Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

Mass General Brigham

Status and phase: Terminated; Phase 2

Conditions: Bipolar Disorder

Treatments: Drug: Placebo; Drug: Simvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT01665950

2011P002545

Details and patient eligibility

About

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).

Full description

(see brief summary)

Enrollment: 4 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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4 participants in 3 patient groups, including a placebo group

Simvastatin-Simvastatin

Experimental group

Description:

Subjects will receive simvastatin in phase 1 (4 weeks) and phase 2 (4 weeks)

Treatment:

Drug: Simvastatin

Placebo->Simvastatin

Experimental group

Description:

Placebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the next 4 weeks

Treatment:

Drug: Placebo

Drug: Simvastatin

Placebo-Placebo

Placebo Comparator group

Description:

Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the subsequent 4 weeks

Treatment:

Drug: Placebo