While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposition underlying suicidal behaviors in diverse populations. This study aimed to conduct a large-scale investigation of the suicidality spectrum (SP) to generate new insights into its biology and epidemiology.

Sexual dysfunctions are a challenging side effect associated with antipsychotic treatment. This protocol outlines a systematic review and meta-analysis to assess the prevalence of overall sexual dysfunction, as well as the specific phases of sexual function affected by antipsychotic medications. Additionally, the analysis will explore the relationship between prolactin levels and sexual dysfunction.

Tardive Dyskinesia (TD) can occur in people exposed to dopamine receptor antagonists (DRAs). Its clinical management remains challenging. We conducted a systematic review/random-effects network meta-analysis (NMA) searching PubMed/MEDLINE/PsycINFO/ClinicalTrials.gov/Cochrane Central Register (22/05/2023, pre-defined protocol https://osf.io/b52ae/), for randomized controlled trials (RCTs) of pharmacological/brain stimulation interventions for DRA-induced TD in adults with schizophrenia or mood disorders. Primary outcomes were TD symptom change (standardized mean difference/SMD) and all-cause discontinuation (acceptability-risk ratio/RR). Sensitivity analyses were conducted. Global, local inconsistencies, risk of bias (RoB-2 tool), and confidence in evidence (CINeMA) were measured. We included 46 trials (n = 2844, age = 52.89 ± 9.94 years, males = 59.8%, schizophrenia = 84.6%, mood disorders = 15.4%), all testing pharmacological interventions versus placebo. We identified three subnetworks. In network 1, several treatments outperformed placebo on TD symptoms with large effect sizes (k = 34, n = 2269), encompassing 22 interventions versus placebo, but 18 had 1 RCTs only, and 15 had n ≤ 20. High heterogeneity (I[2] = 57.1%; tau[2] = 0.0797), and global inconsistency (Q = 32.64; df = 14; p = 0.0032) emerged. No significant differences emerged in acceptability. When restricting analyses to treatments with trials with n > 20 and >1 RCT, only valbenazine (k = 5, SMD = -0.69; 95% CI = -1.00, -0.37) and vitamin E (k = 7, SMD = -0.49; 95% CI = -0.87, -0.11) were superior to placebo. Deutetrabenazine outperformed placebo considering AIMS score and in low risk of bias trials only and with a moderate effect size for 24/36 mg (k = 2, SMD = -0.57/-0.60). Confidence in findings was low for deutetrabenazine and valbenazine, very low for all others. In network 2 (k = 2, n = 63), switch to molindone (k = 1, n = 9) versus switch to haloperidol worsened TD (SMD = 1.68; 95% CI = 0.61,2.76). In network 3 (k = 3, n = 194), antipsychotic wash-out+placebo (k = 1, n = 25) versus TAU+placebo (k = 1, n = 27) worsened TD (SMD = 1.30; 95% CI = 0.36,2.23). Despite large effect sizes for some treatments with very low quality/confidence, when considering higher quality evidence only valbenazine or deutetrabenazine are evidence-based first-line treatments for TD, and potentially vitamin E as second-line. Switching to molindone and antipsychotic washout should be avoided. More treatment options and higher-quality trials are needed.

Because there is no published experience with molindone during breastfeeding, other antipsychotic agents are preferred.

The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.

Psychotic disorders include schizophrenia, the manic phase of manic-depressive illness (bipolar illness), acute psychosis and other conditions marked by acute, severe agitation. The antipsychotic medications are invaluable adjuncts to the treatment of psychosis and bipolar illness and have revolutionized management of these conditions. The antipsychotic agents in clinical use include the phenothiazines and structurally similar compounds such as thioxanthenes, benazepines, butyrophenones, diphenylbutylpiperidines and miscellaneous similar heterocyclic compounds. The antipsychotic medications are usually classified into conventional and atypical agents, based upon relative risks for extrapyramidal side effects that are greater with the older, conventional agents. They are also referred to as first and second generation antipscyhotic agents. The initial antipsychotic medications introduced into clinical practice were the phenothiazines, but they have been largely replaced in recent years by the atypical agents. Phenothiazines in current use (with initial brand names and date of first approval) include chlorpromazine (Thorazine: 1957, the initial prototype antipsychotic agent), fluphenazine (Prolixin: 1972), perphenazine (Trilafon: 1957), prochlorperazine (Compazine: 1956, used mostly as therapy of nausea rather than psychosis), thioridazine (Mellaril: 1978), and trifluoperazine (Stelazine: 1959). Miscellaneous conventional antipsychotic medications include haloperidol (Haldol: 1967), loxapine (Loxitane: 1976), molindone (Moban: 1974) and pimozide (Orap: 1984, used largely for Tourette syndrome). Lithium is also frequently discussed in the context of antipsychotic therapies, although its major use is for stabilization of bipolar illness.

Objective: Catatonia is a life-threatening psychomotor syndrome that occurs in approximately 10% of patients with acute psychiatric illnesses. Although some case reports have argued that first generation antipsychotics (FGAs) are more likely to induce catatonia than second generation antipsychotics (SGAs), no large observational study has confirmed this hypothesis. We investigated whether FGAs were associated with an increased risk of reporting catatonia when compared with SGAs.

Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be challenging due to conflicting information from evidence and guidelines and unidentified care needs may remain unmet.We searched for systematic reviews, meta-analyses and umbrella reviews of EOS pharmacological treatment published in PubMed over the past 10 years and selected five clinical guidelines from Europe, North-America and Australia. Based on predefined outcomes, we critically compared the evidence supporting EOS-approved drugs in Europe and/or North-America with guidelines recommendations. We also evaluated the coverage of these outcomes to identify unmet needs.One systematic review, nine meta-analyses and two umbrella reviews (k=203 trials, N=81,289 participants, including duplicated samples across selected articles) were retrieved. Evidence supported the efficacy of aripiprazole, clozapine, haloperidol, lurasidone, molindone, olanzapine, quetiapine, risperidone and paliperidone in EOS, all of which obtained approval for EOS either in Europe and/or in North-America. Cognition, functioning and quality of life, suicidal behaviour and mortality and services utilisation and cost-effectiveness were poorly covered/uncovered.Among the antipsychotics approved for EOS, aripiprazole, lurasidone, molindone, risperidone, paliperidone and quetiapine emerged as efficacious and comparably safe options. Olanzapine is known for a high risk of weight gain and haloperidol for extrapyramidal side-effects. Treatment-resistant patients should be offered clozapine. Future long-term trials looking at cognition, functioning, quality of life, suicidal behaviour, mortality, services utilisation and cost-effectiveness are warranted. Closer multi-agency collaboration may bridge the gap between evidence, guidelines and approved drugs.

Emotional dysregulation (ED) manifesting as irritability or aggression produces appreciable impairment in children with attention deficit hyperactivity disorder and a main reason why they present for treatment. Central nervous system (CNS) stimulants seem to be a safe and tolerable treatment of most youth with these presentations. Optimization of CNS stimulants dose in combination with psychosocial interventions led to reductions in ED. Randomized controlled trials support that addition of risperidone further reduces aggression when these treatments are not sufficient. There is evidence for the efficacy of divalproex, molindone and selective serotonin reuptake inhibitor improve these outcomes when used as adjunct to CNS stimulants.