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Psychomotor agitation (PMA) is a prominent clinical issue frequently observed in various psychiatric and neurological conditions, including schizophrenia, bipolar disorder, Parkinson disease, dementia and substance use disorder. Characterized by motor restlessness, anxiety and irritability, PMA can rapidly escalate into aggression and violence, necessitating prompt intervention to ensure patient and caregiver safety. The prevalence of PMA in psychiatric emergency settings ranges from 4.3% to 10%, imposing a substantial burden on healthcare systems. Despite the critical nature of PMA, there is a lack of standardized treatment protocols, particularly concerning the use of liquid formulations of antipsychotics such as liquid promazine, which may offer unique advantages in emergency care. This review aims to provide a comprehensive analysis of the existing literature on the efficacy, safety and tolerability of liquid antipsychotics, with a particular focus on promazine, in the management of PMA. An extensive literature search was conducted across publicly available databases with no time limitations to ensure the inclusion of all relevant articles. The findings suggest that liquid promazine offers several benefits, including ease of administration, rapid onset of action and improved patient compliance, making it a valuable option in acute PMA management. However, the review also highlights the need for future research, particularly long-term studies and head-to-head comparisons with other antipsychotics, to better establish the clinical utility of liquid promazine. Future research should focus on expanding the evidence base for liquid antipsychotic formulations, which will contribute to improved clinical outcomes in the management of PMA.

Abstract Background Adverse childhood experiences (ACEs), social–emotional impairments (SEIs), and neurodevelopmental disorders (NDs) are frequent in psychiatric disorders, including substance-use disorders. We aimed to determine the prevalence of ACE, SEI, or ND in individuals with cannabis-use disorder (CUD). We compared individuals with preCUD-onset ACE, SEI, or ND to those without. Methods We crosssectionally studied 323 inpatients or outpatients with a history of past or current CUD, aged 12–35 years (mean age 22.94 ± 4.79), 64.5% of whom were male. The sample was divided into two groups: the non-premorbid (N = 52) and the premorbid ACE/SEI/ND group (N = 271). Within the premorbid group, further subgroups were based on ACEs, SEI, and NDs. We also analyzed other substance use and psychiatric symptoms/diagnoses based on the non-premorbid-premorbid dichotomy in the CUD sample. Results Pre-CUD ACE-SEI-ND had higher prevalence of bipolar, schizoaffective, borderline personality, and attention-deficit/hyperactivity disorders, and a history of agitation, hallucinations, and self-injury. The ACE group had higher rates of agitation, depression, delusions, hallucinations, eating disorders, and use of cocaine, amphetamines, and hallucinogens than the SEI or ND. Patients in the premorbid group initiated cannabis use at an earlier age, experienced the first comorbid psychiatric episode earlier, and were hospitalized earlier than those in the non- premorbid ACE-SEI-ND group. Conclusions PreCUD-onset ACE, SEI, or ND conditions in individuals with CUDare linked to earlier onset of comorbid mental illness. Furthermore, ACEs contribute to significant and potentially severe clinical symptoms, as well as the use of substances other than cannabis.

This post-hoc study was aimed at assessing whether disease severity was higher in a sample of Treatment Resistant Schizophrenia patients (TRS) compared to schizophrenia patients responsive to antipsychotics (non-TRS). Determinants of disease severity were also investigated in these groups. Eligible patients were screened by standardized diagnostic algorithm to categorize them as TRS or non-TRS. All patients underwent the following assessments: CGI-S; PANSS; DAI; NES; a battery of cognitive tests. Socio-demographic and clinical variables were also recorded. TRS patients exhibited significantly higher disease severity and psychotic symptoms, either as PANSS total score or subscales' scores. A preliminary correlation analysis ruled out clinical and cognitive variables not associated with disease severity in the two groups. Hierarchical linear regression showed that negative symptoms were the clinical variable explaining the highest part of variation in disease severity in TRS, while in non-TRS patients PANSS-General Psychopathology was the variable explaining the highest variation. Mediation analysis showed that negative symptoms mediate the effects of verbal fluency dysfunctions and high-level neurological soft signs (NSS) on TRS' disease severity. These results show that determinants of disease severity sharply differ in TRS and non-TRS patients, and let hypothesize that TRS may stem from cognitive disfunctions and putatively neurodevelopmental aberrations.