OBJECTIVE: Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead. METHODS: Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images. RESULTS: After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group. CONCLUSION: This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.
Aripiprazole ; Brain ; Cognition ; Cognitive Therapy ; Dopamine ; Electrons ; Frontal Lobe ; Glucose ; Humans ; Memory, Short-Term ; Metabolism ; Neurotransmitter Agents ; Occipital Lobe ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Prospective Studies ; Psychopathology ; Schizophrenia ; Sulpiride

OBJECTIVES: Relapse prevention is a major therapeutic goal in the treatment of schizophrenia. However, many patients experience multiple functional impairments and treatment resistance due to recurrence. This study was designed to investigate the follow-up of patients with using antipsychotic drugs and to compare the total treatment failure rate, withdrawal reasons, and duration period of antipsychotic drugs. METHODS: The subjects were 1963 patients who taking antipsychotic drugs under the diagnosis of schizophrenia. We selected 1836 patients using 10 antipsychotic drugs according to frequency of using. The rate of total treatment failure of them was divided into 6-month, 1-year, 2-year, 3-year, and 5-year according to the time of drug withdrawal. We compared the total treatment failure rate at 1 and 3-year between 10 antipsychotic drugs. RESULTS: The total treatment failure rate of clozapine was lowest compared with the other 9 antipsychotic drugs in all the surveyed periods. When evaluating actual number of subjects, olanzapine, sulpiride, risperidone, aripiprazole, amisulpride, and haloperidol were lower significantly compared with ziprasidone at 1-year in the total treatment failure rate, but there was no significant difference between them except clozapine at 3-year. The results of the analysis based on the number of prescriptions showed that the total treatment failure rate of the atypical antipsychotic drug was lower than that of the typical antipsychotic drug at 1-year, but the difference was decreased over time except quetiapine and ziprasidone. CONCLUSION: In conclusion, although there is some controversy about which drug to prescribe to the patient, the clinician needs a proper prescription considering various factors such as efficacy, side effects, price, and formulations of each drug.
Antipsychotic Agents* ; Aripiprazole ; Clozapine ; Diagnosis ; Follow-Up Studies ; Haloperidol ; Humans ; Prescriptions ; Quetiapine Fumarate ; Recurrence ; Risperidone ; Schizophrenia ; Secondary Prevention ; Sulpiride ; Treatment Failure

OBJECTIVES: Relapse prevention is a major therapeutic goal in the treatment of schizophrenia. However, many patients experience multiple functional impairments and treatment resistance due to recurrence. This study was designed to investigate the follow-up of patients with using antipsychotic drugs and to compare the total treatment failure rate, withdrawal reasons, and duration period of antipsychotic drugs. METHODS: The subjects were 1963 patients who taking antipsychotic drugs under the diagnosis of schizophrenia. We selected 1836 patients using 10 antipsychotic drugs according to frequency of using. The rate of total treatment failure of them was divided into 6-month, 1-year, 2-year, 3-year, and 5-year according to the time of drug withdrawal. We compared the total treatment failure rate at 1 and 3-year between 10 antipsychotic drugs. RESULTS: The total treatment failure rate of clozapine was lowest compared with the other 9 antipsychotic drugs in all the surveyed periods. When evaluating actual number of subjects, olanzapine, sulpiride, risperidone, aripiprazole, amisulpride, and haloperidol were lower significantly compared with ziprasidone at 1-year in the total treatment failure rate, but there was no significant difference between them except clozapine at 3-year. The results of the analysis based on the number of prescriptions showed that the total treatment failure rate of the atypical antipsychotic drug was lower than that of the typical antipsychotic drug at 1-year, but the difference was decreased over time except quetiapine and ziprasidone. CONCLUSION: In conclusion, although there is some controversy about which drug to prescribe to the patient, the clinician needs a proper prescription considering various factors such as efficacy, side effects, price, and formulations of each drug.
Antipsychotic Agents* ; Aripiprazole ; Clozapine ; Diagnosis ; Follow-Up Studies ; Haloperidol ; Humans ; Prescriptions ; Quetiapine Fumarate ; Recurrence ; Risperidone ; Schizophrenia ; Secondary Prevention ; Sulpiride ; Treatment Failure

Objective: To investigate the clinical effects of aripiprazole on sexual dysfunction induced by amisulpride or risperidone in male patients with schizophrenia. METHODS: This study included 75 male patients with drug-induced secondary sexual dysfunction after treated with amisulpride or risperidone for first-episode schizophrenia between October 2014 and October 2016. We substituted aripiprazole for amisulpride or risperidone, gradually increased the dose from 10 to 30 mg/d within 2 weeks, and maintained 30 mg/d from the 3rd week. At 4 and 8 weeks after medication, we evaluated the sexual function of the patients, measured the levels of serum prolactin (PRL) and testosterone (T), obtained the scores of the Positive and Negative Symptoms Scale (PANSS), recorded adverse reactions, and compared the parameters with those before aripiprazole administration. RESULTS: Compared with pre-aripiprazole administration, the patients showed significant increases after 4 weeks of medication in the sexual function score (24.3 ± 2.1 vs 32.6 ± 3.6, P <0.05) and T level (［13.3 ± 2.7］ vs ［17.4±3.0］ mmol/L, P <0.05) but a decreased level of PRL (［38.5 ± 10.5］ vs ［27.9 ± 8.2］ ng/ml, P <0.05). At 8 weeks, the sexual function score and serum PRL were both restored to the baseline levels at admission, and the erectile function score, ejaculation score, total score, and serum T level even exceeded the baseline, though with no statistically significant differences (P >0.05). In comparison with pre-aripiprazole administration, the PANSS score was significantly decreased at 4 weeks after medication (62.1 ± 4.9 vs 57.2 ± 5.5, P <0.05) and even lower at 8 weeks (51.2 ± 5.2) (P <0.05). The incidence rates of medication-related excitation, dizziness, insomnia, and loss of appetite were 6.7%, 5.3%, 4.0% and 1.3% respectively, and no other serious adverse reactions were observed. CONCLUSIONS Aripiprazole is effective for the treatment of drug-induced sexual dysfunction in schizophrenic men by continuously alleviating their positive and negative symptoms and meanwhile improving their sexual function and restoring their sexual hormone levels.
Amisulpride ; Antipsychotic Agents ; administration & dosage ; adverse effects ; Aripiprazole ; administration & dosage ; Drug Administration Schedule ; Humans ; Male ; Prolactin ; blood ; Risperidone ; adverse effects ; Schizophrenia ; blood ; drug therapy ; Sexual Behavior ; Sexual Dysfunction, Physiological ; blood ; chemically induced ; drug therapy ; Sulpiride ; adverse effects ; analogs & derivatives ; Testosterone ; blood ; Treatment Outcome

BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.
Analgesia ; Animals ; Dopamine ; Microdialysis ; Nefopam* ; Pain Measurement ; Rats* ; Spinal Cord ; Spinal Cord Dorsal Horn ; Sulpiride ; Synaptic Transmission

Pharmacotherapy has been constantly chosen by the clinician among the available treatment options for tinnitus. Medications that have been prescribed off-label to treat tinnitus can be grouped into several categories: benzodiazepines, antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists, dopamine receptor modulators, muscle relaxants, and others. In this article, a wide variety of compounds once used in the treatment of tinnitus and evidenced by clinical trials are reviewed with respect to the mechanisms of action and the drug efficacy. Only a few of the various pharmacological interventions investigated have some beneficial effects against tinnitus: clonazepam, acamprosate, neramexan, and sulpiride. Sertraline and pramipexole were effective in subgroups of patients with psychiatric symptoms or presbycusis. However, no agents have been identified to provide a reproducible long-term reduction of tinnitus in excess of placebo effects. In rodent tinnitus models, L-baclofen, memantine, and KCNQ2/3 channel activators have been demonstrated to reduce tinnitus development. Limitation of the use of an effective high dosage during a longer treatment duration due to dose-dependent side effects of the centrally acting drugs may influence the results in clinical studies. More effective and safer innovative agents should be developed based on the further understanding of tinnitus neural mechanisms and valid animal models, and should be supported by improved clinical trial methodology. The management of tinnitus patients through a tailored treatment approach depending on the detailed classification of tinnitus subtypes will also lead to better treatment outcomes.
Anticonvulsants ; Antidepressive Agents ; Benzodiazepines ; Classification ; Clonazepam ; Dopamine Agonists ; Dopamine Antagonists ; Drug Therapy ; Humans ; Memantine ; Models, Animal ; N-Methylaspartate ; Placebo Effect ; Presbycusis ; Rodentia ; Sertraline ; Sulpiride ; Tinnitus*

Humans ; Serum ; chemistry ; Spectrophotometry, Ultraviolet ; methods ; Sulpiride ; blood

OBJECTIVE: We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. METHODS: With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine, asenapine, iloperidone, lurasidone, perospirone and blonanserin. We applied some bibliometric indicators of paper production and dispersion with Price's law and Bradford's law, respectively. We also calculated the participation index (PI) of the different countries, and correlated the bibliometric data with some social and health data from Korea (such as total per capita expenditure on health and gross domestic expenditure on research and development). RESULTS: We collected 326 original papers published between 1993 and 2011. Our results state fulfilment of fulfilled Price's law, with scientific production on SGAs showing exponential growth (correlation coefficient r=0.8978, as against an r=0.8149 after linear adjustment). The most widely studied drugs were risperidone (91 papers), aripiprazole (77), olanzapine (53), and clozapine (43). Division into Bradford zones yielded a nucleus occupied by the Progress in Neuro-Psychopharmacology and Biological Psychiatry (36 articles). A total of 86 different journals were published, with 4 of the first 10 used journals having an impact factor being greater than 4. CONCLUSION: The publications on SGAs in South Korea have undergone exponential growth over the studied period, without evidence of reaching a saturation point.
Antipsychotic Agents ; Benzodiazepines ; Biological Psychiatry ; Bipolar Disorder ; Clozapine ; Complement Factor B ; Dibenzothiazepines ; Dibenzothiepins ; Health Expenditures ; Heterocyclic Compounds with 4 or More Rings ; Imidazoles ; Indoles ; Isoindoles ; Isoxazoles ; Jurisprudence ; Korea ; Piperazines ; Piperidines ; Pyrimidines ; Quinolones ; Republic of Korea ; Risperidone ; Schizophrenia ; Subject Headings ; Sulpiride ; Thiazoles ; Quetiapine Fumarate ; Aripiprazole ; Lurasidone Hydrochloride

Antipsychotics polypharmacy is a common practice in clinical settings despite the opposition of most guidelines for treatment of schizophrenia. This article reviews the evidence of antipsychotics polypharmacy and summarizes advantages and disadvantages shown in clinical trials. Clinicians choose antipsychotics polypharmacy to control the positive and negative symptoms more effectively especially in treatment resistant patients or to reduce adverse effects. There are some theoretical possibilities that antipsychotics polypharmacy affects a broader range of receptors, enhances D2-receptor blockade and optimizes pharmacokinetic effects. Clinical evidence suggests that clozapine co-administered with risperidone, sulpiride, or amisulpride reduces psychotic symptoms in treatment-resistant patients and that aripiprazole with other antipsychotics reduces metabolic side effects. On the other hand, antipsychotics polypharmacy is associated with problems such as dose-dependent side effects, metabolic problems, increased mortality and treatment cost. Considering pros and cons, antipsychotics polypharmacy must be started after close scrutiny of the patient's medication history not just by clinical judgment. Also, changing the regimen from polypharmacy to monotherapy should be considered as a reasonable option to schizophrenic patients in stationary status.
Antipsychotic Agents* ; Clozapine ; Hand ; Health Care Costs ; Humans ; Judgment ; Mortality ; Piperazines ; Polypharmacy* ; Quinolones ; Risperidone ; Schizophrenia* ; Sulpiride ; Aripiprazole

Tardive blepharospam is characterized by repetitive, forceful, and sustained involuntary contractions of the orbicularis oculi. We report here one case of neuroleptic-induced tardive blepharospasm that developed during high-dose amisulpride treatment and was treated with clozapine. The patient was a 29-year-old man with a 6-year history of schizophrenia. After 33 months of amisulpride treatment (1200 mg/day), involuntary eye-blinking had developed. Following exclusion of all other possible etiopathological causes of the blepharospasm, we decided to switch the drug treatment from amisulpride to clozapine. On the fourteenth day of clozapine (250 mg/day) treatment, we observed significant improvements in eye-blinking and psychotic symptoms. Four months later, the eye-blinking had remitted completely. We suggest that amisulpride may cause blepharospasm and lead to an impaired ability to perform daily activities. Therefore, we recommend that clinicians regularly monitor involuntary movements in patients receiving antipsychotic treatment, especially when high doses of amisulpride are involved.
Adult ; Blepharospasm ; Clozapine ; Contracts ; Dyskinesias ; Humans ; Organothiophosphorus Compounds ; Schizophrenia ; Sulpiride