N-Acetyl Cysteine and Aspirin as an Adjunctive Treatment for Bipolar Disorder
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Intervention: Aspirin; N-acetyl-cysteine (NAC); Sugar Pill
Intervention description: aspirin 1000mg (2 capsules of 500mg) every morning in addition to his/her antidepressant and/or mood stabilizer medicine; taking N-acetyl-cysteine (NAC) 1000mg (2 capsules of 500mg) two times a day in addition to his/her antidepressant and/or mood stabilizer medicine; research subject will be taking placebo in addition to his/her antidepressant and/or mood stabilizer medicine
Intervention MeSH terms: Aspirin; Acetylcysteine; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Bipolar Disorder; Mood Disorder; Bipolar Depression; Mood Swings

Summary:

      We propose to conduct a double-blind placebo-controlled trial with a widely available and
      prototypical non-steroidal anti-inflammatory agent, aspirin, and an antioxidant agent, NAC,
      involving symptomatic Bipolar Disorder type I and II patients having a depressive or mixed
      episode currently. This will be the first controlled study to test the hypothesis that
      aspirin and NAC, by themselves or in combination, will be beneficial in treating depression
      in bipolar disorder patients and in promoting mood stabilization.

      Our study has the following Aims:

      Aim I - Examine efficacy of aspirin in treating depression in bipolar patients in a
      double-blind placebo-controlled add-on design; Aim II - Examine efficacy of NAC in treating
      depression in bipolar patients in a double-blind placebo-controlled add-on design; Aim III -
      Examine efficacy of combined treatment with aspirin and NAC looking for synergistic,
      potentiating effects; Aim IV - Examine the role of markers of neuroinflammation, as possible
      mediators or modulators in therapeutic response in the treatment of depression in patients
      with Bipolar Disorder.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 to 65 years

          2. A diagnosis of BD type I or II according to SCID-I interview;

          3. Currently in a depressive or mixed episode, based on DSM-IV/ SCID-I criteria;

          4. MADRAS >20 at entry in the study;

          5. No CURRENT liver, kidney, heart disease or ulcers or bleeding dyscrasia;

          6. No HYSTORY of kidney dysfunction or cardiac problems;

          7. ON therapeutic doses of a mood stabilizing drug (lithium, anticonvulsants, any
             atypical antipsychotics) or combinations for at least ONE month.

          8. Allowed psychiatric co-morbid conditions, such as anxiety disorders, PTSD and
             substance use (as long as do NOT meet abuse or dependence criteria according to the
             SCID-I in the past 2 months).

        Exclusion Criteria:

          1. CANNOT be on any :

             Anti-inflammatory: NSAIDs: Aspirin (bufferin, bayer aspirin, ecotrin), diflunisal
             (dolobid, diflunisal),Salsalate (amigesic, salflex), Ibuprofen (motrin, advil),
             Naproxen (naprosyn,aleve, midol extended relief), Fenoprofen (nalfon), Ketoprofen
             (actron), dexketoprofen(ketron D), Flurbiprofen (ansaid), Oxaprozin (daypro),
             Loxoprofen (loxfen, loxonin), Indomethacin (indocin, indocin SR), Sulindac (clinoril),
             Etodolac (lodine), Ketorolac (toradol), diclofenac (voltaren, cataflam), Nabumetone
             (Relafen) Piroxicam (feldene), Meloxicam (mobic), Tenoxicam (mobiflex), Lornoxicam
             (xefo),mefenamic acid (ponstel), meclofenamic acid (meclofenamate sodium), celecoxib
             (celebrex) Anticoagulants: Coumadin (Warfarin), Heparin Anti-oxidant agents Fish oil
             NAC ( N-acetyl cysteine)

          2. Pregnancy

          3. CANNOT change the dose of the psychotropic medications during the trial

        Women Able to Become Pregnant: Participation in this study may involve risks to an embryo,
        fetus, or unborn child. If the subject is a female and able to become pregnant, a urine
        pregnancy test will be performed which must be negative prior to enrolling into the study,
        and the subject must agree not to become pregnant during the study. Urine pregnancy tests
        will be performed at Screening visit and week 8. The study staff will review adequate birth
        control methods with the subject and will remind her that she should not become pregnant
        during the study. Appropriate methods of birth control include: hormonal contraceptives
        (such as birth control pills, patches, and implants), barrier methods (such as a condom and
        diaphragms and spermicidal foam or jelly, surgical (hysterectomy or tubal ligation) or
        intrauterine device (IUD). The subject will be instructed to notify the study doctor
        immediately if there is a chance that she has become pregnant.

        Also, if the subject is breast-feeding an infant or plan on breast-feeding an infant, she
        must notify the study doctor. It is not known if this drug is excreted in human milk;
        therefore, breast-feeding is not permitted during the study.

        Patients can be on any mood stabilizing agents or combinations, as well as on other
        psychotropic medications at study entry, and the doses of those medications cannot be
        changed during the trial. They cannot be on any anti-inflammatory or anti-oxidant agents or
        anticoagulant at the point they are enrolled. If patients decompensate significantly,
        and/or become acutely suicidal, participation on the trial will be terminated.