Gamma-band neural oscillations are critically involved in working memory and are disrupted in schizophrenia. Transcranial alternating current stimulation (tACS) at gamma frequency is a promising noninvasive approach to restore oscillatory synchrony and enhance cognition. This randomized, double-blind trial tested whether 40 Hz tACS targeting frontoparietal networks modulates gamma-band activity and connectivity during working memory, and whether these electrophysiological changes relate to cognition in schizophrenia. Patients with schizophrenia (n = 33) were randomized to 10 sessions of active or sham tACS over the left dorsolateral prefrontal cortex (F3) and right parietal cortex (P4), with cognition assessed using standardized neurocognitive measures (MATRICS Consensus Cognitive Battery, MCCB) and an n-back working-memory task. EEG during an n-back task was recorded pre- and post-intervention to assess gamma power, phase-locking value (PLV), and phase-amplitude coupling (PAC). A significant Group × Time interaction indicated that 1-back minus 0-back PLV increased in the active group but not in sham (P = 0.048, Cohen's d = 1.08). For PAC, a significant interaction showed that delta-high gamma coupling at F3 remained stable in the active group but declined in sham (P = 0.036, Cohen's d = 1.00). There was no significant correlation with n-back measures of working memory, but an exploratory significant finding linking this modulation to visual learning at 4-week follow-up. No significant group differences were found for MCCB total scores; however, a significant Group × Time interaction emerged for 0-back accuracy during EEG recording (P = 0.029, Cohen's d = 1.19). These findings demonstrate that 40 Hz tACS can enhance and preserve gamma synchrony in frontoparietal circuits during working memory. The maintained delta-gamma coupling in our exploratory findings on visual learning may suggest a relationship to sustained improvements in cognition over time, but needs additional confirmation.

Importance:There is an urgent need for algorithm trials that address treatment steps in schizophrenia sequentially. Moreover, there is a debate about whether clozapine should be used after 1 failed antipsychotic drug trial. Objective:To investigate whether switching to clozapine is effective in patients with first-episode psychosis (FEP) who have not responded to 1 previous antipsychotic drug. Design, Setting, and Participants:This was a sequential, assessor-blind trial with 2 randomizations conducted across 7 centers in China from February 2019 to October 2022. Included were individuals aged 16 to 45 years and with FEP (schizophrenia, schizophreniform disorder, or schizoaffective disorder). In phase 1, patients with FEP were randomized to receive oral olanzapine, risperidone, amisulpride, aripiprazole, or perphenazine for 8 weeks. In phase 2, nonresponders were rerandomized to receive olanzapine, amisulpride, or clozapine for another 8 weeks. Responders entered a 1-year naturalistic follow-up. Study data were analyzed from February to August 2025. Interventions:Specific antipsychotic drugs. Main Outcomes and Measures:The primary outcomes were as follows (1) symptomatic response, defined as the proportion of patients achieving a greater than or equal to 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score and (2) time to all-cause discontinuation, defined as discontinuation of antipsychotic drugs for any reason. Results:A total of 762 participants were randomized, and 654 (mean [SD] age, 26.9 [7.5] years; 328 male [50.2%]) were eligible for the study. Of the eligible participants, 556 (85.4%) completed phase 1, and 359 (55.1%) responded to treatment. Response rates were 60.5% (78 of 129) for olanzapine, 63.4% (83 of 131) for risperidone, 61.8% (81 of 131) for amisulpride, 44.3% (58 of 131) for aripiprazole, and 45.7% (59 of 129) for perphenazine (χ2 = 18.3; P = .001). In phase 2, 111 nonresponders were rerandomized (41 taking olanzapine, 38 taking amisulpride, and 32 taking clozapine). A total of 92 patients (82.9%) completed phase 2, and the following achieved a response: 13 (31.7%) taking olanzapine vs 17 (44.7%) taking amisulpride and 20 (62.5%) taking clozapine (χ2 = 6.9; P = .03). Conclusions and Relevance:The majority of patients with FEP responded to an initial antipsychotic drug trial, with risperidone and amisulpride being superior to aripiprazole and perphenazine. In those who initially did not respond to antipsychotic treatment, clozapine was more efficacious than olanzapine and amisulpride based on the PANSS ratings criteria outcome. This study provides some evidence for clinicians to consider regarding use of clozapine as the next sequential treatment after patients have failed an adequate trial with 1 of the more traditional antipsychotics. Trial Registration:ClinicalTrials.gov Identifier: NCT03510325.

This randomized clinical trial investigates if clozapine is more efficacious than olanzapine or amisulpride in patients who fail to respond to an initial antipsychotic drug trial. QuestionsIs clozapine more efficacious than olanzapine or amisulpride in patients who fail to respond to an initial antipsychotic drug trial?FindingsIn this randomized clinical trial including 654 participants, clozapine was found to be more efficacious than olanzapine or amisulpride, and there was no clear difference in all-cause treatment discontinuation between treatment groups.MeaningClozapine may be considered as a preferred subsequent option for patients with first-episode psychosis who have not responded to an initial antipsychotic drug. ImportanceThere is an urgent need for algorithm trials that address treatment steps in schizophrenia sequentially. Moreover, there is a debate about whether clozapine should be used after 1 failed antipsychotic drug trial.ObjectiveTo investigate whether switching to clozapine is effective in patients with first-episode psychosis (FEP) who have not responded to 1 previous antipsychotic drug.Design, Setting, and ParticipantsThis was a sequential, assessor-blind trial with 2 randomizations conducted across 7 centers in China from February 2019 to October 2022. Included were individuals aged 16 to 45 years and with FEP (schizophrenia, schizophreniform disorder, or schizoaffective disorder). In phase 1, patients with FEP were randomized to receive oral olanzapine, risperidone, amisulpride, aripiprazole, or perphenazine for 8 weeks. In phase 2, nonresponders were rerandomized to receive olanzapine, amisulpride, or clozapine for another 8 weeks. Responders entered a 1-year naturalistic follow-up. Study data were analyzed from February to August 2025.InterventionsSpecific antipsychotic drugs.Main Outcomes and MeasuresThe primary outcomes were as follows (1) symptomatic response, defined as the proportion of patients achieving a greater than or equal to 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score and (2) time to all-cause discontinuation, defined as discontinuation of antipsychotic drugs for any reason.ResultsA total of 762 participants were randomized, and 654 (mean [SD] age, 26.9 [7.5] years; 328 male [50.2%]) were eligible for the study. Of the eligible participants, 556 (85.4%) completed phase 1, and 359 (55.1%) responded to treatment. Response rates were 60.5% (78 of 129) for olanzapine, 63.4% (83 of 131) for risperidone, 61.8% (81 of 131) for amisulpride, 44.3% (58 of 131) for aripiprazole, and 45.7% (59 of 129) for perphenazine (chi 2 = 18.3; P = .001). In phase 2, 111 nonresponders were rerandomized (41 taking olanzapine, 38 taking amisulpride, and 32 taking clozapine). A total of 92 patients (82.9%) completed phase 2, and the following achieved a response: 13 (31.7%) taking olanzapine vs 17 (44.7%) taking amisulpride and 20 (62.5%) taking clozapine (chi 2 = 6.9; P = .03).Conclusions and RelevanceThe majority of patients with FEP responded to an initial antipsychotic drug trial, with risperidone and amisulpride being superior to aripiprazole and perphenazine. In those who initially did not respond to antipsychotic treatment, clozapine was more efficacious than olanzapine and amisulpride based on the PANSS ratings criteria outcome. This study provides some evidence for clinicians to consider regarding use of clozapine as the next sequential treatment after patients have failed an adequate trial with 1 of the more traditional antipsychotics.Trial RegistrationClinicalTrials.gov Identifier: NCT03510325

BACKGROUND:Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS:In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happé animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS:The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group × time interaction. No serious adverse events occurred. CONCLUSIONS:These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Objective: There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. We conducted a 24-week, double-blind, placebo-controlled study, in Hunan, China, to assess the effect of high-dose sulforaphane (Nutramax extra strength sulforaphane tablets glucoraphanin content 30 mg/ tablet) on reducing negative symptoms in antipsychotic-treated patients with schizophrenia. Methods: Participants were recruited from August 2020 to August 2022 and met DSM-5 criteria for schizophrenia. Participants were randomly assigned (2:1) to receive antipsychotics plus sulforaphane (1,700 mg Avmacol Extra Strength sulforaphane daily) or antipsychotics plus placebo for 24 weeks. Fifty-three patients treated with sulforaphane and 24 patients treated with placebo who had at least 1 postintervention clinical scale evaluation were analyzed. The primary outcome measure was change in the Positive and Negative Syndrome Scale (PANSS) negative symptoms. Results: Sulforaphane-treated patients showed a significantly greater decrease in PANSS negative symptom total score (P = .01) and PANSS negative factor score (P = .02) than placebo-treated patients, with the most prominent difference occurring at 24 weeks (P ≤ .001) with a large effect size at this time point (d = 0.8). Sulforaphane's effect on decreasing negative symptoms was not mediated by changes in scores of depression or cognitive factors on the PANSS. Conclusions: The results of this study suggest that add-on high-dose sulforaphane may reduce negative symptoms in patients with schizophrenia. The clinical significance of this reduction in negative symptoms needs further evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT04521868.

Transcranial alternating current stimulation (tACS) may have effects on cognition and symptoms in psychiatric illness but there have been few randomized controlled studies in people with schizophrenia. We conducted a randomized sham-controlled double-blind study of 40 Hz tACS on measures of cognition and symptoms scores in 50 patients diagnosed with DSM-5 schizophrenia. tACS was delivered in 10 sessions (20 min each) over a 2-week period. Evaluations were conducted with multiple cognitive and symptom batteries after 10 sessions and at 2 weeks and 4 weeks post-treatment, and also on-line during the tACS stimulation session 1. The primary outcome measured changes in the MATRICS overall composite score. The results showed no statistically significant (P < 0.05) effects of active vs. sham on improvement in any of the cognitive measures or PANSS rated positive or negative symptoms. There was a trend (P < 0.06) for the MATRICS Domain score of verbal learning to show greater improvement of active tACS compared to sham within 1-2 days after the 10 tACS sessions. Additional trials are needed to determine the effective tACS parameters targeting cognition and symptoms of schizophrenia.

Background:Non-invasive brain stimulation (NIBS) provides adjunctive therapeutic options for individuals with schizophrenia if medications are insufficient to produce clinical response, but guidelines remain controversial on whether NIBS is effective, and which NIBS methods and targets are preferred. We aimed to compare the efficacy and safety of NIBS for treatment-resistant schizophrenia (TRS). Methods:This systematic review and network meta-analysis of randomised controlled trials investigated NIBS interventions, including electroconvulsive therapy, magnetic seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), and transcranial electric stimulation (tES), as adjunctive treatment for TRS. We searched the Cochrane Schizophrenia Group's specialised register from inception to 2025.07.13, and three Chinese databases from inception to 2024.10.30. The primary outcome was overall symptoms, and adverse events were analysed as secondary outcomes. We synthesized the data using random-effects network meta-analysis. Sensitivity analyses examined the robustness of the findings and the effects of the detailed NIBS protocols. The protocol was pre-registered with PROSPERO (CRD42023410645) and published in a scientific journal. Findings:We identified 21710 references and included 78 trials with a total of 3416 participants (1216 women, 1733 men; mean age 37.06 years, range 25.55-48.38; ethnicity data were not recorded). Compared with sham stimulation, rTMS (SMD -0.47, 95% CI [-0.62; -0.31]) was more efficacious in improving overall symptoms; but not in a sensitivity analysis excluding studies from Chinese mainland (-0.19, [-0.38; 0.01]). No clear differences between rTMS specific protocols in terms of stimulation targets and protocols were detected. No clear differences were found for electroconvulsive therapy (-0.20, [-0.78; 0.37]), tES (-0.08, [-0.38; 0.22]), and MST (-0.30, [-1.73; 1.13]) compared to sham stimulation. Treatment as usual might be less efficacious than sham (1.13, [-0.13; 2.38]), based on indirect evidence. NIBS was generally safe (rTMS produced headaches and local reactions), but information about adverse events was rarely reported. Interpretation:rTMS may be efficacious in individuals with TRS, but this finding was driven mainly by studies from Chinese mainland. No clear differences were observed for electroconvulsive therapy, tES, and MST, but the findings were imprecise and inconclusive. Funding:German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung/BMBF; 01KG2206).

Introduction People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies. Methods In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin’ Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression. Results Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor. Discussion Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.

Background Although epigenetic dysregulation has long been proposed to promote the onset of schizophrenia, the landscape of the methylomic changes across the whole genome is yet established. Methods Using Infinium Human Methylation 850 BeadChip Array and MethylTarget sequencing method, we investigated the genome-wide methylation profiles and further validated methylation profiles of target genes in peripheral blood lymphocytes between individuals with psychosis risk syndrome (PRS), patients with first-episode schizophrenia (FES) and healthy controls (HC) in Chinese Han population. Results We detected 372 sites between psychosis risk syndrome (PRS) and healthy controls (HC), which increased to 460 sites in first-episode schizophrenia (FES) with 207 sites shared. Both PRS and FES featured profound hypomethylation within gene body. Gene ontology and network annotation merged on loci enriched in disease associated signaling pathways (MAPK(Mitogen Activated Protein Kinases), Glutamatergic, GABAergic etc.). Conclusions Our study implicated characteristic hypomethylation in both the discovery and validation cohorts in SYNGAP1 , one of the frequently studied genes in neurodevelopmental disorders. This is the first methylome-wide association study between PRS and FES in Chinese Han population. Our findings provide potential biomarkers that can be used for future development of disease therapy and management.

assigned to an extended clozapine treatment or modi fi ed electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAsnotpreviously used inphase 1 and2 (Phase3B). The primaryoutcomefor thetreatment phaseisthetreat- ment ef fi cacy rate, which is de fi ned as at least 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score. We hypothesize that clozapine is more therapeutically effective than any other SGAs to patients who failed to meet ef fi cacy criteria in Phase 1, and earlier treatment with clozapine can improve the functional outcomes of schizophrenia patients. As for the naturalistic follow-up phase, time to all-cause treatment failure, marked by its discontinuation is selected as the primary outcome, since it re fl ects both ef fi cacy and side effects. The all-cause discontinuation is de fi ned as discontinuing for any reasons, including poor ef fi cacy, intolerance of adverse reactions, poor compliance and other reasons. The results of the SMART-CAT trial will provide evidence for the selection of antipsychotics in FES patients who failtorespond tothe fi rst trial of anantipsychotic drug.It will also provide evidencefor theef fi cacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs. The study is based on the combination of sequential therapy and dynamic therapy, which can be more suitable to assess the effectiveness of treatment options in the real-world clinical setting. As a result, we hope that this study can provide guidance for an optimal treatment algorithm in fi rst-episode schizophrenia patients.

Some of the biochemical abnormalities underlying schizophrenia, involve differences in methylation and methylating enzymes, as well as other related target genes. We present results of a study of differences in mRNA expression in peripheral blood lymphocytes (PBLs) and post-mortem brains of chronic schizophrenics (CSZ) and non-psychotic controls (NPC), emphasizing the differential effects of sex and antipsychotic drug treatment on mRNA findings. We studied mRNA expression in lymphocytes of 61 CSZ and 49 NPC subjects using qPCR assays with TaqMan probes to assess levels of DNMT, TET, GABAergic, NR3C1, BDNF mRNAs, and several additional targets identified in a recent RNA sequence analysis. In parallel we studied DNMT1 and GAD67 in samples of brain tissues from 19 CSZ, 26 NPC. In PBLs DNMT1 and DNMT3A mRNA levels were significantly higher in male CSZ vs NPC No significant differences were detected in females. The GAD1, NR3C1 and CNTNAP2 mRNA levels were significantly higher in CSZ than NPC. In CSZ patients treated with clozapine, GAD-1 related, CNTNAP2, and IMPA2 mRNAs were significantly higher than in CSZ subjects not treated with clozapine. Differences between CSZ vs NPC in these mRNAs was primarily attributable to the clozapine treatment. In the brain samples, DNMT1 was significantly higher and GAD67 was significantly lower in CSZ than in NPC, but there were no significant sex differences in diagnostic effects. These findings highlight the importance of considering sex and drug treatment effects in assessing the substantive significance of differences in mRNAs between CSZ and NPC.

Schizophrenia is characterized by persistent cognitive deficits. Transcranial direct current stimulation (tDCS) is a safe and noninvasive brain stimulation method, and several studies showed that it can improve cognitive function in schizophrenic. The current study was a double-blind sham-controlled study to investigate neural alternations before and after tDCS under different task demands.

Background: Epigenetic dysregulation may be involved in the underlying molecular deficits in schizophrenia (SZ). Previous research by our group has show hypermethylation of GABAergic promoter gene in and increases in DNMT1 and DNMT3A in post mortem brain samples of patients with SZ. We have also shown that difference sin DNMT1 and other epigenetically related enzymes are also found in the lymphocytes of living patients with chronic schizophrenia (CSZ). We now report preliminary results on epigenetic related mRNA’s in lymphocytes on a larger sample of CSZ. Methods: CSZ (n = 29) and nonpsychotic controls (NPC) (n = 31) subjects had a blood sample (60–80 cc) drawn, and lymphocyte pellet extracted by Ficoll gradient procedure. qPCR assays were used to measure epigenetically related mRNA’s—DNMT1, DMNT3A, TET1, TET2, TET3, BDNF, NR3C (glucocorticoid receptor).We also assayed several immunological related mRNA (which appeared as strong hits from RNA sequence analysis) T-Cell Surface Glycoprotein CD4, CCR1 (C-C motif chemokine receptor 1), FPRL3 (Formyl Peptide Receptor). Assays were performed using Taqman probes with B-Actin as housekeeping gene. Patients were also evaluated with psychopathology with PANSS, for cognitive function with MATRICS, and for odor identification and discrimination with Sniff and Sticks smell test. Results: In this sample CSZ showed significantly higher DMNT3A (P = .048) than NPC Male CSZ showed significantly higher DNMT1 than NPC (P = .014), but the total sample there was a trend but no significant difference in DNMT1. Compared to NPC, CSZ subjects showed significantly higher levels of GABAergic enzymes measured by the GAD1 probe (which assays GAD67 and GAD25 mRNA) (P = .030), higher levels of glucocorticoid receptor measured by the NRC3 probe (P = .006), and significantly lower levels of FRPRL3(P = .039). Higher levels FPRL3 and CD4 were moderately correlated with PANSS positive symptoms in CSZ (FRPL3 r = +.43 P = .019, CD4 r = +.37 P = .054) and these correlations were slightly stronger in male CSZ. Higher DNMT1 and DNMT3A levels in lymphocytes of CSZ correlated negatively with scores n MATRICs battery (DNMT1—attention/vigilance—r = −.41, P = .031, working memory r = −.37, P = .048, composite score r = −.36, P = .063). Conclusion: CSZ demonstrate differences in epigenetically related mRNA’s in their lymphocytes. In CSZ higher levels of DNMT were related to poorer cognitive performance and higher levels of immunological related mRNA to greater positive symptom scores. Some potential differences to our previously published results may be related to differences in mRNA’s measured by the Taqman probes and earlier research with specifically generated sequence probes.

Schizophrenic patients have a high rate of smoking and cognitive deficits which may be related to a decreased number or responsiveness of nicotinic receptors in their brains. Varenicline is a partial nicotinic agonist which is effective as an antismoking drug in cigarette smokers, although concerns have been raised about potential psychiatric side-effects. We conducted a double-blind placebo controlled study in 87 schizophrenic smokers to evaluate the effects of varenicline (2 mg/day) on measures of smoking, cognition, psychiatric symptoms, and side-effects in schizophrenic patients who were cigarette smokers. Varenicline significantly decreased cotinine levels (P<0.001), and other objective and subjective measures of smoking (P < .01), and responses on a smoking urges scale (P = .02), more than placebo. Varenicline did not improve scores on a cognitive battery designed to test the effect of drugs on cognitive performance in schizophrenia (the MATRICS battery), either in overall MATRICS battery Composite or individual Domain scores, more than placebo. There were no significant differences between varenicline vs. placebo effects on total symptom scores on psychiatric rating scales, PANSS, SANS, or Calgary Depression scales, and there were no significant drug effects in any of these scales sub-scores when we used Benjamin-Hochberg corrected significance levels (α = .05). Varenicline patients did not show greater side-effects than placebo treated patients at any time point when controlled for baseline side-effect scores. Our study supports the use of varenicline as a safe drug for smoking reduction in schizophrenia but not as a cognitive enhancer. Trial Registration: ClinicalTrials.gov 00802919

Back to table of contents Previous article Next article Communications and UpdatesFull AccessHistory of Psychopharmacology, Volumes 1–4Robert C. Smith, M.D., Ph.D.Robert C. SmithSearch for more papers by this author, M.D., Ph.D.Published Online:1 Mar 2015https://doi.org/10.1176/appi.ajp.2015.14121588AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail edited by Francisco López-Munoz, Cecilio Álamo, and Edward F. Domino. Arlington, Mass., NPP Books, 2014, 2182 pp., $109.00 (paperback).This is a three-volume work plus an index comprising the fourth volume reviewing the history of psychopharmacology from ancient times through the development of modern psychopharmacology in psychiatry in the 20th century. It is best used as a reference work for scholars of psychopharmacology or as part of a reference library where one would read a chapter, or a few chapters, at a time. I reviewed a paperback print copy. It would receive wider use and distribution, and be more readily available to many psychiatrists and researchers, as an e-book (or if accessible in electronic form), but such a format has not yet been considered, since I did not see any electronic version represented on the publisher’s website (www.nppbooks.com). The book was originally published in Spanish (2007) and now is available in an English edition translation, which was supervised by Professor Edward Domino. It has a wide range of scientific contributors from around the world but mostly from Europe, with a large number from Spain, and North America.The chapters cover a range of topics, with an emphasis on those aspects relevant to the development of modern psychopharmacology. These include the history of psychiatry and psychiatric treatments, the development of neurobiology and molecular biology, the development of specific drugs and classes of psychopharmacological agents, psychopharmacology theories of the neurobiology underlying specific psychiatric and neurological disorders, and institutional, social, and legal issues relevant to psychopharmacology and its contribution to modern psychiatry. The chapters range in style from ones that focus on developments in the field as part of an intellectual and social history to ones that present summaries of current understanding of the mechanisms of actions of drugs or neurobiological mechanisms without any clear historical context. There is no central theme or development of a coordinated history or viewpoint.I found many of the individual chapters interesting and informative for different purposes. The many historical chapters covering the period prior to the development of modern psychopharmacology in the latter part of the 20th century provide a wealth of information about treatment of mental illness and detail psychopharmacological approaches (herbal, drug, physical, and social approaches), as well as provide background information (with illustrations) about physicians, scientists, and political and religious figures who influenced treatment of mental illness. A chapter on intercellular neurobiology and signaling provides a good scientific summary of currently understood intracellular signaling mechanisms, with discussion on phosphorylation, ion channels, map kinases, and other signaling cascades. Although I was aware of this area of neurobiology from skimming journals and scientific conference lectures, I did not have a coordinated overview and summary in a more concise form, which the chapter provides. There are also detailed histories and/or summaries of current pharmacology of most of the major specific drugs used in modern psychopharmacology, as well as details with regard to the physicians and scientists involved in their discovery or development.This is not a book one would want to read through in one sitting, and its heft and size make it uncomfortable to carry around on trips (on airplanes and trains) for perusing a chapter at leisure. An electronic form that could be accessed by computer or iPad would be more useful for casual reading, and an electronic form that detailed searchable electronic indices would be more useful for research purposes, especially in the history of science and psychiatry, and for education purposes on specific topics. I would urge the publisher to consider adding these alternative forms to the current version of this multivolume work.Dr. Smith is a Research Professor of Psychiatry at New York University Medical School, New York, and a Research Psychiatrist at the Nathan Kline Institute for Psychiatric Research, Orangeburg, N.Y.The author reports no financial relationships with commercial interests. FiguresReferencesCited byDetailsCited byNone Volume 172Issue 3 March 01, 2015Pages 297-297 Metrics PDF download History Accepted 1 January 2015 Published online 1 March 2015 Published in print 1 March 2015

We report an incident of delayed onset of true vocal fold paralysis with continuous interscalene brachial plexus block. A 51 year old woman underwent left shoulder manipulation and lysis of adhesions with fluoroscopy and general anesthesia. An interscalene brachial plexus block was performed and a catheter with a continuous infusion pump was placed for postoperative pain control. Following hospital discharge, approximately 8 hours after the initial catheter bolus the patient developed hoarseness, dysphagia, and dyspnea, secondary to left vocal fold palsy. The patient was admitted for observation and the catheter was discontinued with no intubation required. By the next morning, the patient’s dysphagia and dyspnea had resolved and her hoarseness improved.

Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants.

BACKGROUND Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoaffective disorder, there have been no studies on the glycemic effects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone. METHODS An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. After a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily. RESULTS Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, primarily due to psychotic relapse. There was a statistically significant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m(2) mean reduction). There was also a reduction in the use of antidiabetic medications after the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74). CONCLUSIONS This study suggests significant improvement in metabolic side effects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. There was a large discontinuation rate, which limited the sustained beneficial effects of ziprasidone. The decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefits and the potential relapse risks of the individual patient first and foremost.