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Ksenija Yeeles

University of Oxford, Psychiatry, Faculty Member

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Papers by Ksenija Yeeles

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2)

Trials, 2019

Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifi... more Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods: We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2-4 consecutive days no later than 7 days from baseline. It will continue 4-5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2-3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion: The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies.

Patient experiences with receiving financial incentives for anti-psychotic maintenance medication

Study of immunotherapy in antibody positive psychosis: feasibility and acceptability (SINAPPS1)

Journal of neurology, neurosurgery, and psychiatry, Jan 11, 2018

Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets ... more Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets are recognised associations of immunotherapy-responsive autoimmune encephalitis. Initially, patients present with symptoms of behavioural change and psychosis, often subsequently developing seizures and cognitive impairment, rapidly progressing over a few weeks to develop a life-threatening combination of autonomic instability and loss of consciousness.1 There is in vitro and in vivo evidence that these antibodies are pathogenic and directly cause encephalitis. Although never formally demonstrated in a controlled trial, open label clinical studies show that patients receiving immunotherapy, such as intravenous immunoglobulins (IVIG) or plasma exchange (PLEX) with or without corticosteroids, have better recovery and reduced relapse rates. Therefore, clinical consensus guidelines recommend that immunotherapy should be given as soon as possible after diagnosis.2 Several studies have assessed the prevalence of these antibodies in purely psychiatric presentations. NMDAR antibodies are the most commonly identified; in some studies, these are twice as prevalent in patients with early psychosis than in healthy controls, being seen at rates of between 4% and 12% of cases (OR 2.70, 95% CI 1.11 to 6.56).3 We have seen a number of such cases which respond to immunotherapy in an uncontrolled study.4 We have therefore proposed a randomised, placebo-controlled trial of immunotherapy in psychosis associated with antineuronal antibodies, to inform clinical practice and to advance understanding of the …

Cost-Effectiveness of Financial Incentives to Promote Adherence to Depot Antipsychotic Medication: Economic Evaluation of a Cluster-Randomised Controlled Trial

PloS one, 2015

Offering a modest financial incentive to people with psychosis can promote adherence to depot ant... more Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of 'good' adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. ...

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study

by Matina Marougka, Felicitas Rost, and Ksenija Yeeles

This study aimed to investigate factors linked to perceived coercion at admission and during trea... more This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.

Community treatment orders: clinical and social outcomes, and a subgroup analysisfrom the OCTET RCT

Operationalising the capability approach for outcome measurement in

Amartya Sen's multidimensional capability approach focuses on the importance of freedoms to be or... more Amartya Sen's multidimensional capability approach focuses on the importance of freedoms to be or do things people have reason to value. It is an alternative to standard utilitarian welfarism, the theoretical approach to quality-adjusted life years (QALYs) and cost-utility analyses. Despite the limitations of the utility approach in capturing non-health benefits and broader welfare inequalities, there have been very limited applications of the capability approach in the mental health context where these issues are imperative.

Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial

Pressures to adhere to treatment (‘leverage’) in English mental healthcare

Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial

Background Compulsory supervision outside hospital has been developed internationally for the tre... more Background Compulsory supervision outside hospital has been developed internationally for the treatment of mentally ill people following widespread deinstitutionalisation but its effi cacy has not yet been proven. Community treatment orders (CTOs) for psychiatric patients became available in England and Wales in 2008. We tested whether CTOs reduce admissions compared with use of Section 17 leave when patients in both groups receive equivalent levels of clinical contact but diff erent lengths of compulsory supervision.

Family Caregivers' Experiences of Involuntary Psychiatric Hospital Admissions of Their Relatives -- a Qualitative Study

PLOS One, 2011

Background: Family caregivers of people with mental disorders are frequently involved in involunt... more

Predictors of clinical and social outcomes following involuntary hospital admission: a prospective observational study

European Archives of Psychiatry and Clinical Neuroscience

The Study aimed to assess clinical and social outcomes following involuntary admissions over 1 ye... more The Study aimed to assess clinical and social outcomes following involuntary admissions over 1 year and identify socio-demographic and clinical patient characteristics associated with more or less favourable outcomes. Seven hundred and seventy-eight involuntary patients admitted to one of 22 hospitals in England were assessed within the first week after admission and at 1 month, 3 month and 12 month follow-ups. Outcome criteria were symptom levels, global functioning, objective social outcomes, and subjective quality of life (SQOL). Baseline characteristics and patients’ initial experience were tested as predictors. Symptom levels and global functioning improved moderately. Objective social outcomes showed a small, but statistically significant deterioration, and SQOL a small, but significant improvement at 1 year. In multivariable analyses, admission due to risk to oneself and receiving benefits predicted poorer symptom outcomes. Female gender and higher perceived coercion were associated with better objective social outcomes, whilst higher initial satisfaction with treatment predicted more positive SQOL at follow-ups. Over a 1-year period following involuntary hospital admission, patients on average showed only limited health and social gains. Different types of outcomes are associated with different predictor variables. Patients’ initial experience of treatment, in the form of perceived coercion or satisfaction with treatment, has predictive value for up to a year following the admission.

Differences between patients with positive and negative views regarding justification of involuntary admission

BMC Psychiatry, 2007

Many patients do not participate in research. Can results still be generalised

BMC Psychiatry, 2007

As in all studies of this kind, not all eligible patients participate. Out of more than 1,650 pat... more As in all studies of this kind, not all eligible patients participate. Out of more than 1,650 patients who were eligible to participate in the study, more than 800 (ranging between 40 -59% at 4 sites) were not interviewed for varying reasons. At the time of the first interview within one week after admission many couldn't be contacted for organizational reasons, did not want to take part in the study, were too ill to give informed consent, were already discharged, transferred to another hospital, transferred to prison, hospital staff said they were too ill to approach, hospital staff refused contact because patients were too violent/dangerous/unpredictable or sedated, or the patient simply refused to see anyone. This significant group of non-recruited patients required us to have systematic data describing the eligible sample and the sample actually interviewed. Exclusion of non-participants could bias data collection. For all patients who met the inclusion criteria within the study period and were therefore eligible to participate but were not interviewed for the above reasons data on age, gender, ethnicity, legal status of admission, discharge diagnosis (ICD-10), length of index admission, time until readmission, number and length of further admissions to psychiatric hospital care within a one year of follow-up were collected from records or obtained in aggregate form. This paper will present findings of the comparison of baseline characteristic and outcomes between the investigated sample and non-participants. Presented findings will show how representative the recruited sample (N = 843) is for all involuntarily admitted patients and estimate in what way the findings of the investigated sample can be generalised to all involuntarily admitted patients in England.

Patients' views and readmissions 1 year after involuntary hospitalisation

British Journal of Psychiatry, 2009

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study

Psychiatry Research, 2011

This study aimed to investigate factors linked to perceived coercion at admission and during trea... more This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2)

Trials, 2019

Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifi... more Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods: We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2-4 consecutive days no later than 7 days from baseline. It will continue 4-5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2-3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion: The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies.

Patient experiences with receiving financial incentives for anti-psychotic maintenance medication

Study of immunotherapy in antibody positive psychosis: feasibility and acceptability (SINAPPS1)

Journal of neurology, neurosurgery, and psychiatry, Jan 11, 2018

Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets ... more Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets are recognised associations of immunotherapy-responsive autoimmune encephalitis. Initially, patients present with symptoms of behavioural change and psychosis, often subsequently developing seizures and cognitive impairment, rapidly progressing over a few weeks to develop a life-threatening combination of autonomic instability and loss of consciousness.1 There is in vitro and in vivo evidence that these antibodies are pathogenic and directly cause encephalitis. Although never formally demonstrated in a controlled trial, open label clinical studies show that patients receiving immunotherapy, such as intravenous immunoglobulins (IVIG) or plasma exchange (PLEX) with or without corticosteroids, have better recovery and reduced relapse rates. Therefore, clinical consensus guidelines recommend that immunotherapy should be given as soon as possible after diagnosis.2 Several studies have assessed the prevalence of these antibodies in purely psychiatric presentations. NMDAR antibodies are the most commonly identified; in some studies, these are twice as prevalent in patients with early psychosis than in healthy controls, being seen at rates of between 4% and 12% of cases (OR 2.70, 95% CI 1.11 to 6.56).3 We have seen a number of such cases which respond to immunotherapy in an uncontrolled study.4 We have therefore proposed a randomised, placebo-controlled trial of immunotherapy in psychosis associated with antineuronal antibodies, to inform clinical practice and to advance understanding of the …

Cost-Effectiveness of Financial Incentives to Promote Adherence to Depot Antipsychotic Medication: Economic Evaluation of a Cluster-Randomised Controlled Trial

PloS one, 2015

Offering a modest financial incentive to people with psychosis can promote adherence to depot ant... more Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of 'good' adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. ...

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study

by Matina Marougka, Felicitas Rost, and Ksenija Yeeles

This study aimed to investigate factors linked to perceived coercion at admission and during trea... more This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.

Community treatment orders: clinical and social outcomes, and a subgroup analysisfrom the OCTET RCT

Operationalising the capability approach for outcome measurement in

Amartya Sen's multidimensional capability approach focuses on the importance of freedoms to be or... more Amartya Sen's multidimensional capability approach focuses on the importance of freedoms to be or do things people have reason to value. It is an alternative to standard utilitarian welfarism, the theoretical approach to quality-adjusted life years (QALYs) and cost-utility analyses. Despite the limitations of the utility approach in capturing non-health benefits and broader welfare inequalities, there have been very limited applications of the capability approach in the mental health context where these issues are imperative.

Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial

Pressures to adhere to treatment (‘leverage’) in English mental healthcare

Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial

Background Compulsory supervision outside hospital has been developed internationally for the tre... more Background Compulsory supervision outside hospital has been developed internationally for the treatment of mentally ill people following widespread deinstitutionalisation but its effi cacy has not yet been proven. Community treatment orders (CTOs) for psychiatric patients became available in England and Wales in 2008. We tested whether CTOs reduce admissions compared with use of Section 17 leave when patients in both groups receive equivalent levels of clinical contact but diff erent lengths of compulsory supervision.

Family Caregivers' Experiences of Involuntary Psychiatric Hospital Admissions of Their Relatives -- a Qualitative Study

PLOS One, 2011

Background: Family caregivers of people with mental disorders are frequently involved in involunt... more

Predictors of clinical and social outcomes following involuntary hospital admission: a prospective observational study

European Archives of Psychiatry and Clinical Neuroscience

The Study aimed to assess clinical and social outcomes following involuntary admissions over 1 ye... more The Study aimed to assess clinical and social outcomes following involuntary admissions over 1 year and identify socio-demographic and clinical patient characteristics associated with more or less favourable outcomes. Seven hundred and seventy-eight involuntary patients admitted to one of 22 hospitals in England were assessed within the first week after admission and at 1 month, 3 month and 12 month follow-ups. Outcome criteria were symptom levels, global functioning, objective social outcomes, and subjective quality of life (SQOL). Baseline characteristics and patients’ initial experience were tested as predictors. Symptom levels and global functioning improved moderately. Objective social outcomes showed a small, but statistically significant deterioration, and SQOL a small, but significant improvement at 1 year. In multivariable analyses, admission due to risk to oneself and receiving benefits predicted poorer symptom outcomes. Female gender and higher perceived coercion were associated with better objective social outcomes, whilst higher initial satisfaction with treatment predicted more positive SQOL at follow-ups. Over a 1-year period following involuntary hospital admission, patients on average showed only limited health and social gains. Different types of outcomes are associated with different predictor variables. Patients’ initial experience of treatment, in the form of perceived coercion or satisfaction with treatment, has predictive value for up to a year following the admission.

Differences between patients with positive and negative views regarding justification of involuntary admission

BMC Psychiatry, 2007

Many patients do not participate in research. Can results still be generalised

BMC Psychiatry, 2007

As in all studies of this kind, not all eligible patients participate. Out of more than 1,650 pat... more As in all studies of this kind, not all eligible patients participate. Out of more than 1,650 patients who were eligible to participate in the study, more than 800 (ranging between 40 -59% at 4 sites) were not interviewed for varying reasons. At the time of the first interview within one week after admission many couldn't be contacted for organizational reasons, did not want to take part in the study, were too ill to give informed consent, were already discharged, transferred to another hospital, transferred to prison, hospital staff said they were too ill to approach, hospital staff refused contact because patients were too violent/dangerous/unpredictable or sedated, or the patient simply refused to see anyone. This significant group of non-recruited patients required us to have systematic data describing the eligible sample and the sample actually interviewed. Exclusion of non-participants could bias data collection. For all patients who met the inclusion criteria within the study period and were therefore eligible to participate but were not interviewed for the above reasons data on age, gender, ethnicity, legal status of admission, discharge diagnosis (ICD-10), length of index admission, time until readmission, number and length of further admissions to psychiatric hospital care within a one year of follow-up were collected from records or obtained in aggregate form. This paper will present findings of the comparison of baseline characteristic and outcomes between the investigated sample and non-participants. Presented findings will show how representative the recruited sample (N = 843) is for all involuntarily admitted patients and estimate in what way the findings of the investigated sample can be generalised to all involuntarily admitted patients in England.

Patients' views and readmissions 1 year after involuntary hospitalisation

British Journal of Psychiatry, 2009

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study

Psychiatry Research, 2011

This study aimed to investigate factors linked to perceived coercion at admission and during trea... more This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.