Medication Nonadherence, Schizo Affective Disorder, Schizophrenia
Conditions
Keywords
nonadherence, Schizophrenia, Africa, Schizoaffective
Brief summary
The proposed, three phase project will refine and test a first-ever care approach in SSA that combines LAI with a behavioral program specifically intended to promote medication adherence in chronic psychotic disorders (CPDs). In addition to the novel focus, innovative elements include: 1.) a manualized curriculum that targets specific barriers and facilitators to medication adherence in Tanzanians with CPD, 2.) targeting known, high-risk individuals with CPD (those who miss ≥20% of prescribed antipsychotic medication, and 3.) using existing injection clinic health workers to deliver the adherence promotion program. Strengths include the highly generalizable methods and use of LAIs that are available in low-resource settings.
Detailed description
In this Phase 3 portion, the study team will select appropriate measures, train staff and build capacity in measure implementation, and finalize the intervention for delivery by healthcare workers. Finally, in a training/proof-of-concept exercise, the healthcare workers will implement the adapted CAE-L in a high-risk sample of Tanzanians with CPD (individuals with schizophrenia or schizoaffective disorder who have had recent medication adherence problems). Taken together, the proposed project has substantial public health importance. It will provide the prerequisite materials, training and infrastructure needed for a prospective trial in reducing CPD burden and improving brain health in Tanzania and other countries in Sub-Saharan Africa. The focus of this project is on feasibility, patient acceptability, and research capacity-building. Therefore a specific hypothesis is not being tested. The investigators will assess descriptive statistics and change from baseline in the primary and secondary measures using standard pre-post techniques.
Interventions
BEHAVIORALCustomized Adherence Enhancement
Customized Adherence Enhancement (CAE): CAE targets key areas relevant to adherence in chronic psychotic disorders (CPD): 1.) inadequate understanding of mental disorder, 2.) lack of adequate medication-taking routines, 3.) poor communication with care providers and 4.) substance use which interferes with adherence and recovery. CAE delivered components are selected based upon findings from the ROMI and AMSQ. CAE will be delivered in approximately 8 sessions by a nurse interventionist, ideally at the same time that the long-acting injectable (LAI) is administered.The intervention is guided by a detailed manual and uses components and resources that are available in lower- and middle-income countries (LMICs). Social worker interventionists will be trained to deliver CAE-L.
Long-acting injectable (LAI): Patients on oral haloperidol will be switched to haloperidol decanoate per manufacturer's package insert. Individuals not on antipsychotic medication at the time of screening assessment or who are on a different antipsychotic medication, will receive an oral tolerance test (OTT) consisting of up to 14 days of oral haloperidol 2-5 mg once or twice daily. If the OTT suggests good tolerability, the participant will then receive LAI (haloperidol decanoate) intramuscularly after completion of baseline assessments. Dosing of LAI will be as clinically indicated using conservative dosing to minimize drug-related adverse effects. In the CWRU studies, mean end-point dose of haloperidol decanoate was 68.0 mg, SD 21.1, Range 50-100 mg/monthly injection. It is anticipated that patients will continue on the same dose for 6 months, although dose changes will be permitted based upon clinical status. Each study participant will receive up to 8 injections during the study.
Sponsors
National Institute of Mental Health (NIMH)
Case Western Reserve University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 and older * Diagnosis of schizophrenia or schizoaffective disorder * Known to have medication treatment adherence problems as identified by the TRQ (20% or more missed medications in past week or past month) * Ability to be rated on psychiatric rating scales * Willingness to take long-acting injectable medication * Able to provide written, informed consent to study participation
Exclusion criteria
* History of allergy or intolerance to haloperidol or haloperidol decanoate * Individuals on long-acting injectable antipsychotic medication immediately prior to study enrollment * Medical condition or illness, which in the opinion of the research psychiatrist, would interfere with the patient's ability to participate in the trial * Physical dependence on substances (alcohol or illicit drugs) likely to lead to withdrawal reaction during the course of the study in the clinical opinion of the treated research psychiatrist * Immediate risk of harm to self or others * Female who is currently pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tablets Routine Questionnaire (TRQ) | Change from Baseline to 6 month visit | The TRQ evaluates adherence to medications via a brief self-report instrument that has been validated in populations with bipolar disorder medication adherence. The TRQ identifies nonadherent individuals, defined as those who miss 20-30% or more of their medication in the last week or month. Total scores are represented as a percentage and range from 0 to 100, with higher scores indicating a greater level of nonadherence (higher scores indicate worse adherence to medications). |
| Long-Acting Injectable Adherence (LAI Adherence): Count of Participants Who Received All LAI Injections: | Baseline to 6 month visit | LAI injection adherence will be determined as a count of participants who received LAI injections at the appropriate time (within 7 days of scheduled time). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Psychiatric Rating Scale (BPRS) | Baseline to 6 month visit | The BPRS measures levels of mania. There are 24 items, scored on a 7-point scale ranging from 0 to 6. Total scores range from 0 to 42, with higher scores indicating higher levels of mania. |
| Clinical Global Impressions (CGI) | Baseline to 6 month visit | The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. |
| Social and Occupational Functioning Scale (SOFAS) | Baseline to 6 month visit | The SOFAS measures social and occupational functioning independent of the overall severity of the individual's psychological symptoms. The minimum score is 0 and the maximum score is 100. A higher rating implies a higher level of functioning. |
| Body Mass Index | Baseline to Month 6(week 25) | Body Mass Index kg/m\^2 of participants |
| ESRS-A Dystonia | Baseline to 6 months(25 weeks) | Extrapyramidal Symptoms Scale-Abbreviated version for dystonia- drug-induced dystonia is a muscle disorder in which movements are jerky or twisting. Due to the 0.00 values at baseline and 25 weeks, unable to perform t-test and get a p value so no statistical analysis section is reported for this Outcome Measure. Each item is rated on a 4 point scale: 0=absent, 3=severe with the higher numbers indicating worse dystonia and worse outcomes. |
| ESRS-A Dyskinesia | Baseline to 6 months(25 weeks) | Extrapyramidal Symptoms Scale-Abbreviated version for Dyskinesia- drug-induced dyskinesia which is repetitive and involuntary movements. Each item is rated on a 4 point scale: 0=absent, 3=severe and higher values indicate greater severity of dyskinesia and worse outcomes. |
| ESRS-A Akathisia | Baseline to 6 months(25 weeks) | Extrapyramidal Symptoms Scale-Abbreviated version for akathisia- drug-induced akathisia consists of inner restlessness and urge to move. Items are measured on a 4 value scale: 0=absent, 3=severe, and higher values indicate more severe akathisia and worse outcomes. |
| ESRS-A Parkinsonism | Baseline to 6 months(25 weeks) | Extrapyramidal Symptoms Scale-Abbreviated version for Parkinsonism. It looks at drug-induced Parkinsonism which is made up of motor disturbances. Rigidity, tremor, reduced facial expression/speech, impaired gait/posture, postural instability, and bradykinesia. Each item is rated on a 4 point scale: 0=absent, 3=severe. The higher the value the more severe the Parkinsonism and worst outcomes. |
| Drug Attitude Inventory (DAI) | Baseline to 6 month visit | DAI-10 scoring ranges from -10 to +10 with a total score \>0 indicating a positive attitude toward psychiatric medications and a total score of \<0 indicating a negative attitude toward psychiatric medications. |
Countries
Tanzania
Participant flow
Recruitment details
The study setting was Muhimbili National Hospital, a 70-bed national referral hospital located in urban Dar es Salaam, Tanzania. Patients were referred from 4 catchment zones that include 3 regional public and private hospitals and were recruited from inpatient and outpatient settings. 19 adult patients ≥ age 18 with schizophrenia who self-reported missing 20% or more of antipsychotic medication demonstrating poor adherence.
Pre-assignment details
38 individuals were assessed for preliminary eligibility. 16 people were excluded, 5 were unable to contact, 2 were not interested, 3 did not meet criteria, and 6 were no-shows for screening. 22 provided informed consent initially. 2 of these people failed the oral tolerance test and 1 did not complete baseline measures. 19 participants enrolled and attended visits 1-6 and 18 attended all 7 visits.
Participants by arm
| Arm | Count |
|---|---|
| CAE + LAI Treatment The sample comprised adult patients ≥ age 18 with schizophrenia who self-reported missing 20% or more of antipsychotic medication within the last month, an established benchmark for poor adherence who were given a long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L). | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | CAE + LAI Treatment | — |
|---|---|---|
| Age, Continuous | 38.79 years STANDARD_DEVIATION 9.31 | — |
| Age of CPD(chronic psychotic disorder) onset | 19.89 years STANDARD_DEVIATION 4.47 | — |
| ASSIST score | 1.58 units on a scale STANDARD_DEVIATION 2.65 | — |
| AUDIT score | 1.84 units on a scale STANDARD_DEVIATION 3.13 | — |
| Baseline TRQ(tablets routine questionnaire) | 12.94 units on a scale STANDARD_DEVIATION 11.93 | — |
| Body Mass Index(BMI) | 22.70 kg/m^2 STANDARD_DEVIATION 4.89 | — |
| Duration of CPD(chronic psychotic disorder) | 18.89 years STANDARD_DEVIATION 10.87 | — |
| Educational level | 8.37 years STANDARD_DEVIATION 2.99 | — |
| Employment Full-time | 4 Participants | — |
| Employment Part-time | 3 Participants | — |
| Employment Unemployed | 12 Participants | — |
| Family history of mental illness | 10 Participants | — |
| Family history of substance abuse | 10 Participants | — |
| Marital status Married | 2 Participants | — |
| Marital status Separated/divorced | 4 Participants | — |
| Marital status Single/never married | 12 Participants | — |
| Marital status Widowed | 1 Participants | — |
| Number of previous hospitalizations For CPD(chronic psychotic disorders) | 6.16 hospitalizations STANDARD_DEVIATION 7.55 | — |
| Number of previous hospitalizations For substance abuse | 0.05 hospitalizations STANDARD_DEVIATION 0.23 | — |
| Past oral medication history Chlorpromazine | 8 Participants | — |
| Past oral medication history Fluphenizine | 11 Participants | — |
| Past oral medication history Haloperidol | 14 Participants | — |
| Past oral medication history Olanzapine | 3 Participants | — |
| Past oral medication history Promethazine | 8 Participants | — |
| Past oral medication history Risperidone | 5 Participants | — |
| Past physical abuse | 6 Participants | — |
| Past sexual abuse | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Screening TRQ(tablets routine questionnaire) | 21.84 units on a scale STANDARD_DEVIATION 13.83 | — |
| Self-reported Charlson Index score | 0.37 units on a scale STANDARD_DEVIATION 0.5 | — |
| Sex: Female, Male Female | 5 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 13 / 19 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Long-Acting Injectable Adherence (LAI Adherence): Count of Participants Who Received All LAI Injections:
LAI injection adherence will be determined as a count of participants who received LAI injections at the appropriate time (within 7 days of scheduled time).
Time frame: Baseline to 6 month visit
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L). LAI injection frequency was 100%.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAE + LAI Treatment | Long-Acting Injectable Adherence (LAI Adherence): Count of Participants Who Received All LAI Injections: | 18 Participants |
Primary
Tablets Routine Questionnaire (TRQ)
The TRQ evaluates adherence to medications via a brief self-report instrument that has been validated in populations with bipolar disorder medication adherence. The TRQ identifies nonadherent individuals, defined as those who miss 20-30% or more of their medication in the last week or month. Total scores are represented as a percentage and range from 0 to 100, with higher scores indicating a greater level of nonadherence (higher scores indicate worse adherence to medications).
Time frame: Change from Baseline to 6 month visit
Population: Since participants stopped using oral medications once they were stable on LAI, there were only two participants remaining at 25 Week visit and therefore analysis was not done. As only 2 individuals were on concommittent oral CPD medication at 25 week follow up, mean change in TRQ was not calculated. This was just done to enter into clinical trials.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Tablets Routine Questionnaire (TRQ) | TRQ Week adherence | -57 percentage of change in adherence | Standard Deviation 60.8 |
| CAE + LAI Treatment | Tablets Routine Questionnaire (TRQ) | TRQ Month adherence | -23 percentage of change in adherence | Standard Deviation 0 |
Secondary
Body Mass Index
Body Mass Index kg/m\^2 of participants
Time frame: Baseline to Month 6(week 25)
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Body Mass Index | Baseline | 22.79 kg/m^2 | Standard Deviation 5.02 |
| CAE + LAI Treatment | Body Mass Index | 25 Weeks | 22.92 kg/m^2 | Standard Deviation 5.58 |
p-value: 0.75t-test, 2 sided
Secondary
Brief Psychiatric Rating Scale (BPRS)
The BPRS measures levels of mania. There are 24 items, scored on a 7-point scale ranging from 0 to 6. Total scores range from 0 to 42, with higher scores indicating higher levels of mania.
Time frame: Baseline to 6 month visit
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Brief Psychiatric Rating Scale (BPRS) | Baseline | 27.00 score on a scale | Standard Deviation 10.26 |
| CAE + LAI Treatment | Brief Psychiatric Rating Scale (BPRS) | 25-Weeks | 25.06 score on a scale | Standard Deviation 8.53 |
p-value: 0.43t-test, 2 sided
Secondary
Clinical Global Impressions (CGI)
The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.
Time frame: Baseline to 6 month visit
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Clinical Global Impressions (CGI) | Baseline | 2.88 units on a scale | Standard Deviation 1.32 |
| CAE + LAI Treatment | Clinical Global Impressions (CGI) | 25 Weeks | 2.24 units on a scale | Standard Deviation 1.09 |
p-value: 0.07t-test, 2 sided
Secondary
Drug Attitude Inventory (DAI)
DAI-10 scoring ranges from -10 to +10 with a total score \>0 indicating a positive attitude toward psychiatric medications and a total score of \<0 indicating a negative attitude toward psychiatric medications.
Time frame: Baseline to 6 month visit
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Drug Attitude Inventory (DAI) | 25 Weeks | 9.83 score on a scale | Standard Deviation 0.52 |
| CAE + LAI Treatment | Drug Attitude Inventory (DAI) | Baseline | 7.89 score on a scale | Standard Deviation 2.72 |
p-value: 0.001t-test, 2 sided
Secondary
ESRS-A Akathisia
Extrapyramidal Symptoms Scale-Abbreviated version for akathisia- drug-induced akathisia consists of inner restlessness and urge to move. Items are measured on a 4 value scale: 0=absent, 3=severe, and higher values indicate more severe akathisia and worse outcomes.
Time frame: Baseline to 6 months(25 weeks)
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | ESRS-A Akathisia | Baseline | 0.28 score on a scale | Standard Deviation 0.75 |
| CAE + LAI Treatment | ESRS-A Akathisia | Week 25 | 0.00 score on a scale | Standard Deviation 0 |
p-value: 0.14t-test, 2 sided
Secondary
ESRS-A Dyskinesia
Extrapyramidal Symptoms Scale-Abbreviated version for Dyskinesia- drug-induced dyskinesia which is repetitive and involuntary movements. Each item is rated on a 4 point scale: 0=absent, 3=severe and higher values indicate greater severity of dyskinesia and worse outcomes.
Time frame: Baseline to 6 months(25 weeks)
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | ESRS-A Dyskinesia | Baseline | 0.17 score on a scale | Standard Deviation 0.51 |
| CAE + LAI Treatment | ESRS-A Dyskinesia | Week 25 | 0.11 score on a scale | Standard Deviation 0.47 |
p-value: 0.75t-test, 2 sided
Secondary
ESRS-A Dystonia
Extrapyramidal Symptoms Scale-Abbreviated version for dystonia- drug-induced dystonia is a muscle disorder in which movements are jerky or twisting. Due to the 0.00 values at baseline and 25 weeks, unable to perform t-test and get a p value so no statistical analysis section is reported for this Outcome Measure. Each item is rated on a 4 point scale: 0=absent, 3=severe with the higher numbers indicating worse dystonia and worse outcomes.
Time frame: Baseline to 6 months(25 weeks)
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | ESRS-A Dystonia | Baseline | 0.00 score on a scale | Standard Deviation 0 |
| CAE + LAI Treatment | ESRS-A Dystonia | Week 25 | 0.00 score on a scale | Standard Deviation 0 |
Secondary
ESRS-A Parkinsonism
Extrapyramidal Symptoms Scale-Abbreviated version for Parkinsonism. It looks at drug-induced Parkinsonism which is made up of motor disturbances. Rigidity, tremor, reduced facial expression/speech, impaired gait/posture, postural instability, and bradykinesia. Each item is rated on a 4 point scale: 0=absent, 3=severe. The higher the value the more severe the Parkinsonism and worst outcomes.
Time frame: Baseline to 6 months(25 weeks)
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | ESRS-A Parkinsonism | Baseline | 0.06 score on a scale | Standard Deviation 0.24 |
| CAE + LAI Treatment | ESRS-A Parkinsonism | 25 Weeks | 0.06 score on a scale | Standard Deviation 0.24 |
p-value: 1t-test, 2 sided
Secondary
Social and Occupational Functioning Scale (SOFAS)
The SOFAS measures social and occupational functioning independent of the overall severity of the individual's psychological symptoms. The minimum score is 0 and the maximum score is 100. A higher rating implies a higher level of functioning.
Time frame: Baseline to 6 month visit
Population: Poorly adherent patients with schizophrenia who received long-acting injectable antipsychotic medication and a customized adherence enhancement behavioral intervention (CAE-L).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CAE + LAI Treatment | Social and Occupational Functioning Scale (SOFAS) | Baseline | 62.17 score on a scale | Standard Deviation 18.28 |
| CAE + LAI Treatment | Social and Occupational Functioning Scale (SOFAS) | 25 Weeks | 68.39 score on a scale | Standard Deviation 15.28 |
p-value: 0.1t-test, 2 sided