Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-Blind Trial of Methylene Blue for Cognitive Dysfunction in Bipolar Disorder
Brief Summary: While many bipolar patients treated with mood stabilizing medications experience improvement in their symptoms, some continue to have ongoing difficulties with concentration and memory. The purpose of this study is to look at whether these symptoms can be improved by adding the compound methylene blue to the treatment plan of patients who are already taking lamotrigine.

Methylene blue is an available 'over the counter medication' in Canada. It has been studied in the long-term treatment of mood symptoms in bipolar disorder. Several clinical studies done in bipolar disorder report that methylene blue has had positive effects on both cognition and mood. It is important to do further research in this area as we know that, for patients who continue to have ongoing cognitive difficulties, there is no recognized standard of care for bipolar patients who experience these type of deficits.


Options:
A: 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.
B: Inclusion Criteria:

* Men or women between the ages of 18 and 65 who meet both RDC and DSM-IV criteria for bipolar I or bipolar II disorder will be recruited.
* All subjects will be interviewed using SADS interview (40) with added questions as to arrive at DSM-IV diagnoses as well.
* The patients will be treated with lamotrigine as their main mood stabilizer. Patients recruited for the study will show at least partial response to prophylactic treatment with respect to the mood symptoms.
* HAM-D (17 item) scores at study entry will be 15 or lower and Y MRS scores will be less than 15.

Exclusion Criteria:

* Patients not able to give informed consent
* Patients with active substance abuse or dependence or a history of such within the past two years
* Physical illness, mainly liver and kidney disorders and G-6-PD deficiency
* Subjects previously treated with methylene blue
* Pregnant or breast-feeding women
* Subjects who have had ECT within the past two years
* Patients with known brain injury or loss of consciousness of duration greater than ten minutes
* Subjects taking concurrent medications that are known to have cognitive effects (eg. beta blockers)
C: Inclusion Criteria:

* Male or female patients between 18 and 85 years of age at screening.
* Patients must provide written informed consent prior to study entry.
* Patients must meet DSM-IV-TR (Diagnostic and Statistical Manual IV Text Revision) criteria for Major Depressive Episode of a severity mild, moderate or severe or in partial remission, as confirmed by the MINI.
* Patients must have a HAM-D (17-item) score of 16 or higher.
* Patients must have been on 1 of the following medications for 4 or more weeks at or above the listed dose with no psychiatric medication dose changes for the past 25 days:

  * 20 mg qD of fluoxetine (Once Daily)
  * 50 mg qD of sertraline
  * 20 mg qD of paroxetine
  * 200 mg qD of fluvoxamine
  * 20 mg qD of citalopram
  * 10 mg qD of escitalopram
  * 150 mg qD of venlafaxine or venlafaxine sustained release
  * 300 mg qD of bupropion or bupropion sustained or extended release
  * 15 mg qD of mirtazapine
  * 60 mg qD of duloxetine
* Participants must agree to keep the dose of their existing antidepressant(s) constant throughout the 8-week trial.

Exclusion Criteria:

* Diagnosis of bipolar disorder or schizophrenic or schizoaffective disorder.
* History of alcohol or drug abuse or dependence within 6 months of enrollment.
* Patients who have received ECT (Electroconvulsive Therapy) in the past 3 months.
* History of seizures.
* Moderate dementia (MMSE score of 20 or less).
* Active suicidal ideation: endorsing a 3 (most severe score) on QIDS-SR (Quick Inventory of Depression Symptomatology Self Reports) suicide item OR a score of 2 or higher for the past week on Suicide Scale items 4 or 5 (current suicidal ideation moderate or strong or would avoid taking steps to save life).
* Currently taking a mood stabilizer or antipsychotic (except lithium clearly used as an augmenting agent).
* Patients who, in the opinion of the investigator, might not be suitable for the study.
D: Inclusion Criteria:

* Adult patients, 18-65 years of age
* Major depression disorder without psychotic features
* Inadequate response to current, ongoing antidepressant treatment as defined by protocol
* Having at least one but no more than 2 antidepressant treatment trial failures
* Body mass index (BMI) 18.0-35.0 kg/m2 inclusive

Exclusion Criteria:

* Patient currently receives treatment with a combination of 3 or more antidepressants
* Significant ongoing use of high doses of barbiturates, benzodiazepines or other anxiolytic drugs
* Patient previously received RO4995819
* Patient participated in an investigational drug or device trial within 6 months of screening
* History of non-response to, or current use of non-pharmacological treatment including Electroconvulsive Therapy (ECT), Vagus Nerve Stimulation (VNS), or Repetitive Transcranial Magnetic Stimulation (RTMS)
* Past or present psychotic symptoms

Answer: B