A Double-blind Randomized Placebo-controlled Study of Aspirin and N-acetyl Cysteine as Adjunctive Treatments for Bipolar Disorder Patients (SMRI 11T-009)

study design: BD type I or II patients (n=160), on a depressive or mixed episode, who were on therapeutic doses of any of the commonly utilized mood stabilizing agents (lithium, anticonvulsants, atypical antipsychotics) for at least one month and who were still symptomatic (MADRAS >20) will be enrolled. Patients will be randomly assigned to orally receive one of 4 conditions: aspirin 1000 mg (2 capsules of 500 mg) qam, NAC 1000 mg (2 capsules of 500 mg) bid, combined aspirin and NAC at same doses as given individually or matched placebo, as an add-on medication to their ongoing treatment regimen, for an 16-week double-blind trial. After the first 8 week of the double blind treatment, the responders will keep taking the same study drug, whichever it is. And the non-responders will be re-randomized for one of the other three groups of study drugs they haven't tried yet.

Procedures to be used:

The study will be carried out at the outpatient clinics affiliated with the UT Health Science Center at Houston. After signing informed consent, patients will be submitted initially to a structure psychiatric diagnostic interview(SCID-I) to confirm the psychiatric diagnosis, followed by a physical examination and routine labs (CBC, liver function tests, electrolytes, kidney functions tests, thyroid function tests, urinalyses) to rule out relevant medical problems. Physically healthy BD patients on psychotropic medications or combinations will be enrolled and randomly assigned to receive, orally, aspirin 1000 mg qam, NAC 1000 mg bid, combination of aspirin 1000 mg qam and NAC 1000 mg bid, or placebo. The study drugs doses will remain the same for the duration of the study.

If patients qualify for the study initially based on SCID-I interview, physical examination, and routine labs (CBC, liver functions tests, electrolytes, kidney function tests, thyroid function tests, and urinalyses), but are not currently taking an approved psychotropic medication or combinations they are eligible to participate in a lead-in phase. This phase would be starting at their screening visit and last approximately 6 to 8 weeks depending on the patient's mood. During this lead-in phase, either the PI or Co-PI will evaluate the patient and prescribe either Lithium or Depakote. The patient will be monitored during this treatment phase by the PI or Co-PI and will return after two weeks for an evaluation. The evaluation will include the Columbia-Suicide Severity Rating Scale(CSSR-S) to assess risk of suicide, the Montgomery-Asberg Depression Rating Scale(MADRAS) to assess the severity of depression and the UKU side effects rating scale. If the patient is prescribed lithium, their lithium levels will be tested. The patient will continue to follow up every two weeks. At the 4 week visit, the patient will also come in for evaluation (CSSR-S MADRAS and UKU side effects rating scale).

At the 6 week visit, the patient will be re-evaluated for the double-blind study trial. If the patient has been on an adequate dose of the psychotropic medication for at least 4 weeks and score greater than 20 on the Montgomery-Asberg Depression Rating Scale (MADRS), then they will be enrolled.