Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

Western Australia's response to the COVID-19 pandemic was swift and effective in implementing public health protections and preventing the spread of the virus for the first 2 years. However, healthcare staff continued to be at increased risk of mental health concerns.

To investigate the longitudinal patterns of post-traumatic stress symptoms (PTSS), depression and anxiety among healthcare workers in Western Australia, and the risk and protective factors associated with changes in status during the first wave.

Participants comprised 183 healthcare staff working at tertiary hospitals and major clinics across Perth, for whom longitudinal data were available. Questionnaire data were collected before Western Australia's first major COVID-19 community wave in early 2022 and following the first wave in late 2022. Online surveys comprised validated measures assessing psychological symptoms, risk and protective factors, and original measures of workplace factors.

Overall rates of PTSS, depression and anxiety remained stable across the two assessment points. However, latent growth models revealed that those with lower PTSS, depression or anxiety symptoms at baseline reported a larger increase in symptoms over time, and those with higher symptoms at baseline had a smaller decline over time, indicating a ‘catch-up’ effect. Workplace stressors, sleep difficulties and trauma exposure were key risk factors for changes in psychological symptoms from baseline, and workplace and social supports played protective roles.

Improvements in systemic workplace factors are needed to support healthcare workers’ mental health during periods of acute stress, even in settings with high levels of emergency preparedness.

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

It is clinically imperative to better understand the relationship between trauma, auditory hallucinations and dissociation. The personal narrative of trauma has enormous significance for each individual and is also important for the clinician, who must use this information to decide on a diagnosis and treatment approach.

To better understand whether dissociation contributes in a significant way to hallucinations in individuals with and without trauma histories.

Three groups of participants with auditory hallucinations were recruited, with diagnoses of: schizophrenia (without trauma) (n = 18), post-traumatic stress disorder (PTSD, n = 27) and comorbid schizophrenia and PTSD (SCZ+PTSD), n = 26). Clinician-administered measures included the PTSD Symptoms Scale Interview (PSSI-5), the Clinician-Administered Dissociative States Scale (CADSS) and the Psychotic Symptom Rating Scales (PSYRATS).

Dissociative symptoms were significantly higher in participants with trauma histories (PTSD and SCZ+PTSD groups) and significantly correlated with hallucinations in trauma-exposed participants, but not in participants with schizophrenia (without trauma history). Hallucination severity was correlated with the CADSS amnesia subscale score, but depersonalisation and derealisation were not.

Dissociation may be a mechanism in trauma-exposed individuals who hear voices, but it does not explain all hallucinatory experiences. The SCZ+PTSD group were in an intermediary position between schizophrenia and PTSD on dissociative and hallucination measures. The PTSD and SCZ+PTSD groups experienced dissociative phenomena much more frequently than the schizophrenia group, with a significant trend towards the amnesia subtype of dissociation.

Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.

To review systematically all evidence relating to jitteriness/ anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.

A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.

Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.

Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

The importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known. A key role for postsynaptic 5-HT1A receptors has recently been suggested in studies of genetic knockout mice.

To measure 5-HT1A receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs).

Nine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT1A tracer [11C]WAY-100635.

In comparison with controls, both presynaptic and postsynaptic 5-HT1A receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala. In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding.

Panic disorder is associated with reduced 5-HT1A receptor availability, which is also known to have a key role in depression.