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

NCT ID: NCT00156715

Last Updated: 2018-03-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Study Completion Date

2008-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Schizophrenia Schizoaffective Disorder Psychotic Disorder Substance Abuse Alcohol Abuse

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Quetiapine

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Seroquel

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Augusta University

OTHER

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Alan Green

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alan I Green, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

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Medical College of Georgia

Augusta, Georgia, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

West Central Behavioral Health

Lebanon, New Hampshire, United States

Site Status

Mental Health Center of Greater Manchester

Manchester, New Hampshire, United States

Site Status

Countries

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United States

References

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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.

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Green AI, Alam MY, Sobieraj JT, Pappalardo KM, Waternaux C, Salzman C, Schatzberg AF, Schildkraut JJ. Clozapine response and plasma catecholamines and their metabolites. Psychiatry Res. 1993 Feb;46(2):139-49. doi: 10.1016/0165-1781(93)90016-a.

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Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry. 1999 Mar-Apr;6(6):287-96. doi: 10.3109/10673229909017206.

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Small JG, Hirsch SR, Arvanitis LA, Miller BG, Link CG. Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Arch Gen Psychiatry. 1997 Jun;54(6):549-57. doi: 10.1001/archpsyc.1997.01830180067009.

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Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI. Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. J Clin Psychopharmacol. 2000 Feb;20(1):94-8. doi: 10.1097/00004714-200002000-00016.

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Arvanitis LA, Miller BG. Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Biol Psychiatry. 1997 Aug 15;42(4):233-46. doi: 10.1016/s0006-3223(97)00190-x.

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Other Identifiers

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IRUSQUET0063

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

16563

Identifier Type: -

Identifier Source: org_study_id

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