The impact of the number of electroconvulsive therapy sessions on relapse in major depressive disorder.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment of major depressive disorder (MDD). However, high relapse rates after ECT represent clinical problems. To date, influence of number of ECT sessions on relapse rate remains to be elucidated. We evaluated associations between number of ECT sessions and relapse rate. METHODS: This retrospective review collected clinical data of 53 patients with MDD who received ECT. They underwent a 1-year follow-up after their last ECT session. We performed survival analysis to evaluate associations between number of ECT sessions and time until rehospitalisation or suicide. RESULTS: The patients were divided into a higher number of ECT group (≧8 sessions) and lower number of ECT group (<8 sessions). No significant difference was found regarding the patients' clinical and demographic data. Survival analysis using log-rank test revealed that the cumulative survival rate in the higher number of ECT group (79%) was higher compared with the lower number of ECT group (49%) (p = 0.042). CONCLUSION: Patients who underwent a higher number of ECT had improved survival rate compared with those who received a lower number. Therefore, additional sessions might be necessary, even in patients who achieved remission within seven ECT sessions, to prevent relapse.Key pointsHigh rate of relapse after ECT is a key problem.Impact of the Number of ECT sessions on relapse remains to be elucidated.In the present study, the patients with MDD who underwent eight or more sessions of ECT showed significant lower relapse rate compared with those who received less than eight sessions.

Risperidone and 5-HT2A Receptor Antagonists Attenuate and Reverse Cocaine-Induced Hyperthermia in Rats.

BACKGROUND: Cocaine (benzoylmethylecgonine) is one of the most widely used illegal psychostimulant drugs worldwide, and mortality from acute intoxication is increasing. Suppressing hyperthermia is effective in reducing cocaine-related mortality, but a definitive therapy has not yet been found. In this study, we assessed the ability of risperidone to attenuate acute cocaine-induced hyperthermia and delineated the mechanism of its action. METHODS: Rats were injected i.p. with saline, risperidone, ketanserin, ritanserin, haloperidol, or SCH 23 390 before and after injection of cocaine (30 mg/kg) or with WAY-00 635, SB 206 553, or sulpiride before cocaine injection; thereafter, the rectal temperature was measured every 30 minutes for up to 4 hours. In vivo microdialysis was used to reveal the effect of risperidone on cocaine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline concentrations in the anterior hypothalamus. For post-administration experiments, saline or risperidone (0.5 mg/kg) were injected into rats, and cocaine (30 mg/kg) was injected 15 minutes later. For every 30 minutes thereafter, DA, 5-HT, and noradrenaline levels were measured for up to 240 minutes after cocaine administration. RESULTS: Risperidone, 5-HT2A receptor antagonists, and D1 receptor antagonistic drugs prevented and reversed cocaine-induced hyperthermia. In contrast, receptor antagonists for 5-HT1A, 5-HT2B/2C, and D2 did not alter cocaine-induced hyperthermia. Risperidone treatment further attenuated cocaine-induced elevation of DA. CONCLUSIONS: Our results indicate that risperidone attenuates cocaine-induced hyperthermia primarily by blocking the activities of the 5-HT2A and D1 receptors and may be potentially useful for treating cocaine-induced acute hyperthermia in humans.

An Inpatient Observational Study: Characteristics And Outcomes Of Avoidant/Restrictive Food Intake Disorder (ARFID) In Children And Adolescents In Japan.

PURPOSE: To determine the clinical characteristics and course of severe avoidant/restrictive food intake disorder (ARFID) in hospitalized children and adolescents and compare them with those of patients with restricting-type anorexia nervosa (R-AN). PATIENTS AND METHODS: We conducted a retrospective chart review of inpatients diagnosed with ARFID or R-AN based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at Jichi Children's Medical Center Tochigi between April 1, 2007 and March 31, 2017. We compared the characteristics of the ARFID and R-AN patients at admission, during hospitalization, and after discharge. RESULTS: Both the ARFID (n=13) and R-AN (n=79) patients required hospitalization for their medically unstable state. The features of ARFID group included concern about the aversive consequences of eating and avoidance of eating due to sensory concerns. Significant differences were found at admission between ARFID and R-AN groups in age (10.7 vs 12.7 years), family history of mental disorders (46.2% vs 17.7%), comorbid developmental disorders (6 vs 3 cases), and the time from onset to admission (3.9 vs 6.3 months). The body weight status, % ideal body weight (%IBW), % expected body weight (%EBW), <75% IBW rate, and <75% EBW rate did not differ significantly between the two groups at admission or discharge. The duration of post-discharge outpatient follow-up treatment did not differ significantly between ARFID and R-AN groups (15.3 vs 18.4 months); however, ARFID group recovery rate was significantly higher than that of R-AN group (77% vs 43%). The reasons that the patients with ARFID had significantly better outcomes than the R-AN patients remain unclear. Compared to those in previous studies, the present patients were younger and demonstrated better outcomes. Our results indicate that the body weight status is similar between ARFID and R-AN patients, but the ARFID patients achieved better outcomes. CONCLUSION: These findings suggest that early onset in childhood, early disease recognition, and early intervention are important factors for achieving better outcomes for patients with ARFID.

[Hospital Acquired Pneumonia in General Hospital Psychiatric Ward A Retrospective Study].

(Introduction) Pneumonia is a well-known major physical complication that can occur in the course of treatment for severe psychiatric disorders and antipsychotic treatment. However, there are few reports indicating the differences between pneumonia in the field of psychiatric medicine and the more commonly encountered type of pneumonia. In the present study, we examined the specific characteristics of in-hospital pneumonia in psychiatric wards and factors influencing the aggravation of this infection. (Methods) We retrospectively analyzed 22 patients in the psychiatric ward of Jichi Medi- cal University Hospital, which also has general wards, in whom pneumonia developed during hospitalization. We extracted occurrence, outcome, and sputum culture test results as charac- teristics. Severity of pneumonia was classified using the Pneumonia Severity Index (PSI) as follows : classes I -III, minor group (MG : 15 patients) and classes IV-V, moderate to severe group (MSG: seven patients). We examined the following factors related to the aggravation of pneumonia: body mass index (BMI), length of psychiatric treatment, number of hospital admis- sions, Global Assessment of Functioning (GAF) score, dose of antipsychotics, dose of benzodi- azepines (chlorpromazine and diazepam equivalent doses), and dose of antiparkinsonian agents (biperiden equivalent dose). (Results) Aspiration occurred prior to the onset of pneumonia in one patient, and one patient required ventilator management. There were no patient deaths. Streptococcus pneu- moniae and Staphylococcus aureus were detected in five and four patients, respectively. Nei- ther methicillin-resistant Staphylococcus aureus nor Pseudomonas aeruginosa was detected. In comparison with MG patients, MSG patients had significantly lower BMI (18.3 ?2.6 vs. 21.2? 3.5), significantly higher numbers of hospital admissions (3.4?i3.3 times vs. 1.1+?L1.4 times), and a significantly higher ratio of GAF scores of 30 or less (85.7% VS 33.3%). The doses of benzo- diazepines and antiparkinsonian agents were significantly higher for MSG patients in comparison with MG patients (benzodiazepines : 2.3?2.4 mg vs. 0.4?i1.1 mg; antiparkinsonian agents: 2.3?2.4 mg vs. 0.4? 1.1 mg). No significant differences were observed in the doses of antipsy- chotics. Sputum culture tests were performed in 18 patients. (Conclusion) Outcomes were comparatively favorable and the results of bacterial culture tests tended to show no antibiotic-resistant bacteria, differing in that regard from hospital- acquired pneumonia. In fact, the characteristics of cases of pneumonia in hospitalized psychiatric patients were similar to those of community-acquired pneumonia. Low BMI, multiple psychiatric ward admissions, and GAF scores of 30 or less all reflect poor mental control. The results of the present study suggest a relationship between the severity of pneumonia and both insufficient psychiatric treatment and the use of benzodiazepines and antiparkinsonian agents.

Differences in vulnerability to traumatic stress among patients with psychiatric disorders: One-year follow-up study after the Great East Japan Earthquake.

AIMS: The aim of this study was to evaluate differences in vulnerability to traumatic stress and the 1-year course of post-traumatic stress symptoms among patients with pre-existing psychiatric disorders after the Great East Japan Earthquake. METHODS: The Impact of Event Scale-Revised (IES-R) was used to assess post-traumatic stress symptoms in 612 patients with schizophrenic (ICD-10 F2; n = 163), mood (F3; n = 299), or neurotic disorders (F4; n = 150) at 1-4 months and again at 13-16 months after the disaster (retention rate: 68%). RESULTS: The mean IES-R total score for all diagnostic groups was 18.6 at index and 13.4 at follow up. The mean IES-R total score for patients with neurotic disorders (22.5) was significantly higher than that of patients with mood disorders (18.1) and schizophrenic disorders (15.9). At follow up, these scores decreased for all groups and inter-group differences were not observed. CONCLUSIONS: Vulnerability to traumatic stress after a disaster was most severe in patients with neurotic disorders, followed by mood disorders, and, lastly, schizophrenic disorders. This difference among the three diagnostic groups was not found 1 year after the disaster.

Unilateral hippocampal infarction associated with an attempted suicide: a case report.

INTRODUCTION: In our case report we describe the case of a patient who experienced a stroke in her left hippocampus that was found following an attempted suicide via glyphosate overdose. To the best of our knowledge this is the first case report to describe a hippocampal infarction associated with a drug overdose. CASE PRESENTATION: A 64-year-old Japanese woman was brought to our emergency department after ingestion of an unknown dose of glyphosate surfactant herbicide in order to attempt suicide. On admission, she was assumed to be presenting with depression or psychiatric illness, however, sudden-onset memory deficit became apparent. The patient manifested delirium, confusion, and severe anxiety. In addition, short-term memory loss was prominent, with the patient forgetting her attempted suicide. Following an array of standard tests and a brain computed tomography scan (which only showed an old infraction), we performed a magnetic resonance imaging scan and neuropsychological evaluations. The brain magnetic resonance image revealed a small high-intensity lesion in the dorsal part of the left hippocampal body, and memory tests demonstrated severe short-term recall deficits. We diagnosed her with a left hippocampal infarction and administered a course of 75mg of clopidogrel. She gradually became less confused over the course of a week, and a follow-up memory test revealed partial improvement in some domains. No abnormalities were found on a follow-up brain scan. However, despite rehabilitation, memory impairments remain. CONCLUSIONS: It is important to note that had the symptom of short-term memory been absent or less severe, she might have been misdiagnosed with depression or another psychiatric illness. Although a computed tomography scan failed to detect hippocampal lesions, a diffusion-weighted magnetic resonance imaging scan clearly revealed a lesion within the left hippocampus. Therefore, in addition to assessments focusing on psychiatric illnesses that might be the root cause of an attempted suicide, organic factors should be considered along with radiological examination and precise memory assessments for diagnosing similar cases.

Second case report of successful electroconvulsive therapy for a patient with schizophrenia and severe hemophilia A.

Electroconvulsive therapy (ECT) is used for medication-resistant and life-threatening mental disorders, and therefore it occupies an important position in psychiatric treatment. ECT reportedly increases intracranial pressure and is suspected of increasing the risk of intracranial hemorrhage, especially in patients with hemorrhagic diseases such as hemophilia. A decrease in or loss of blood coagulation factors, including factor VIII and factor IX, are found in hemophilia A and B, respectively. Psychiatrists may hesitate to perform ECT on patients with bleeding tendencies, such as in hemophilia. Here, we report the successful use of ECT on a neuroleptic-resistant patient with schizophrenia and severe hemophilia A. We performed ECT 16 times supplemented with coagulation factor VIII to prevent intracranial and systematic hemorrhage. We administered factor VIII concentrates to the patient to keep factor VIII activity at 30%-40% during ECT. The patient did not show bleeding or other complications during the ECT sessions. We suggest that pretreatment with factor VIII can help manage the increased risks of intracranial and systematic bleeding during ECT that is present in patients with hemophilia A. The present report supports the idea of performing ECT safely on patients with hemophilia A by administering factor VIII.

Anger with murderous impulse induced by lamotrigine.

OBJECTIVE: To report two cases of major depressive disorder in which lamotrigine (LTG) induced anger with murderous impulse. PATIENTS: Case 1 was a 22-year-old man with symptoms of obsessive-compulsive disorder who developed major depressive disorder with antidepressant-induced hypomanic episodes. Case 2 was a 23-year-old woman experiencing an antidepressant-refractory depressive episode for whom remission was achieved by switching to a mood stabilizer and antipsychotics. In both cases LTG was started to treat the depressive episode. RESULTS: Case 1 manifested with anger and murderous impulse when taking 125 mg/day of LTG. A reduction to 75 mg/day calmed this anger. Case 2 manifested with the same symptom when taking 25 mg/day of LTG, and the symptom immediately disappeared upon stopping LTG. CONCLUSIONS: Use of LTG for epilepsy in intellectually disabled patients was reported to be associated with onset or exacerbation of aggressive or violent behavior. The two cases would suggest that LTG may cause anger so severe as to be accompanied with murderous impulse when administered to patients with mood disorders. Physicians should be cognizant of this possible, albeit infrequent, adverse effect even in use of LTG for mood disorders.

[Effects of psychological distress due to the Great East Japan Earthquake, tsunami, Fukushima Nuclear Power Plant disasters on psychiatric symptoms in patients with mental disorders: observational studies in Tochigi].

BACKGROUND: The Great East Japan Earthquake and subsequent tsunami of March 11, 2011 severely damaged a widespread region of northeastern Japan. Consequently, the Fukushima Nuclear Power Plant experienced a level seven 3 reactors melted down, which released a large amount of radioactive materials into the air. Due to the structural damage and radiation leaks, the victims are facing prolonged psychological distress. METHODS: Eighty-two subjects with mental disorders who made their initial visit during the first 4 months after the earthquake and one hundred and ninety-four subjects with mental disorders who had been admitted during the first one year after the earthquake to the Jichi Medical University Hospital, which is located at the edge of the disaster-stricken region, were recruited for this study. Enrolled participants were assessed according to ICD-10. A questionnaire survey was employed to evaluate the severity of psychological distress and total amount of damage. RESULTS: The conditions of 22% of the outpatients had been worsened by the psychological distress related to the earthquake. Seven percent of the patients who had been hospitalized showed marked exacerbations due to the psychological distress associated with the disaster. COMMENTS: It is of note that the exacerbation of psychiatric symptoms due to the disaster was evident among patients with mental disorders who lived even at the edge of the disaster area (i. e., subject to an earthquake intensity of 5 upper and 150 km from the Fukushima Nuclear Power Plant). The results suggest that the close follow-up of disaster victims with mental disorders is of critical importance.

Memantine attenuates 3,4-methylenedioxymethamphetamine-induced hyperthermia in rats.

3,4-Methylenedioxymethamphetamine (MDMA) is an illegal drug that can induce life-threatening hyperthermia. No effective pharmacological treatment for MDMA-induced hyperthermia has yet been established. We investigated the effects of memantine, a non-competitive N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist and an α-7 nicotinic acetylcholine receptor (nAChR) antagonist, on MDMA-induced hyperthermia in rats. Treatment of animals with memantine (10 or 20 mg/kg) either before or after MDMA (10 mg/kg) administration significantly decreased the peak body temperature. Results from our microdialysis study indicated that pretreatment with memantine (20 mg/kg) before MDMA administration had no effect on the MDMA-induced increase in serotonin (5-HT) and dopamine (DA) levels in the anterior hypothalamus. MDMA-induced hyperthermia was significantly suppressed by pretreatment with the non-competitive NMDA receptor antagonist MK-801 (0.5 mg/kg) and the competitive NMDA antagonist CGS 19755 (5 mg/kg), but not by the selective α-7 nAChR antagonist methyllycaconitine (6 or 10 mg/kg). These results indicate that the inhibitory effect of memantine on MDMA-induced hyperthermia may be due to its activity as an NMDA receptor antagonist and not as a result of a direct effect on the 5-HT or DA systems. The present study suggests that moderate doses of memantine may be useful for the treatment of MDMA-induced hyperthermia in humans.

Effectiveness of Electroconvulsive Therapy for Depression and Cotard's Syndrome in a Patient with Frontotemporal Lobe Dementia.

In the field of psychogeriatrics, the differential diagnosis of depression and dementia, as well as the treatment of depression and comorbid dementia, is an important issue. In this paper, the authors present the case of a 72-year-old woman with Cotard's syndrome and frontotemporal dementia (FTD) who was admitted to a psychiatric hospital with delusions of negation accompanied by depressive symptoms. Pharmacotherapy over a 2-year hospitalization was unsuccessful, and she was subsequently transferred to our university hospital. A total of 18 sessions of electroconvulsive therapy released her from psychomotor inhibition, appetite loss, and Cotard's delusions. The indication for electroconvulsive therapy in patients with dementia is discussed.

Risperidone attenuates the increase of extracellular nitric oxide and glutamate levels in serotonin syndrome animal models.

Serotonin (5-hydroxytryptamine; 5-HT) syndrome is a potentially life-threatening neurotoxic condition provoked by pharmacologically induced excess serotonergic activity. Several studies report that nitric oxide (NO) and glutamate play a role in psychostimulant-induced hyperthermia related to neurotoxicity. In the present study, the involvement of NO and glutamate, as well as the effect of risperidone, a potent 5-HT(2A) and D(2) (and a less potent D(1)) receptor antagonist, were investigated in animal models of 5-HT syndrome. Two 5-HT syndrome animal models were utilized. The first model was induced by administration of tranylcypromine, a nonselective monoamine oxidase (MAO) inhibitor, and fluoxetine, a selective 5-HT reuptake inhibitor. The second model was induced by the administration of clorgyline, an MAO-A inhibitor, and 5-hydroxy-l-tryptophan, a precursor of 5-HT. Changes in the level of NO metabolites and glutamate in the anterior hypothalamus were measured using microdialysis. In both models, NO metabolite levels significantly increased, and this increase was significantly attenuated by risperidone pretreatment. Extracellular levels of glutamate were increased only in the tranylcypromine and fluoxetine model, and this increase was significantly attenuated by risperidone pretreatment. These results indicate that NO and glutamate may be involved in the development of 5-HT syndrome and that risperidone may be effective against neurotransmitter abnormalities in 5-HT syndrome.

The effects of mirtazapine and fluoxetine on hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats.

The use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") as a recreational drug has spread worldwide. Fatal hyperthermia is a likely side effect of using MDMA in combination with monoamine oxidase inhibitors. However, most antidepressants do not pose a high risk of developing hyperthermia when used in conjunction with MDMA. Mirtazapine is a novel antidepressant and a potent 5-HT(2A) receptor antagonist. It remains to be elucidated whether mirtazapine is unlikely to have life-threatening implications in combination with MDMA. In the present study, we evaluated whether mirtazapine and fluoxetine influence MDMA-induced hyperthermia in rats. The rectal temperature of the rats increased to above 41°C following an injection of MDMA (10mg/kg). Pre- and post-treatment administration of mirtazapine (5mg/kg) significantly attenuated MDMA-induced hyperthermia. Administration of WAY100635 (1mg/kg), a 5-HT(1A) receptor antagonist, did not influence the ability of mirtazapine to decrease hyperthermia induced by MDMA. Although pretreatment administration of fluoxetine (10mg/kg) significantly attenuated MDMA-induced hyperthermia, post-treatment administration of the same drug had no effect. The differences in body temperature between the groups post-treated mirtazapine and the groups post-treated fluoxetine may be due to differing mechanisms of action of the two antidepressants. The present study indicates that mirtazapine is unlikely to induce fatal hyperthermia when used with MDMA, and it may be rather effective against MDMA-induced hyperthermia. Considering our previous study demonstrating that potent 5-HT(2A) antagonists completely inhibit MDMA-induced hyperthermia, the findings of the present study suggest that mirtazapine inhibits MDMA-induced hyperthermia mainly by blocking the activation of 5-HT(2A) receptors.

Mirtazapine abolishes hyperthermia in an animal model of serotonin syndrome.

Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. Hyperthermia is the most serious symptom of this syndrome. Hyperthermia in 5-HT syndrome is reportedly the result of activation of 5-HT(2A) receptors. Mirtazapine is a novel antidepressant and a potent 5-HT(2) receptor antagonistic. Although mirtazapine has been reported to cause 5-HT syndrome, the pharmacological profile of mirtazapine suggests that it improves hyperthermia in 5-HT syndrome. In the present study, we evaluated whether mirtazapine attenuates hyperthermia in a rat model of 5-HT syndrome. This model was induced by administration of tranylcypromine, a nonselective monoamine oxidase inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor. Upon injection of these two drugs, the rectal temperature of the rats increased to over 40 degrees C. Pre- and post-administration of mirtazapine abolishes hyperthermia in this model of 5-HT syndrome. Post-administration of ritanserin, a 5-HT(2A) receptor antagonist, completely inhibited hyperthermia and pre-administration of WAY100635, a 5-HT(1A) receptor antagonist, significantly attenuated the ability of mirtazapine to abolish hyperthermia. The results of the present study suggest that mirtazapine inhibits hyperthermia in an animal model of 5-HT syndrome by blocking the activation of 5-HT(2A) receptors, and that it partly inhibits hyperthermia by activating the 5-HT(1A) receptors. The present study indicates that mirtazapine is unlikely to cause 5-HT syndrome and may be a useful drug for treating this condition.

Effect of risperidone on acute methamphetamine-induced hyperthermia in rats.

The abuse of methamphetamine (METH) is popular in many parts of the world. The number of fatal cases related to METH-induced hyperthermia is increasing, but no definitive therapy has yet been found. In the present study, we investigated the ability of risperidone to attenuate acute METH-induced hyperthermia and the mechanism of its action. When administered before and after a single high METH dose (10 mg/kg), risperidone significantly suppressed acute METH-induced hyperthermia in a dose-dependent manner. The same effect was produced by dopamine-1 (DA(1)) and serotonin-2A (5-HT(2A)) receptor blockers, but not by D2, 5-HT(1A), 5-HT(2B/2C), or 5-HT(2C) receptor blockers, demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D(1) and 5-HT(2A) receptors. A microdialysis study showed that when METH (10 mg/kg) was subcutaneously injected into rats, the levels of DA, 5-HT, glutamate, and the nitric oxide (NO) metabolites NOx (NO2⁻+ NO3⁻) in the anterior hypothalamus increased. Risperidone pretreatment significantly attenuated increases in the levels of DA, 5-HT, glutamate, and NOx. The present study indicates that risperidone may be an effective drug for treating METH-induced hyperthermia in humans and that METH influences the DA and 5-HT neuron systems as well as other neuron systems, including the glutamate and NO systems.

Risperidone attenuates and reverses hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug. Despite an increase in the number of fatalities related to its use, no definite therapeutic method has been established thus far. In the present study, risperidone's ability to attenuate MDMA-induced hyperthermia and its mechanism of action were investigated in rats. The pharmacological effect of MDMA was evaluated using microdialysis. In the body temperature experiment, administration of risperidone before and after MDMA administration significantly suppressed MDMA-induced hyperthermia in a dose-dependent fashion. Furthermore, risperidone completely inhibited MDMA-induced hyperthermia at a low ambient temperature. Moreover, pretreatment with ritanserin, ketanserin, or R-96544, all of which are 5-HT(2A)-receptor antagonists, significantly prevented MDMA-induced hyperthermia. On the other hand, pretreatment with WAY-100635 (a 5-HT(1A) receptor antagonist), SB 206553 (a 5-HT(2B/2C) receptor antagonist), or SB 242084 (a 5-HT(2C) receptor antagonist) did not prevent MDMA-induced hyperthermia. Pretreatment with haloperidol, which blocks the dopamine (DA) receptors D(2) and D(1), significantly prevented MDMA-induced hyperthermia. However, sulpiride and L-741626, which are D(2) receptor blockers, did not prevent MDMA-induced hyperthermia. Pretreatment with SCH 23390 (a D(1) receptor antagonist) significantly prevented MDMA-induced hyperthermia. Furthermore, postadministration of ritanserin, haloperidol, and SCH23390 reversed MDMA-induced hyperthermia. These results demonstrate that the mechanism underlying the suppression of MDMA-induced hyperthermia by risperidone is primarily based on the drug's potent 5-HT(2A) receptor blocking effect, and to a lesser extent, on its D(1) receptor blocking effect. A microdialysis study showed that when MDMA (10mg/kg) was subcutaneously (s.c.) injected into the rats, the DA and serotonin (5-HT) levels in the anterior hypothalamus of the rats increased approximately 10- and 50-fold, respectively, as compared to their preadministration levels. These increases in the DA and 5-HT levels after MDMA injection were significantly suppressed by pretreatment with risperidone (0.5mg/kg). This suggested that both the DA and 5-HT systems were involved in the induction of hyperthermia by MDMA. Taken together, the present study's results indicate that risperidone may be an effective drug for the treatment of MDMA-induced hyperthermia in humans.