Field Of Psychopharmacology Research Articles

Exploring the Therapeutic Potential of Terpenoids for Depression and Anxiety.

This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α-pinene, β-caryophyllene, α-phellandrene, limonene, β-linalool, 1, 8-cineole, β-pinene, caryophyllene oxide, p-cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti-inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well-tolerated treatments in the field of psychopharmacology.

Diagnosis and treatment of depression according to the functional recovery paradigm

Since the appearance of the first antidepressants, ideas about the goals of long-term treatment of depression have changed considerably. The prevailing priority in the 1960s to 1980s of relieving current depressive symptoms and ending the current episode – shifted to achieving remission in the early 1990s and functional recovery in the mid-2010s. The general recognition of a new approach to the treatment of depression is reflected in the inclusion of functional disorder in the ICD-11 diagnostic criteria for a depressive episode. The paradigm shift in therapy has been driven by advances in the field of psychopharmacology that have led to the development of antidepressants with a fundamentally new mechanism of action that provides a broader therapeutic effect combined with a more favorable tolerability profile. Agomelatine provides a harmonious and complete reduction of depression symptoms, including those resistant to other antidepressants, and a stable clinical and functional remission of high quality, i.e., it allows the achievement of all three therapeutic goals.

Microbiome: The Next Frontier in Psychedelic Renaissance.

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome-the ecosystem of microorganisms in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut-brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy's effectiveness. By integrating insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

Tools to reduce prescribing errors of psychotropic drugs in older adults

Inappropriate prescribing is a major problem in psychiatric care in older adults. Factors such as the high proportion of older people with a high prevalence of mental disorders, the physiological changes typical of aging, multimorbidity, polypharmacy, the lack of evidence in treatment guidelines for this population, the degree of professional ignorance; give rise to the propensity to make prescription errors of various kinds. To review and summarize the available prescription tools that can provide support to improve prescription practices in psychopharmacology of the elderly. Method: A bibliographic review of the tools to reduce prescription errors in older adults was carried out: pharmacological reconciliation, interaction check, prevention, detection and reversal of prescription cascades and tools with explicit and implicit criteria (MAI, Beers, STOPP/START, FORTA, IFAsPIAM). A clipping was made that groups the recommendations in the field of psychopharmacology. As there are no specific tools to improve practices in geriatric psychopharmacology, a compendium of its recommendations can be of orientation to the psychiatrist of older adults.

Recent Advances in Psychopharmacology: From Bench to Bedside Novel Trends in Schizophrenia.

Research in the field of psychopharmacology is ongoing to develop novel compounds which can revolutionize the treatment of psychiatric disorders. The concept of bench-to-bedside is a tedious process, transforming the initial research performed in the laboratories into novel treatment options. Schizophrenia (SCZ) is a chronic psychiatric illness with significant morbidity and mortality. SCZ not only presents with psychotic symptoms including hallucinations and delusions but also with negative and cognitive symptoms. The negative symptoms include the diminished ability to express emotions, loss of pleasure, and motivation with minimal social interactions. Conventional antipsychotics primarily target positive symptoms with minimal therapeutic benefits for negative and cognitive symptoms along with metabolic side effects. Researchers have explored novel targets to develop new compounds to overcome the above limitations. The glutamatergic system has provided new hope in treating schizophrenia by targeting negative and cognitive symptoms. Other receptor modulators, including serotonergic, phosphodiesterase, trans-amine-associated receptors, etc., are novel targets for developing new compounds. Future research is required in this field to explore novel compounds and establish their efficacy and safety for the treatment of schizophrenia. Last but not least, pharmacogenomics has effectively utilized genetic information to develop novel compounds by minimizing the risk of failure of the clinical trials and enhancing efficacy and safety.

J Guy Edwards, FRCPsych, FRCP, FRCGP (Hon), DPM, HonMFPH, Founding Editor of Human Psychopharmacology.

J Guy Edwards, FRCPsych, FRCP, FRCGP (Hon), DPM, HonMFPH, Founding Editor of Human Psychopharmacology.

Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis.

The monoamine hypothesis of psychopharmacology has been dominating the biological psychiatric research field for decades. Currently psychiatric research has increasingly appreciated psychiatric disorders and suicidal behavior as being highly complex and multi-etiological. In this pathway the gut microbiome and its interrelationship with the brain is gaining traction. The usage of selective serotonin reuptake inhibitors (SSRIs) is increasing in the general population. This is due to their effect on a broad range of psychiatric disorders, and their favorable side effect profile. Still, there are enigmatic aspects about SSRIs, such as the difficulty to predict effect in individual patients, inter-individual differences in side effect, tachyphylaxis (a sudden loss of response to a certain drug), and to date, uncertainties on how they exert their clinical effect. A majority of the serotonin in the human body is produced within the gut, and SSRIs affect enteric neurons. They also exhibit antimicrobial properties that comes with the potential of disrupting microbial hemostasis. We propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted. With this article, together with similar articles, we would like to provide a hypothetical framework for future studies within this field. We believe that this would have the potential to provide a paradigm shift within the field of psychopharmacology, and result in findings that potentially could contribute to the development of a more personalized and tailored treatment.

Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy.

Several mood-stabilizing atypical antipsychotics and antidepressants weakly block serotonin (5-HT) receptor type-7 (5-HT7R); however, the contributions of 5-HT7R antagonism to clinical efficacy and pathophysiology are yet to be clarified. A novel mood-stabilizing antipsychotic agent, lurasidone exhibits predominant binding affinity to 5-HT7R when compared with other monoamine receptors. To date, we have failed to discover the superior clinical efficacy of lurasidone on schizophrenia, mood, or anxiety disorders when compared with conventional mood-stabilizing atypical antipsychotics; however, numerous preclinical findings have indicated the possible potential of 5-HT7R antagonism against several neuropsychiatric disorders, as well as the generation of novel therapeutic options that could not be expected with conventional atypical antipsychotics. Traditional experimental techniques, electrophysiology, and microdialysis have demonstrated that the effects of 5-HT receptor type-1A (5-HT1AR) and 5-HT7R on neurotransmission are in contrast, but the effect of 5-HT1AR is more predominant than that of 5-HT7R, resulting in an insufficient understanding of the 5-HT7R function in the field of psychopharmacology. Accumulating knowledge regarding the pharmacodynamic profiles of 5-HT7R suggests that 5-HT7R is one of the key players in the establishment and remodeling of neural development and cytoarchitecture during the early developmental stage to the mature brain, and dysfunction or modulation of 5-HT7R is linked to the pathogenesis/pathophysiology of neuropsychiatric and neurodevelopmental disorders. In this review, to explore candidate novel applications for the treatment of several neuropsychiatric disorders, including mood disorders, schizophrenia, and other cognitive disturbance disorders, we discuss perspectives of psychopharmacology regarding the effects of 5-HT7R antagonism on transmission and intracellular signaling systems, based on preclinical findings.

Prescription audit and drug utilization pattern in outpatients of psychiatry department of tertiary care teaching hospital: an observational study

Background: The domain of psychiatric illnesses is grossly underrepresented in the current health care scenario especially due to overreliance on mortality rather than the morbidity or dysfunction. The field of psycho-pharmacology is witnessing constant development and introduction of new drugs for which holistic utilization, effectiveness, and side effects studies are the need of the hour. In addition, inappropriate use of drugs poses a potential hazard to patients. Our current study aims at studying the morbidity pattern of various psychiatric ailments and focuses on the prescribing trends of psychotropic drugs.Methods: A prospective observational study was conducted in psychiatry out-patient department of a tertiary care hospital for a period of 12 months. Prescription pattern of psychotropic drugs was analyzed using predesigned format. Prescriptions were collected from OPD and hospital pharmacy. Prescriptions were analysed as per WHO indicators for prescriptions. Descriptive statistics were used for analysis.Results: Depression was found to be the most common psychiatric disorder encountered (32.6%). Average number of psychotropic drugs prescribed per patient 2.45±1.013. Antidepressants along with BZD were the most frequently prescribed psychotropic drugs in various psychiatric disorders. Among the total of 2445 psychotropic drugs prescribed, 99.98% were oral formulations. Psychotropic fixed dose combinations were present in 1.68% of the prescriptions. Only 28% of medicines were prescribed by generic names. Utilization of drugs from the WHO’s 18th list of essential medicines of India was 29%. PDD of risperidone was 1.57mg in schizophrenia. Escitalopram, resperidone and propranolol were the most commonly prescribed drugs for mood disorders, schizophrenia and anxiety respectively.Conclusions: The concomitant use of two psychotropic drugs was the preferred therapy. FDC of anti-cholinergics with both typical and atypical antipsychotics were used. Benzodiazepins were significant part of therapy.

Psychopharmacology curriculum for psychiatric residents

Summary Background: Postgraduate teaching of psychiatric residents in the important field of psychopharmacology and pharmacotherapy is insufficient regarding number of hours of theoretical teaching and practical training, content and structure and varies widely. Education based on controlled trials (evidence-based) may interfere with daily life real world experience and questions of doctors. Method: Data available from national psychiatric societies and from the literature are presented as well as a recently proposed German curriculum and learning catalogue. The latter includes general pharmacology including pharmacokinetics, neurobiological principles, clinical pharmacology of different classes of psychotropics (antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, stimulants etc.), special aspects (e.g. pregnancy, geriatric patients) as well as ethical, legal and economic aspects. About 160 hours of theoretical education are proposed, clinical teaching should be interactive, with vignettes and supervision covering about 300 hours. There is a need for standardization of psychopharmacology-pharmacopsychiatry teaching at the European level.

Electric foot shock stress: a useful tool in neuropsychiatric studies.

Electric foot shock is a complex stressor with both physical and emotional components. It has been employed as an important tool to develop diverse animal models in the field of psychopharmacology. The electric foot shock paradigm includes acute or chronic exposures of shocks of varying intensity and duration on an electrified grid floor in an electric foot shock apparatus. Research evidence reveals that foot shocks of varying intensity produce behavioral and neurochemical changes reflecting depression, anxiety, and post-traumatic stress disorder (PTSD) in humans. Animals generally do not habituate to foot shocks in comparison to other stressors, including loud noise, bright light, and hot and cold temperatures. Additionally, it offers an experimental advantage of control over intensity and duration; therefore, by varying its application parameters, different disorder models have been created. Electric foot shock fear conditioning-induced ultrasonic vocalization and fear-potentiated startle have been explored to develop models of anxiety and panic. Similarly, fear conditioning in the form of foot shock exposure followed by situational reminders has been used to develop a model of PTSD. Electric foot shock-induced conflict has been explored to develop operant conflict models (Geller-Seifter and Vogel tests), which in turn are pharmacologically validated to screen potential anti-anxiety agents. Inescapable electric shock-induced 'learned helplessness' mimics the symptomology of depression, and this phenomenon has been employed to develop the model of depression. The present review describes the pharmacologically validated models of anxiety, depression, and PTSD involving electric foot shock as an aversive stimulus.

Assessing Change in Core Autism Symptoms: Challenges for Pharmacological Studies

[Author Affiliation]Michael G. Aman. The Nisonger Center UCEDD, Ohio State University, Columbus, Ohio.L. Eugene Arnold. The Nisonger Center UCEDD, Ohio State University, Columbus, Ohio.Jill A. Hollway. The Nisonger Center UCEDD, Ohio State University, Columbus, Ohio.Address correspondence to: Michael G. Aman, PhD, Professor Emeritus of Psychology, The Nisonger Center (OCEDD) Ohio State University, 1581 Dodd Drive, Columbus, Ohio 43210, E-mail: Michael.Aman@osumc.eduThese days, there is considerable interest in attempts to treat certain developmental disabilities pharmacologically. In this discussion, we periodically step outside the fields of psychopharmacology or autism to see what lessons can be learned for the study of core autism features. If we explore Clinicaltrials.gov, we see approximately 20 studies underway or recently completed among patients with autism spectrum disorder (ASD), Down syndrome, or Fragile X syndrome.Recently, we completed a small trial of mecamylamine in children with autism and pervasive developmental disorder not otherwise specified (Arnold et al., 2012). This trial was the occasion for reflections on the issue of how to measure change in the core symptoms of autism in the context of pharmacological intervention. The purpose of this editorial is to make some observations, pose questions, and offer some suggestions regarding the measurement of ASD core symptoms. We also comment on the clinical and research context in which such investigations must take place.Autism Spectrum Disorder as a Developmental Disability: Implications for PharmacotherapyASD is a neurodevelopmental disorder--i.e., it becomes evident in the course of development, usually within the first three years of life. As a developmental disability, we see three areas of profound social impairment involving failure to develop normally. First, there are profound deficits in social-emotional reciprocity (APA, 2013). The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), gives the following examples of deficits in social and emotional reciprocity: Poor social approach, failure to engage in reciprocal conversations, reduced sharing of thoughts, experiences, and emotions. Second, there are deficits in nonverbal communication, including the ability to integrate gesture, eye contact, facial expressions, and body language when communicating with others. Third, there are deficits in the development and understanding of relationships, which may include a lack of interest in others and lack of joint interactive imaginative play (APA, 2013). Also included in the diagnostic criteria are behavioral excesses encompassing restricted, repetitive, or narrow patterns of behaviors and interests, including repetitive physical movements or speech, insistence on sameness or routines, narrow or fixated interests, and odd reactions (often increased or muted) to sensory aspects of the environment.The key issue here is that these developmental deficits suggest months and (usually) years of failure to develop and progress at normal rates. When practiced in the general population, the field of psychopharmacology tends to focus on recovery to the premorbid status (i.e., on reversible symptoms, such as major depression or significant anxiety disorder). In the case of ASD, there is usually no premorbid period in which patients had essentially normal behavior or development, unless we count the first months of life before the problems are noted. The study participants have not stored up the relevant developmental information to be released later with the onset of successful pharmacotherapy. Hence, true therapeutic success for individuals with ASD is likely to require months or even years to reach the patient's new adaptive level. This has obvious implications for pharmacological trials, including matters related to duration of the trial, ideal age of the participants (younger children may be more plastic than older adults), and therapeutic medium in which participants are embedded (e. …

Temporal analysis of free exploration of an elevated plus-maze in mice.

The elevated plus-maze (EPM) is a very common rodent test of anxiety. It is based on an approach-avoidance conflict between secure closed arms and aversive open arms. However, discrepancies remain on the interpretation of animals' behavior in this assay. The purpose of our study was to get a better understanding of the mouse behavior in the EPM. We applied a minute-by-minute analysis to compare the behavior of mice forcibly exposed to the maze or set free to explore the maze from a familiar box. Three strains of mice (CD1, BALB/c, and C57Bl/6) were tested. The combination of our different conditions of the test with the minute-by-minute analysis showed that mice did not avoid open arms during the first 2 min of the test when they were forcibly exposed to the EPM. Conversely, free exploration of the EPM resulted in a pattern of behavior characterized by open arm avoidance from the outset, demonstrating that open arm avoidance in mice is unconditioned. These findings generalize across the 3 mouse strains. These data suggest that rodents enter the open arms to complete spatial information about the apparatus as a whole before their natural tendency to avoid them is expressed. Our data also indicate that a detailed behavioral analysis is needed whenever BALB/c mice are to be exposed by force to the EPM. Further studies are required to fully understand the behavior of rodents in the EPM and to avoid false interpretations in the fields of psychopharmacology and behavioral neuroscience.

On the Mechanism of Action of Antipsychotic Drugs: A Chemical Reaction Not Receptor Blockade

Over forty years ago, biochemist Lauro Galzigna conducted an in-vitro experiment showing that the antipsychotic chlorpromazine reacted with the putative psychotogen adrenochrome to form a polymer resembling melanin. The field of psychopharmacology has essentially ignored that simple but illustrative experiment in the intervening time. The present study reproduces principle elements of Galzigna's experiment and expands the scope to include the antipsychotic medications olanzapine and minocycline. The rate of reaction was slow, with maximal yield of black polymer being achieved by 4, 10 and 7 days with chlorpromazine, olanzapine and minocycline, respectively. Changing the pH was most informative for chlorpromazine and minocycline reactions, where yield increased sharply between pH 6.1 and 6.9, and decreased slightly between pH 6.9 and 7.8, consistent with reaction profiles expected for aromatic substitution. Preincubation of olanzapine with iodine doubled the polymer yield, facilitated by the addition of iodine to the aromatic ring and presumably followed by its departure as a "leaving group". Increasing the salt concentration 1.5-fold depressed yields for all three drugs, most likely via ionic shielding of charged functional groups, diminishing reactivity. The results are discussed in regards to the mechanism of action of antipsychotic medications, casting doubt on commonly held theories. The time course of the chemical reactions presented here and the concentrations required, are much more consistent with clinical results than are models concerning receptor-mediated mechanisms. Furthermore, minocycline was effective in this model, but does not appear to have affinity for the primary receptor families thought by many to mediate antipsychotic efficacy.

Today's Psychopharmacological Treatments: Results, Problems, New Perspectives

ABSTRACTDespite all efforts even in the half of the first quarter of the twenty-first century, psychiatric disorders are still lifelong conditions, which cannot be treated fully and mostly continue to be chronic. Therefore, psychiatric disorders and their treatments require more skills and care than physical disorders. In the area of preclinical research in psychopharmacology, clinical trials, research, meta-analyses, and clinician experiences provide useful information for psychopharmacological applications. Although there is still a long distance to cover andat times opposing views, developments in the field of psychopharmacology are rapid and satisfactory. In this review, current issues in psychopharmacology, such as effectiveness, efficacy, new avenues of enquiry, side effects, adverse effects, and drug interactions of psychotropics, generic and reference drug issues, and pharmacoeconomics will be discussed.

Intensive care in psychiatry

Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others. Besides treating the underlying psychiatric diagnoses, it is also necessary to take care of severe somatic comorbidity, which is often impeded by patients’ limited ability to cooperate. Treatment often requires the administration of sedative medication and occasionally the use of medical restraints. Involuntary commitment, involuntary treatment and the usage of physical restraints is regulated by national mental health laws. Medical professionals working in the field of psychiatric intensive care must have expert knowledge in the fields of psychopharmacology and intensive care medicine. Treatment concepts should be aimed to provide optimized care for psychiatric inpatients in a potentially life-threatening phase of their illness. This article outlines current clinical practice at the psychiatric intensive care unit of the Medical University of Vienna (Austria). Furthermore, we present diagnoses, diagnostic procedures and specific treatments of a sample of 100 consecutive inpatients treated in the years 2008 and 2009 at this ward.

Evaluation of anti-depressant and anxiolytic activity of Rasayana Ghana Tablet (A compound Ayurvedic formulation) in albino mice.

In recent years, many Ayurvedic formulations are being researched to provide an effective antidepressant and anxiolytic drug in the field of psycho-pharmacology. The present study was planned to evaluate the anti-depressant and anxiolytic activity of Rasayana Ghana Tablet comprising three herbs Guduchi (Tinospora cordifolia Miers), Aamalaki (Emblica officinalis Garten) (RGT) and Gokshura (Tribulus terrestris Linn). Swiss albino mice were divided into four groups of six animals each, comprising of both male and female in each group. Group I received water served as normal control (WC), group II received vehicle and served as vehicle control (VC), group III received Rasayana Ghana tablet and group IV received standard drug diazepam (2 mg/kg) for anxiolytic study in elevated plus maze and standard antidepressant imipramine (5 mg/kg) for anti-depressant activity in behavior despair test. Rasayana Ghana tablet along with ghee and honey as vehicle is found to be having antidepressant and anxiolytic activity in experimental animals. Thus, this formulation can be used in prevention and treatment of depression and anxiety.

A Bibliometric Analysis of Research in Psychopharmacology by Psychology Departments (1987–2007)

From the very outset of scientific Psychology, psychologists have shown interest for drugs and their effects on behavior. This has given rise to numerous contributions, mostly in the form of Psychopharmacology publications. The aim of this study was to quantitatively evaluate these contributions and compare them with other academic disciplines related to Psychopharmacology. Using the PubMed database, we retrieved information about articles from 15 journals included in the Pharmacology and Pharmacy category of the Journal Citation Reports database for a 21-year period (1987 to 2007). There were 37540 articles which about 52% were represented by 3 journals. About 70% of psychology publications were represented by 2 of these journals. Psychology departments accounted for the 11% of the published papers, which places Psychology third behind Psychiatry and Pharmacology, which contributed to 22.69 and 13% respectively. Psychology contributed to the greatest number of studies in 3 journals, second in 3 and third in 8. This report represents the first effort to explore the contribution of academic Psychology to the multidisciplinary science of psychopharmacology. Although leaders of production of psychopharmacology research were from Psychiatry and Pharmacology, Psychology departments are an important source of studies and thus of knowledge in the field of Psychopharmacology.

Pharmacological characterization of α 2D-adrenergic receptor-mediated [ 35S]GTPγS binding in rat cerebral cortical membranes

Using the rat cerebral cortical membranes that had once been frozen and stored at −80 °C, the stimulation of specific guanosine-5′- O-(3-[ 35S]thio)triphosphate ([ 35S]GTPγS) binding mediated through α 2-adrenergic receptors (α 2-ARs) was pharmacologically characterized. The stimulatory effects of (−)-noepinephrine ((−)-NE) and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK-14,304) at maximally effective concentrations were prominent only in the presence of micromolar to submillimolar levels of GDP, with the greatest signal/noise ratio achieved at 100 and 30–100 μM GDP for (−)-NE and UK-14,304, respectively. The α 2-AR-mediated [ 35S]GTPγS binding was also critically dependent on the presence of millimolar concentrations of MgCl 2 in assay medium. The maximum stimulation induced by UK-14,304 was equivalent to, or even greater than, that of an endogenous ligand (−)-NE at lower concentrations of NaCl, while it became a partial agonist with higher concentrations of NaCl. Concentration–response curves for several agonists revealed that the omission of NaCl from incubation buffer generally shifted the curves leftward and increased the relative efficacies as compared to the endogenous ligand. The pharmacological profile characterized with a series of adrenergic agonists and antagonists indicated that this response was derived from activation of G proteins coupled with α 2-ARs, in particular α 2D-AR subtype, though the possible involvement of α 2C-ARs was not completely excluded. However, the stimulatory effects of several adrenergic compounds, such as rauwolscine and yohimbine, were ascribed to their agonist properties at 5-HT 1A receptors. This method serves as a simple but useful strategy for investigating the functional interaction between α 2D-ARs and their coupled G proteins in rat native cerebral cortical membranes, especially in the field of psychopharmacology and biological psychiatry.

Half a Century of Antidepressant Drugs

MILESTONES OF PHARMACOLOGICAL TREATMENT The 50th anniversary of antidepressant pharmacotherapy is worth remembering. We review the onset of drug treatment with convincing antidepressive efficacy in 2 parts, and in this first part, we recapitulate on the development and clinical introduction of monoamine oxidase inhibitors (MAOI). Before the clinical introduction of the first antidepressants, imipramine and iproniazid, the therapeutic choice in dealing with mood disorders was extremely small. In the early 20th century, the agents used were chloral hydrate, barbiturates, amphetamines, and even opiate derivatives in agitated melancholic patients. During the first half of that century biological treatments were insulin coma, chemical and electric shock therapy, or the famous and widespread Bsleep cures.[ Available chemical preparations were only some nonspecific ones, such as succinic dinitrite, malonic nitrite, or lactic acid with rather unsatisfactory antidepressant results. In the 1950s, a veritable revolution took place in the fields of psychopharmacology and psychiatry with the clinical introduction of the main groups of psychoactive substances still used today. Chance played an important role in the discovery of the majority of psychotropic drugs in the early phases of psychopharmacology; in addition, a large dose of wisdom and astute clinical observation3 was truly important to the final results of these research processes. It suffices to highlight, apart from the discovery of imipramine and the psychiatric use of iproniazid, the discovery of the antimanic properties of lithium in 1949, the clinical introduction of chlorpromazine in 1952 and meprobamate in 1954, and, finally, the introduction of chlordiazepoxide in 1960. This contributes to the 1950s being considered to be the Bgolden decade of psychopharmacology.[