History of Psychiatric Medication

History of Psychiatric Medication. Introduction

Mental illness is an age-old human experience, spanning millennia. In ancient times, prehistoric individuals grappled with conditions resembling modern mental illnesses. When confronted with perplexing behaviours, our ancestors often attributed them to external forces or divine influences, like demonic possession or religious beliefs.

It was first in the Ancient Greece where physicians acknowledged the biological root cause of mental illness. Hippocrates, a pioneer in medicine, proposed that mental disorders arose from imbalances in the four ‘humours,’ hinting at a biological origin. Although his metaphor was inaccurate, it marked a shift from mysticism to understanding mental health as a brain-related issue. Looking bac at the history of psychiatric medication we have to acknowledge the role of alchemists as the predecessor of today’s pharmacology. Even though they were looking for the philosopher’s stone and were interested in the transformation of mercury into gold, they discovered valuable substances used for healing illnesses. It were such alchemists as Robert Boyle, Antoine Lavoisier and John Dalton who transmuted alchemy into modern science, chemistry.

Development of Psychopharmacotherapy

Throughout history, humans have engaged with psychoactive substances long before psychiatry’s formal inception. The modern history of psychopharmacology, however, takes root in the pivotal year of 1950, marking four distinct eras.

The prehistory of modern psychopharmacology, (mid-1800s to 1950), laying the foundation for future developments.
The second era, initiated by the synthesis of chlorpromazine in 1950 and lasting until the mid-1960s. This era witnessed the discovery of all current psychotropic drug classes. Intriguingly, psychiatrists embraced these innovations with mixed feelings, often using them as supplementary to their core psychosocial and psychotherapeutic practices.
The third era, spanning the mid-1960s to the late 1980s, brought about profound shifts in psychiatry, brain science, patient care, and conventional views on disease and therapeutics. Psychotropic drugs played a pivotal role in these transformative changes.
Finally, the fourth era, characterized by the heyday of blockbuster antidepressants and antipsychotics, commenced with the introduction of Prozac in 1988. Over three decades, these new drugs promised radical transformation in the mental health landscape.

1. History of Psychiatric Medication from Mid-Nineteenth Century to 1950

Before the emergence of modern psychopharmacology, dating from the mid-nineteenth century to 1950, physicians relied heavily on sedatives and hypnotics. They administered drugs like bromides, chloral hydrate, Scopolamine, Paraldehyde, Sulfonal, and narcotics such as Opium and even for a brief time Cocaine liberally. These substances were not seen as treatments for mental illness but rather as means to sedate and calm patients, akin to physical restraint.

Occasionally, there were enthusiastic reports about the effects of specific sedative drugs. Hyoscine, for instance, was initially praised for its ability to control bouts of furious excitement and maniacal outbursts. However, renowned psychiatrist Henry Maudsley expressed scepticism, noting that these drugs were more about quieting patients than curing them. He argued that drugs couldn’t directly quell insane delusions or eradicate envy and ambition.

Maudsley raised concerns about chemical restraint’s impact, like what would be debated about newer tranquilizing agents over 50 years later. He questioned whether chemical restraint, despite its subtlety compared to mechanical restraint, did more harm by paralyzing the brain and rendering patients docile.

The twentieth century brought the discovery of barbiturates in 1903 by Emil Fischer and Joseph von Mering. These drugs, including barbiturate acid and its derivatives, offered a simpler way to sedate patients, continuing the tradition of interventions that were useful but not necessarily curative.

2. History of Psychiatric Medication 1950-164 and the Birth of Modern Psychopharmacology

Modern psychopharmacology had its inception in 1950 with the synthesis of chlorpromazine, marketed as Thorazine in the United States by SKF. Unlike earlier sedatives and hypnotics, psychiatrists believed chlorpromazine was a drug to treat genuinely mental illnesses rather than merely masking symptoms.

2.1 Discovery and serendipity

Many of these breakthroughs were serendipitous, such as chlorpromazine, which emerged from a long chemical evolution. Chlorpromazine’s potential in calming anxious patients with minimal sedation was recognized, leading to its marketing as Thorazine in 1954. Another drug, reserpine, was derived from the plant Rauwolfia serpentina in 1954, and despite its challenges, it contributed to the expansion of psychopharmacology.

Psychiatrists of this era used terms like “major tranquilizers,” “ataractics,” and “neuroleptics” instead of “antipsychotic” to describe these drugs. Major tranquilizers induced emotional calmness with minimal sedation for psychotic patients, while minor tranquilizers were used for psychoneurotic problems with fewer side effects. Neuroleptics, characterized by extrapyramidal motor side effects, were introduced in 1955.

Clinical applications of chlorpromazine included treating conditions involving vegetative disturbances, including anxiety states, severe neurosis, schizophrenia, and psychosomatic disorders, and quelling extreme forms of violence and agitation, replacing drastic treatments like lobotomy and ECT.

Alongside chlorpromazine, various other psychotropic drug categories came to light in the postwar era. Tricyclic antidepressants such as imipramine, which debuted in 1955, exhibited significant antidepressant efficacy. Monoamine Oxidase Inhibitors (MAOIs) like Iproniazid played a crucial role in advancing the understanding of depression as a treatable condition. Meprobamate and Benzodiazepines, exemplified by drugs like Librium and Valium, were instrumental in managing anxiety disorders.

2.2 Expanding the Concept of Pathology

State hospital admissions before and after World War II showed a significant increase in patients with nonpsychotic diagnoses, expanding the boundaries of psychiatric treatment. Psychological problems, previously seen as daily life challenges, became legitimate subjects for psychiatric care.

2.3 Psychodynamic Influence

The 1952 DSM-I integrated psychoanalytic principles into psychiatry. It reflected the influence of Adolf Meyer, who believed psychiatric diseases stemmed from a mix of biological, social, and psychological factors. The term “reaction” was used to describe major psychiatric diseases, highlighting their complex origins.

2.4 Dimensional Perspective on Schizophrenia

Eugen Bleuler’s dimensional perspective gained prominence in the 1950s. The DSM-I adopted “schizophrenia” over Emil Kraepelin‘s “dementia praecox.” Bleuler’s view aligned with psychoanalysis, leading to a more flexible understanding of psychiatric disorders, from nearly normal to overtly psychotic.

2.5 Psychotherapy and Psychotropic Drugs

In the 1950s, there was a cooperative relationship between psychodynamic psychiatry and psychopharmacology. Psychoanalysis expanded the scope of psychiatric diseases, making psychological issues treatable with psychotropic drugs.

Psychotherapy remained the primary intervention in treating psychiatric disorders, with drugs seen as complementary. However, as psychopharmacology evolved, questions arose about the role and efficacy of psychotherapy, a development few anticipated.

3. Transforming Psychiatry and Psychiatric Medication: 1964–1988

American psychiatry underwent a radical transformation between the mid-1960s and late 1980s. In the 1950s, psychoanalysis dominated intellectually, and state hospitals played a major clinical role. But within two decades, both psychoanalysis and state hospitals faded into obscurity.

3.1 Macro-Level Forces and Psychiatry

Larger political, economic, and cultural factors played significant roles in shaping psychiatry and psychopharmacology during this period.

3.2 Psychopharmacology’s Role

Psychopharmacology contributed to two significant trends from the mid-1960s to late 1980s. First, the discovery of psychotropic drugs in the 1950s propelled the explosive growth of neurosciences. Second, psychiatry adopted the Randomized Controlled Trial (RCT) to evaluate antipsychotics, shifting from a dimensional view of disease to a more categorical one.

3.3 Creating Modern Neuroscience

Prior to the 1950s, scientists believed neurons communicated via electrical impulses. However, the discovery of chemical neurotransmitters in the Central Nervous System (CNS) changed this. For instance, dopamine’s role in phenothiazines’ mechanism of action was confirmed.

3.4 Serotonin’s Role

Serotonin, identified as a neurotransmitter in mammalian brains, was linked to sanity. Researchers demonstrated serotonin’s physiological role and its depletion by reserpine, shedding light on its importance.

3.5 The Dopamine Hypothesis of Schizophrenia (DHS)

Carlsson’s work contributed to the DHS, suggesting an excess of dopamine-dependent neural activity in schizophrenia. Despite some scepticism, the DHS influenced psychiatric research and the view of psychiatric diseases.

3.6 Monoamine Hypothesis of Depression

Antidepressants’ mechanism of action led to the catecholamine hypothesis of depression. It shifted the focus toward biological treatments, potentially overshadowing psychotherapy.

3.7 The Rise of Randomized Controlled Trials (RCTs)

The FDA‘s 1962 amendment made the RCT the gold standard for evaluating drug efficacy. This shift emphasized quantitative outcomes, population-based research, and measurable results, reducing the role of individual clinical expertise.

3.8 RCTs in Psychiatry

The RCT challenged traditional clinical methods. Psychodynamic psychiatrists criticized it for disregarding the doctor-patient relationship. However, the RCT became pivotal in defining psychiatric illnesses and treatments.

3.9 Phenothiazines’ Efficacy

A landmark RCT in 1964 provided definitive proof of phenothiazine efficacy in treating schizophrenia. This study solidified the relationship between drug effects and psychiatric disorders.

4. History of Psychiatric Medication from Late 1980s to the Present

In the late 1980s, the outlook for psychopharmacology seemed bleak. Despite DSM-III’s release, psychiatric progress stagnated, and new drugs were scarce. But a glimmer of hope emerged from an unexpected source: the rediscovery of a drug synthesized in the 1950s.

Clozapine, a unique antipsychotic that lacked the typical side effects, was born in 1958. Early testing yielded mixed results. Still, it showed promise in the 1960s by effectively treating psychosis without motor side effects.

The term “atypical” was coined for drugs like clozapine in the 1960s, describing their unconventional nature. However, safety concerns led to a halt in development in 1975. In 1984, new trials demonstrated clozapine’s efficacy, and with strict monitoring, it gained FDA approval in 1990.

This development challenged the dopamine hypothesis, inspiring Janssen Pharmaceuticals to create risperidone in 1984, later marketed as Risperdal. Other atypical antipsychotic drugs followed, changing the landscape of psychiatric treatment.

In the 1990s, these drugs were celebrated as breakthroughs, supposedly superior to their predecessors. They were promoted as safer and more effective, especially for core symptoms of schizophrenia.

Simultaneously, SSRIs (Selective Serotonin Reuptake Inhibitors) like Fluoxetine (brand name: Prozac) rose to prominence in treating depression.

While psychotropic drug sales skyrocketed in the late ’90s and early 2000s, the growth rate declined, partly due to market saturation and generics. Pharmaceutical executives might have wagered that replicating the success of drugs like Prozac would be challenging.