The prescription of antidepressants, such as selective serotonin reuptake inhibitors, have grown exponentially since their launch in the 1990s. Today, one in seven Australian adults take an antidepressant. Medicine and culture’s current default mode is that a person who is distressed, or sad, has a chemical imbalance in their brain and this can be managed with medication.    But do depressed individuals really have a chemical imbalance? Do antidepressants work above and beyond a placebo? Could any chemical imbalance even be a deliberate move by the body to help deal with the distress? What does blunting that with medication mean for the long term?   Also, if depression is a chemical imbalance restricted to the brain, what explains the myriad of physical comorbidities that frequently occurs with depression such as metabolic and cardiovascular disease?    With claims of a mental health crisis and an epidemic of depression, perhaps its time to reframe depression and explore the new science that goes beyond a chemical imbalance to uncover other treatment options.    To help reframe depression and understand new models and treatment methods we are going to look at radically honest sugar pills, lessons from man flu, ice hockey legend Wayne Gretkzy, Justin Beiber, and the amputation of an imaginary limb.