Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

(see brief summary)

Inclusion:

- Age 18-65

- written informed consent

- meets DSM-IV criteria (by SCID-I/P) for bipolar I disorder, current episode depressed

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

- 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.