Clinical trial NCT01665950: Simvastatin Augmentation of Lithium Treatment in Bipolar Depression
Official title: Simvastatin Augmentation of Lithium Treatment in Bipolar Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Bipolar Disorder
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2012-08-16
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: (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 \<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.

Primary outcomes:
measure: Change in MADRS (4 Weeks)
timeFrame: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4)
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Roy H Perlis, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: