz demonstrated to be strongly effective in the treatment of NIA in 9 female schizophrenic patients. OBJECTIVE: On the basis of the results of this pilot study, we investigate further the efficacy of Trz in the treatment of NIA in a double-blind, placebo (Pla)-controlled, crossover design. METHODS: Thirteen inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizo-affective disorder and with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition NIA with a severity of at least mild akathisia according to the Barnes Akathisia Rating Scale participated in the study. Patients were randomly assigned to either the order Trz-Pla or the order Pla-Trz in the treatment periods. Each period lasted for 3 consecutive days (days 1-3 and 4-6). Eight patients were treated with the Trz-Pla order (100 mg/d before bedtime); and 5, with the opposite order (Pla-Trz). RESULTS: Statistically significant improvement in most symptoms of NIA, as measured by the Barnes Akathisia Rating Scale, was detected with Trz compared with Pla treatment. CONCLUSIONS: The findings of this double-blind, placebo-controlled, crossover study indicate the efficacy of Trz in the management of NIA, corroborating the results of a preliminary pilot study. We suggest that Trz's property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.