Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder

This study has been completed.
Sponsor:
Collaborators:
Georgia Regents University
AstraZeneca
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00156715
First received: September 6, 2005
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to examine the efficacy of quetiapine (Seroquel) in reducing substance use in persons diagnosed with schizophrenia. The primary hypothesis is that quetiapine treatment will be associated with a decrease in substance use.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Psychotic Disorder
Substance Abuse
Alcohol Abuse
Drug: Quetiapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Efficacy of Quetiapine in Treating Patients With Active Substance Use Disorder and Schizophrenia

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Mean Number of Drinking Days Per Week [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Timeline Follow-back (TLFB) procedure was used at screening and baseline to establish current substance use, and it was also used weekly during the course of the study to assess continued alcohol and other substance use. TLFB cosisted of using a calendar and sasking participants to report alcohol and other drug use since last visit. At the screening visit, the TLFB was done for the four weeks prior to the visit.


Secondary Outcome Measures:
  • Clinical Symptoms [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    The main outcome measure of clinical symptoms was the Positive and Negative Symptoms Scale. This is a 30 item scale for assessing patients diagnosed with schizophrenia. Each item is rated on a 1 (absent) to 7 (extreme) scale. The minimum total score is 30 and the maximum is 210.


Enrollment: 23
Study Start Date: March 2004
Study Completion Date: October 2008
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quetiapine
After patients provided informed consent and completed baseline measures, quetiapine was initiated in all participants and titrated up to a target dose of 600 mg (in divided daily doses) over two weeks as the previous antipsychotic medication was slowly tapered and discontinued. Participants met with study physicians weekly to assess tolerability and response to the medication. Concomitant medications were held constant. After the initial titration period, quetiapine was dosed in a flexible manner up to 800 mg /day, with dose adjustments based on symptomatic response and side effects.
Drug: Quetiapine
After patients provided informed consent and completed baseline measures, quetiapine was initiated in all participants and titrated up to a target dose of 600 mg (in divided daily doses) over two weeks as the previous antipsychotic medication was slowly tapered and discontinued. Participants met with study physicians weekly to assess tolerability and response to the medication. Concomitant medications were held constant. After the initial titration period, quetiapine was dosed in a flexible manner up to 800 mg /day, with dose adjustments based on symptomatic response and side effects.
Other Name: Seroquel

Detailed Description:

Comorbid alcohol/substance use disorder (SUD) in schizophrenia is a major concern, both in view of the high frequency of SUD among patients with schizophrenia and the difficulty in managing such patients. Though antipsychotic medications are effective in reducing symptoms and impairment in persons with schizophrenia, the typical antipsychotic agents are of limited value in controlling alcohol/substance use in these patients. Extrapyramidal, dysphoric side effects of conventional neuroleptics may actually promote the use of substances in an attempt to counteract these effects.

Novel antipsychotics have radically altered treatment expectations and outcomes for patients with severe forms of schizophrenia. With the greater availability of novel agents in clinical practice, it has been noted that these benefits have also extended to specific subgroups of patients including patients with comorbid SUD. Several retrospective studies have demonstrated a decrease in comorbid substance use in patients with schizophrenia treated with clozapine. There is little data available, however, on the efficacy of quetiapine in patients with schizophrenia and comorbid SUD. Its receptor profile, including a weak Dopamine2 (D2) receptor blocking ability and substantial effects at noradrenergic receptors, makes it a logical antipsychotic to use in the comorbid population.

The study is an open-label investigation of the efficacy of quetiapine in a group of 30 patients with schizophrenia and comorbid substance use disorder. Patients diagnosed with schizophrenia or schizoaffective disorder and a comorbid substance use disorder are switched to quetiapine for 12 weeks. We hypothesize that quetiapine treatment will be associated with a decrease in substance use. Moreover, we further hypothesize that measures of symptoms, cognition and quality of life will also improve over baseline assessments in patients treated with quetiapine. Data suggesting a beneficial effect of quetiapine will have to be confirmed in a prospective double-blind study. This pilot investigation will provide preliminary data and effect sizes that will be used in the design of this subsequent investigation.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65
  • Schizophrenia or schizoaffective disorder
  • Meets Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) criteria for a substance use disorder (alcohol use disorder [AUD]; abuse or dependence)
  • Active substance use on at least 8 days during the 4 weeks prior to randomization.
  • Current treatment with antipsychotic medication.
  • Able to provide informed consent, or in the case of patients with legal court appointed guardians willing to give assent, with the consent of the guardian.
  • Not actively suicidal.

Exclusion Criteria:

  • Current treatment with, decanoate antipsychotic, clozapine, or doses of quetiapine not approved by the team of investigators. Individuals treated with depot antipsychotic must wait until the end of their injection cycle before starting on study medication.
  • Currently pregnant, planning to become pregnant, or unwilling to use an acceptable form of birth control.
  • Currently residing in a residential program designed to treat substance use disorders.
  • Treatment at baseline with a psychotropic agent proposed to curtail substance use.
  • Patients who, in the opinion of the investigator, are judged unsuitable to participate in the study.
  • Unable to take part in the assessments in a meaningful way
  • Hypersensitivity/intolerance to quetiapine
  • Serious, unstable medical condition
  • Participation in clinical trial of an investigational drug within 30 days of baseline visit, or concurrent participation in a treatment study of a psychosocial intervention
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00156715

Locations
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
West Central Behavioral Health
Lebanon, New Hampshire, United States, 03766
Mental Health Center of Greater Manchester
Manchester, New Hampshire, United States, 03101
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Georgia Regents University
AstraZeneca
Investigators
Principal Investigator: Alan I Green, MD Dartmouth-Hitchcock Medical Center
  More Information

Publications:
Buckley PF, Naber D: Quetiapine and sertindole: clinical use and experience. In: Schizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice. Edited by PF Buckley and JL Waddington. Butterworth-Heinemann, 2000.
Buckley P, McCarthy M, Chapman P, Richman C, Yamamoto B. Clozapine treatment of comorbid substance abuse in patients with schizophrenia. Schizophr Res 1999; 36: 272.
Conley R, Gale E, Hirsch K. Olanzapine response in therapy-refractory schizophrenia with substance abuse (SA) [abstract]. Schizophr Res 1997; 24: 190.
Meats P. Quetiapine (seroquel): an effective and well-tolerated atypical antipsychotic. Intl J Psychiatry Clin Prac 1997; 1(4): 231-239.
Weiden PJ. Quetiapine ('seroquel'): a new 'atypical' antipsychotic. J Prac Psychiatry and Behav Health 1997; 3(6): 368-374.

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00156715     History of Changes
Other Study ID Numbers: 16563, IRUSQUET0063
Study First Received: September 6, 2005
Results First Received: November 19, 2010
Last Updated: February 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Quetiapine
Seroquel
Schizophrenia
Dual Diagnosis
Substance Abuse
Alcohol Abuse

Additional relevant MeSH terms:
Disease
Mental Disorders
Psychotic Disorders
Schizophrenia
Substance-Related Disorders
Chemically-Induced Disorders
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
Quetiapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014