Comparative Effectiveness of Adaptive Treatment Strategies for Schizophrenia

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02775864
• Collaborator: Rutgers University (Other), Patient-Centered Outcomes Research Institute (Other)
• Enrollment: 81,921
• Duration (Months): 35

Study Details

Study Description

Brief Summary

The study is a retrospective cohort study of adults with schizophrenia that will compare outcomes of new users of alternative psychotropic medication strategies using 10 years of Medicaid data. The primary comparative effectiveness analyses will focus on subgroups of patients with schizophrenia facing common clinical situations.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: Antipsychotic; Drug: Antidepressant; Drug: Benzodiazepine; Drug: Mood stabilizer

Detailed Description

This retrospective cohort study will use data from national (45-state) Medicaid Analytic Extracts data (2001-2010). The cohort will consist of adults who are 18 to 64 years old and diagnosed with schizophrenia who initiate a new psychotropic medication after a period of stable antipsychotic treatment.

The eligibility criteria select a cohort of individuals diagnosed with schizophrenia, have received antipsychotic monotherapy prior to the index date, and are still experiencing problems for which a new psychotropic medication strategy was initiated. A 1-year period of eligibility prior to follow-up initiation ensures sufficient time to collect service use related covariates to characterize cohort members.

Five clinical subgroups will be defined based on the presence of psychiatric diagnoses during the 30 days prior to and inclusive of the treatment change under study (index date) and who have this same diagnostic code from more than one provider to increase the validity of the diagnostic groups. The subgroups will be defined by codes to capture 1) uncomplicated schizophrenia; 2) schizoaffective disorder; 3) depression; 4) mania; and 5) anxiety. These subgroups are defined to reflect the reason for the change in treatment.

Pharmacological treatment options for patients with schizophrenia who are nonresponsive to antipsychotic monotherapy will include (1) initiation of a second antipsychotic, (2) initiation of an antidepressant, (3) initiation of a mood stabilizer and (4) initiation of a benzodiazepine.

The primary effectiveness outcome will be time to psychiatric hospitalization. Secondary measures include time to index treatment discontinuation, time to introduction of another psychotropic medication, psychiatric emergency department visits, all-cause hospitalization, and death.

Study Design

• Study Type: Observational
• Actual Enrollment: 81921 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Comparative Effectiveness of Adaptive Treatment Strategies for Schizophrenia
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Antipsychotic Individuals initiating treatment with an antipsychotic medication	Drug: Antipsychotic; New initiation of any antipsychotic medication
Antidepressant Individuals initiating treatment with an antidepressant medication	Drug: Antidepressant; New initiation of any antidepressant medications
Benzodiazepine Individuals initiating treatment with a benzodiazepine	Drug: Benzodiazepine; New initiation of any benzodiazepine
Mood stabilizer Individuals initiating treatment with a mood stabilizer	Drug: Mood stabilizer; New initiation of lithium or any mood stabilizing anti-epileptic drug

Outcome Measures

Primary Outcome Measures

1. Psychiatric Hospitalization [One year]

   Number of participants hospitalized for a mental health reason

Secondary Outcome Measures

1. Emergency Department Visit for Mental Health Reason [One year]

   Number of Participants with an Emergency Department visit for mental health reason

2. Death [One year]

   Participants who died

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The data source will be national (45-state) Medicaid Analytic Extracts data (2001-2010). The cohort will consist of adults who are 18 to 64 years old and diagnosed with schizophrenia who initiate a new psychotropic medication after a period of stable antipsychotic treatment.

• Schizophrenia will be defined as ≥2 outpatient claims or ≥1 inpatient claim for schizophrenia [ICD-9-CM: 295] during 365 days of consecutive Medicaid enrollment immediately prior to the index date. Stable antipsychotic monotherapy will be defined by filled prescriptions for only one second-generation antipsychotic, and no other psychotropics, for ≥ 90 days immediately preceding the start of the index medication (t0). After the ≥90 days of stable treatment with a single second-generation antipsychotic, study patients will have had a change in therapy defined as (1) addition of a second antipsychotic or (2) addition of a different psychotropic drug class (antidepressant, mood stabilizer, or benzodiazepine). To ensure the patients are in active treatment there must be an active supply of antipsychotic medication on t0.

Exclusion Criteria:

• Medicare recipients

• Patients receiving clozapine

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• New York State Psychiatric Institute
• Rutgers University
• Patient-Centered Outcomes Research Institute

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 23, 2016

More Information

Publications

None provided.

• Responsible Party: Scott Stroup, Professor, Columbia University
• ClinicalTrials.gov Identifier: NCT02775864
• Other Study ID Numbers: 7226
• First Posted: May 18, 2016
• Last Update Posted: Jun 7, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Antipsychotic Agents; Antidepressive Agents

Study Results

Participant Flow

Arm/Group Title	Antipsychotic	Antidepressant	Benzodiazepine	Mood Stabilizer
Arm/Group Description	Individuals initiating treatment with an antipsychotic medication Antipsychotic: New initiation of any antipsychotic medication	Individuals initiating treatment with an antidepressant medication Antidepressant: New initiation of any antidepressant medications	Individuals initiating treatment with a benzodiazepine Benzodiazepine: New initiation of any benzodiazepine	Individuals initiating treatment with a mood stabilizer Mood stabilizer: New initiation of lithium or any mood stabilizing anti-epileptic drug
Period Title: Overall Study
STARTED	26014	31117	11941	12849
COMPLETED	22772	26218	10081	10765
NOT COMPLETED	3242	4899	1860	2084

Baseline Characteristics

Arm/Group Title	Antipsychotic	Antidepressant	Benzodiazepine	Mood Stabilizer	Total
Arm/Group Description	Individuals initiating treatment with an antipsychotic medication Antipsychotic: New initiation of any antipsychotic medication	Individuals initiating treatment with an antidepressant medication Antidepressant: New initiation of any antidepressant medications	Individuals initiating treatment with a benzodiazepine Benzodiazepine: New initiation of any benzodiazepine	Individuals initiating treatment with a mood stabilizer Mood stabilizer: New initiation of lithium or any mood stabilizing anti-epileptic drug	Total of all reporting groups
Overall Participants	26014	31117	11941	12849	81921
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.5 (12.5)	40.5 (12.4)	40.5 (12.5)	40.3 (12.5)	40.5 (12.5)
Sex: Female, Male (Count of Participants)
Female	11914 45.8%	14283 45.9%	5553 46.5%	5975 46.5%	37725 46.1%
Male	14100 54.2%	16834 54.1%	6388 53.5%	6874 53.5%	44196 53.9%
Race/Ethnicity, Customized (Count of Participants)
White, non-Hispanic	9645 37.1%	10998 35.3%	5186 43.4%	4261 33.2%	30090 36.7%
Black, non-Hispanic	10371 39.9%	12459 40%	3731 31.2%	5465 42.5%	32026 39.1%
Hispanic or Latino	2517 9.7%	3196 10.3%	1159 9.7%	1263 9.8%	8135 9.9%
Asian	645 2.5%	461 1.5%	252 2.1%	237 1.8%	1595 1.9%
Hawaiian or Pacific Islander	782 3%	744 2.4%	339 2.8%	287 2.2%	2152 2.6%
Native American or Alaskan Native	240 0.9%	305 1%	104 0.9%	87 0.7%	736 0.9%
More than one race	51 0.2%	67 0.2%	19 0.2%	26 0.2%	163 0.2%
Unknown	2763 10.6%	2787 9%	1152 9.6%	1223 9.5%	7925 9.7%

Outcome Measures

1. Primary Outcome

Title	Psychiatric Hospitalization
Description	Number of participants hospitalized for a mental health reason
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antipsychotic	Antidepressant	Benzodiazepine	Mood Stabilizer
Arm/Group Description	Individuals initiating treatment with another second-generation antipsychotic medication (other than clozapine	Individuals initiating treatment with an antidepressant medication	Individuals initiating treatment with a benzodiazepine	Individuals initiating treatment with a mood stabilizer
Measure Participants	26014	31117	11941	12849
Count of Participants [Participants]	4965 19.1%	5247 16.9%	2385 20%	3093 24.1%

2. Secondary Outcome

Title	Emergency Department Visit for Mental Health Reason
Description	Number of Participants with an Emergency Department visit for mental health reason
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antipsychotic	Antidepressant	Benzodiazepine	Mood Stabilizer
Arm/Group Description	Individuals initiating treatment with another second-generation antipsychotic medication (other than clozapine)	Individuals initiating treatment with an antidepressant medication	Individuals initiating treatment with a benzodiazepine	Individuals initiating treatment with a mood stabilizer
Measure Participants	26014	31117	11941	12849
Count of Participants [Participants]	5505 21.2%	6508 20.9%	2930 24.5%	3429 26.7%

3. Secondary Outcome

Title	Death
Description	Participants who died
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antipsychotic	Antidepressant	Benzodiazepine	Mood Stabilizer
Arm/Group Description	Individuals initiating treatment with another second-generation antipsychotic medication (other than clozapine)	Individuals initiating treatment with an antidepressant medication	Individuals initiating treatment with a benzodiazepine	Individuals initiating treatment with a mood stabilizer
Measure Participants	26014	31117	11941	12849
Count of Participants [Participants]	259 1%	327 1.1%	204 1.7%	161 1.3%

Adverse Events

Time Frame	365 days
Arm/Group Title	Antipsychotic		Antidepressant		Benzodiazepine		Mood Stabilizer
Arm/Group Description	Individuals initiating treatment with another second-generation antipsychotic medication (other than clozapine)		Individuals initiating treatment with an antidepressant medication		Individuals initiating treatment with a benzodiazepine		Individuals initiating treatment with a mood stabilizer
All Cause Mortality
	Antipsychotic		Antidepressant		Benzodiazepine		Mood Stabilizer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	259/26014 (1%)		327/31117 (1.1%)		204/11941 (1.7%)		161/12849 (1.3%)
Serious Adverse Events
	Antipsychotic		Antidepressant		Benzodiazepine		Mood Stabilizer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/26014 (0.3%)		102/31117 (0.3%)		43/11941 (0.4%)		41/12849 (0.3%)
Cardiac disorders
Admission for Cardiovascular Disease	67/26014 (0.3%)		102/31117 (0.3%)		43/11941 (0.4%)		41/12849 (0.3%)
Other (Not Including Serious) Adverse Events
	Antipsychotic		Antidepressant		Benzodiazepine		Mood Stabilizer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	967/21738 (4.4%)		1004/26062 (3.9%)		424/9764 (4.3%)		423/10564 (4%)
Endocrine disorders
Incident cases of diabetes mellitus	967/21738 (4.4%)	967	1004/26062 (3.9%)	1004	424/9764 (4.3%)	424	423/10564 (4%)	423

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.