Mirtazapine in Cancer-related Poly-symptomatology
Mirtazapine in Cancer-related Poly-symptomatology
Multicenter, prospective, randomized, controlled trial based on a mixed-method methodology
 using parallel groups, of oral mirtazapine (intervention) compared with oral escitalopram
 (control), with a 56 days follow-up. Improvement of the Global health Status (issued from the
 EORTC-QLQ-C30 (Quality of Life Questionnaire)) will be used as the primary outcome on day 56.
 Semi-structures interviews will be performed on a purposive sample for qualitative analysis.
 The 418 participants will be followed-up at day 7, 14, 28 and 56 for a 56 days period. A
 sub-group of participants will be invited to take part into qualitative interviews at
 baseline and day 56. Recruitment of participants to the qualitative part will be based on a
 purposive sampling.
Inclusion Criteria:

 -  Being over 18 years old

 -  Suffering from advanced cancer

 -  Having a clinically estimated life expectancy over 3 months.

 -  Being diagnosed from having a depressive syndrome by a Hospital Anxiety and Depression
 Scale-D over 11.

 -  Being in need of an antidepressant treatment.

 -  Suffering from at least one under-controlled symptom (defined as a score over 3 on the
 Edmonton Symptom Assessment Scale) among: pain, nausea, vomiting, breathlessness, lack
 of appetite, sleep disorders, anxiety or impaired wellbeing.

 -  Having or not a cancer treatment.

 -  Being able to understand the information related to the study, and to sign informed
 consent.

 -  Having agreed to take part to the study.

 -  Being able to fill Patient Reported Outcomes questionnaires.

 -  Being available to be call on days 7 and 14.

 -  Having a social security affiliation.

 Exclusion Criteria:

 -  Being treated by an antidepressive agent during the four weeks before inclusion.

 -  Having had a hypersensitivity event to mirtazapine, escitalopram of any excipient.

 -  Having had a prior inefficient treatment by mirtazapine or escitalopram.

 -  Having postural hypotension or arterial systolic hypotension inferior to 90 mmHg
 measured following the guidelines of the European Society of Cardiology

 -  Having a QT interval over 420 ms.

 -  Having uncontrolled hearth rhythm disorder or uncontrolled conduction disorder.

 -  Having had or having bipolar disorder.

 -  Having uncontrolled seizure or epilepsy (relative non-inclusion criteria needing a
 neurology specialist opinion)

 -  Having or having history of closed-angle glaucoma.

 -  Having bone marrow aplasia.

 -  Practicing breast-feeding or being pregnant.

 -  Women of childbearing age with no contraception method.

 -  Having a treatment with:

 -  Monoamine oxidase inhibitors (Selegiline, Moclobemide, Isocarboxazid, Nialamide,
 Phenelzine, Tranylcypromine, Iproniazid, Iproclozide, Toloxatone, Linezolid,
 Safinamide, Rasagiline)

 -  One of the following antiarrhythmic drugs: Flecainide, Propafenone, any class IA and
 III antiarrhythmic drug (amiodarone, disopyramide, hydroquinidine, quinidine,
 procainamide, sparteine, ajmaline, prajmaline, lorajmine, bretylium tosilate,
 bunaftine, dofetilide, ibutilide, tedisamil, dronedarone).

 -  Antipsychotic drugs (phenothiazine antipsychotics, pimozide, haloperidol)

 -  Linezolid, sparfloxacin, moxifloxacin, macrolides (IV erythromycin, josamycin,
 clarithromycin, telithromycin), pentamidin, halofantrine, HIV protease inhibitors
 (ritonavir, nelfinavir, amprenavir, indinavir), azolic antifungal agents
 (ketoconazole, itraconazole, miconazole, fluconazole, voriconazole)

 -  Mizolastine and Cimetidine

 -  Ticlopidine

 -  Metoprolol

 -  Methadone

 -  Ketamine

 -  Triptan drugs

 -  Dapoxetine

 -  St. John's wort

 -  Antidepressant drug

 -  Any other medication known to cause prolonged QT intervals.

 -  Having genetic galactose intolerance or glucose-galactose malabsorption.

 -  Having one of the following electrolyte disorders not corrected at the time of
 inclusion: hyponatremia, hyperkalemia, hypokalemia, hypermagnesemia, and
 hypomagnesemia.

 -  Having end-stage renal disease with a creatinine clearance inferior to 15 ml/min
 calculated using the Cockroft's formula.

 -  Having hepatic failure.

 -  Having legal incapacity