Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management.

A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores.

Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P-scores (0.8186), followed by beta-blockers and NaSSA.

Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement.

The development of an extrapyramidal syndrome (EPS) is assumed to be a potential and important consequence of organophosphate poisoning (OP). Even though its causal relationship is firmly established, the information available in the literature regarding the orientation to be given is scarce, and its approach remains shrouded in a significant degree of uncertainty. Catatonia, as a neuropsychiatric condition, may present a marked overlap with the set of extrapyramidal symptoms developed after OP. Does the overlap between the symptoms seen in catatonia and in EPS make differential diagnosis fundamental or does it have no relevance in relation to the approach to be established?

To discuss the therapeutic approach to be implemented in the extrapyramidal symptoms resulting from OP and reflect on the overlap between catatonia and EPS.

Presentation of a clinical case and review of the literature.

A 50-year-old woman with major depressive disorder developed a condition marked by exuberant extrapyramidal symptoms 3 weeks after OP. Significant stiffness, tremor, dysphagia and facial hypomimia were some of the symptoms observed. Therapy was started with amantadine 100mg daily, with complete resolution of the symptoms after 5 days. Follow-up revealed reversal of extrapyramidal symptoms, in the absence of any neuroimaging changes or any other neuropsychiatric manifestations.

The possible overlap between catatonia and EPS is remarkable. The two conditions, regardless of their differentiation, may benefit from an identical approach using dopaminergic drugs. The use of amantadine, even in low doses, may be an option in the rapid reversal of extrapyramidal symptoms resulting from OP.

No significant relationships.

Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia.

This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values.

Of 478 patients entering this study, 236 (49%) continued from a previous 12-week, phase 3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23% of patients received AL 882 mg (N = 368) and 441 mg (N = 110), respectively. AEs occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was reported as an AE in 3.8% of the overall population, with higher rates in patients initiating AL on study entry than those continuing on AL. EPS-related AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically relevant changes were observed for metabolic parameters. The overall incidence of ISRs was 3.8%; most were associated with the initial injections in patients receiving their first injection in this study.

Long-term treatment with AL is generally well tolerated, with a safety profile consistent with that of oral aripiprazole. It is a suitable option for patients with schizophrenia.

To evaluate the tolerability and efficacy of risperidone in childhood autistic disorder.

A multicenter, open-label, dose-titration study involving seven autistic children (mean age 7.6 years) receiving risperidone for 4 weeks.

Mean dose was 0.01 mg/kg/day on day 1, 0.019 mg/kg/day on day 7 (range 0.01–0.041 mg/kg/day) and 0.035 mg/kg/day on day 28 (range 0.014–0.064 mg/kg/day). Over the 4-week period, the Ritvo–Freeman Real Life Rating Scale total score measuring autistic behavior was significantly decreased (P = 0.019), as was the affectual reactions subscale (P = 0.029). Aberrant Behavior Checklist total score was significantly improved (P < 0.001), as were all subscales except inappropriate speech. Visual Analog Scale for individual target symptoms was significantly decreased (P = 0.001), and Clinical Global Impression severity of illness score was significantly improved (P = 0.006). The incidence of adverse effects was low, and no extrapyramidal symptoms were observed. No significant changes or clinically relevant abnormalities occurred in laboratory tests, vital signs or electrocardiograms. Plasma concentrations of the drug were similar to those in adult patients.

These favorable results suggest that larger controlled trials of risperidone should be performed in autistic or mentally retarded patients with behavioral disturbances.

Long-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of iloperidone.

Patients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.

A total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.

This study further supports the long-term safety and tolerability of iloperidone for the treatment of schizophrenia, including iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.

There is a lack of consistent evidence regarding associations of neurological soft signs (NSS) with illness-related variables in schizophrenia. This study examined NSS in first-episode psychotic patients with respect to their factor structure and associations with risk factors, pre-morbid characteristics, psychopathology and spontaneous extrapyramidal syndromes.

First-episode, drug-naive patients with schizophrenia-spectrum disorders (n=177) were assessed for NSS using the Neurological Evaluation Scale, and its 26 constituting items were factor analysed. The identified neurological dimensions were then entered into hierarchical regression models as outcome dependent variables of a set of predictors including risk factors (familial loading for schizophrenia, obstetric complications), pre-morbid characteristics (neurodevelopmental delay, symptoms of attention deficit–hyperactivity disorder, pre-morbid functioning), psychopathological domains (reality distortion, disorganization, negative symptoms, mania, depression, catatonia) and spontaneous extrapyramidal syndromes (parkinsonism, dyskinesia, akathisia).

Five neurological domains were identified: sequencing, release signs, sensory integration, abnormal movements and coordination. Multivariate analyses showed independent associations (p<0.01) of sequencing with familial liability to schizophrenia, deterioration of pre-morbid adjustment and parkinsonism; release signs with obstetric complications, catatonic symptoms and parkinsonism; sensory integration with familial liability to schizophrenia; abnormal movements with familial liability to schizophrenia, obstetric complications, parkinsonism and dyskinesia; and coordination with neurodevelopmental delay. The empirically derived factors explained additional variance over and above that explained by subscale scores across the examined variables.

Familial liability to schizophrenia, obstetric complications, neurodevelopmental delay, deterioration in pre-morbid functioning and observable motor disorders appear to contribute independently to domains of neurological dysfunction. The findings support a neurodevelopmental model of NSS in schizophrenia.