Depressions are the most common psychiatric diseases. For treatment, plant extracts have been used for thousands of years: examples are extracts from the (sleeping) poppy (opium), deadly nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine), and St. John’s wort (hypericum oil). In addition, psychotherapeutic measures, like playing music, dancing, playing theater, and also the temple sleep, were used. In the 19th century, the introduction of bromide (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy. The modern thymoleptic therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed. New drug developments should be characterized mainly by an improvement in tolerance. (J. Geriatric Psychiatry Neurol. 1994; 7(suppl 1): S3-S5).

Depression has always counted among the most common psychiatric disorders, and today, the treatment of depression is one of the prime objectives of psychiatric therapy. A brief review of the history of psychiatry illustrates just how long attempts have been made to counter depression both with drugs and by other means.

More than 3,000 years of plant-based remedies and milieu therapy

The opium poppy (Papaver somniferum), a drug that enhanced well-being, was already known as the “Plant of Joy” to the Sumerians in the 3rd millennium BC.

Opium, the latex from unripe poppy capsules, was also common in Minoan culture; during the Bronze Age in the 3rd and 2nd millennium BC, it was a widely traded commodity. Until modern times, opium was used as an antidepressant in the form of “tinctura opii”, prescribed in various dosages.

Atropa belladonna, from the deadly nightshade, which has calming effects and stabilizes the autonomic nervous system in small doses, finds mention in the Assyrian Herbal, a formulation stemming from the 3rd millennium BC, together with hashish. The ancient Egyptian kingdoms also knew of the psychotropic alkaloids hyoscyamine (from henbane) and scopolamine (from thorn apple), as well as alcohol; the latter was venerated as a remedy for melancholy in the Eber Papyrus dated 1600 BC. It was used in this capacity until the first half of this century, and has probably remained the most commonly used, and abused, psychotropic substance.

Ancient Egyptian and Greek medicine also practiced playing music, dancing, and acting as forms of therapy in addition to the cathartic function of sleeping in temples. Pythagorean physicians, such as Alemaeon of Croton (around 570-500 BC) and Hippocrates (46O-377 BC), declared insanity to he a disturbance of somatic function as part of their tenet of humoral pathology; their compendium of remedies included approximately 250 drugs.

In the late Hippocratic schools, medicamental therapy underwent vigorous expansion. In particular, phytotherapeutic polypragmasy developed; for example, not only extracts from poppy and mandrake were used to treat melancholy, but ass’ milk and barley gruel were also recommended. The euphoric effect of hypericum oil was also applied for the treatment of depression. Although late Greek and Roman medical teaching was somatically oriented, it did also include psychological therapies such as music, entertainment, work, and distraction, as well as physiotherapy with baths, massage, and gymnastics.

The medical art embodied by Asclepiades (124-56 BC) and, above all, Galen (129-199 AD) gradually faded during the Middle Ages. Although the early Christian monasteries and communities still considered care of the emotionally disturbed a special Christian duty, medieval medicine inexorably sank into magic, mysticism, and alchemy. At the same time, during the 14th century, hospices for the insane were founded, so-called “madhouses,” which more resembled dungeons than hospitals. One of the first to be established was the grim and menacing Bedlam in London in 1377.

In contrast, Islamic religion and Greek medicine gradually merged and developed into the outstandingly humane and profoundly scientific Arabic medicine. As early as 765 AD, an exemplary hospital for emotional and nervous disorders was established in Baghdad. This was followed by others in Damascus, Fez, and Cairo. Under the Arabic influence, the first modern psychiatric hospital on European soil was founded in Seville in 1409. The famous Arabic doctors, Rhazes (856-925) and Avicenna (980-1037), doggedly fought against superstition and charlatanism, and practiced modern psychiatric methods that included milieu therapy and psychogogic measures. For instance, attempts were made to cheer and encourage melancholic patients with readings, music, and sexual stimulation. Alcohol, caffeine, cannabis, and opium were administered as antidepressants.

Despite countless pharmacologic trials during modern times, represented by the towering medical figure of Paracelsus (1493-1541), during which time St. John’s wort played a role as “arnica for the nerves,” psychiatric care and treatment was ultimately completely abandoned until the onset of a reform movement in England, France, and Germany during the last century. It still took over 100 years for the chains used to manacle patients finally to be banned from the madhouses.

Advances in pharmacotherapy during the 19th century

There had been no genuine advances in pharmacologic treatment for hundreds of years. The most common substances were opium and alcohol, as well as extracts from thorn apple, henbane, and deadly nightshade. The anatomist and psychiatrist Reil (1759-1813), a friend of Goethe and publisher of various medical journals, who was the first to use the term “psychiatry,” warned against the indiscriminate administration of drugs and, instead, emphasized the use of psychogogics, occupation, playing music, and acting in his therapeutic program, “Rhapsodies” on the application of emotional cures on “rain of the mind.” The treatment of melancholy included pleasing physical stimuli such as heat, studying esthetic paintings, strolling, and swinging.

The increasing application of science in medicine, which began around the middle of the 19th century, also benefited psychiatry. In 1811, a chair of psychiatry was inaugurated in Leipzig. Based on his understanding of psychophysiology and pathology, Greisinger (1817-1868), who finally became Professor of psychiatry in Berlin, postulated the physical origins of psychiatric illnesses, which he attributed to disturbances of the brain; on the other hand, he also fully acknowledged that psychodynamic processes could cause such conditions.

Tangible advances were made in pharmacology. In 1826, bromide was introduced as a sedative and hypnotic agent, and codeine was first used in 1832. In 1869, chloral hydrate was administered as the first synthetic sedative in the Berlin Charite psychiatric clinic; paraldehyde was introduced in 1882. The barbiturates have been known since the turn of the century.

In parallel with these developments, suggestive psychotherapy gradually became established, followed by psychoanalysis in the early years of this century; and behavioral therapy based on the learning psychology and behaviorism of the 20th century.

The upswing in psychiatry was not only interrupted by national socialism, it was also perverted for eliminating the insane and emotionally disturbed with sterilization and euthanasia programs. This was compounded by the mass emigration and deportation of Jewish psychologists, psychotherapists, and psychiatrists.

After World War II, Germany had great trouble catching up with the international standards in psychiatry. It has only been during the last few decades, especially after the stock-taking associated with the psychiatry etiquette of 1975, that clear improvements became apparent, especially in terms of psycho- and psychotherapeutic treatment methods.

A new era of psychiatric therapy dawned in 1945 with the development of tranquilizers, first with meprobamate by Berger and Bradley, and shortly afterward with benzodiazepine by Sternbach. In 1952, the neuroleptic chlorpromazine was introduced into clinical psychiatry.

Advent of modern thymoleptic therapy with imipramine in 1957

The first thymoleptic to be developed to clinical maturity was imipramine by Kuhn in 1957. In the same year, the first MAO inhibitor, iproniazide, was introduced by Loomer, Saunders, and Kline. Over the following years, these were joined by many similar preparations, and later by tetracyclic and chemically different substances. The first-generation MAO inhibitors were followed by the so called reversible MAO inhibitors. The so-called selective serotonin-reuptake inhibitors achieved a considerable reduction in undesirable anticholinergic effects.

The pivotal element of the mechanism of antidepressant action appears to be the central serotonin system, which dearly plays its part in the control of vigilance, emotional stability, analysis, impulse control, and social behavior.

The anti-manic action of lithium was discovered by Cade as early as 1949, although it was not systematically used prophylactically to suppress mood cycles until 1960 by Schou and Baastrup. Over the last few years, carbamazepine, with similar effects, has become increasingly popular, especially for rapid cyclers.

Of the remaining somatotherapeutic measures, iatrogenic sleep deficit, as part of a sleep deprivation program, has been successfully applied in the treatment of endogenous and chronic neurotic depression. Total sleep deprivation is gradually being replaced by the partial form in which patients are kept awake during the second half of the night, or from around 2 AM onwards. If this is practiced approximately twice a week, there is a remission rate of about 50%, although thymoleptic therapy must be continued. The selective sleep deprivation method, in which the patient is wakened during a REM phase, can only be applied successfully in a sleep laboratory.

Sleep deprivation therapy, which was conceived by Schulte at the beginning of the 1970s, is based on the hypothesis that a transient desynchronization of the circadian rhythm exists in the depressed.

In contrast, sleep therapy based on barbiturates, which was practiced until the ’50s and even the ’60s, especially for depressive exhaustion, no longer plays such an important role.

Phototherapy for seasonal depressives is also worthy of mention. Treatment with bright light is founded on the hypothesis of positive effects on impaired melatonin metabolism using 1- to 2-hour sessions of illuminating the patient with 2500-lux bright light, which produces the best results if applied in the morning and evening.

Electroconvulsive therapy may still be indicated for severe, protracted forms of depression. Sadly, such therapy has been plagued with a negative image by ideologic campaigns. In terms of the mode of application, enormous strides have been made over the last decade with the use of muscle relaxants and short-acting anesthesia, as well as unilateral administration to the non-dominant hemisphere. As a rule, several applications are necessary, preferably two to four times a week.

Besides supportive and interpersonal psychotherapy, the nonsomatically-oriented treatment methods are dominated today by cognitive behavioral therapy. The objective here is to identify and cancel negative, distorted, “irrational” convictions and thought stereotypes caused by habitual thinking and imaginative patterns, and replace them with new, realistic, and positive cognitions. Graded activities, self-confidence training, and pleasant activities potentiate the effects.

The new classification system adopted from North American psychiatry does not differentiate as clearly between neurotic and endogenous depression as has always been the case in German-speaking countries. As a result, the ranges of indications for somatic and psychotherapeutic treatment methods can easily become blurred. Although both systems must be applied integratively and in combination with one another, the accent in treatment is placed on psychological methods for neurotic depressions, and on somatotherapeutic procedures, above all psychopharmacotherapy, for endogenous depression.

The field of pharmacotherapy currently embraces a broad range of around 40 commercially available thymoleptic antidepressants within the major groups. Since all these tend to be accompanied by adverse drug reactions, for instance anticholinergic effects on the autonomic nervous system or even cardiovascular symptoms, research must now be aimed at developing substances with fewer side effects, or at least better tolerance, without sacrificing efficacy. The current heightened interest in plant-based drugs can be understood against this background. Phytotherapeutic agents are generally considered to have better tolerability; on the other hand, it is most important that their effectiveness be demonstrated. In this respect, the present studies for demonstrating the efficacy of hypericum are a major step forward and soon must be followed by others that clarify its mechanisms of action.