General Psychiatry

Article information
Title: Suicide risk among emergency care patients: Exploring incidental risk detection during routine care
PubMed ID: 42214265
First Author Last Name: Boudreaux

Abstract:
Background:
Universal screening improves detection of suicide risk in emergency department (ED) patients presenting with a medical chief complaint, referred to as incidental risk. We sought to better understand characteristics of individuals who present with incidental suicide risk and evaluate their suicide-related outcomes after the ED visit.

Methods:
The Emergency Department Safety Assessment and Follow-up Evaluation 2 (ED-SAFE 2) trial involved eight geographically diverse EDs. We randomly sampled data from two samples (cross-sectional, longitudinal) to compare patients with incidental risk to those with either negligible (i.e., screened negative for suicide risk) or congruent risk (i.e., behavioral health patients with suicide risk), as well as evaluate suicide-related outcomes in the 24 weeks after the ED visit. Chi-square tests, Student's t-tests, Fisher's exact tests, and one-way ANOVAs were used.

Results:
The relative percentage of incidental versus congruent risk was largely similar across sex, race, and ethnicity groups. Those with congruent or incidental risk were younger than those with negligible risk. Compared to congruent risk, incidental risk was driven more frequently by a past suicide attempt without recent ideation and was less likely to result in a behavioral health evaluation or intervention during the visit. Both congruent and incidental risk groups had substantial post-visit suicidal behavior, though rates were higher with congruent risk.

Conclusions:
ED patients with suicide risk incidental to their chief complaint often have significant risk factors for suicide and exhibit elevated post-visit suicidal behavior but are less likely than those with congruent risk to receive a behavioral health evaluation or intervention during the visit.

Annotation
The finding:
In this observational sub-analysis from a large study of ED-based suicide screening and risk reduction (ED-SAFE 2), the authors tracked suicide-related outcomes for ~3,500 ED patients with congruent positive suicide screens (i.e. they screened positive for suicidality and their reason for ED presentation was related to this suicidality) and ~1,000 ED patients with incidental positive screens (i.e. they screened positive for suicidality but had presented to the ED for unrelated reasons). Those with incidental positive screens had a lower, but still substantial, rate of a composite of suicide death or repeat suicide-related ED presentation: 7% vs. 14% over 4 weeks. Incidentally identified patients were much less likely to see a mental health provider (~30% vs. ~90%) or be psychiatrically admitted (~10% vs. ~50%).

Strength and weaknesses:
This study represents a truly astounding amount of manual chart review – two separate samples of about 7,000 patients each. For some outcomes, such as identifying a patient’s disposition or whether they saw a mental health provider, manual chart review is the gold standard means of ascertainment, and no computerized approach can compare. But for other outcomes, such as repeat ED presentations or suicide attempts in general, other means of outcome ascertainment such as claims data would likely capture many more events.

Relevance:
This paper provides some intriguing insights into a common but under-studied scenario – the patient who comes to the ED for a physical health concern, but winds up seeing a psychiatrist after being screened for suicidality in triage. It’s easy to feel dismissive about these consultations – after all, the mere fact of having come to the hospital for medical concerns demonstrates future orientation – but this paper suggests you should avoid that impulse. While patients with incidentally positive suicide screens did indeed have lower rates of subsequent suicidal behavior, it wasn’t that much lower – and a recently-published paper from the same research group using a different sample (Boudreaux, Archives of Suicide Research 2025) actually found equivalent rates of subsequent suicidality in incidentally identified vs. congruent patients.

Article information
Title: Mirtazapine for Methamphetamine Use Disorder A Randomized Clinical Trial
PubMed ID: 41920558
First Author Last Name: McKetin

Abstract:
Importance:
Methamphetamine use disorder is a global health challenge for which there are no approved pharmacotherapies. The safety and effectiveness of mirtazapine, a promising candidate for methamphetamine use disorder, has not been established in routine clinical practice.

Objective:
To determine the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder in routine clinical practice.

Design, setting, and participants:
This phase 3, parallel-group, double-blind, placebo-controlled randomized clinical trial was conducted between November 16, 2022, and May 1, 2025, at 6 outpatient alcohol and other drug clinics in Australia among adults with moderate to severe methamphetamine use disorder. Data analysis was conducted from May to September 2025.

Intervention:
Mirtazapine (30 mg daily for 12 weeks) or equivalent placebo.

Main outcomes and measures:
The primary end point was the change in days of methamphetamine use in the past 28 days from baseline to week 12. Secondary end points were depression, insomnia, HIV risk behavior, quality of life, and methamphetamine-negative oral fluid samples.

Results:
Of 344 participants randomized, 339 participants received the intervention (167 in the placebo group and 172 in the mirtazapine group). Mean (SD) age was 42.0 (8.6) years, 126 participants (37.2%) were female, and participants had used methamphetamine for a median (IQR) of 24 days (17-28) of the past 28 days at baseline. The mean reduction in days of methamphetamine use from baseline to week 12 was greater in the mirtazapine group (7.0 days of 28 days) than in the placebo group (4.8 days of 28 days; mean difference, 2.2 days; 95% CI, -4.2 to -0.2 days; P = .02). More participants in the mirtazapine group reported drowsiness (47% vs 33%) and weight gain (10% vs 3%). Forty participants (23%) discontinued mirtazapine due to adverse events compared to 25 participants (15%) in the placebo group. No significant effects of mirtazapine on secondary end points were found.

Conclusions and relevance:
In this parallel-group randomized clinical trial, mirtazapine delivered in routine clinical practice reduced methamphetamine use in adults with methamphetamine use disorder. No unexpected safety concerns delivering mirtazapine in this setting were found; this finding has important clinical implications in the absence of any approved pharmacotherapies for methamphetamine use disorder.

Annotation
The finding:
In this well-sized RCT in outpatients with fairly severe methamphetamine use disorder (using >80% of days on average), mirtazapine met its primary endpoint: it reduced the number of days per month that patients reported using methamphetamine by about 2 compared to placebo. Unfortunately, its overall effect size was small, and it notably did not produce a statistically significant effect on confirmatory biochemical tests – the rate of methamphetamine-negative oral fluid samples increased only from 12.0% to 13.2%.

Strength and weaknesses:
This is a well-powered, well-conducted study in a challenging population. Given the modest benefits of mirtazapine identified, I’d be more convinced of its genuine efficacy if there was clear concordance between primary and secondary outcomes, or between self-report and biochemical outcomes – but that’s not a knock on the design of the study itself. Previous RCTs of mirtazapine for methamphetamine use disorder have focused on a subpopulation of men who have sex with men, and have tended to find small but significant benefits. This study expands eligibility to a broader population and includes a larger sample of patients, both of which are significant contributions.

Relevance:
There are few pharmacologic treatments that have been shown to effectively treat methamphetamine use disorder, and none that have dramatic efficacy – so relative to what else is available, mirtazapine seems to work decently well, and that’s now been demonstrated in three credible RCTs. Don’t expect miracles, but especially for patients with other indications for mirtazapine, it’s worth a shot in patients with intractable methamphetamine use.

Article information
Title: Comparative effectiveness and safety of pharmacological treatments for rapid tranquilisation in emergency settings: a systematic review and individual participant data network meta-analysis
PubMed ID: 42259329
First Author Last Name: Siafis

Abstract:
Background:
Several medications are available for rapid tranquilisation in psychomotor agitation, but choosing among them varies across local practices and this variation is compounded by inconsistent guidelines. We performed a systematic review with individual participant data network meta-analysis to inform evidence-based recommendations.

Methods:
In this systematic review and individual participant data meta-analysis, we searched multiple databases from database inception to Nov 14, 2025, for randomised trials comparing intramuscular or intravenous treatments for rapid tranquilisation (primary outcome defined as sedation within 15-30 min) in patients with psychomotor agitation in general or psychiatric emergency settings. Anonymised individual participant data were collected and harmonised into a common dataset. Risk of bias was assessed using the RoB 2 tool. We performed Bayesian one-stage random-effects individual participant data network meta-regressions, accounting for between-study heterogeneity, drug classes, prognostic factors, and subgroup effects based on agitation severity. We combined individual participant data and aggregate data to evaluate side-effects. Confidence in the evidence was assessed using the Confidence In Network Meta Analysis (CINeMA) framework. People with lived experience were involved in the design and interpretation of the findings. The protocol was registered with PROSPERO (CRD42023402365).

Findings:
We included 18 trials across eight regions (3411 participants; 1988 [58·3%] men, 1423 [41·7%] women; mean age 36·0 [SD 11·7] years), of which 13 trials (2705 participants) provided individual participant data for antipsychotics, benzodiazepines, and their combination. In moderate agitation, odds of achieving sedation relative to haloperidol monotherapy were higher with antipsychotic-benzodiazepine combinations (odds ratio [OR] 12·93, 95% credible interval [95% CrI] 3·00-50·91; relative risk [RR] 1·58), benzodiazepines (5·52, 1·37-21·02; 1·49), and other antipsychotics (4·54, 1·35-14·45; 1·45). In severe agitation, antipsychotic-benzodiazepine combinations were more effective than haloperidol (4·86, 1·28-17·54; 1·73), whereas results were uncertain for benzodiazepines (2·09, 0·58-6·99; 1·38) and other antipsychotics (1·70, 0·62-4·59; 1·28). Confidence in these estimates was very low, mainly due to imprecision and heterogeneity. Haloperidol monotherapy was associated with higher risk of extrapyramidal side-effects and benzodiazepines, alone or in combination, with hypotension.

Interpretation:
Antipsychotic-benzodiazepine combinations might be among the most effective options for rapid tranquilisation in patients with psychomotor agitation but carry a risk of hypotension, whereas haloperidol monotherapy appeared among the least effective and is associated with extrapyramidal side-effects. These findings should be contextualised to the specific setting and patient characteristics, including the underlying agitation aetiology. Large trials are needed to provide more precise recommendations.

Annotation
The finding:
In this network meta-analysis comparing various treatments for agitation in emergency department settings, several noteworthy differences between medications emerged. Haloperidol was consistently the least effective medication at establishing rapid sedation and carried the highest risk of extrapyramidal side effects. When grouped by class, other antipsychotics, benzodiazepines alone, and antipsychotics plus benzodiazepines all outperformed haloperidol. And when broken down by individual medication (as shown in the supplementary appendix), differences were largely nonsignificant, but revealed the following ranking of efficacy, from fastest to slowest: droperidol-midazolam, midazolam, droperidol, haloperidol-midazolam, olanzapine, haloperidol, lorazepam.

Strength and weaknesses:
The authors went to great lengths to gather as much individual patient data as possible to inform their analysis – even to the point of harassing researchers by phone when they didn’t respond to email requests to share their data! However, these efforts did not yield a lot of statistically significant findings, which the authors tried to address by grouping medications into larger categories – but unfortunately, their use of pharmacologic categories winds up combining medications with quite different speeds of onset (e.g. lorazepam and midazolam), which I worry only clouds their overall findings.

Relevance:
While CL psychiatrists will continue to use IV haloperidol in medical inpatients, there’s little justification for using it as monotherapy in agitated ED patients – it works slowly (putting patients and staff at risk of violence) and it carries a high risk of EPS to boot. Droperidol, olanzapine, midazolam, and combinations of these agents are all more rapidly effective than haloperidol – with droperidol-midazolam likely the best combination to reach for (short of ketamine) when a patient is agitated enough to require the fastest sedation possible.