Open-Label Pilot Study to Examine the Value of Substituting Quetiapine for Benzodiazepines
Condition: Major Depression; Generalized Anxiety Disorder
MeSH terms: Depression; Depressive Disorder; Anxiety Disorders; Depressive Disorder, Major
Intervention: quetiapine
Intervention description: Dosing will begin with Seroquel-XR 50 mg. at bedtime and will escalate weekly to Seroquel-XR 100mg., Seroquel-XR 200mg. and Seroquel-XR 300 mg depending on clinical response and side effects.
Intervention MeSH terms: Quetiapine Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Major Depression; Generalized Anxiety Disorder; Benzodiazepine; Quetiapine

Summary:

      The hypothesis of this study is that symptoms of anxiety, depression and insomnia; and
      indices of psychosocial function will all improve, while BZ use will decrease significantly
      during a twelve-week trial period of substituting quetiapine for benzodiazepines.
    

Eligibility criteria:

        Inclusion Criteria:

        For inclusion in the study subjects must fulfil all of the following criteria:

          1. Provision of written informed consent

          2. A diagnosis of a current major depressive episode (n =20) or generalized anxiety
             disorder (n = 20) of at least 4 weeks duration, as defined by Diagnostic and
             Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) and assessed on the
             SCID. Subjects may be included if they meet criteria for double depression, i.e.,
             current major depression with antecedent dysthymic disorder, major depression in
             partial remission or bipolar depression. MDD subjects must have a 24 item Hamilton
             Depression Rating Scale Score (HAM-D) at intake >/= 20. GAD subjects must have a
             Hamilton Anxiety Rating Scale Score (HAM-A) at intake >/= 20. Patients who meet
             criteria for current GAD only during a current episode of MDD will be considered to
             have MDD, according to DSM-IV convention.

          3. Females and/or males aged 18-65 years

          4. Female patients of childbearing potential must be using a reliable method of
             contraception and have a negative urine human chorionic gonadotropin (HCG) test at
             enrolment

          5. Able to understand and comply with the requirements of the study

          6. All subjects must report BZ use more days than not persistent for more than 6 months
             and a stable regimen of mood stabilizers and/or antidepressant medication for at least
             8 weeks.

             -

        Exclusion Criteria:

          -  Any of the following is regarded as a criterion for exclusion from the study:

               1. Pregnancy or lactation

               2. Any DSM-IV Axis I disorder not defined in the inclusion criteria

               3. Axis II diagnosis of antisocial, schizotypal or severe borderline personality
                  disorder(defined as patients who are high risk for being unable to complete the
                  study due to hospitalization, suicide attempts, significant self-mutilation, or
                  other self-injurious or destructive behavior).

               4. Patients who, in the opinion of the investigator, pose an imminent risk of
                  suicide or a danger to self or others

               5. Known intolerance or lack of response to quetiapine fumarate as judged by the
                  investigator

               6. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days
                  preceding enrolment including but not limited to: ketoconazole, itraconazole,
                  fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir,
                  ritonavir, fluvoxamine and saquinavir

               7. Use of any of the following cytochrome P450 inducers in the 14 days preceding
                  enrollment including but not limited to: phenytoin, carbamazepine, barbiturates,
                  rifampin, St. John's Wort, and glucocorticoids

               8. Administration of a depot antipsychotic injection within one dosing interval (for
                  the depot) before randomisation

               9. Substance or alcohol dependence at enrolment (except dependence in full
                  remission, and except for caffeine or nicotine dependence), as defined by DSM-IV
                  criteria

              10. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by
                  DSM-IV criteria within 4 weeks prior to enrolment

              11. Medical conditions that would affect absorption, distribution, metabolism, or
                  excretion of study treatment

              12. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris,
                  hypertension) as judged by the investigator

              13. Involvement in the planning and conduct of the study

              14. Previous enrolment or randomisation of treatment in the present study.

              15. Participation in another drug trial within 4 weeks prior enrolment into this
                  study or longer in accordance with local requirements