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

NCT00156715 | Completed Phase 4 Results DMC

• 2 other identifiers: 16563IRUSQUET0063
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Psychotic Disorder; Substance Abuse; Alcohol Abuse

Keywords

Quetiapine; Seroquel; Schizophrenia; Dual Diagnosis; Substance Abuse; Alcohol Abuse

Outcome Measures

Primary Outcomes (1)

• Mean Number of Drinking Days Per Week

  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.

  12 Weeks

Secondary Outcomes (1)

• Clinical Symptoms

  12 Weeks

Study Arms (1)

Quetiapine

EXPERIMENTAL

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

Interventions

Quetiapine 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.

Also known as: Seroquel

Quetiapine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Augusta University: collaborator
• AstraZeneca: collaborator

Study Sites (4)

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

West Central Behavioral Health

Lebanon, New Hampshire, 03766, United States

Location

Mental Health Center of Greater Manchester

Manchester, New Hampshire, 03101, United States

Location

Related Publications (26)

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  PMID: 8166327 BACKGROUND

• Bartels SJ, Teague GB, Drake RE, Clark RE, Bush PW, Noordsy DL. Substance abuse in schizophrenia: service utilization and costs. J Nerv Ment Dis. 1993 Apr;181(4):227-32. doi: 10.1097/00005053-199304000-00003.

  PMID: 8473874 BACKGROUND

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  PMID: 1970670 BACKGROUND

• Brown ES, Nejtek VA, Perantie DC, Rajan Thomas N, Rush AJ. Cocaine and amphetamine use in patients with psychiatric illness: a randomized trial of typical antipsychotic continuation or discontinuation. J Clin Psychopharmacol. 2003 Aug;23(4):384-8. doi: 10.1097/01.jcp.0000085412.08426.08.

  PMID: 12920415 BACKGROUND

• 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.

  BACKGROUND

• Buckley P, Thompson PA, Way L, Meltzer HY. Substance abuse and clozapine treatment. J Clin Psychiatry. 1994 Sep;55 Suppl B:114-6.

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• Buckley PF. Novel antipsychotic medications and the treatment of comorbid substance abuse in schizophrenia. J Subst Abuse Treat. 1998 Mar-Apr;15(2):113-6. doi: 10.1016/s0740-5472(97)00134-7.

  PMID: 9561949 BACKGROUND

• Buckley PF. Substance abuse in schizophrenia: a review. J Clin Psychiatry. 1998;59 Suppl 3:26-30.

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• Buckley PF, Miller A, Chiles JA, Sajatovic M. Implementing effectiveness research and improving care for schizophrenia in real-world settings. Am J Manag Care. 1999 Jun 25;5 Spec No:SP47-56.

  PMID: 10538860 BACKGROUND

• 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.

  BACKGROUND

• Carey KB, Cocco KM, Simons JS. Concurrent validity of clinicians' ratings of substance abuse among psychiatric outpatients. Psychiatr Serv. 1996 Aug;47(8):842-7. doi: 10.1176/ps.47.8.842.

  PMID: 8837156 BACKGROUND

• Conley RR, Kelly DL, Gale EA. Olanzapine response in treatment-refractory schizophrenic patients with a history of substance abuse. Schizophr Res. 1998 Sep 7;33(1-2):95-101. doi: 10.1016/s0920-9964(98)00062-0.

  PMID: 9783349 BACKGROUND

• Drake RE, Osher FC, Noordsy DL, Hurlbut SC, Teague GB, Beaudett MS. Diagnosis of alcohol use disorders in schizophrenia. Schizophr Bull. 1990;16(1):57-67. doi: 10.1093/schbul/16.1.57.

  PMID: 2333482 BACKGROUND

• Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull. 2000;26(2):441-9. doi: 10.1093/oxfordjournals.schbul.a033464.

  PMID: 10885642 BACKGROUND

• 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.

  PMID: 8483973 BACKGROUND

• Green AI, Alam MY, Boshes RA, Waternaux C, Pappalardo KM, Fitzgibbon ME, Tsuang MT, Schildkraut JJ. Haloperidol response and plasma catecholamines and their metabolites. Schizophr Res. 1993 Jun;10(1):33-7. doi: 10.1016/0920-9964(93)90074-s.

  PMID: 8369230 BACKGROUND

• 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.

  PMID: 10370435 BACKGROUND

• Heinrichs DW, Hanlon TE, Carpenter WT Jr. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull. 1984;10(3):388-98. doi: 10.1093/schbul/10.3.388.

  PMID: 6474101 BACKGROUND

• Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985 Nov;142(11):1259-64. doi: 10.1176/ajp.142.11.1259.

  PMID: 3904487 BACKGROUND

• Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997 Jan-Feb;4(5):231-44. doi: 10.3109/10673229709030550.

  PMID: 9385000 BACKGROUND

• Meats P. Quetiapine ('Seroquel'); an effective and well-tolerated atypical antipsychotic. Int J Psychiatry Clin Pract. 1997;1(4):231-9. doi: 10.3109/13651509709024734.

  PMID: 24946189 BACKGROUND

• Siris SG. Pharmacological treatment of substance-abusing schizophrenic patients. Schizophr Bull. 1990;16(1):111-22. doi: 10.1093/schbul/16.1.111.

  PMID: 1970669 BACKGROUND

• 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.

  PMID: 9193196 BACKGROUND

• 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.

  PMID: 10653215 BACKGROUND

• 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.

  PMID: 9270900 BACKGROUND

• Weiden PJ. Quetiapine ('seroquel'): a new 'atypical' antipsychotic. J Prac Psychiatry and Behav Health 1997; 3(6): 368-374.

  BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Substance-Related Disorders; Alcoholism

Interventions

Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Lack of a control group; Small study group size, and the consequent lack of power to detect a significant change; Differences between the populations at the two sites.

Results Point of Contact

• Title: Christopher OKeefe, M.A
• Organization: Dartmouth Medical School

chris.okeefe@hitchcock.org

603-271-5287

Study Officials

• Alan I Green, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 12, 2005
• Study Start: March 1, 2004
• Primary Completion: September 1, 2006
• Study Completion: October 1, 2008
• Last Updated: March 14, 2018
• Results First Posted: December 21, 2010

Record last verified: 2018-03

Locations

US (4)