Long-term prescription opioid use occurs in a substantial proportion of new opioid users. Most concerning is that high risk patients with comorbid depression, anxiety, nicotine dependence, and substance use disorders, compared to patients without these factors, continue to be prescribed higher opioid doses for longer durations, and are more likely to receive opioids with high abuse potential. To understand this phenomenon, we must consider the relationships between pain, mental illness, substance use disorder and long-term prescription opioid use. While separate fields have investigated the bi-directional relationships between depression, pain, and long-term prescription opioid use independently of one another, there is no text which has brought together the complex interaction of all three together. Drawing on contributions from neuroscience, pain psychiatry, clinical epidemiology, pharmacoepidemiology, clinical trials and research on social determinants of health, Pain, the Opioid Epidemic, and Depression is the first book to integrate currently siloed areas of investigation and clinical knowledge. This book takes a comprehensive approach, from neurophysiology to epidemiology to clinical practice, and explains the processes driving maintenance of chronic pain, persistent depression, and long-term prescription opioid use, as well as taper and buprenorphine treatment for opioid use disorder. Readers will come to understand the central role of depression, other psychiatric disorders, and social determinants that contribute to pain management outcomes, the opioid epidemic, and our response to opioid dependence and opioid use disorder. By taking a multidisciplinary approach to compiling what is known about the relationships between pain, depression, other psychiatric disorders and opioids, this volume will be a valuable clinical resource for a range of healthcare and mental health professionals who encounter chronic pain and comorbid mood disorders, while also spawning new directions for researchers.