Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

• Status: Terminated
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Aim: To estimate the antidepressant efficacy of simvastatin versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotic therapy among individuals with bipolar I disorder in a nonpsychotic major depressive episode.

Hypothesis: Simvastatin will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Simvastatin

Criteria

Inclusion:

• Age 18-65

• written informed consent

• meets Diagnostic and Statistical Manual - IV (DSM-IV) criteria (by Structured Clinical Interview for DSM-IV (SCID-I/P)) for bipolar I disorder, current episode depressed

• Montgomery-Asberg Depression Scale (MADRS) score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit

• Young Mania Rating Scale (YMRS) score < 12 at screen and baseline visit

• currently treated with a lithium preparation (carbonate or citrate) at stable dose for at least 4 wks with level >0.4 and <1.0; and/or valproate at stable dose for at least 4 wks at level >60 and <110; and/or other atypical antipsychotic at stable dose for at least 4 weeks (at least minimum FDA-labeled dose).

Exclusion:

• Psychotic features in the current episode, as assessed by YMRS item #8>6

• felt by the study clinician to require inpatient hospitalization for adequate management

• more than 3 failed pharmacologic interventions in the current major depressive episode, exclusive of primary mood stabilizer

• current substance use disorder other than nicotine, by SCID-I/P

• pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)

• women who are breastfeeding

• serious suicide or homicide risk, as assessed by evaluating clinician

• other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests

• patients who have taken an investigational psychotropic drug within the last 30 days

• patients receiving additional anticonvulsant, antipsychotic, or antidepressant within 1 week prior to study entry

• patients requiring continued treatment with excluded medications (see below).

Excluded medications: other statins, which could influence Wnt signaling; any other drug known to interact with simvastatin, including potent inhibitors/inducers of CYP3A4 such as itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, voriconazole, cyclosporine or danazol; gemfibrozil or other lipid-lowering drugs that can cause myopathy when given alone; amiodarone, ranolazine, verapamil, diltiazem, or amlodipine; niacin; digoxin; coumarin anticoagulants; colchicine; nefazodone; protease inhibitors including ritonavir, indinavir, nelfinavir, or saquinavir.

Allowed: benzodiazepines and sedative-hypnotic agents if dosage has been stable for 2 weeks prior to study entry; thyroid or estrogen replacement provided dosage has been stable for 1 month; antidepressants, antipsychotics, and anticonvulsants provided dosage has been stable for 1 week prior to study entry.