The effect of new atypical antipsychotic drugs on the expression of transcription factors regulating cytochrome P450 enzymes in rat liver.

BACKGROUND: Our recent studies showed that prolonged administration of novel atypical antipsychotics affected the expression and activity of cytochrome P450 (CYP), as demonstrated in vitro on human hepatocytes and in vivo on the rat liver. The aim of the present work was to study the effect of repeated treatment with asenapine, iloperidone, and lurasidone on the expression of transcription factors regulating CYP drug-metabolizing enzymes in rat liver. METHODS: The hepatic mRNA (qRT-PCR) and protein levels (Western blotting) of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor (PPARγ) were measured in male Wistar rats after 2 week-treatment with asenapine, iloperidone or lurasidone. RESULTS: The 2-week treatment with asenapine significantly diminished the AhR and PXR expression (mRNA, protein level), and CAR mRNA level in rat liver. Iloperidone lowered the AhR and CAR expression and PXR protein level. Lurasidone did not affect the expression of AhR and CAR, but increased PXR expression. The antipsychotics did not affect PPARγ. CONCLUSIONS: Prolonged treatment with asenapine, iloperidone, or lurasidone affects the expression of transcription factors regulating the CYP drug-metabolizing enzymes. The changes in the expression of AhR, CAR, and PXR mostly correlate with alterations in the expression and activity of respective CYP enzymes found in our previous studies. Since these transcription factors are also engaged in the expression of phase II drug metabolism and drug transporters, changes in their expression may affect the metabolism of endogenous substrates and pharmacokinetics of concomitantly used drugs.

Spectroscopic studies under properties of chlorpromazine conjugated to gold nanoparticles.

Scientific studies have demonstrated that conjugates of anticancer drugs with metal nanoparticles (MeNPs) lead to a more effective deactivation of tumor cells compared to free drugs. Similarly, it has been established that conjugates of antibiotics with MeNPs exhibit higher biocidal activity against bacteria than their unbound counterparts. However, limited information is available regarding conjugates formed from drugs other than anticancer and antibiotics. Therefore, our research aims to develop synthesis methods for conjugates of chlorpromazine (CPZ), a neuroleptic, with gold nanoparticles (AuNPs). CPZ-AuNP conjugates were prepared through a ligand exchange reaction conducted on the surface of quasi-spherical, negatively charged citrate-stabilized TC-AuNPs with an average size of 55 ± 5 nm. UV-vis spectroscopy was employed to determine the stability range of the conjugates under controlled conditions of pH and ionic strength. Based on electrokinetic measurements, it was observed that the zeta potential of CPZ-AuNP conjugates strongly depends on the amount of CPZ adsorbed on the TC-AuNP surface. Additionally, the conjugates exhibited an isoelectric point at pH 8.8. Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRA) were employed to elucidate the adsorption structure of CPZ on TC-AuNPs. The interpretation of the spectra was conducted based on the Raman and FTIR spectra of CPZ, along with calculations performed using Density Functional Theory (DFT). The results indicated that CPZ primarily interacts with the TC-AuNP surface through the angularly oriented phenothiazine ring and the propylene bridge. Furthermore, it was demonstrated that the C-N-C fragment is perpendicular to the surface of the TC-AuNP with which it interacts. The findings from this analysis suggest the potential for further research on the use of these conjugates in biomedical applications.

[Drug-induced movement disorders : nosology and treatment]. / Mouvements anormaux iatrogènes : aspects nosologiques et thérapeutiques.

Movements disorders are frequently encountered in general practice and emergency departments and are in many cases of iatrogenic origin. Dopamine D2 receptor blocking agents (DRBA), mainly neuroleptics, are most often incriminated. These drug-induced movement disorders (DIMD) can be classified according to the kinetics of the manifestations (acute DIMD and tardive syndromes), the phenomenology of the abnormal movements observed or depending on the pharmacological agent involved. The diagnosis is based on the time course of the events, clinical examination and meticulous anamnesis of the patient's previous and current treatments. Management is always based on the interruption of the suspected causal treatment when possible. Some cases have a severe prognosis and require immediate treatment.

Les mouvements anormaux sont fréquemment rencontrés en médecine générale et aux urgences et sont, dans de nombreux cas, d'origine iatrogène. Les molécules les plus souvent incriminées sont les agents bloqueurs des récepteurs dopaminergiques D2 (DRBA) et principalement les neuroleptiques. Ces mouvements anormaux iatrogènes (MAI) peuvent être classés selon la cinétique des manifestations (MAI aigus et syndromes tardifs), la sémiologie des mouvements observés, ou encore, selon l'agent pharmacologique en cause. Le diagnostic repose sur le décours temporel des manifestations, l'examen clinique et une anamnèse fouillée des traitements antérieurs et actuels du patient. La prise en charge repose toujours sur l'arrêt du traitement causal quand cela est possible. Il existe des situations urgentes grevées d'un pronostic sévère et redevables d'un traitement rapide.

Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal mechanisms?

Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.

Hyperactive delirium during emergency department stay: analysis of risk factors and association with short-term outcomes.

To investigate factors related to the development of hyperactive delirium in patients during emergency department (ED) stay and the association with short-term outcomes. A secondary analysis of the EDEN (Emergency Department and Elderly Needs) multipurpose multicenter cohort was performed. Patients older than 65 years arriving to the ED in a calm state and who developed confusion and/or psychomotor agitation requiring intravenous/intramuscular treatment during their stay in ED were assigned to delirium group. Patients with psychiatric and epileptic disorders and intracranial hemorrhage were excluded. Thirty-four variables were compared in both groups and outcomes were adjusted for age, sex, Charlson Comorbidity Index, Barthel Index and polypharmacy. Hyperactive delirium that needed treatment were developed in 301 out of 18,730 patients (1.6%). Delirium was directly associated with previous episodes of delirium (OR: 2.44, 95% CI 1.24-4.82), transfer to the ED observation unit (1.62, 1.23-2.15), chronic treatment with opiates (1.51, 1.09-2.09) and length of ED stay longer than 12 h (1.41, 1.02-1.97) and was indirectly associated with chronic kidney disease (0.60, 0.37-0.97). The 30-day all-cause mortality was 4.0% in delirium group and 2.9% in non-delirium group (OR: 1.52, 95% CI 0.83-2.78), need for hospitalization 25.6% and 25% (1.09, 0.83-1.43), in-hospital mortality 16.4% and 7.3% (2.32, 1.24-4.35), prolonged hospitalization 54.5% and 48.6% (1.27, 0.80-2.00), respectively, and 90-day post-discharge combined adverse event 36.4% and 35.8%, respectively (1.06, 0.82-2.00). Patients with previous episodes of delirium, treatment with opioids and longer stay in ED more frequently develop delirium during ED stay and preventive measures should be taken to minimize the incidence. Delirium is associated with in-hospital mortality during the index event.

When the fever will not stop, stop the pills! A case report

ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

Risk Stratification of QTc Prolongation in Critically Ill Patients Receiving Antipsychotics for the Management of Delirium Symptoms.

BACKGROUND: Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk. METHODS: Searches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias. RESULTS: Most antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed. CONCLUSIONS: Antipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias. AIMS: This review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.

A Systematic Review on the Effectiveness of Antipsychotic Drugs on the Quality of Life of Patients with Schizophrenia.

Pharmacological antipsychotic drug interventions represent the cornerstone of the management of patients with schizophrenia and other psychotic spectrum disorders. The choice of the "best" treatment should be made on the basis of several clinical domains. However, despite available treatments, the quality of life reported by patients with schizophrenia taking antipsychotics is still very poor, and this outcome is rarely taken into account in trials assessing the efficacy and effectiveness of antipsychotic treatments. Therefore, we performed a systematic review in order to assess the impact of antipsychotic treatment on patients' quality of life. In particular, we aimed to identify any differences in the improvement in quality of life according to the (a) type of formulation of antipsychotic drugs (i.e., oral vs. depot vs. long-acting injectable); (b) type of the drug (first vs. second vs. third generation); and (c) patients' clinical characteristics. One hundred and eleven papers were included in the review. The main findings were as follows: (1) quality of life is usually considered a secondary outcome in trials on the efficacy and effectiveness of drugs; (2) second-generation antipsychotics have a more positive effect on quality of life; and (3) long-acting injectable antipsychotics are associated with a more stable improvement in quality of life and with a good safety and tolerability profile. Our systematic review confirms that quality of life represents a central element for selecting the appropriate treatment for people with schizophrenia. In particular, the availability of new treatments with a better tolerability profile, a proven effectiveness on patients' cognitive and social functioning, and with a more stable blood concentration might represent the appropriate strategy for improving the quality of life of people with schizophrenia.

Time-dependent effect of antipsychotic discontinuation and dose reduction on social functioning and subjective quality of life-a multilevel meta-analysis.

Background: Meta-analyses indicate superiority of antipsychotic maintenance treatment over discontinuation within up to 24 months after treatment initiation for patients with schizophrenia-spectrum disorders. In terms of functional recovery, long-term trials show improved functioning after discontinuation, suggesting a time-dependent effect of antipsychotic maintenance. However, these trials were not included in previous meta-analyses. We therefore investigated whether the effect of antipsychotic maintenance treatment vs. discontinuation on social functioning and quality of life varies by trial length. Methods: The study was preregistered with PROSPERO (CRD42021248933). PubMed, PsycINFO, Web of Science, Embase and trial registers were systematically searched on 8th November 2021 and updated on 25th June, 2023 and 10th August, 2023 for studies that compared antipsychotic maintenance to discontinuation and reported data on social functioning or subjective quality of life in patients with schizophrenia-spectrum disorders. Risk of bias was assessed with the RoB 2, the ROBINS-I and the RoB-ME tools. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Findings: We included k = 35 studies (N = 5924) with follow-ups between one month and 15 years. Overall, maintenance and discontinuation did not differ on social functioning (k = 32; n = 5330; SMD = 0.204; p = 0.65; 95% CI [-0.69, 1.10]) or quality of life (k = 10; n = 943; SMD = -0.004; p = 0.97; 95% CI [-0.22, 0.21]), whilst subgroup analyses of middle- (2-5 years; k = 7; n = 1032; SMD = 0.68; 95% CI [0.06, 1.28]) and long-term follow-ups (>5 years; k = 2; n = 356; SMD = 1.04; 95% CI [0.82, 1.27]) significantly favoured discontinuation. However, the quality of evidence was rated as very low. Interpretation: Although our findings suggest a time-dependent decrease in the effect of maintenance treatment on social functioning, interpretation of these findings is limited by the serious risk of bias in middle- and long-term trials. Therefore, any conclusions regarding the long-term benefits of antipsychotic treatment or discontinuation for functional recovery are premature and more high-quality trials tailored to comparing state of the art maintenance treatment vs. discontinuation are needed. Funding: None.

Overview of Movement Disorders Secondary to Drugs.

Drug-induced movement disorders affect a significant percentage of individuals, and they are commonly overlooked and underdiagnosed in clinical practice. Many comorbidities can affect these individuals, making the diagnosis even more challenging. Several variables, including genetics, environmental factors, and aging, can play a role in the pathophysiology of these conditions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Statistical Classification of Diseases and Related Health Problems (ICD) are the most commonly used classification systems in categorizing drug-induced movement disorders. This literature review aims to describe the abnormal movements associated with some medications and illicit drugs. Myoclonus is probably the most poorly described movement disorder, in which most of the reports do not describe electrodiagnostic studies. Therefore, the information available is insufficient for the diagnosis of the neuroanatomical source of myoclonus. Drug-induced parkinsonism is rarely adequately evaluated but should be assessed with radiotracers when these techniques are available. Tardive dyskinesias and dyskinesias encompass various abnormal movements, including chorea, athetosis, and ballism. Some authors include a temporal relationship to define tardive syndromes for other movement disorders, such as dystonia, tremor, and ataxia. Antiseizure medications and antipsychotics are among the most thoroughly described drug classes associated with movement disorders.

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.

Innate Vascular Failure by Application of Neuroleptics, Amphetamine, and Domperidone Rapidly Induced Severe Occlusion/Occlusion-like Syndromes in Rats and Stable Gastric Pentadecapeptide BPC 157 as Therapy.

Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, "bypassing key" (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine.

Positive allosteric adenosine A2A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice.

Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A2A receptors (A2ARs) leads to slow-wave sleep without cardiovascular side effects in contrast to A2AR agonists. Methods: We investigated the hypnotic effects of A2AR positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A2AR PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam. Results: A2AR PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A2AR PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep. Conclusion: A2AR allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis.

Síndrome de Wells secundario a dimetilfumarato. A propósito de un caso clínico / Dimethyl fumarate induced Wells syndrome. A case report

Introducción: El síndrome de Wells, también conocido como celulitis eosinofílica, es una rara dermatosis con aproximadamente 200 casos descritos en la bibliografía. Aquí presentamos un caso clínico de un paciente con esclerosis múltiple y síndrome de Wells secundario a dimetilfumarato (DMF). Caso clínico: Mujer de 41 años que en julio de 2021 inició el tratamiento con DMF. Una semana más tarde, comenzó con prurito en las extremidades derechas, seguido por la aparición de zonas eritematosas con vesículas. El hemograma mostró elevación del recuento de los eosinófilos hasta 2.000 µL. El estudio anatomopatológico evidenció un infiltrado eosinófilo a nivel de la dermis compatible con síndrome de Wells. La evolución clínica fue favorable, con resolución de las lesiones y normalización de la eosinofilia aproximadamente en cuatro semanas. No fue necesario administrar corticoesteroides. Conclusiones: La eosinofilia es rara en los pacientes con EM tratados con DMF y generalmente no precisa ajuste de dosis. A pesar de que las manifestaciones clínicas de la eosinofilia en estos pacientes sean raras, es importante que el médico reconozca los síntomas. Numerosos neurolépticos pueden causar eosinofilia y síntomas sistémicos; por lo tanto, los facultativos deben conocer los riesgos de la asociación entre DMF y neurolépticos, en particular por la quetiapina, que contiene fumarato.(AU)

Introduction: Wells syndrome, also known as eosinophilic cellulitis, is a rare dermatosis with approximately 200 cases previously described in the literature. Here, we present a case of a patient with multiple sclerosis with Wells syndrome induced by dimethyl fumarate (DMF). Case report: A 41-year-old Caucasian woman was treated with DMF in July 2021. One week later, she experienced itching on her upper and lower right arm, followed by the appearance of erythematous plaques covered with vesicles. The complete blood count showed an increased eosinophil count of up to 2,000 µL. The histological images demonstrated dermal eosinophil infiltration concordant with Wells syndrome. The clinical course was benign, with complete resolution of the lesions and normalization of the eosinophil count within four weeks. Administration of corticosteroids was not necessary. Conclusions: Eosinophilia is rare in patients with multiple sclerosis treated with DMF and usually does not require dosage adjustments. Although clinical manifestations of eosinophilia in these patients are very rare, it is important for practitioners to recognize the symptoms. Many neuroleptic drugs can induce eosinophilia and systemic symptoms; therefore, physicians must be aware of the risks associated with DMF and neuroleptic drugs, particularly for quetiapine, which contains fumarate.(AU)

Office-based General Anesthesia for a Patient With a History of Neuroleptic Malignant Syndrome.

First described in 1956 subsequent to a reaction reported to the newly introduced antipsychotic drug chlorpromazine, neuroleptic malignant syndrome (NMS) is a rare, potentially life-threatening reaction to antipsychotic drugs characterized by high fever, muscle rigidity, altered mental status, and autonomic instability. All neuroleptics, including newer antipsychotics, have been linked to this condition. Due to similar symptoms, it is debatable if individuals with NMS can be susceptible to malignant hyperthermia (MH). This case report presents the anesthetic care of a 30-year-old male undergoing general anesthesia in the office-based dental environment. The rationale behind the selected total intravenous anesthesia technique without NMS or MH triggering agents is outlined as well as other agents that may still be questionable regarding their trigger effect for NMS.

Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report.

We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances. Despite bio-humoral and instrumental investigations and DaTScan were negative, MRI post-analysis evidenced a 6.5% loss in brain volume. Specifically, irreversible cortical and sub-cortical grey matter reduction and cerebrospinal fluid space enlargement with spared white matter were found. Our observations suggest that the sudden availability of Fluphenazine results in a kind of plateau effect of parkinsonism presentation, partially reversible due to the neurotoxic drug effect on the cortical and sub-cortical grey matter, resulting in asymmetric EPS and stable memory loss, respectively. Our report confirms the debated neurotoxicity of first-generation neuroleptics and the postulated theory of differential susceptibility to the cytotoxic stressors on the central nervous system.

Antipsychotic Drugs Efficacy in Dextromethorphan-Induced Psychosis.

Psychosis is known as a broad term of symptoms that cause serious disorganization of behavior, thinking, and perception of reality. One of the medicines that recently gained much attention in terms of its psychotic potential is dextromethorphan (DXM). DXM, a widely used antitussive drug, is a commonly abused drug because of its euphoric, hallucinogenic, and dissociative properties. To date, DXM is a legally marketed cough suppressant that is neither a controlled substance nor a regulated chemical under the Controlled Substances Act. The management of DXM-related psychosis is dependent on the type of psychotic symptoms. Atypical neuroleptics (i.e., olanzapine, risperidone, quetiapine) and typical haloperidol have been used in symptomatic treatment due to their efficacy, especially in positive symptoms (hallucinations and delusions). These agents are also recognized as the preferred option in the symptomatic treatment of DXM-related psychosis due to their better efficacy and safety profile than typical haloperidol in the short-term course. The focus of the present review concerns the current stage of knowledge about DXM psychotic potency as well as the management of DXM-related psychoses with a special emphasis on atypical antipsychotic drugs (i.e., olanzapine, risperidone, quetiapine, and haloperidol).

Long-Acting Injectable Antipsychotics-A Review on Formulation and In Vitro Dissolution.

Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation aspects of LAI neuroleptics, with particular emphasis on analysis of drug release profiles as a critical test to guarantee drug quality and relevant therapeutical activity. While there is no officially approved procedure for depot parenteral drug formulations, various dissolution tests which were developed by LAI manufacturers are described. In vitro dissolution tests also possess a critical function in the estimation of the in vivo performance of a drug formulation. For that reason, thorough inspection of the in vitro-in vivo correlation (IVIVC) is also discussed.