Hypothyroidism is a clinical syndrome due to deficiency of thyroid hormone. Thyroid hormone is responsible for maintaining the brain hemostasis and helps in central nervous system global development. There have been studies on the association of psychiatric illness with thyroid deficiency and strikingly found to be presenting feature of hypothyroidism in many patients. Literature evidence also says that underlying hypothyroidism may lead to failure of psychiatric treatment. Hence, we report a case of hypertensive patient on medications started with antidepressants and antipsychotics after being diagnosed of depression but was found to be resistant to psychiatric medications and later successfully treated with levothyroxine for underlying hypothyroidism with myxedema.