simvastatin augmentation of lithium treatment in bipolar depression

Conditions: Bipolar Disorder

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).

(see brief summary)

Eligibility 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 \ 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.