Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth. A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders. Intervention to improve compliance with pediatric anticonvulsant therapy. Study protocol for a randomised controlled trial of CBT vs antipsychotics vs both in 14–18-year-olds: Managing Adolescent first episode Psychosis: a feasibility study (MAPS) Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Cardiovascular and Neurological Adverse Events Associated With Antidepressant Treatment in Children and Adolescents Paediatric Atypical Antipsychotic Monitoring Safety (PAMS) Study Working alliance and its relationship to outcomes in a randomized controlled trial (RCT) of antipsychotic medication Antipsychotic medication for childhood-onset schizophrenia. Cognitive-Behavioral Therapy as Continuation Treatment to Sustain Response After Electroconvulsive Therapy in Depression: A Randomized Controlled Trial Electroconvulsive therapy improves antipsychotic and somnographic responses in adolescents with first-episode psychosis — A case–control study Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus Comparison of longer-term safety and effectiveness of 4 atypical antipsychotics in patients over age 40: a trial using equipoise-stratified randomization. Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics. Children presenting with convulsions (including status epilepticus) to a paediatric accident and emergency department: an audit of a treatment protocol A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression.
OBJECTIVES To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to , or having unacceptable side-effects from , their current medication . DESIGN Two pragmatic , r and omised controlled trials ( RCTs ) were undertaken . The first RCT ( b and 1 ) compared the class of older , inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders , whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects . The second RCT ( b and 2 ) compared the new ( non-clozapine ) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs . Both RCTs were four-centre trials with concealed r and omisation and three follow-up assessment s over 1 year , blind to treatment . SETTING Adult mental health setting s in Engl and . PARTICIPANTS In total , 227 participants aged 18 - 65 years ( 40 % of the planned sample ) were r and omised to b and 1 and 136 ( 98 % of the planned sample ) to b and 2 . INTERVENTIONS Participants were r and omised to a class of drug . The managing clinician selected the individual drug within that class , except for the clozapine arm in b and 2 . The new atypical drugs included risperidone , olanzapine , quetiapine and amisulpride . The conventional drugs included older drugs , including depot preparations . As in routine practice , clinicians and participants were aware of the identity of the prescribed drug , but clinicians were asked to keep their participating patient on the r and omised medication for at least the first 12 weeks . If the medication needed to be changed , the clinician was asked to prescribe another drug within the same class , if possible . MAIN OUTCOME MEASURES The primary outcome was the Quality of Life Scale ( QLS ) . Secondary clinical outcomes included symptoms [ Positive and Negative Syndrome Scale ( PANSS ) ] , side-effects and participant satisfaction . Economic outcomes were costs of health and social care and a utility measure . RESULTS Recruitment to b and 1 was less than anticipated ( 40 % ) and diminished over the trial . This appeared largely due to loss of perceived clinical equipoise ( clinicians progressively becoming more convinced of the superiority of new atypicals ) . Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75 % power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks . The recruitment to b and 2 was approximately as planned . Follow-up assessment s were completed at week 52 in 81 % of b and 1 and 87 % of b and 2 participants . B and 1 data showed that , on the QLS and symptom measures , those participants in the conventional arm tended towards greater improvements . This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample . Participants reported no clear preference for either class of drug . There were no statistically significant differential outcomes for participants entering b and 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance . Net costs over the year varied widely , with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group , not a statistically significant difference . Of these costs , 2.1 % and 3.8 % were due to antipsychotic drug costs in the conventional and atypical group , respectively . There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year . The results for b and 2 showed an advantage for commencing clozapine in quality of life ( QLS ) at trend level ( p = 0.08 ) and in symptoms ( PANSS ) , which was statistically significant ( p = 0.01 ) , at 1 year . Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects . Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05 ) . Net costs of care varied widely , but were higher than in b and 1 , with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group . Of these costs , 4.0 % and 3.3 % , respectively , were due to antipsychotic drug costs . The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug . There was a trend towards higher mean participant utility scores in the clozapine group . CONCLUSIONS For b and 1 , there is no disadvantage in terms of quality of life and symptoms , or associated costs of care , over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs . Conventional drugs were associated with non-significantly better outcomes and lower costs . Drug costs represented a small proportion of the overall costs of care ( < 5 % ) . For b and 2 , there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs , but with increased associated costs of care . The results suggest that conventional antipsychotic drugs , which are substantially cheaper , still have a place in the treatment of patients unresponsive to , or intolerant of , current medication . Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance , valid measures of utility in serious mental illness , low-dose ' conventional ' treatment in first episode schizophrenia , QLS validity and determinants of QLS score in schizophrenia , and into the possible financial and other mechanisms of rewarding clinician participation in trials BACKGROUND The use of antipsychotics , especially second-generation antipsychotics ( SGAs ) , for children with mental health disorders in Canada has increased dramatically over the past five years . These medications have the potential to cause major metabolic and neurological complications with chronic use . OBJECTIVE To synthesize the evidence for specific metabolic and neurological side effects associated with the use of SGAs in children , and provide evidence -based recommendations for the monitoring of these side effects . METHODS A systematic review of controlled clinical trials of SGAs involving children was performed . Recommendations for monitoring SGA safety were made according to a classification scheme based on the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . When there was inadequate evidence , recommendations were based on consensus and expert opinion . A multidisciplinary consensus group review ed all relevant evidence and reached consensus on the recommendations . RESULTS The present guidelines provide evidence -based recommendations for monitoring SGA safety . The strength of recommendations for specific physical examination manoeuvres and laboratory tests are provided for each SGA medication at specific time points . CONCLUSION Multiple r and omized controlled trials evaluated the efficacy of many of the SGAs in paediatric mental health disorders . These benefits , however , are not without risks - both metabolic and neurological side effects occur in children treated with SGAs . The risk of weight gain , increased body mass index and abnormal lipid levels is greatest with olanzapine , followed by clozapine and quetiapine . The risk of neurological side effects of the treatment is greatest with risperidone , olanzapine and aripiprazole . Appropriate monitoring procedures for adverse effects will improve the quality of care of children treated with these medications OBJECTIVE There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics ( SGAs ) have been undertaken . To plan the design of a subsequent r and omized controlled trial ( RCT ) , the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocol s. METHOD Thirty children and adolescents ( 20 males , 10 females ) , ages 10 - 18 years , who met unmodified Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) criteria for a schizophrenia-spectrum disorder ( schizophrenia , schizoaffective , schizophreniform , psychotic disorder not otherwise specified ) were r and omized to receive 12 weeks of open-label , flexibly dosed treatment with either risperidone ( mean [ st and ard deviation , SD ] dose = 3.4 mg [ 1.5 ] ) , olanzapine ( mean [ SD ] dose = 14.0 mg [ 4.6 ] ) or quetiapine ( mean [ SD ] dose = 611 mg [ 253.4 ] ) . RESULTS Twenty one ( 70 % ) of 30 subjects completed the study . There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale ( PANSS ) total scores in treatment efficacy observed ( F((2,24 ) ) = 3.13 , p = 0.06 ) . However , the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine ( risperidone vs. quetiapine , d = 1.10 [ 95 % confidence interval , CI , 0.09 - 2.01 ] ) was suggested by the point estimate . CONCLUSIONS These preliminary data , viewed together with the extant literature , suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinical ly significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses . Additional challenges and considerations for mounting a larger RCT are explored Daily anticonvulsant drug therapy is the major treatment of seizure disorders . Compliance with the prescribed therapy is essential but not always achieved . Among 201 pediatric seizure clinic patients taking phenobarbital and phenytoin , 70 ( 35 % ) were judged noncompliant on at least one medication . The mothers of these patients were r and omly assigned to experimental or control groups . An educational intervention in the form of a mothers ' group discussion led by the clinic social worker was tested . On follow-up , medication compliance in the intervention group was judged significantly greater than that of the control group Background Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis . The National Institute for Clinical Excellence ( NICE ) recommend that adolescents with first episode psychosis ( FEP ) should be offered a combination of antipsychotic medication ( APs ) , cognitive behavioural therapy ( CBT ) and family intervention ( FI ) . The evidence for APs in treating psychosis is limited in adolescents compared to adults . Nevertheless , it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects , including cardiovascular and metabolic effects , than in adults . CBT and FI can improve outcomes in adults , but there are no studies of psychological interventions ( PI ) in patients under 18 years old . Given this limited evidence base , NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP . Methods / design The current study aim ed to establish the feasibility and acceptability of conducting such a trial by recruiting 14–18-year-olds with a first episode of psychosis into a feasibility prospect i ve r and omised open blinded evaluation ( PROBE ) design , three-arm , r and omised controlled trial of APs alone versus PI alone versus a combination of both treatments . We aim ed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites .  APs were prescribed by participants ’ usual psychiatrists . PI comprised st and ardised cognitive behavioural therapy and family intervention sessions . Discussion This is the first study to compare APs to PI in an adolescent population with FEP . Recruitment finished on 31 October 2018 . The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences . Trial registration Current controlled trial with IS RCT N , IS RCT N80567433 . Registered on 27 February 2017 BACKGROUND Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics . Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis . OBJECTIVE The effects of oral antipsychotics versus risperidone long-acting injection ( RLAI ) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa . METHODS Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a r and omized controlled trial of flexible doses of oral risperidone or haloperidol .  Inclusion criteria for both studies were age 16 to 45 years ; confirmed diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder ; < or=2 hospitalizations for psychosis ; and lifetime exposure to < or=12 weeks of antipsychotic medication . The dose of RLAI was 25 mg every 2 weeks , which could be increased to 50 mg . Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d ( 8 mg/d in exceptional cases ) . Study assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Extrapyramidal Symptom Rating Scale ( ESRS ) , and body mass index ( BMI ) . RESULTS The RLAI group included 50 patients ( 32 men and 18 women ; mean [ SD ] age , 25.4 [ 7.4 ] years ; BMI , 20.6 [ 4.6 ] kg/m(2 ) ) . The oral risperidone or haloperidol group included 47 patients ( 27 men and 20 women ; mean [ SD ] age , 25.9 [ 5.8 ] years ; BMI , 20.1 [ 3.4 ] kg/m(2 ) ) . Compared with patients treated with oral risperidone or haloperidol , RLAI-treated patients had significantly fewer all-cause discontinuations ( 26.0 % [ 13/50 ] vs 70.2 % [ 33/47 ] at 24 months ; P < 0.005 ) , greater reduction on the PANSS total score ( -39.7 vs -25.7 ; P = 0.009 ) , higher remission rate ( 64.0 % [ 32/50 ] vs 40.4 % [ 19/47 ] ; P = 0.028 ) , and lower relapse rate ( 9.3 % [ 4/43 ] vs 42.1 % [ 16/38 ] ; P = 0.001 ) among the responders . Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol , as measured by the maximum change in the mean [ SD ] ESRS total score ( 1.40 [ 2.60 ] vs 5.61 [ 5.21 ] vs 9.04 [ 6.21 ] , respectively ; P < or= 0.001 ) . The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients ( mean [ SD ] , 3.9 [ 1.9 ] vs 2.2 [ 1.3 ] kg/m(2 ) ; P = 0.001 ) but not significantly different from oral risperidone ( 3.4 [ 2.0 ] kg/m(2 ) ; P = NS ) . Four patients in the RLAI group had adverse events that were possibly related to prolactin , compared with 1 each in the oral risperidone and haloperidol groups . CONCLUSIONS The findings of this post hoc analysis suggest that there were advantages in terms of efficacy , fewer extrapyramidal symptoms , and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis A retrospective cohort design of Medicaid medical and pharmacy cl aims for 1996 through 2005 was employed for 14 171 children and adolescents prescribed an antidepressant medication and a r and om sample of 4500 children not treated with any class of psychotropic medication to compare the prevalence rates of cardiovascular and neurological adverse events . The treated cohort evinced a higher prevalence of cardiovascular events , orthostatic hypotension , seizures , insomnia , and headaches . In the treated cohort , patients were at a significantly higher risk for incident cardiovascular events when exposed to selective serotonin reuptake inhibitors and weight-inducing antidepressants , mood stabilizers , and antipsychotics .  Incident orthostatic hypotension was associated with weight-inducing antidepressants and mood stabilizers .  Incident seizures and extrapyramidal symptoms were unrelated to antidepressant or co-prescribed psychotropic medications , but both were significantly associated with comorbid central nervous system , organic brain/mental retardation , or preexisting cardiovascular or cerebrovascular conditions . Headaches and dizziness were significantly related to taking mood stabilizers Abstract Background : In the UK , treatment with  antipsychotic medications  for children is usually initiated by specialists in secondary care . Recent studies have shown an increase in the prescribing of atypical antipsychotics in children . The severity of possible adverse effects to antipsychotics in adults has lead to awareness of the importance of investigating the potential adverse effects of these agents in children . Additionally , there have been many reports proposing that the newer atypical antipsychotics are associated with many of the same adverse effects seen with the older generation drugs in children . The aim of the Paediatric Atypical Antipsychotic Monitoring Safety ( PAMS ) study was to determine the feasibility of conducting a prospect i ve targeted pharmacovigilance study to monitor adverse drug reactions ( ADRs ) associated with atypical antipsychotic therapy in children seen in secondary - and tertiary-care setting s. Methods : Participants were identified from the clinical members of the UK Paediatric Psychopharmacology Groups in London and the West Midl and s. Participating clinicians reported the number of patients ( aged ≤18 years ) taking atypical antipsychotic treatment who were under their care and any reportable ADRs experienced by these patients during the period September 2006–September 2007 . Participants contributed data via password protected online data collection forms . Results : A total of 35 clinicians consented to participate in the study . However , data from 22 of the participating clinicians were excluded because of incomplete reporting . Data from the remaining 13 ( 37 % ) clinicians were eligible for the final analysis . There were 281 patients who received atypical antipsychotic treatment under the care of the 13 participating clinicians . From these 281 patients , 40 ADR reports ( 0.14 ADR reports per patient ; 95 % CI 0.10 , 0.19 ) from 37 patients were entered into the data base . Of the 37 patients , 13 experienced more than one ADR , bringing the total number of ADRs to 56 ( 0.20 ADR per patient ; 95 % CI 0.15 , 0.25 ) . The most commonly reported ADRs were weight gain , extrapyramidal symptoms and hyperprolactinaemia . Rare ADRs , including neuroleptic malignant syndrome , were also reported . The duration s of atypical antipsychotic drug exposure were recorded for 54 of the 56 ADRs reported . The median duration of exposure was 42 days ( interquartile range 23.25–90 days ) . Conclusions : Our study demonstrates that a clinician-based targeted pharmacovigilance study on  atypical antipsychotics in children provides useful qualitative data . However , this pilot study raised many method ological issues , which should be addressed for the study to be extended nationally . Specifically , significant funding is needed to improve the reporting rate and the overall data obtained . Furthermore , the study yielded a very high incidence of serious ADRs , thus supporting the need for a larger and improved pharmacovigilance study to evaluate the safety of atypical antipsychotics in children Background Long acting injections ( LAI ) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications . Method R and omized controlled trial with ( 50 ) participants with a diagnosis of schizophrenia r and omized to risperidone LAI or oral atypical antipsychotic medication .  The main outcome was the Working Alliance Inventory ( WAI ) with background variables ( symptoms , side effect , social functioning , quality of life ) measured before r and omization and at two years . Results At follow-up ( 14 risperidone LAI and 16 oral medication ) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change . Sensitivity analyses showed ( i ) a significant detrimental effect of LAI on WAI and ( ii ) the pattern of results was not affected by change in symptoms over the study . Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment BACKGROUND : Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years . Although it is rare , people who suffer from schizophrenia at an early age appear to have a clinical ly severe form of the illness with poor long-term prognosis . Antipsychotic medication is one way of managing this rare but serious mental illness . OBJECTIVES : To examine the effects of antipsychotic medication for childhood-onset schizophrenia . SEARCH STRATEGY : We search ed the Cochrane Schizophrenia Group Trials Register ( November 2006 and February 2007 ) , inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information . SELECTION CRITERIA : We included all r and omised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia ( i.e. with a diagnosis of schizophrenia before the age of 13 ) comparing any antipsychotic drug with another antipsychotic or placebo . DATA COLLECTION AND ANALYSIS : We reliably selected , quality assessed and extracted data from trials . We excluded data where more than 50 % of participants in any group were lost to follow up . For homogenous dichotomous data we calculated r and om effects , relative risk ( RR ) and its 95 % confidence interval ( CI ) and , where appropriate , number needed to treat ( NNT ) on an intention-to-treat basis . For normal continuous data we calculated the weighted mean difference ( WMD ) . MAIN RESULTS : From a total of 2062 citations , we identified six relevant trials . We categorised trials into three comparisons : atypical versus typical , atypical versus atypical and typical versus typical antipsychotic drugs . The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs . A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia ( n=21 , WMD CGAS 17.00 CI 7.74 to 26.26 ; n=21 , WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56 ) . Participants on clozapine , however , were three times more likely to have drowsiness ( 1 RCT , n=21 , RR 3.30 CI 1.23 to 8.85 , NNH 2 CI 2 to 17 ) and half of the children receiving clozapine had neutropenia ( 1 RCT , n=21 , RR 12 , CI 0.75 to 192.86 ) . AUTHORS ' CONCLUSIONS : There are few relevant trials and , presently , there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia . Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects . Larger , more robust , trials are required BACKGROUND Although electroconvulsive therapy ( ECT ) is the most effective acute antidepressant intervention , sustained response rates are low . It has never been systematic ally assessed whether psychotherapy , continuation ECT , or antidepressant medication is the most efficacious intervention to maintain initial treatment response . METHODS In a prospect i ve , r and omized clinical trial , 90 in patients with major depressive disorder ( MDD ) were treated with right unilateral ultra-brief acute ECT . Electroconvulsive therapy responders received 6 months guideline -based antidepressant medication ( MED ) and were r and omly assigned to add-on therapy with cognitive-behavioral group therapy ( CBT-arm ) , add-on therapy with ultra-brief pulse continuation electroconvulsive therapy ( ECT-arm ) , or no add-on therapy ( MED-arm ) . After the 6 months of continuation treatment , patients were followed-up for another 6 months . The primary outcome parameter was the proportion of patients who remained well after 12 months . RESULTS Of 90 MDD patients starting the acute phase , 70 % responded and 47 % remitted to acute ECT . After 6 months of continuation treatment , significant differences were observed in the three treatment arms with sustained response rates of 77 % in the CBT-arm , 40 % in the ECT-arm , and 44 % in the MED-arm . After 12 months , these differences remained stable with sustained response rates of 65 % in the CBT-arm , 28 % in the ECT-arm , and 33 % in the MED-arm . CONCLUSIONS These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates . However , the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients OBJECTIVE Previous studies have demonstrated the effectiveness of electroconvulsive therapy ( ECT ) in pharmacotherapy-resistant neuropsychiatric conditions . This study aim ed to evaluate the efficacy and safety of ECT in adolescents with first-episode psychosis . METHOD This case-control study was conducted in in patients aged 13 - 20 years with first-episode psychosis . Every three similar age and same gender patients consecutively recruited were r and omly allocated to control and ECT group at a ratio of 1:2 , while they had antipsychotic treatment . ECT treatment was performed for 3 sessions per week with a maximum of 14 sessions . The endpoint was discharge from hospital . Clinical outcomes were measured using hospital stay days , the Positive and Negative Syndrome Scale ( PANSS ) and response rate . Polysomnography ( PSG ) was conducted at baseline and at week 2 . Safety and tolerability were also evaluated . RESULTS Between March 2004 and November 2009 , 112 eligible patients were allocated to control ( n=38 ) and ECT ( n=74 ) group .  Additional ECT treatment significantly reduced hospital stay compared to controls ( 23.2±8.2 days versus 27.3±9.3 days , mean±SD , P=0.018 ) . Survival analysis revealed that the ECT-treated group had a significantly higher cumulative response rate than controls ( 74.3 % versus 50 % , relative risk (RR)=1.961 , P=0.001 ) . Additional ECT also produced significantly greater improvement in sleep efficiency , rapid eye movement ( REM ) latency and density than control condition . The PSG improvement significantly correlated with reduction in scores on overall PANSS , positive symptoms , and general psychopathology . No patients discontinued ECT treatment regimen during hospital stay . The incidence of most adverse events was not different in the two groups , but ECT-treated group had more complaints of transient headache and dizziness than controls . CONCLUSIONS ECT is an effective and safe intervention used in adolescents with first-episode psychosis . Its antipsychotic effects are associated with improved PSG variables . ECT can be considered as an early psychosis intervention Importance Treatment delay for seizures can lead to longer seizure duration . Whether treatment delay is associated with major adverse outcomes , such as death , remains unknown . Objective To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes . Design , Setting , and Participants This multicenter , observational , prospect i ve cohort study included 218 pediatric patients admitted between June 1 , 2011 , and July 7 , 2016 , into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group . Patients , ranging in age from 1 month to 21 years , with refractory convulsive status epilepticus ( RCSE ) that did not stop after the administration of at least 2 antiseizure medications were included . Patients were divided into 2 cohorts : those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset ( untimely ) . Data were collected and analyzed from June 1 , 2011 , to July 7 , 2016 . Main Outcomes and Measures The primary outcome was death during the related hospital admission . The secondary outcome was the need for continuous infusion for seizure termination . Multivariate analysis of mortality controlled for structural cause , febrile RCSE , age , and previous neurological history ( including previous RCSE events ) . Use of continuous infusions was additionally adjusted for generalized RCSE , continuous RCSE , and 5 or more administrations of antiseizure medication . Results A total of 218 patients were included , among whom 116 ( 53.2 % ) were male and the median ( interquartile range ) age was 4.0 ( 1.2 - 9.6 ) years . The RCSE started in the prehospital setting for 139 patients ( 63.8 % ) . Seventy-four patients ( 33.9 % ) received their first-line benzodiazepine treatment in less than 10 minutes , and 144 ( 66.1 % ) received untimely first-line benzodiazepine treatment . Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death ( adjusted odds ratio [ AOR ] , 11.0 ; 95 % CI , 1.43 to ∞ ; P = .02 ) , had greater odds of receiving continuous infusion ( AOR , 1.8 ; 95 % CI , 1.01 - 3.36 ; P = .047 ) , had longer convulsive seizure duration ( AOR , 2.6 ; 95 % CI , 1.38 - 4.88 ; P = .003 ) , and had more frequent hypotension ( AOR 2.3 ; 95 % CI , 1.16 - 4.63 ; P = .02 ) . In addition , the timing of the first-line benzodiazepine treatment was correlated with the timing of the second-line ( 95 % CI , 0.64 - 0.95 ; P < .001 ) and third-line antiseizure medications ( 95 % CI , 0.25 - 0.78 ; P < .001 ) . Conclusions and Relevance Among pediatric patients with RCSE , an untimely first-line benzodiazepine treatment is independently associated with a higher frequency of death , use of continuous infusions , longer convulsion duration , and more frequent hypotension . Results of this study raise the question as to whether poor outcomes could , in part , be prevented by earlier administration of treatment OBJECTIVE To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics ( aripiprazole , olanzapine , quetiapine , and risperidone ) in 332 patients , aged > 40 years , having psychosis associated with schizophrenia , mood disorders , posttraumatic stress disorder , or dementia , diagnosed using DSM-IV-TR criteria . METHOD We used equipoise-stratified r and omization ( a hybrid of complete r and omization and clinician 's choice methods ) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk . Patients were followed for up to 2 years , with assessment s at baseline , 6 weeks , 12 weeks , and every 12 weeks thereafter . Medications were administered employing open-label design and flexible dosages , but with blind raters . The study was conducted from October 2005 to October 2010 . OUTCOME MEASURES Primary metabolic markers ( body mass index , blood pressure , fasting blood glucose , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and triglycerides ) , percentage of patients who stay on the r and omly assigned atypical antipsychotic for at least 6 months , psychopathology , percentage of patients who develop metabolic syndrome , and percentage of patients who develop serious and nonserious adverse events . RESULTS Because of a high incidence of serious adverse events , quetiapine was discontinued midway through the trial . There were significant differences among patients willing to be r and omized to different atypical antipsychotics ( P < .01 ) , suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems . Yet , the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures . Overall results suggested a high discontinuation rate ( median duration 26 weeks prior to discontinuation ) , lack of significant improvement in psychopathology , and high cumulative incidence of metabolic syndrome ( 36.5 % in 1 year ) and of serious ( 23.7 % ) and nonserious ( 50.8 % ) adverse events for all atypical antipsychotics in the study . CONCLUSIONS Employing a study design that closely mimicked clinical practice , we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40 , with relatively few differences among the drugs . Caution in the use of these drugs is warranted in middle-aged and older patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00245206 OBJECTIVE The aim of this study was to improve and evaluate the practibility of a method for the assessment of drug-associated side effects , and we implemented a clinical drug monitoring for atypical neuroleptics . METHODS Side effects of initially hospitalized patients treated with clozapine ( n = 16 ) , olanzapine ( n = 16 ) , and risperidone ( n = 19 ) were prospect ively monitored on a weekly basis for the first 3 weeks . In the case of stable medication , measurements of all variables were made every 4 weeks or upon discharge . We used the  Dosage Record Treatment Emergent Symptom Scale ( DOTES ) in a supplemented version to measure the presence and severity of side effects . RESULTS Drowsiness and decreased motor activity were common , especially in the first 2 weeks . Orthostatic hypotension , increased salivation , constipation , and nasal congestion were seen in more than 30 % to 60 % of patients treated with clozapine and were less common in adolescents treated with olanzapine and risperidone . Rigidity , tremor , and dystonia were seen in 5 % to 15 % of patients treated with risperidone and olanzapine . The average weight gain after 6 weeks of treatment with the atypical neuroleptics was significantly higher for the olanzapine group ( 4.6 + /- 1.9 kg ) than for the risperidone ( 2.8 + /- 1.3 kg ) and clozapine ( 2.5 + /- 2.9 kg ) groups . CONCLUSIONS The authors ' supplemented DOTES version is generally applicable to clinical use in mental health centers . The differences among the side effects of these three agents may affect compliance with medication and medical risks of metabolic syndrome , diabetes , and cardiovascular disease . More research on the short- and long-term safety of psychotropic drugs in children and adolescents , using st and ardized methods , should be considered All children who presented in a convulsion , including convulsive status epilepticus , to the accident and emergency department over a 12‐month period and who required treatment , were review ed retrospectively to identify the effectiveness and safety of a specific treatment protocol . This protocol recommends the initial use of one , or if necessary , two doses of rectal or intravenous diazepam ( 0.4 mg/kg ) followed by the simultaneous administration of phenytoin ( 18 mg/kg ) and rectal paraldehyde ( 0.4 mL/kg ) , with instructions for maximum doses and timings of administration . Eighty‐one evaluable children ( 52 male ) were audited . The mean age of the study population was 4.1 ( range 0.1 to 14.9 ) years . Overall , the presenting convulsion was successfully terminated in 76 children ( 94 % ) within the accident and emergency department . In 69 children ( 85 % of the entire study population ) this was after a single dose of diazepam ( rectal in 41 and intravenous in 28 ) . In only an additional two children did the presenting convulsion stop after a second dose of diazepam . In five of the 10 children ( 50 % ) who received paraldehyde and phenytoin as a combination , the convulsion stopped . Nine patients ( 11 % ) required admission to the intensive‐care unit , five because of persisting convulsive activity , and four because of respiratory depression . The results of this retrospective audit suggest that the current treatment protocol appears to be effective and relatively safe in treating acute convulsions , including convulsive status epilepticus . The audit is to be repeated prospect ively to either confirm or refute these findings before recommending any changes to the protocol OBJECTIVE To determine amitriptyline 's ( AMI )  efficacy in the acute treatment of adolescent major depressive disorder ( MDD ) . METHOD Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD , diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children ( K-SADS ) , participated in a 2-week placebo-washout followed by an 8-week , r and omized , double-blind , parallel- design , placebo-controlled trial of AMI , 5 mg/kg per day . The K-SADS nine-item scale , the Hamilton Depression Rating Scale , and the Clinical Global Impressions rating scale were used as outcome measures . RESULTS Thirty-one subjects were r and omized ( 18 AMI , 13 placebo ) . Twenty-two subjects were study completers ( 12 AMI , 10 placebo ) . AMI 's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data . Perhaps the primary limitation of the current study is its small sample size . CONCLUSION No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD
In several small , single-site RCTs , valproate and sulthiame were better than placebo for the management of recurrent aggression .
Conclusions : Currently available RCTs do not support the efficacy of anticonvulsants as mood stabilizers in children .
There is some preliminary evidence from small RCTs of the efficacy of some anticonvulsants in the control of aggression and behavioral dyscontrol in conduct disorder , autism , and intellectual disability
Aim : Anticonvulsant medications are frequently used in clinical practice to treat psychiatric disorders in children and adolescents , but the evidence for their efficacy is uncertain .
We conducted a systematic review of published r and omized controlled trials ( RCT ) that assessed the psychiatric benefit of anticonvulsants  in patients under 18 years of age .