The history of Italian general psychiatry and forensic psychiatry over the last 50 years has been unique in the European and Western healthcare landscape. Western politicians often visit Italy to observe the successful community-based systems that have developed in that country.

This article represents a first step toward a necessary attempt, to explore how specific political decisions, such as the Italian one, have produced positive outcomes for patients with psychotic disorders, outcomes not observed in many Western countries, which are instead grappling with negative outcomes such as the complicated management of homelessness and the incarceration of people who would instead require psychiatric care.

In its historical context, the 1978 decision to abandon the asylum tradition in favor of socialization for patients living with severe mental disorders represented a difficult choice. This choice led to inevitable critical issues, which today are still not completely dormant.

This choice has also, undoubtedly, restored dignity to people living with serious mental illness, even when that person commits a crime.

To understand these changes, it is appropriate to mention the regulations that finally led to Law number 180 of 1978, which decreed the closure of psychiatric hospitals (Ospedale Psichiatrico) throughout Italy and continued after 2015 with the closure of high-security psychiatric hospitals (Ospedale Psichiatrico Giudiziario) as well.

Culturally, much has changed throughout this time in assistance to the mentally ill in Europe.

Schizophrenia is a severe mental disorder with heterogeneous outcomes that depend heavily on symptom stability as a prerequisite for psychosocial rehabilitation and reintegration. Long-acting injectable antipsychotics (LAIs) are a relevant treatment tools that can help advance meaningful outcomes through improved antipsychotic adherence and relapse prevention, deliver pharmacokinetic advantages less achievable with oral formulations, improve patient autonomy, increase functioning, and reduce the risk of premature mortality even more than oral antipsychotics. However, LAIs remain largely underutilized. Non-modifiable and modifiable risk factors for relapse are summarized, potential advantages and disadvantages of LAIs are reviewed, and myths and misconceptions regarding LAIs are outlined and contrasted with evidence. This information is crucial when engaging in shared decision-making and motivational interviewing to educate patients and caregivers about the treatment option of LAIs, including in early illness stages. Since the first episode and early phases of schizophrenia are a defining time, choosing treatments with the greatest potential for improved outcomes is key. In adults with multi-episode schizophrenia, LAIs have shown superiority over oral antipsychotics for relapse/hospitalization and a variety of multiple other efficacy, effectiveness, functionality, and survival metrics. Additionally, LAIs have shown superiority over oral antipsychotics in patients with first-episode/ or early-phase illness, at least in meaningful subgroups of studies and patients that point toward superiority in settings, individuals, and treatment paradigms that more closely match clinical care. Based on this evidence, hesitancies to discuss and offer LAIs in clinical care need to be overcome, framing LAIs not as a last resort but a viable first-line/earlyphase treatment option that can meaningfully transform the long-term course of schizophrenia.

Ayahuasca is a botanical hallucinogen traditionally used for therapeutic and ritual purposes by indigenous groups from Northwestern Amazonian countries such as Brazil, Peru, Colombia, and Ecuador. Ayahuasca is made by the decoction of two plants, which are rich in the 5-HT1A/2A partial agonist dimethyltryptamine or DMT (from the leaves of the Psychotria viridis bush) and β-carbolines such as harmine, from the stalks of the Banisteriopsis caapi vine. There is an increasing interest in the possible therapeutic effects of ayahuasca, especially for psychiatric disorders (major depression, posttraumatic stress disorder, and substance use disorder). This review summarizes information on the pharmacology, safety, and therapeutic potentials of ayahuasca. Although human experimental and naturalist studies published until now suggest a good safety and tolerability profile, often associated with improvements in depressive and anxious symptoms, there are few controlled studies, with small sample sizes, using only single doses, and with short follow-ups. Potential benefits of ayahuasca should be evaluated in larger samples in both experimental and observational studies and using different doses in controlled trials.

In this review, the aim is to differentiate between the 3 second-generation antipsychotics available as long-acting injectables (risperidone/paliperidone, aripiprazole, and olanzapine) and their varied formulations. Differences and similarities among the available products are discussed, including the amenities of care: route of administration (intramuscular or subcutaneous), injection frequency, needle gauge and length, injection volume, injection site, reconstitution procedures, initiation with oral medication or multiple injections, refrigeration requirements, post-injection observation requirements, drug–drug interactions preventing use or requiring dosing adjustments, adjustments requirements for late or missed doses, availability of patient assistance programs, and access barriers for off-label use. Effectiveness in acute and maintenance treatment are reviewed using the metrics of number needed to treat and number needed to harm.

Balancing autonomy and beneficence remains an ongoing challenge in the ethical treatment of patients with schizophrenia and other psychiatric disorders of thought. Psychiatric advance directives (PADs) offer one mechanism through which individuals can guide their own care, but unlike medical advance directives, they are not widely utilized in the United States. They are also highly limited by state law in the scope of their legal authority. This article explores the evidentiary basis for PADs as well as the legal and ethical issues that arise in the use of PADs in individuals with schizophrenia, arguing that providers’ fears of complete opt-out from care by patients are likely unfounded and that PADs offer a powerful tool through which individuals with schizophrenia can ensure meaningful consideration of their own values and goals.

Non-adherence and even partial adherence to antipsychotic treatment can increase the risk of relapse in patients with schizophrenia. One strategy to improve adherence is through the use of long-acting injectable (LAI) antipsychotics. Multiple LAI antipsychotic options are available, which differ in terms of their formulation, administration, initiation, and maintenance dosing schedule. This article provides a practical guide to the conversion from oral to LAI antipsychotic treatment for the available LAI formulations as well as evidence-based principles for maintenance treatment.

The failure to make LAI the default route over the same oral when both are available is a lost opportunity to improve outcomes for people with schizophrenia. A striking example is the lost opportunity to improve life expectancy. A sophisticated pharmacoepidemiologic study from Sweden matched antipsychotic prescriptions with mortality rates and found that receiving an LAI version improved longevity by about 30% compared to its equivalent oral counterpart. Published a decade ago, it seems to have had little impact within US mental health services. This paper attempts to explain some of the reasons for complacency in adapting LAIs as a preferred approach for oral that have an LAI option available. Hypotheses include (1) not appreciating the importance of accurate information to guide present and future treatment recommendations, (2) considering LAIs primarily for adherence interventions rather than their more general benefit as a superior information platform, (3) how fear of disclosing nonadherence is a primary cause of misinformation, and (4) complacency with status quo acceptance of misinformation without fully appreciating how it harms future outcomes. The outcome benefits that come from changing from the oral to the LAI, if available, will continue. Advances in formulation technology have greatly improved the safety and flexibility of recent LAIs compared to earlier formulations, and formulation advances will allow for additional antipsychotics currently limited to oral formulation to expand to having an LAI version readily available.

This article presents a comprehensive neuroethical framework that seeks to deepen our understanding of human consciousness and free will, particularly in the context of psychiatric and neurological disorders. By integrating insights from neuroscience with philosophical reflections on freedom and personal identity, the paper examines how various states of consciousness from interoception to self-awareness influence an individual’s autonomy and decision-making capabilities. The discussion utilizes a multidimensional, bottom-up approach to explore how neurobiological processes underlie different levels of conscious experience and their corresponding types of freedom, such as “intero-freedom” related to internal bodily states and “self-freedom” associated with higher self-awareness. This stratification reveals the profound impact of neurological conditions on patients’ freedom of choice and the ethical implications therein. The insights gained from this analysis aim to inform more tailored and effective treatments for psychiatric patients, emphasizing the restoration of autonomy and respect for their inherent dignity. This work underscores the essential unity of the human person through the lens of neuroethics, advocating for healthcare policies that recognize and enhance the personal freedom of those with mental health challenges.

This article, titled “A Unified Understanding of the Human Mind - A Neuroethical Perspective,” examines the evolution of the concept of the human mind in Western thought and its integration with neuroscience, psychology, psychiatry, and relational dimensions. The author explores how the understanding of the mind has changed over time, influenced by shifts in philosophical paradigms, scientific advancements, and societal perspectives. The article traces the historical development of the mind’s concept, starting from ancient Greece, through influential thinkers like Plato and René Descartes, and progressing to contemporary perspectives. It highlights various philosophical and scientific approaches, including structuralism, functionalism, empiricism, and associationism, which have shaped our understanding of the mind. The article also delves into contemporary integration, where advancements in neuroimaging and the rise of holistic approaches offer a more nuanced understanding of the human mind. The author emphasizes the importance of the relational dimension and the interconnectedness of mental processes, the brain, and the external environment. This integrated perspective can benefit psychiatric treatment and psychological assessments by fostering a holistic approach to mental health. In conclusion, the article advocates for a multidimensional perspective that bridges subjective and objective aspects of human experience, offering promise for theoretical knowledge and practical applications in psychology, psychiatry, and neuroscience.

Long-acting injectable (LAI) antipsychotics are not routinely offered and, thus, are underutilized despite their many advantages over oral formulations. In this special collection of articles, the reader will find overviews of the art and science of prescribing this important treatment option. Guidance is offered regarding incorporating LAIs in treatment planning, including inpatient, outpatient, and jail settings. Reviewed is the evidence surrounding the use of LAIs for patients in their first episode of schizophrenia, as well as switching from oral agents and other common issues that come up in day-to-day practice. Also provided is a comprehensive summary of each of the currently available formulations of LAIs, and some pragmatic reasons why one would be considered over another. In the end, the reader will come away with the notion that LAIs are not a “last resort” but an important and useful treatment modality that ought to be considered more often.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanism of postsynaptic dopamine D2 receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine’s superiority to risperidone for negative symptoms. The muscarinic M1/M4 agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks any D2 receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinic M1 receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

This article reviews the development of mental health and psychiatric services in Australia for the international reader. The development of relevant legislation, health-care systems, and the effectiveness of treatment for people with schizophrenia is reviewed. Gaps in service delivery and future directions are considered.

My name is Bethany Yeiser, and I am an individual living with schizophrenia. My schizophrenia has been in full remission since 2008, thanks to treatment with clozapine, the vastly underutilized medication for refractory schizophrenia.

The link between creativity and serious mental illness (SMI) is widely discussed. Jackson Pollock is one example of a giant in the field of art who was both highly creative and experiencing an SMI. Pollock created a new genre of art known as abstract expressionism (“action painting”) defined as showing the frenetic actions of painting. The question arises whether his SMI played any role in the way he created his drip paintings, especially when he was overactive and manic. Furthermore, did visual hallucinations or enhanced visual perception associated with mania or psychosis facilitate Pollock in embedding and camouflaging images under layers of thrown paint? Seeing images in Pollocks drip paintings has been a controversy ever since these paintings were created. Some experts attribute this to pareidolia—perceiving specific images out of random or ambiguous visual patterns—a phenomenon known to be enhanced by fractal fuzzy edges such as seen in Rorschach ink blots as well as in Pollock drip paintings. So, are Pollock’s drip paintings merely giant Rorschach images, or did Pollock insert polloglyphs—images that are encrypted that tell a story about Pollock’s inner being—into his paintings and then disguise them with drippings? Here, we explore answers to these questions and discuss images that Pollock included in his earliest sketches and used repeatedly in his abstract paintings and later in his drip paintings to argue that these images are not accidental.

A description is provided of the current situation in Aotearoa New Zealand with regard to compulsory treatment of people with schizophrenia. This is placed within the context of homelessness in New Zealand and the provision of services to the incarcerated mentally ill. There are high rates of homelessness and incarceration and services are struggling to meet their needs. This is particularly a problem for the indigenous population. The current Mental Health Act allows for compulsory treatment of people who as a result of schizophrenia are seriously impaired in their capacity to care for themselves, and this will include people where there is a nexus between homelessness and their illness. The Mental Health Act is being reformed, with a new act likely to emphasize autonomy and capacity to a greater degree. Finally, the author considers the learnings from 5 years working within the Fixated Threat Assessment Centre, which provides a unique perspective on these issues.

The perspective article explores systemic issues in psychiatric care, particularly the barriers to timely treatment and the ethical dilemmas involved in involuntary interventions. It further examines the impact of anosognosia—lack of disease insight—on treatment, noting the difficulties in managing care for those unaware of their illness, and scrutinizes training materials from international organizations that might mislabel necessary psychiatric practices as human rights violations, thereby complicating the care landscape. The discussion extends to the legal and societal implications of psychiatric interventions, using Massachusetts’ Rogers Guardianship as a case study to highlight the consequences of legalistic approaches to mental health treatment.

The article calls for destigmatizing psychiatric treatment and integrating robust, evidence-based practices to improve patient outcomes and healthcare equity. The global mental health policy landscape is urged to recognize the critical role of psychiatric care in restoring health and dignity to individuals with serious mental illnesses, advocating for a more nuanced understanding and application of human rights in mental health.

Schizophrenia is a highly heterogenous disorder with substantial interindividual variation in how the illness is experienced and how it presents clinically. The disorder is composed of primary symptom clusters—positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. These, along with duration, severity, and excluding other possible etiologies, comprise the diagnostic criteria for the disorder outlined in the two commonly used diagnostic classification systems—the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition, Text Revision and the International Classification of Diseases, 11th Revision. These primary symptoms as well as accessory symptoms (mood disturbances, anxiety, violence) and comorbidities (substance use, suicidality) bear upon each other to varying degrees and impact functional outcomes. The following review presents two patient cases illustrating the clinical heterogeneity of schizophrenia, the natural history of the illness and diagnosis, followed by the current understanding of the primary symptom clusters, accessory symptoms, and comorbidities. In addition to noting symptom prevalence, onset, and change over time, attention is paid to the impact of symptoms on functional outcome.

Schizophrenia spectrum disorders are brain diseases that are developmental dementias (dementia praecox). Their pathology begins in utero with psychosis most commonly becoming evident in adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate that these brain diseases are about 80% determined by genes and about 20% determined by environmental risk factors. Inheritance is polygenic with some 270 gene loci having been identified as contributing to the risk for schizophrenia. Interestingly, many of the identified gene loci and gene polymorphisms are involved in brain formation and maturation. The identified genetic and epigenetic risks give rise to a brain in which neuroblasts migrate abnormally, assume abnormal locations and orientations, and are vulnerable to excessive neuronal and synaptic loss, resulting in overt psychotic illness. The illness trajectory of schizophrenia then is one of loss of brain mass related to the number of active psychotic exacerbations and the duration of untreated illness. In this context, molecules such as dopamine, glutamate, and serotonin play critical roles with respect to positive, negative, and cognitive domains of illness. Acutely, antipsychotics ameliorate active psychotic illness, especially positive signs and symptoms. The long-term effects of antipsychotic medications have been debated; however, the bulk of imaging data suggest that antipsychotics slow but do not reverse the illness trajectory of schizophrenia. Long-acting injectable antipsychotics (LAI) appear superior in this regard. Clozapine remains the “gold standard” in managing treatment-resistant schizophrenia.

Throughout its two and a half centuries in existence, US mental health policy has repeatedly failed people living with schizophrenia. The failures are cyclical—the inhumane conditions uncovered in the first 75 years of existence were addressed with the construction of state asylums to deliver moral treatment. One hundred years later, the asylums were themselves revealed to be inhumane. Deinstitutionalization, the response to the failure of asylums starting in the 1960s, now drives outcomes such as homelessness, incarceration, and early death for people living with psychotic illnesses. In all cases, well-intentioned policy reform has failed at the level of implementation, largely due to a lack of accountability. The result has been a consistent failure to adequately treat people living with schizophrenia, which is now understood to be a highly treatable condition. As the country passes into a quarter millennium in existence, reform is once again underway. Unlike other points in history, there is good news. Other countries, such as Italy, have successfully leveraged reform to achieve greatly improved outcomes. Understanding US history and the successful implementation of policy change in other countries is imperative and teaches us that accountability in implementation is necessary to break the cycle of policy failure.

This chapter explores the complex and controversial path of MDMA-assisted therapy (MDMA-AT) for treating post-traumatic stress disorder (PTSD) and other behavioral disorders. It covers MDMA’s history from research to recreation to medicine, the pivotal trials, and the challenges faced by researchers. Despite recent setbacks for the clinical application of MDMA, the chapter argues that it holds potential for transforming psychiatry and discusses the uncertain future amidst ongoing debates over ethics, methodology, and political influence.