Comparison of the effectiveness of brand-name and generic antipsychotic drugs for treating patients with schizophrenia in Taiwan.

The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients.

Augmentation with amisulpride for schizophrenic patients non-responsive to risperidone monotherapy.

INTRODUCTION: The combination of antipsychotic drugs is a therapeutic resource in clinical practice. This study aimed to evaluate the efficacy and security of adding amisulpride in patients who at least partially responded to risperidone. METHODS: A 3-month, open, observational study was undertaken to evaluate the effectiveness of adding amisulpride in subjects who scored at least 25 on the brief psychiatric rating scale (BPRS) after risperidone monotherapy. Patients were evaluated with BPRS, the Clinical Global Impressions Severity of Illness scale (CGI-S) and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at baseline, 1 and 3 months. RESULTS: Coadjuvant treatment with amisulpride achieves a statistically significant improvement in mental status over a period of 3 months when measured with BPRS, CGI and UKU scales. The response rate was 70 (45%) in the oral risperidone and 74 (28%) in the parenteral risperidone groups. DISCUSSION: The addition of amisulpride could lead to an improvement in schizophrenia symptoms in patients that do not, or only partially, respond to risperidone. Further research is required into alternative therapies for poor responders.

Cannabis and schizophrenia.

BACKGROUND: Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. OBJECTIVES: To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. SELECTION CRITERIA: We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. MAIN RESULTS: We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. AUTHORS' CONCLUSIONS: Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.

Effects of dopamine D2/D3 blockade on human sensory and sensorimotor gating in initially antipsychotic-naive, first-episode schizophrenia patients.

It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating deficits in a longitudinal study of a large group of initially antipsychotic-naive, first-episode patients with schizophrenia. Our finding that amisulpride effectively reduced symptom severity in our patients without reducing their PPI deficits indicates that increased activity of dopamine D2 receptors may be involved in symptomatology of patients with schizophrenia, but not in their sensorimotor gating deficits.

[Integrative medicine in the management of functional dyspepsia. Role of the herbal preparation STW5]. / La medicina integrativa en el manejo de la dispepsia funcional. Papel del preparado herbal STW5.

Functional dyspepsia is defined as a group of symptoms, whether related or unrelated to intake, localized in the upper abdomen, that manifest in the form of discomfort or epigastric pain, postprandial fullness and early satiety, in the absence of any demonstrable organic or structural anomaly. The etiopathogenesis and physiopathology of the process are unknown but factors that may be involved include gastric motility disorders, visceral hypersensitivity, psychological and genetic factors, Helicobacter pylori infection, and gastric acid hypersecretion. There is still no etiological treatment and consequently treatment is empirical and based on symptoms. This article reviews the main therapeutic options currently available, with special emphasis on the use of certain phytoceuticals (STW 5), in an attempt to integrate with traditional scientific medicine. This article also proposes an integrative therapeutic algorithm.

Anxiolytic-like effect of quinpirole in combination with a low dose of 17ß-estradiol in ovariectomized rats.

The aim of this study was to explore effects on anxiety-like behavior of the D2 dopamine receptor agonist, quinpirole and of the D2 dopamine receptor antagonist, sulpiride given alone or in combination with a low dose of 17ß-estradiol (17ß-E2) to ovariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17ß-E2 (5.0 µg/rat, s.c.), quinpirole (0.1 mg/kg, i.p.), sulpiride (10.0 mg/kg, i.p.), quinpirole plus 17ß-E2 or sulpiride plus 17ß-E2. The animals were then tested in the black and white model (BWM) and the open field test (OFT). Quinpirole (0.1 mg/kg, i.p.) administered alone or in a combination with a low dose of 17ß-E2 (5.0 µg/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM. Repeated treatment of quinpirole and 17ß-E2 profoundly increased anxiolytic-like effect of the single substances they exert per se. Co-administration of quinpirole with 17ß-E2 increased frequency of rearing and grooming in OVX rats in the OFT. Sulpiride (10.0 mg/kg, i.p.) treatment failed to alter anxiety-like behavior in OVX rats in the BWM. In addition, sulpiride blocked the anxiolytic-like effect of 17ß-E2 in OVX rats. Application of neither sulpiride nor sulpiride plus 17ß-E2 led to any changes of rearing and grooming behavior in OVX rats in the OFT. The results of the present study suggest that 17ß-E2 and quinpirole interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other. Further research is needed to elucidate detailed mechanisms by which quinpirole and 17ß-E2 exert synergistic effect on anxiety-related behavior.

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.

Spinal segmental and supraspinal mechanisms underlying the pain-relieving effects of spinal cord stimulation: an experimental study in a rat model of neuropathy.

Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs). Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6-C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50 Hz, 0.2 ms, 2-4V, 5 min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABA(A)), saclofen (GABA(B)), ketanserine (5HT(2)), methysergide (5HT(1-2)), phentolamine (α-adrenergic), propranolol (ß-adrenergic), sulpiride (D(2)/D(3) dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation. Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems.

Anxiolytic effects of a semipurified constituent of guaraná seeds on rats in the elevated T-maze test.

The objective of this study was to investigate the effects of chronic administration of a semi-purified extract (Purified Extract A--PEA; 4, 8, or 16 mg/kg) of PAULLINIA CUPANA (guaraná) seeds on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine (PAR; 3 mg/kg), was used as a positive control. To evaluate possible serotonergic and dopaminergic neurotransmission involvement in the action of PEA during the ETM test, ineffective doses of metergoline (MET; 5-HT (2A/2C) antagonist receptor) or sulpiride (SUL; dopaminergic receptor antagonist) were acutely administered together with the PEA. The locomotion of the rats was assessed in a circular arena following each drug treatment. Both PEA (8 and 16 mg/kg) and PAR (3 mg/kg) increased one-way escape latencies from the open arm of the ETM, indicating a panicolytic effect compared to the control group. MET, in higher doses (1, 2 or 3 mg/kg), produced a panicolytic effect in the ETM test, whereas SUL did not (10, 20 or 40 mg/kg). The panicolytic effect produced by PEA (8 mg/kg) was blocked by both MET (2 mg/kg) and SUL (20 mg/kg), whereas the panicolytic effect produced by PAR (3 mg/kg) was blocked only by MET (2 mg/kg). These results show that chronic treatment with PEA produces a panicolytic effect during the ETM test, and that the dopaminergic and the serotonergic neurotransmission systems are involved in this effect.

[Levosulpiride in the management of functional dyspepsia and delayed gastric emptying]. / Levosulpirida en el manejo de la dispepsia funcional y la gastroparesia.

Levosulpiride is a sulpiride isomer that exerts its prokinetic action through a dual mechanism: 1) as a D(2) dopamine receptor antagonist and 2) as a serotonin 5HT(4) receptor agonist, conferring this drug with a cholinergic effect. At a dosage of 25mg three times daily, levosulpiride accelerates gastric and gallbladder emptying. Clinical trials have shown that this agent is more effective than placebo in reducing the symptoms of dyspepsia, while comparative studies have demonstrated that its effect is similar or superior to that of other dopamine antagonists. The safety profile of levosulpiride is good and the frequency of adverse events is similar to that of other D(2) dopamine antagonists. Therefore, this drug is a useful therapeutic option in the management of patients with functional dyspepsia, as well as in those with delayed gastric emptying.

Treatment with amisulpride of addicted patients to psychoactive substances and psychotic symptoms.

INTRODUCTION: There is ever more available information on the effectiveness of second-generation antipsychotic drugs used in addictive behaviour patients with psychotic symptoms. Due to its characteristics, Amisulpride is a medicine that can be considered as a valid therapeutic option to treat this group of patients. OBJECTIVE: To assess the value of Amisulpride to treat patients with addictive behaviours, and the associated morbidity. METHOD: An experimental, prospective study was conducted. A total of 97 ambulatory patients, who were initiating, or already receiving, treatment at the Addictive Behaviours Unit in Paterna, Valencia (Spain), were selected to take part in the study. Inclusion criteria included female and male patients, diagnosed of missusing any of the following substances: alcohol, heroine, cocaine or cannabis, who having overcome the detoxification phase, presented one or more of the following symptoms: paranoid ideas, hostility, severe irritative or impulsive behaviours, interpersonal sensitivity, and hearing or visual allucinations. An initial dose of Amisulpride, standardized in two ranges (100-300 mg y >/= 400 mg) was used. It was progressively increased according to the clinical response. Four assessments were conducted at months 0, 3, 6 and 9. RESULTS: Out of a total of 97 patients, 14 were excluded due to violation of the protocol. Twenty patients dropped out and 63 completed the follow-up period. Mean Amilsupride daily dose was 493.5 ± 197.1 mg In those patients who completed the treatment, an overall improvement in their psychological distress, a decreased in craving and an improvement in their psychological and social functioning were found. CONCLUSION: Treatment with Amisulpride seems to be effective in patients who are on different addictive substances, and its associated morbidity, both at a short and a medium period of time.

Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease.

OBJECTIVE: The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD). METHODS: Fifteen patients with AD (mean age: 80.2+/-4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D(2) selective antipsychotic, was performed for 12 weeks. RESULTS: Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted. CONCLUSIONS: Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.

Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine.

BACKGROUND: Schizophrenic patients exhibit impairments in prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR). Recent studies suggested that PPI deficits and habituation deficits are normalized after antipsychotic treatment. Despite clear evidence of gating and habituation mechanisms in animal models, it is still unknown which neurotransmitter systems are involved in schizophrenic patients. Thus, we compared the effects of a combined 5-HT2A/D2 and a pure D2/D3 antagonist on PPI and habituation of ASR in patients with schizophrenia. METHODS: The ASR was measured in 37 acute schizophrenic patients who were randomized and double-blinded as to treatment with amisulpride or olanzapine. Patients were assessed during the first week and after four and eight weeks of treatment. Twenty healthy matched control subjects were examined likewise. RESULTS: Schizophrenic patients showed a significant PPI deficit and significantly decreased startle amplitude at baseline. The gating deficit disappeared after antipsychotic treatment in both treatment groups. Amisulpride sensitized the startle amplitude, whereas startle amplitude was not changed by olanzapine. After correcting for startle amplitude, patients did not show a habituation deficit; however, amisulpride accelerated habituation, whereas olanzapine had no effect. CONCLUSIONS: Our findings suggest that the PPI-restoring effect of antipsychotics is probably attributed to a dopamine D2 receptor blockade.

D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.

UNLABELLED: Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. METHODS: Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. RESULTS: In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. CONCLUSION: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

Effects of Yoku-kan-san on undifferentiated somatoform disorder with tinnitus.

Up to the present, there have been few strategies that are completely effective in treating undifferentiated somatoform disorder with tinnitus. We herein report that Yoku-kan-san (TJ-54), one of Japan's traditional herbal medicines, is an effective treatment for tinnitus in undifferentiated somatoform disorder complicated with headache and insomnia. TJ-54 has been also used as an effective treatment for insomnia and irritability in recent centuries and is considered to have some effects on the excitability of nerves. Further studies are needed to confirm the efficacies of Japanese herbal medicines.

Alternatives to estrogen.

For many years, women have sought alternative therapies for menopausal symptoms and for general health overall. The highly publicized findings from the Women's Health Initiative have led to an increased pressure on the medical community to find safe and alternative medications for female health. This article reviews the challenges and problems with the use of alternative medicines, and the clinical trials that prove their efficacy, and discusses the safety issues that may occur with these types of products.

Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients.

OBJECTIVE: Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors or 2) selective action at limbic cortical dopamine D(2)-like receptors with modest striatal D(2) receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D(2)/D(3) dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D(2)/D(3) receptor blockade in vivo. METHOD: Five hours of dynamic single photon emission tomography data were acquired after injection of [(123)I]epidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). RESULTS: Eight amisulpride-treated patients (mean dose=406 mg/day) showed moderate levels of D(2)/D(3) receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). CONCLUSIONS: Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D(2)/D(3) receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D(2) receptor occupancy and preferential occupancy of limbic cortical dopamine D(2)/D(3) receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT(2A) receptor antagonism.