The currently accepted term antipsychotic was first coined by Heinz E. Lehmann and was not widely used until the late 1960s. Subsequently, supervised efforts were made by different research interests to ascertain the possible clinical benefits of the new medications in the treatment of depression, psychosis, acute confusional schizophrenia, schizoaffective psychoses, anxiety, arteriosclerotic psychosis, and excited chronic schizophrenia. The beginning of the modern psychopharmacology era also featured different research and animal model studies sponsored by pharmaceutical interests. These sponsorships led to the synthesis and characterization of drugs that defined the future classes of psychotropic drugs in human medicine. These include anxiolytic drugs (meprobamate and chlordiazepoxide), monoamine oxidase inhibitors (MAOIs), antidepressants (iproniazide), antipsychotic drugs (chlorpromazine), and tricyclic antidepressants (imipramine). However, to understand how the era of modern psychopharmacology ushered in the wave of clinical practices that culminated in the golden age of psychopharmacology, it is important to analyze how this era introduced the use of various new drugs in psychiatry. The most important drug of emphasis during the era included the following: Monoamine Oxidase Inhibitors. Psychiatry as a branch of medicine received huge attention in the late 1960s. This surge in interest is unconnected with the significant increase in the incidence of psychiatric conditions in the global population. This incidence is primarily linked to the surge in the proliferation and use of psychoactive substances derived from both animal and plant sources for recreational purposes. Monoamine oxidase inhibitors were formally studied as a class of drug during this era, with iproniazid as the first of many. This class of drugs was generally accepted and described for their antidepressant activities in animal model experiments and clinical studies using human subjects. Iproniazid was released with imipramine as the first set of monoamine oxidase inhibitors to help promote the case for psychopharmacological agents in the management of depression. As with almost every psychoactive drug of this era, the monoamine oxidase inhibitor drugs were discovered serendipitously. In the wake of World War II, the pharmaceutical company, Hoffman–LaRoche procured a large consignment of hydralazine that had been intended for use as a component of German rocket fuel. Leveraging advancements in chemical synthesis, the company synthesized two different drugs from hydralazine. Both drugs - iproniazid and isoniazid - were introduced to the market in 1951 as potent antituberculosis agents. In 1952, researchers experimenting with these drugs documented that iproniazide had the unexpected effect of lifting patients’ moods. A few years later, the clinical evidence supporting the mood-elevating effects of iproniazid in tuberculosis patients led to different clinical trials exploring the pharmacological effects of iproniazid in non-tuberculosis patients. Researchers would later confirm that iproniazide, in clinically safe quantities, elevates the mood of depressed non-tuberculosis patients. This discovery ultimately led to the introduction of iproniazide as an antidepressant effective in the management of different forms of depression. By the late 1950s, three new antidepressants categorized with the monoamine oxidase inhibitors had been synthesized, trialed, and introduced for clinical use: Isocarboxazid (Marplan; Hoffman–LaRoche), phenelzine (Nardil; Warner Chilcott), and tranylcypromine (Parnate; SKF). However, monoamine oxidase inhibitors failed to match the commercial profitability of chlorpromazine and the early tranquilizers. This was in large part due to the observation that these drugs precipitate a hypertensive crisis in patients who ingest food that is too high in tyramine. The tyramine contraindication significantly limited the use of monoamine oxidase inhibitors in many depressed patients. Tricyclic Antidepressants. Because there were uncertainties in the market demand for a drug indicated for depression,
only a few pharmaceutical companies had initially sponsored research in this regard. However, the commercial success of chlorpromazine and other tranquilizers forced many pharmaceutical companies into the psychoactive drug development business. In part, this led to the development of a new class of antidepressants - tricyclic antidepressants. In 1955, with the backing of Geigy, the Swiss psychiatrist Roland Kuhn trialed the clinical effects of a promising compound - an iminodibenzyl - in human subjects. Documenting his findings with the new compound, Kuhn noted that iminodibenzyl lacked the tranquilizing and antipsychotic effects similar to chlorpromazine. However, in clinically safe quantities, the compound exerted significant clinical effects in depressed patients by altering and elevating their mood. Kuhn would eventually publish his full finding on the iminodibenzyl compound, now named imipramine, in 1957. In his documentation, Kuhn noted: “[T]he compound has potent antidepressant action. Best responses were obtained in cases of endogenous depression showing typical symptoms of mental and motor retardation, fatigue, feeling of heaviness, hopelessness, guilt, and despair.” However, there are modern-day concerns about Kuhn’s method of clinically characterizing imipramine (Helmchem, 2022). For instance, he had no control group, implemented no rating scale for the clinical effects described, and submitted limited information on the dose–effect relationship of imipramine. These points contributed to the modern-day criticism of how Kuhn’s clinical characterization of imipramine would have failed if subjected to the current standards of clinical trials. The discovery of imipramine and further studies on the clinical effects of tricyclic antidepressants championed a new wave of clinical intervention focused on the treatment of depression. Compared to electroconvulsive therapy and amphetamines, imipramine helped epidemiologists better understand the prevalence of depression. Amitriptyline, sold as Elavil, was subsequently manufactured by Merck as another important tricyclic antidepressant. Although initially trialed for possible antipsychotic effects, it was later determined that the new drug exerts antidepressant effects similar to imipramine. It reportedly showed significant clinical benefits in the management of neurological conditions characterized by symptoms such as loss of interest, psychomotor retardation, social withdrawal, depressed mood, loss of interest, feelings of guilt, insomnia, anorexia, and functional somatic complaints. The commercial success of tricyclic antidepressants was largely affected by a traditional narrative that diseases of the mind were largely untreatable by the new drugs. The development of the Hamilton Depression Rating Scale played a huge role in overturning this narrative by helping researchers rate the severity of depression and the improvement in symptomatology as a result of antidepressant therapy. Subsequently, the antidepressant qualities of this class of medications were established during this era of psychopharmacology. Meprobamate and Benzodiazepines. The documentation on meprobamate as the first genuine psychiatric drug to attain commercial heights in the global drug market can be traced back to the mid-1950s. Categorized as a minor tranquilizer, meprobamate was first synthesized in 1951 and was commercially available under the tradename Miltown in 1955. As far back as 1946, English researcher Frank Berger started experimenting with mephenesin, testing it for psychological activities in animal models. Preliminary reports showed that mephenesin caused sedation in test subjects and also improved the symptomatology profile in different animal models of depression. In humans, mephenesin also improved the symptoms of anxiety and exerted significant relaxation effects on the muscles.
EliteLearning.com/Psychology
Book Code: PYFL4024
Page 159
Powered by FlippingBook