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The SSRIs (selective serotonin reuptake inhibitors) are generally recommended as first-line therapies for depressed patients with heart failure. If SSRI therapy is not well tolerated or adjunctive therapy is required, bupropion, mirtazapine, venlafaxine, and duloxetine may be suitable alternatives for certain patients. Here we report a 16-years-old male with Danone disease (an X-linked dominant multisystem disorder resulting in cardiomyopathy, myopathy and intellectual disability), Wolf Parkinson White syndrome (WPW) and hypertrophic cardiomyopathy, who later developed depression and significant weight loss and treated successfully with mirtazapine without any cardiac failure and arrhythmia attacks. A 16-year-old male living with his father and stepmother. He left school because of his cardiac disease. His biological mother had died because of a similar cardiac disease, when he was 10 years old. He referred to pediatric cardiology clinic because of prolonged supraventricular tachycardia (SVT) that caused heart failure. Cryoablation attempts were unsuccessful. An Implantable Cardioverter Defibrillator (ICD) was implanted via transvenous approach and the patient was discharged with oral medication (propafenone, cordarone, enalapril and warfarine). Because he had a very depressed mood and significant weight loss, he was referred to child and adolescent psychiatry. Mirtazapine was started due to availability in liquid form and adverse effects on weight. In a few weeks his mood has elevated and he gained weight. During the follow up period of 10 months, none of his serial ECG and 24 hour holter monitoring recordings showed SVT. Although our patient had significant cardiac risk factors (cryoablation resistant SVT, hypertrophic cardiomyopathy and heart failure) mirtazapine did not worsen cardiologic status. Besides it helped our patient to improve depressed mood and to gain weight.