Predominant Negative Symptoms Research Articles

ANTIPSYCHOTICS: FROM THE FIRST TO THE THIRD GENERATION

The review is devoted to comparative analysis of antipsychotics of three generations. When writing the review, a systematic search in the databases PubMed, Medline, Elsevier was carried out, a simple filter for keywords was used. Pharmacological and clinical issues of antipsychotic therapy were considered, the mechanisms of action of antipsychotics of different generations were revealed. Current trends in the development of approaches to the therapy of schizophrenia and the concept of atypicality of antipsychotics were discussed. A comparative analysis of indications for use, tolerance (safety of use) and efficacy of various antipsychotic drugs with an emphasis on the effect on negative (primary, persistent) symptoms has been conducted. The hypothesis underlying new approaches to the therapy of schizophrenia, based on the effect on dopamine autoreceptors, consisting of a high density of D2 and low density of D3 receptors, has been presented. It has been shown that antipsychotics of the third generation open up new possibilities in the therapy of psychosis within the framework of a personalized approach in psychiatry with the achievement of functional recovery of patients. The characteristics of the drugs representatives of the third generation of antipsychotics aripiprazole and cariprazine were given. The uniqueness of cariprazine as the only drug that inhibits D3 receptors in vitro, as well as in vivo in patients with schizophrenia was emphasized. The data of evidence-based studies of the effectiveness of cariprazine in the treatment of negative, including predominant negative symptoms were presented.

Serum levels of neuropeptide Y in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the double-blind randomized controlled PULSAR study).

Modulation of glutamatergic neurotransmission in schizophrenia by sarcosine leads to a reduction in primary negative symptoms, while its metabolic profile is safe. In order to extend research in the area, we assessed serum levels of neuropeptide Y (NPY), a hypothalamic hormone related to anxiety and depression, also involved in mechanisms inducing weight gain. Additionally, we analyzed associations between NPY concentrations and its changes with severity of symptoms and metabolic parameters. A prospective 6-month, randomized, double-blind placebo-controlled trial was completed by 57 subjects with chronic schizophrenia with predominant negative symptoms and stable antipsychotic treatment. The participants received 2 g of sarcosine (n = 28) or placebo (n = 29) daily. We assessed serum NPY concentrations and severity of symptoms (with the Positive and Negative Syndrome Scale [PANSS] and Calgary Depression Scale for Schizophrenia) at the beginning of the study, after 6 weeks and 6 months. Sarcosine did not affect NPY levels in all time points. The highest decrease in NPY concentrations was observed in the subjects who were initially depressed, who became euthymic at the last visit. We noticed an improvement in the total PANSS score, and negative symptom and general psychopathology subscales in the sarcosine group, however, without any correlation with NPY levels. The use of sarcosine does not change NPY levels. Peripheral NPY concentrations may be related to depressive symptoms in schizophrenia.

"Cool" and "Hot" Executive Functions in Patients With a Predominance of Negative Schizophrenic Symptoms.

BackgroundPatients with psychosis often present significant neurocognitive deficits, with executive function deficits (EEFF) being one of the most relevant cognitive impairments with the greatest impact on the functioning of their daily lives. However, although various findings of executive involvement were reported, it is not entirely clear whether there is a differential pattern of involvement according to the clinical symptoms or the deficits occur in all or only in some subcomponents of EEFF.ObjectiveThe present study had a double objective: to study the specific deficits in the cool and hot EEFF in a group of psychotic patients with a predominance of negative symptoms; and determine the possible associations between the performance of the patients in the cool an hot EEFF tasks with the negative symptoms, and with the behavioral alterations associated with the dysexecutive syndrome.Method:66 participants, 33 psychotic patients with a predominance of negative symptoms and 33 healthy control subjects matched in gender, age and educational level participated. Both groups were administered 4 cool EEFF tasks (coding/maintenance and updating of information in working memory, ability to change the mental set and planning), and 3 hot EEFF tasks (decision making in situations of uncertainty, recognition of emotions through facial expressions and theory of mind). In the group of patients, the Negative symptoms were evaluated through the Scale for the Evaluation of Negative Symptoms (SANS), and the behavioral alterations associated with dysexecutive syndrome through the subscale of “Executive Dysfunction” of the Frontal Systems Behavior Scale.ResultsPatients performed worse on three cool EEFF tasks and on two of the hot EEFF tasks. Additionally, we found a correlation between the SANS score and the “executive dysfunction” subscale, with the cold EEFF task that measures planning.ConclusionOur findings showed that in psychotic patients with a predominance of negative symptoms, both, the cognitive (cool) and emotional (hot) components of executive functions are affected. The results reinforce the need for a cognitive rehabilitation treatment of the executive components of the working memory and of those more socio-emotional aspects.

Amisulpride - is it as all other medicines or is it different? An update.

Amisulpride is an antipsychotic available in Europe since 1990s, in Poland since 2000. Subsequent years brought to Polish market more second-generation compounds such as ziprasidone and aripiprazole. In 2018, the Agency for Health Technology Assessment and Tariff System issued positive recommendation for lurasidone in schizophrenia (Recommendation 30/2018) facilitating its entry to the market. Thanks to new molecules, therapeutic possibilities of medicines consequently rise, however, higher number of available substances of different properties brings also more dilemmas which one to pick. Since new publications of comparative drug trials, meta-analyses and systematic reviews are issued regularly, the authors present herein publications issued within last ten years focusing on amisulpride as opposed to other neuroleptics used in Poland. Although in many aspects it is equivalent to other atypical antipsychotics, it still has some advantages. Amisulpride seems to have better outcome than classic and atypical neuroleptics when it comes to depressive symptoms and predominant negative symptoms. It might also be superior to haloperidol in inducing symptomatic remission in first episode schizophrenia. Except for prolactin increase its side effects profile is favorable - it rarely leads to extrapyramidal symptoms (which are dose-dependent) and sedation. Therefore many patients accept treatment with amisulpride for its measurable clinical gains, such as improvement of positive symptoms and higher quality of life, compared to typical neuroleptics. Pharmacokinetics of amisulpride also encourage its wider use, especially when there is either a need for combined psychopharmacotherapy or comorbidity with general medical condition rises a need for somatic parallel treatment.

Negative Symptoms of Schizophrenia: New Prospects of Cariprazine Treatment.

Cariprazine is a new piperazine derivative atypical antipsychotic, like aripiprazole and brexpiprazole. It has been approved for treating schizophrenia in many countries and has recently been included on the List of Essential Medicines in Russia. Unlike most other atypical antipsychotics, it shows high in vivo occupancy of dopamine D2 and D3 receptors at clinically relevant doses. In animal models, cariprazine has demonstrated dopamine D3 receptor-dependent pro-cognitive and anti-anhedonic effects, suggesting its potential for treating negative symptoms. This review summarizes the efficacy of cariprazine in the treatment of negative symptoms of schizophrenia. A literature search of databases covering international and Russian journals, for articles published between 1st January 2010 and 1st June 2020. Cariprazine demonstrated at least comparable efficacy in the treatment of schizophrenia symptoms to active comparators including risperidone, olanzapine or aripiprazole. The drug has a good safety profile. It appeared to be associated with a lower risk of metabolic syndromes and most extrapyramidal symptoms. The positive effect of cariprazine on the negative symptoms of schizophrenia may be associated with the elimination of secondary negative symptoms. However, of all the atypical antipsychotics to date, only cariprazine has a convincingly, methodologically robust proven advantage over risperidone in eliminating the predominant negative symptoms of schizophrenia. Yet only four studies have investigated the effect of cariprazine on the negative symptoms of schizophrenia. There is a lack of research into its direct impact on emotional-volitional disorders, anhedonia, cognitive symptoms and personality changes. However, there is evidence to suggest cariprazine is effective in treatment-resistant cases, but this requires further confirmation. Cariprazine is an effective and well-tolerated agent for the treatment of schizophrenia and may be effective in cases where other antipsychotics have failed. Cariprazine has been shown to have a positive effect on negative symptoms. Further studies are needed to collect more data on long-term treatment of schizophrenia and especially negative symptoms.

Adjunct high-frequency transcranial random noise stimulation over the lateral prefrontal cortex improves negative symptoms of schizophrenia: A randomized, double-blind, sham-controlled pilot study

High-frequency transcranial random noise stimulation (hf-tRNS) is a non-invasive neuromodulatory technique capable of increasing human cortex excitability. There were only published case reports on the use of hf-tRNS targeting the lateral prefrontal cortex in treating negative symptoms of schizophrenia, thus necessitating systematic investigation. We designed a randomized, double-blind, sham-controlled trial in a cohort of stabilized schizophrenia patients to examine the efficacy of add-on hf-tRNS (100–640 Hz; 2 mA; 20 min) using a high definition 4 × 1 electrode montage (anode AF3, cathodes AF4, F2, F6, and FC4) in treating negative symptoms (ClinicalTrials.gov ID: NCT04038788). Participants received either active hf-tRNS or sham twice daily for 5 consecutive weekdays. Primary outcome measure was the change over time in the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), which was measured at baseline, after 10-session stimulation, and at one-week and one-month follow-ups. Among 36 randomized patients, 35 (97.2%) completed the trial. Intention-to-treat analysis showed a significantly greater decrease in PANSS-FSNS score after active (−17.11%) than after sham stimulation (−1.68%), with a large effect size (Cohen's d = 2.16, p < 0.001). The beneficial effect lasted for up to one month. In secondary-outcome analyses, the authors observed improvements with hf-tRNS of disorganization symptoms, unawareness of negative symptoms, subjective response to taking antipsychotics, and antipsychotic-induced extrapyramidal symptoms. No effects were observed on the neurocognitive performance and other outcome measures. Overall, hf-tRNS was safe and efficacious in improving negative symptoms. Our promising findings should be confirmed in a larger sample of patients with predominant negative symptoms.

Comparative Efficacy and Tolerability of 32 Oral Antipsychotics for the Acute Treatment of Adults With Multi-Episode Schizophrenia: A Systematic Review and Network Meta-Analysis.

(Reprinted with permission from the Lancet 2019; 394: 939-51).

Synthetic Cannabinoids and Its Association With Persistent Negative Symptoms of Schizophrenia

Schizophrenia has a multidomain symptom cluster, including positive, negative, and cognitive symptoms. Synthetic cannabinoids (SC) commonly perpetuate the positive symptoms of schizophrenia. We present a case of predominant negative symptoms following the use of SC even though our patient had a consistent history of experiencing positive symptoms in the past. The hypoactive dopaminergic system in the prefrontal cortex can induce negative symptoms in schizophrenia. However, the modulating properties of SC on cannabinoid receptors can feed into the negative symptom progression. The psychoactive properties of SC need further research to understand its clinical characteristics.

Leki przeciwpsychotyczne II generacji w terapii objawów negatywnych schizofrenii

Farmakoterapia schizofrenii jest trudnym i złożonym procesem, szczególnie w kontekście objawów negatywnych. Konieczne jest właściwe rozpoznanie grup pacjentów, a w szczególności indywidualnych pacjentów ― w zależności czy objawy negatywne są pierwotne, czy wtórne, przeważające czy znaczące, czy też przeważające i przetrwałe. Piśmiennictwo dotyczące oceny skuteczności różnych leków przeciwpsychotycznych II generacji w leczeniu objawów negatywnych jest niejednorodne, a ocena objawów negatywnych, oparta na różnych metodologiach, dotyczy przede wszystkim różnorodnych grup pacjentów, którzy najprawdopodobniej w zróżnicowany sposób reagują na badane leki, w zależności od tego, czy wykazują znaczące, przeważające lub też przeważające i przetrwałe objawy negatywne. Dodatkowo zdecydowana większość badań dotyczy ogólnej populacji chorych na schizofrenię, wśród których oceniano między innymi nasilenie objawów negatywnych. W związku z tym ocena tych badań i ich porównanie między sobą jest praktycznie niemożliwe. Wybór leku przeciwpsychotycznego II generacji, który wykazywałby zdecydowaną przewagę nad innymi, jest również trudny. W ramach niniejszego opracowania wykonano przegląd literatury dotyczącej badań randomizowanych bezpośrednio porównujących kluczowe leki przeciwpsychotyczne II generacji stosowane w terapii objawów negatywnych. W większości analizowanych badań nie wykazano istotnych statystycznie różnic pomiędzy analizowanymi lekami (porównanie risperidonu, amisulprydu, arypiprazolu, olanzapiny pomiędzy sobą). Tylko w pojedynczych badaniach wykazano przewagę olanzapiny nad risperidonem w ocenie wpływu obu tych leków na objawy negatywne. Należy jednak podkreślić, że wyniki cechowały się ograniczoną wiarygodnością w zakresie możliwości wnioskowania o bezpośrednim wpływie leków na objawy negatywne. Przyczynę takiego stanu rzeczy należy upatrywać między innymi w tym, że w badaniach tych nie korygowano uzyskiwanych efektów o czynniki zakłócające, których wpływ na objawy negatywne został potwierdzony. Natomiast w grupie chorych z przeważającymi i przetrwałymi objawami negatywnymi stwierdza się przewagę kariprazyny nad risperidonem. Uzupełniająca analiza opracowań wtórnych dla analizowanych leków wykazała wyższą skuteczność leków II generacji nad lekami I generacji i placebo w różnych grupach pacjentów z objawami negatywnymi. Należy jednak podkreślić, że badania ze względu na swoją niejednorodność są trudne do porównania. Dodatkowym problemem, który pojawia się w kontekście badań klinicznych, a także codziennej praktyki, jest właściwa diagnoza i odróżnienie pierwotnych objawów negatywnych od wtórnych objawów negatywnych.

M37. THERAPEUTIC EFFECT OF TRANSCRANIAL DIRECT CURRENT STIMULATION ON WORKING MEMORY OF PATIENTS WITH RECENT ONSET SCHIZOPHRENIA: A RANDOMIZED CONTROLLED STUDY

BackgroundWorking memory is impaired in many patients with psychotic disorder and influence their daily living. This study aimed to evaluate therapeutic effect of transcranial direct current stimulation (tDCS) on working memory of patients with recent onset schizophrenia.Methods40 patients with schizophrenia randomized to either 6 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4, duration of 30 minutes and 72 hours in between). Patients with predominant negative symptoms were excluded. Primary outcome was improvement of working memory performance on letter-number sequencing test and secondary outcome was reduction in Positive and Negative Syndrome Scale (PANSS).ResultsMajority of patients (90%) were male. Mean age was 34.12 (±11.20) ranging from 27 to 59 years. Mean score of PANSS was 9.8±2.1 in negative, 17.4±4.0 in positive and 19.2±3.2 in general symptoms. Cognitive performance of patients receiving tDCS improved significantly (7.7±2.3 to 10.3±1.7, p=0.001) compared to the sham group (8.9±3.5 to 9.1±2.4). PANSS score did not change significantly and had the same trend in the two groups.DiscussionThe results of the present study indicate that prefrontal tDCS may be a promising intervention for cognitive rehabilitation in patients with recent onset schizophrenia with prominent positive symptoms.

Cognitive Enhancing Effect of High-Frequency Neuronavigated rTMS in Chronic Schizophrenia Patients With Predominant Negative Symptoms: A Double-Blind Controlled 32-Week Follow-up Study.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927.

Folic Acid and Vitamin B12 Supplementation on Male Patients with Schizophrenia Predominant Negative Symptoms

Background: Schizophrenia is a chronic mental disorder that affects approximately 1% of the world’s population. Particularly, negative symptoms are frequently resistant and are the main contributors to the disability on schizophrenia patients. Folic acid and vitamin B12 supplementation is the safe and affordable approach, which can significantly improve the outcome on the patients with residual symptoms. Objectives: We aimed to understand the difference of negative subscale of Positive and Negative Syndrome Scale (PANSS) Score on patients with schizophrenia who receive risperidone with the addition folic acid and Vitamin B12 and patients who receive only risperidone after 6 weeks. Methods: This study is a quasi experimental pre-test and post-test designs that are divided into two groups, they are group receiving risperidone with the addition of folic acid and vitamin B12 and the group receiving only risperidone. Diagnosis of schizophrenia according to the International Classification of Diseases (ICD-10) criteria and negative symptoms assessed by using negative subscale of PANSS Scores are observed. Statistical analysis is conducted using Statistical Package for the Social Sciences (SPSS) software. Results: There was a significant difference in the mean score of negative-scale PANSS scores at the end of week 6 between the group receiving folic acid and vitamin B12 supplementation and the group receiving only risperidone with p = 0.002; p &lt;0.05. Conclusion: Folic acid and vitamin B12 Supplementation provide benefits to patients schizophrenia.

Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia.

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Negative symptom severity at discharge from an index hospitalization and subsequent use of psychiatric care resources: A retrospective 1-year follow-up study on 450 patients with schizophrenia spectrum disorders

Negative symptoms of schizophrenia have a great impact on patients' functioning and are among the most important contributors to subject's disability. However, few studies have assessed the role of type and severity of symptomatology of schizophrenia on the psychiatric care resource utilization.We investigated if the clinical profile of patients at discharge from an index hospitalization might be associated with a different use of psychiatric care resources in the subsequent 1-year period in a large population of patients with schizophrenia spectrum disorders.Clinical records of 450 patients with schizophrenia spectrum disorders admitted in an acute psychiatric inpatient service and subsequently followed in the outpatient services of the same Department were reviewed.Patients with more severe negative symptoms at discharge from hospital showed a higher number and duration of hospitalizations in the 1-year follow-up, as well as a higher number of rehabilitative residential admissions than patients with milder severity of negative symptoms. The same was true for patients with predominant negative symptoms. A global resource utilization index indicated a higher use of psychiatric resources in patients with higher severity of negative symptoms.In conclusion, showing moderate to severe negative symptoms versus positive symptoms at discharge from a hospitalization for an acute exacerbation of schizophrenia spectrum disorder does predict a higher use of psychiatric care resources. This underlines the importance of relieving negative symptoms even in the acute phase of treatment and the need to develop more effective treatments for this symptom dimension.

Deep Transcranial Magnetic Stimulation for the Treatment of Negative Symptoms in Schizophrenia: Beyond an Antidepressant Effect.

Negative symptoms of schizophrenia show limited response to both typical and atypical antipsychotics. Repetitive transcranial magnetic stimulation applied over the prefrontal cortex (PFC) has been proposed as an adjuvant to pharmacological treatment of negative symptoms in schizophrenia, but whether the improvements obtained are specific to negative symptoms or attributable to antidepressant effects is still unclear. The aim of the present study is to determine to which extent the improvements in negative symptoms of schizophrenia obtained after high-frequency stimulation of the bilateral PFC using deep TMS (dTMS) are attributable to antidepressant effects. Repetitive dTMS was administered to the PFC in a cohort of 16 patients with schizophrenia under successful pharmacological control of positive symptoms and predominant negative symptoms. Patients were treated using high-frequency (18 Hz) bilateral stimulation applied over the lateral PFC bilaterally using Brainsway H-2 coil. The effects of dTMS on negative symptoms were measured using the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scales. We then compared the improvements in negative symptoms obtained in patients showing depressive symptoms (≥7 points) with those found in patients without depression (>7 points), as determined by the Calgary Scale for Depression. Repetitive dTMS treatment induced significant improvements in negative symptoms as assessed using both Scale for the Assessment of Negative Symptoms and Positive and Negative Syndrome Scales. Comparison of the improvements obtained in patients with or without depression at the beginning of treatment revealed similar improvements in negative symptoms, irrespective of subjacent depression. Our data suggest that the beneficial effects of high frequency dTMS of the PFC cannot be attributed solely to its antidepressant effects.

P.388 Clinical improvement of patients with predominant negative symptoms of schizophrenia: Post-hoc analysis of cariprazine versus risperidone

P.388 Clinical improvement of patients with predominant negative symptoms of schizophrenia: Post-hoc analysis of cariprazine versus risperidone

Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia

Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003). Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. ClinicalTrials.gov identifier: NCT02535676.

Med Check: Alzheimer’s Therapy; Adhansia XR; Dasotraline for Binge-Eating Disorder; Somryst for Insomnia; Nuplazid

Med Check: Alzheimer’s Therapy; Adhansia XR; Dasotraline for Binge-Eating Disorder; Somryst for Insomnia; Nuplazid

Les symptômes catatoniques des patients autistes hospitalisés en psychiatrie : intérêt d’une différenciation nosologique fine

ObjectivesIn our department that receives autistic adults with severe deficit, we are struck by presence of symptoms of catatonic lineage that are very similar to those observed in catatonic forms of schizophrenia in adults, even if there are, of course, changes due to the appearance of manifestations in early childhood. This corroborates conclusions of many authors who state that catatonic symptoms are common in autism. Symptoms common to both disorders include poor verbal responses, echolalia, repetition of expression or sentence, repetitive behaviors, stereotypy, posture, grimaces, rigidity, mannerisms, and aimless agitation. This comorbidity can be seen in terms of a progression from autistic symptoms to catatonia, as suggested by the different perspectives that we approach. Materials and methodsThe complex relationships between autism spectrum disorder, catatonia and schizophrenia are first approached from a DSM-5 perspective. It is possible to use diagnosis of attenuated psychosis with predominant negative and catatonic symptoms, to consider diagnosis of catatonia, which requires only three out of twelve symptoms, or to seize the possibility of adding the specifier “with catatonia” to autistic spectrum disorder. Then, the return to the phenomena is chosen as the first clinical orientation: absence of natural movements of expression, impression in the contact, withdrawal, subjective capacities. Through several clinical vignettes, we illustrate the richness and scope of the fine nosological differentiations from Karl Leonhard's work. ResultsAutism spectrum disorders can be forms of early expression of catatonic disorders as defined by Karl Leonhard. Thus, some autistic patients evolve favorably during their development and do not become catatonic. This could proceed from stopping the progression of pathological process before it becomes complicated with functional repercussions. It is thus possible that the development of autism takes place in two phases: first the expression movements and the direct emotional contact are affected, then the rest of the motility is affected in case of progression of the disorder towards the emergence of psychomotor disorders. This hypothesis predicts that the same susceptibility genes will be found in autism and catatonia. These genes may be those of GABAa receptor subunits located on the long arm of chromosome 15.

Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

SummaryBackgroundSchizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials.MethodsWe did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919.FindingsWe identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole, for negative symptoms (32 015 participants) from −0·62 (−0·84 to −0·39; clozapine) to −0·10 (−0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from −0·90 (−1·36 to −0·44; sulpiride) to 0·04 (−0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from −0·16 kg (−0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from −77·05 ng/mL (−120·23 to −33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from −2·21 ms (−4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low.InterpretationThere are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences.FundingGerman Ministry of Education and Research and National Institute for Health Research