Everyone feels down now and then. At times, the stresses, losses, and disappointments of life can make such feelings almost unavoidable. However, when painful feelings of sadness, lack of enjoyment, guilt, fatigue, and hopelessness persist for more than two weeks and cause impairment of function at work and in relationships, then the criteria are met for the diagnosis of Major Depression (Major Depressive Disorder, MDD).1 The severity of MDD may vary from person to person, with symptoms classified as mild, moderate, or severe. In mild cases, symptoms cause only minor impairment of function. In the most severe cases, suffering is intense and disabling. It may even be accompanied by psychotic symptoms. MDD may also vary in how often a person suffers the illness. It may occur only once during a stressful time in a person’s life, or it may appear recurrently. In some individuals, MDD recurs in predictable cycles, such as in Seasonal Affective Disorder, in which symptoms of depression emerge during the fall and winter months. In others, depression may return in seemingly unpredictable fashion.
MDD is a common illness, and in any one year it affects nearly 7% of the US population. One in five people, or 20% of the American public can expect to suffer MDD at some time in their lives. Women are roughly twice as likely to be diagnosed with MDD as men, though it is unclear if women actually suffer the illness more often or are simply more willing to seek diagnosis and treatment. MDD is the leading cause of disability in the United States among people 15 to 44 years of age. Suicide, which in most cases occurs in the context of MDD, is the second leading cause of death among people in that age group. Aside from personal cost, MDD is also expensive for society. The economic cost of the illness to the US economy is estimated to be over $200 billion a year.2 Despite many advances in psychiatry and neuroscience, rates of depression in the United States have remained about the same. Sadly, evidence shows the rates of suicide have been increasing.
Medical science has long tried to understand the nature and causes of MDD. Though we tend to think of it as a disease rising from the pressures of modern life, the ancients also suffered from and puzzled over this illness. There is perhaps no better description of MDD than one from a nearly 4,000-year-old cuneiform text from Babylonia.
If he has had misfortune suffering losses and knows not how it came upon him; if he has frequent nervous breakdowns from giving orders with none complying, calling with none answering, and striving to achieve his desires while having to look after his household. If he shakes with fear and his limbs have become weak; if he cannot sleep by day or night and sees disturbing dreams; if he is weak from not eating; if he forgets the word he is trying to say; then the anger of god and goddess is upon him.3
The Babylonians, Egyptians, and many other ancient cultures thought the illness was due to having offended the gods. Accordingly, appeasing the gods was the standard treatment. However, some cultures saw physical components of depression. The ancient Greek physician, Hippocrates, recognized MDD, which he referred to as melancholia. In the fourth century bce, he described symptoms of “aversion to food, despondency, sleeplessness, irritability and restlessness.” The word melancholia arose from the ancient notion of the four humors, or life fluids, that circulated in the body. Melancholia referred to “black bile,” and it was thought that overabundance of black bile in the spleen caused the symptoms of depression. As treatment, Hippocrates advised bloodletting, bathing, exercise, mild diet, and herbs. Among the herbs he prescribed for melancholia were black hellebore, borage, bugloss, marigold, and epithyme.4 However, when the patient did not respond to such measures, Hippocrates, too, entertained the notion of demonic possession.
The Greeks and Romans came to see melancholia as arising from perturbations of spiritual, physical, and psychological factors, and they developed treatments to address these various components. Though shackled by superstitions and lacking the scientific knowledge to understand the physiological complexities of the illness, they attempted to treat the patient in his entirety, not unlike modern “holistic” approaches. The Epicurean and Stoic schools arose in Greek culture a century or so after Hippocrates. They believed that peace and tranquility of mind – the avoidance of despondency and anxiety – could be achieved by developing proper perspectives on life and reasonable management of one’s affairs. Thus, for the educated Greeks, engagement in a form of what we might now call cognitive behavioral psychotherapy prevented and treated depressed mood.
Several hundred years after Hippocrates, the Roman author Aulus Cornelius Celsus wrote a text on ailments of men including various forms of mental illness. He carried forward many Hippocratic notions of physical and mental health. He saw the need to calm the minds of the anxious and fearful, and to enliven the minds of the withdrawn and sorrowful. For mental illnesses, he advocated darkness, calm, and music therapy. “The sorrowful thoughts of others must be dispelled, for which purpose concerts of music, and cymbals and noise are useful.”5 Yet, with more recalcitrant patients, treatment went on to include shackling, starvation, and beating. During this time, herbal treatments continued to be explored and refined. Dioscorides (40–90 ad), a near-contemporary of Celsus, published the text, On Medicinal Substances, in which he discussed the use of nearly a thousand different medicinal plants and thus expanded and consolidated knowledge of the use of herbs to treat human illness. Galen, the great philosopher, anatomist, and physician to emperors of Rome, also amassed a knowledge of herbal treatments. Thus, in the first century, the Greeks and Romans were well-versed in the uses of herbs such as poppy, St John’s wort, hops, valerian, saffron, balm, basil, marjoram, and others that affect the nervous system. Indeed, Dioscorides and Galen are both alternatively known as the Father of Pharmacy.
In Europe during the Middle Ages, the pendulum swung back to religious explanations of mental illness in general. Demons, devils, and falling short of the glory of God were seen as the major causes of madness and melancholia. Exorcisms, beatings, near-drowning and other harsh treatments were applied as penitence and to drive the demons from the bodies of the victims. The Arabs kept alive the views and practices of the Greeks, including the sophisticated herbalism of Galen, and here and there in Europe were Christian oases of kindness and care. Still, the clouds of fear and superstition persisted over Europe, and the brutal practices they spawned persisted well into the Renaissance.
During the Renaissance, the more holistic philosophies of the Greeks were revived. New scientific methods and discoveries changed our ways of seeing the world. An age of humanism began. Man – no longer a mere servant of God – became a focus of study. The discoveries of Galileo whittled away at the power of religion and superstition. The anatomical discoveries of Vesalius demystified the human body. Francis Bacon and the scientific method were born. The work of Ambroise Paré, the first advocate of experimental medicine, provided new means to resolve questions of efficacy of treatment. Knowledge of human anatomy and function grew. By the middle of the 1600s, Dr Thomas Willis, the English anatomist, had explored in detail the structure of the brain. However, diseases of the mind and brain required exploration on microscopic, and even finer, neurochemical levels. The underlying defects in brain function that gave rise to MDD and other mental illnesses thus continued to defy understanding.
Throughout this time, herbs remained a means to relieve human suffering. In 1652, Nicholas Culpeper wrote his famous treatise on herbal medicines, The English Physician. Although steeped in pseudoscientific notions of the astrological significance of plants, his descriptions of the uses of hundreds of European herbs became a mainstay of treatment among healers and laypeople alike. He described 28 different herbs to treat melancholia. His book remains in print to this day.
By the time of Dr Benjamin Rush – signer of the Declaration of Independence and widely recognized Father of American Psychiatry – the treatment of psychiatric illness had not greatly progressed. Rush recommended a variety of herbs, teas, and spirits to calm the spirit. His favorite medication was laudanum, a preparation of opium. In reference to a depressed patient, he noted “Ten drops of laudanum, taken occasionally, saved him from being devoured by melancholy.” His method of treatment included bloodletting, purgatives, emetics, hot baths, cold baths, strict bland diets, music, solitude, exercise, pain, blistering, and other ancient practices. Indeed, the recommendations were similar regardless of the type and manifestation of the psychiatric illness.6
The modern era of medicine can be said to have begun in the mid-1800s. At that time, the great physiologist, Rudolf Virchov, laid the foundations of our modern understanding of the phenomenon of inflammation. Pasteur and Koch developed the germ theory of disease, and Joseph Lister recognized and promoted the notion of antiseptics. In the 1880s, Ivan Pavlov began his study of the conditioned reflex that later earned him the 1904 Nobel Prize. Ramon y Cajal drew and cataloged the microscopic details of the brain’s neurons that led to his Nobel Prize in 1906. In the 1890s, Sir Charles Sherrington began his Nobel-winning research into the mechanisms of action of the nervous system. It was during the late 1800s that German neurologists developed the field that later gave birth to psychiatry as a field unto itself. The German neuropsychiatrist, Wilhelm Griesinger, set the stage for modern psychiatry in his 1848 statement that “mental diseases are brain diseases.”
One of the most important events in the history of psychiatry was the development of psychoanalytic theory by Sigmund Freud. His famous book, The Interpretation of Dreams, was published in 1889. It established the basic tenets of psychoanalytic theory, which were that the mind contains both conscious and subconscious material. He postulated that childhood traumas thwarted natural drives, which led to conflicts between conscious and subconscious processes. As part of this process, individuals build resistance to making these conflicts accessible to awareness. Thus, special techniques were required to free, recognize, experience, and work through those traumas. Freud further proposed that systematic but unfettered release of freely associated thoughts allows unconscious material to emerge, and that skilled interpretation of material at the right stages allows the patient to regain awareness and control.
Nonetheless, Freud was the heir of the great German and French schools of neurology, and he himself believed that the ultimate causes of psychiatric illnesses, such as MDD, were physiological abnormalities of brain function. In 1895, in his book, Project for a Scientific Psychology, he outlined his attempts to understand how consciousness might evolve out of neuronal activity.7 He also experimented with cocaine as a potential miracle drug in the treatment of psychiatric conditions, particularly “nervous exhaustion.” He published his first paper on the subject, Über Coca8 in 1884. His abandonment of medication as a part of psychiatric treatment was thought to have been due to disillusionment after the death of a friend on whom he used cocaine to treat morphine addiction.
At the time of Freud’s ascendency, the armamentarium of medications to treat mental illness remained very limited. The Danish physicians, Carl and Fritz Lange, had successfully used lithium salts to treat mania and depression as early as the 1880s. However, they based this use on the false notion that mania was a manifestation of “gout of the brain.” The drug fell out of favor and did not return to use in psychiatry until Dr John Cade’s landmark publication in 1949.9
Emil Kraepelin is best known for his careful and detailed observations of pati...
