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Research paper thumbnail of Valproate add-on therapy for drug-resistant focal epilepsy

Cochrane Database of Systematic Reviews, 2021

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the e icacy and tolerability of valproate when used as add-on therapy for people with drug-resistant focal epilepsy. Valproate add-on therapy for drug-resistant focal epilepsy (Protocol)

Research paper thumbnail of Antiepileptic drug add-on therapy for focal epilepsy: a network meta-analysis

Cochrane Database of Systematic Reviews, 2021

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compar... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the e icacy and tolerability of antiepileptic drugs (AEDs) taken as add-on treatment for drug-resistant, focal-onset epilepsy, and to generate a clinically useful ranking of available AEDs. Antiepileptic drug add-on therapy for focal epilepsy: a network meta-analysis (Protocol)

Research paper thumbnail of Vigabatrin add-on therapy for drug-resistant focal epilepsy

Cochrane Database of Systematic Reviews, 2020

Editorial group: Cochrane Epilepsy Group. Publication status and date: New search for studies and... more Editorial group: Cochrane Epilepsy Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 7, 2020.

Research paper thumbnail of Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia

JAMA Psychiatry, 2016

In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, cl... more In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION At least 2 independent reviewers selected published and unpublished single-and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (−0.29; −0.56 to −0.02), haloperidol (−0. 29; −0.44 to −0.13), and sertindole (−0.46; −0.80 to −0.06); clozapine was more effective than haloperidol (−0.22; −0.38 to −0.07) and sertindole (−0.40; −0.74 to −0.04); and risperidone was more effective than sertindole (−0.32; −0.63 to −0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Research paper thumbnail of The typology of parricide and the role of mental illness: Data‐driven approach

Aggressive Behavior, 2020

Parricide is a rare type of homicide in which mental illness is often an important factor. The ai... more Parricide is a rare type of homicide in which mental illness is often an important factor. The aims of this study were (a) to describe the characteristics of parricide offenders with a focus on mental illness and clinical care and (b) to examine Heide's widely used typology of parricide through a data-driven approach. We analyzed all homicides in England and Wales between 1997 and 2014. Parricide offenders in our sample were most often male, unmarried, and unemployed, with a third of offenders diagnosed with schizophrenia; 28% had been in contact with mental health services before the offense. The latent class analysis resulted in three types of parricide offenders: middle-aged with affective disorder, previously abused, and seriously mentally Ill, which confirmed, to an extent, Heide's typology. Health and social care services should actively engage with carers of people with mental illness and support to those caring for older relatives and victims of abuse. K E Y W O R D S latent class analysis, mental health services, mental illness, parricide, typology This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Suicide risk assessment in UK mental health services: a national mixed-methods study

The Lancet Psychiatry, 2020

Research paper thumbnail of Treatment of Mental Illness Prior to Suicide: A National Investigation of 12,909 patients, 2001–2016

Psychiatric Services, 2020

Previous research suggests that up to 90% of individuals who die by suicide may have a mental dis... more Previous research suggests that up to 90% of individuals who die by suicide may have a mental disorder at the time of death but that levels of treatment may be low. This study aimed to examine undertreatment among patients with mental health conditions who died by suicide and to assess the association between patients' clinical and sociodemographic characteristics and treatment receipt. Methods: The study's sample included 12,909 patients in England and Wales who died by suicide within 12 months of contact with mental health services between 2001 and 2016. All patients had received a diagnosis of bipolar affective disorder, schizophrenia, depression, or an anxiety disorder. Records of patients who were not receiving treatment as recommended by national clinical guidelines at the time of death were examined for levels of nonprescription of treatment and nonadherence. Results: Twenty-four percent of the patients did not receive treatment, 11% had not been prescribed treatment, and 13% were nonadherent with treatment. These proportions differed by diagnosis. After adjustment for main primary diagnosis, analyses showed that being under age 40, unemployment, living alone, drug misuse, medication side effects, and comorbid personality disorder were independently associated with a decreased likelihood of receiving treatment. Conclusions: One-quarter of patients with mental health conditions who die by suicide may not be receiving relevant interventions at the time of death. Levels of and reasons for nontreatment vary by diagnosis, but measures to address comorbid diagnoses and implement interventions to improve adherence in specific groups could have an impact.

Research paper thumbnail of Valproate add-on therapy for drug-resistant focal epilepsy

Cochrane Database of Systematic Reviews, 2021

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the e icacy and tolerability of valproate when used as add-on therapy for people with drug-resistant focal epilepsy. Valproate add-on therapy for drug-resistant focal epilepsy (Protocol)

Research paper thumbnail of Antiepileptic drug add-on therapy for focal epilepsy: a network meta-analysis

Cochrane Database of Systematic Reviews, 2021

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compar... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the e icacy and tolerability of antiepileptic drugs (AEDs) taken as add-on treatment for drug-resistant, focal-onset epilepsy, and to generate a clinically useful ranking of available AEDs. Antiepileptic drug add-on therapy for focal epilepsy: a network meta-analysis (Protocol)

Research paper thumbnail of Vigabatrin add-on therapy for drug-resistant focal epilepsy

Cochrane Database of Systematic Reviews, 2020

Editorial group: Cochrane Epilepsy Group. Publication status and date: New search for studies and... more Editorial group: Cochrane Epilepsy Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 7, 2020.

Research paper thumbnail of Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia

JAMA Psychiatry, 2016

In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, cl... more In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION At least 2 independent reviewers selected published and unpublished single-and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (−0.29; −0.56 to −0.02), haloperidol (−0. 29; −0.44 to −0.13), and sertindole (−0.46; −0.80 to −0.06); clozapine was more effective than haloperidol (−0.22; −0.38 to −0.07) and sertindole (−0.40; −0.74 to −0.04); and risperidone was more effective than sertindole (−0.32; −0.63 to −0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Research paper thumbnail of The typology of parricide and the role of mental illness: Data‐driven approach

Aggressive Behavior, 2020

Parricide is a rare type of homicide in which mental illness is often an important factor. The ai... more Parricide is a rare type of homicide in which mental illness is often an important factor. The aims of this study were (a) to describe the characteristics of parricide offenders with a focus on mental illness and clinical care and (b) to examine Heide's widely used typology of parricide through a data-driven approach. We analyzed all homicides in England and Wales between 1997 and 2014. Parricide offenders in our sample were most often male, unmarried, and unemployed, with a third of offenders diagnosed with schizophrenia; 28% had been in contact with mental health services before the offense. The latent class analysis resulted in three types of parricide offenders: middle-aged with affective disorder, previously abused, and seriously mentally Ill, which confirmed, to an extent, Heide's typology. Health and social care services should actively engage with carers of people with mental illness and support to those caring for older relatives and victims of abuse. K E Y W O R D S latent class analysis, mental health services, mental illness, parricide, typology This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Suicide risk assessment in UK mental health services: a national mixed-methods study

The Lancet Psychiatry, 2020

Research paper thumbnail of Treatment of Mental Illness Prior to Suicide: A National Investigation of 12,909 patients, 2001–2016

Psychiatric Services, 2020

Previous research suggests that up to 90% of individuals who die by suicide may have a mental dis... more Previous research suggests that up to 90% of individuals who die by suicide may have a mental disorder at the time of death but that levels of treatment may be low. This study aimed to examine undertreatment among patients with mental health conditions who died by suicide and to assess the association between patients' clinical and sociodemographic characteristics and treatment receipt. Methods: The study's sample included 12,909 patients in England and Wales who died by suicide within 12 months of contact with mental health services between 2001 and 2016. All patients had received a diagnosis of bipolar affective disorder, schizophrenia, depression, or an anxiety disorder. Records of patients who were not receiving treatment as recommended by national clinical guidelines at the time of death were examined for levels of nonprescription of treatment and nonadherence. Results: Twenty-four percent of the patients did not receive treatment, 11% had not been prescribed treatment, and 13% were nonadherent with treatment. These proportions differed by diagnosis. After adjustment for main primary diagnosis, analyses showed that being under age 40, unemployment, living alone, drug misuse, medication side effects, and comorbid personality disorder were independently associated with a decreased likelihood of receiving treatment. Conclusions: One-quarter of patients with mental health conditions who die by suicide may not be receiving relevant interventions at the time of death. Levels of and reasons for nontreatment vary by diagnosis, but measures to address comorbid diagnoses and implement interventions to improve adherence in specific groups could have an impact.