Simvastatin add-on Treatment to Standard Antidepressant Therapy in Patients With Comorbid Obesity and Major Depression (SIMCODE)

This is an interventional treatment trial for Depressive Disorder, Major Read More

Inclusion Criteria:

• Written informed consent is present
• The patient has the capacity to give consent (He/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention)
• The patient has a major depressive episode according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders 5th Edition)
• The patient has a score of ≥ 18 in the Montgomery-Asberg Depression Rating Scale (MADRS)
• The patient has a body mass index ≥ 30
• The patient's age is between 18 and 65 years (≥ 18 und ≤ 65)
• The patient has not given childbirth within the 6 months prior to study entry and is not breastfeeding
• In case of non-psychotropic medication: The patient received stable pharmacological medication for at least 14 days prior to study entry (any changes in medication dose or frequency of therapy must be answered with no)
• The patient did not take antidepressants during the last 7 days prior to study entry (discontinuation of effective medication to enable study participation is prohibited)
• The patient did not receive prior treatment with Escitalopram in index episode
• The patient had less than three (<3) trials with antidepressants in index episode
• The patient does not have a history of non-response to Escitalopram
• The patient did not receive treatment with ketamine, irreversible MAO inhibitor (e.g. tranylcypromine), electroconvulsive therapy (ECT) or other stimulatory treatments in index episode
• The patient does not meet any of the following criteria: schizophrenia, schizoaffective disorder, bipolar disorder
• The patient is not diagnosed with dementia and does not have moderate or severe impairment of general cognitive function according to clinical impression
• The patient does not have clinically relevant elevated liver enzymes [GOT or GPT > 3 x upper limit normal (ULN)] and does not have elevated Carbohydrate Deficient Transferrin (CDT) ≥ 2.4 %
• The patient does not meet the criteria for alcohol use disorder (DSM-5: 303.90; ICD-10: F10.20) or substance use disorder (DSM-5: 304; ICD-10: F11.20 - F19.20) in M.I.N.I. for DSM-5 and a urine/serum drug screening is negative (except for benzodiazepines and opiates)
• The patient does not have a history of suicide attempt
• The patient does not have diagnosed epilepsy or increased bleeding diathesis or a history of angle closure glaucoma or other glaucomas
• The patient did not have bariatric surgery prior to study entry
• The patient does not have a known allergy or contraindication against Escitalopram or Simvastatin
• The patient does not meet any of the following criteria: hereditary muscle disease, known history of rhabdomyolysis, elevated creatine kinase (CK) outside of the sex-specific reference intervals, history of muscular symptoms under treatment with statins or fibrates
• The patient does not have elevated TSH level outside of the age- and sex-specific refer-ence intervals.
• The patient does not have insulin-dependent diabetes mellitus
• The patient does not have uncontrolled hepatic disorder, renal or cardiovascular disease
• The patient does not have untreated hypothyroidism
• The patient does not have a history of myocardial infarction or stroke
• The patient does not have symptomatic peripheral arterial disease
• The patient does not have monogenic familial hypercholesterolemia
• The patient does not have clinically significant laboratory abnormalities
• The patient did not participate in other interventional trials during the 6 months before and at the time of this trial
• The patient is not an employee of the investigator study site, or a family member of the employees or the investigator, or otherwise dependent on the sponsor, the investigator or the investigator study site

Exclusion Criteria:

• The patient has current use of statins (for visits 2-6 applies: except for IMP Simvastatin)
• The patient has current use of antidepressants (for visits 2-6 applies: except for standard medication Escitalopram)
• The patient has acute suicidal tendencies (MADRS Item 10 > 4)
• The patient uses potent CYP3A4-inhibitors (e.g. clarithromycin, erythromycin, HIV protease inhibitors - see "Risks, adverse drug reactions, drug interactions, restrictions, contraindications, procedures in case of emergency")
• The patient uses potent CYP3A4 inductors (Carbamazepine, Efavirenz, Nevirapine, Etravirine).
• The patient uses Fibrates, Amiodarone, Amlodipine, Verapamil, Fluconazol, Diltiazem, Fusidic acid, Niacin or Lomitapide or BCRP-Inhibitors (e.g. Elbasvir or Grazoprevir)
• The patient uses Gemfibrozil, Ciclosporin or Danazol
• The patient has known hypersensitivity to other ingredients of Simvastatin and Escitalopram [butylated hydroxyanisole, microcrystalline celluose, citric acid, starch, lactose, magnesium stearate, hypromellose, talc, titanium dioxide, iron oxides, colloidal silicon dioxide, croscarmellose sodium, polyethylene glycol]
• The patient uses medication that is associated with QTc-prolongation [antiarrhythmics class IA and III, antipsychotics (e.g. Haloperidol), phenothiazines, tricyclic antidepressants, antibiotics (e.g. Moxifloxacin), and certain antihistaminergic drugs (e.g. Astemizol, Mizolastine)]
• The patient has clinically significant abnormalities in 12-lead ECG (e.g. QTc-prolongation ≥ 500 ms or increase ≥ 60 ms from baseline visit)
• The patient is pregnant
• The patient with childbearing potential is not willing to use an acceptable form of contraception (defined as Pearl index < 1)
• The patient has current use of psychotropic medication (e.g. antipsychotics, anticonvulsants, lithium or St. John's Wort) except for benzodiazepines, non-benzodiazepines and opiates
• The patient uses nonselective, irreversible monoamine oxidase (MAO) inhibitor (e.g. Tranylcypromine) or selective, reversible inhibitor of monoamine oxidase A (e.g. Moclobemide) or the nonselective, reversible monoamine oxidase inhibitor Linezolid
• The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons
• The patient is legally detained in an official institution