Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response.

To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences treatment response.

An open label extension (OLE) of a randomised controlled trial (RCT) was conducted at seven mood disorder centres in Australasia, enrolling consenting trial participants who had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥20 at post-trial assessment. Participants initially received twice-weekly 0.5 mg/kg subcutaneous racemic ketamine (fixed regimen) for 4 weeks. Dosing was revised after a Data Safety Monitoring Board recommendation, to a ‘flexible regimen’ (0.5–0.9 mg/kg with response-guided increments). Depression and safety outcomes were assessed throughout treatment, and 4 weeks and 6 months later.

130 RCT participants entered the OLE phase of whom 32 underwent the fixed OLE regimen and 98 the flexible regimen. At treatment end, 30% (36/116) had responded (MADRS reduction ≥50%), and 4 weeks later 17% (19/110) were ‘responders’. Over 50% experienced <25% MADRS reduction. There was no difference in depression response at any time point between regimens. Those treated with ketamine during the RCT showed a transient reduced response after first OLE treatment but at no other assessment point. There were no reports of suicide or suicidal behaviour requiring admission and only expected side-effects observed.

In a highly treatment-resistant sample, a 4-week course of subcutaneous racemic ketamine produced short-term clinical benefit in a minority of participants, with response rates declining substantially after treatment cessation, and no unexpected safety concerns. Exploratory subgroup analyses showed no association between prior RCT ketamine exposure and OLE outcomes.

ACTRN12616001096448 at www.anzctr.org.au.

Scimitar syndrome is a rare CHD composed of partial anomalous pulmonary venous connection from the right lung, via a scimitar vein, to the inferior vena cava rather than the left atrium. Genetic conditions associated with scimitar syndrome have not been well investigated at present.

Our study included patients with scimitar syndrome diagnosed at Texas Children’s Hospital from January 1987 to July 2020. Medical records were evaluated to determine if genetic testing was performed, including chromosomal microarray analysis or whole-exome sequencing. Copy number variants identified as pathogenic/likely pathogenic and variants of unknown significance were collected. Analyses of cardiac and extracardiac findings were performed via chart review.

Ninety-eight patients were identified with scimitar syndrome, 89 of which met inclusion criteria. A chromosome analysis or chromosomal microarray analysis was performed in 18 patients (20%). Whole-exome sequencing was performed in six patients following negative chromosomal microarray analysis testing. A molecular genetic diagnosis was made in 7 of 18 cases (39% of those tested). Ninety-six per cent of the cohort had some type of extracardiac finding, with 43% having asthma and 20% having a gastrointestinal pathology. Of the seven patients with positive genetic testing, all had extracardiac anomalies with all but one having gastrointestinal findings and 30% having congenital diaphragmatic hernia.

Genetic testing revealed an underlying diagnosis in roughly 40% of those tested. Given the relatively high prevalence of pathogenic variants, we recommend chromosomal microarray analysis and whole-exome sequencing for patients with scimitar syndrome and extracardiac defects.

Electroconvulsive therapy (ECT) is recommended in treatment guidelines as an efficacious therapy for treatment-resistant depression. However, it has been associated with loss of autobiographical memory and short-term reduction in new learning.

To provide clinically useful guidelines to aid clinicians in informing patients regarding the cognitive side-effects of ECT and in monitoring these during a course of ECT, using complex data.

A Committee of clinical and academic experts from Australia and New Zealand met to the discuss the key issues pertaining to ECT and cognitive side-effects. Evidence regarding cognitive side-effects was reviewed, as was the limited evidence regarding how to monitor them. Both issues were supplemented by the clinical experience of the authors.

Meta-analyses suggest that new learning is impaired immediately following ECT but that group mean scores return at least to baseline by 14 days after ECT. Other cognitive functions are generally unaffected. However, the finding of a mean score that is not reduced from baseline cannot be taken to indicate that impairment, particularly of new learning, cannot occur in individuals, particularly those who are at greater risk. Therefore, monitoring is still important. Evidence suggests that ECT does cause deficits in autobiographical memory. The evidence for schedules of testing to monitor cognitive side-effects is currently limited. We therefore make practical recommendations based on clinical experience.

Despite modern ECT techniques, cognitive side-effects remain an important issue, although their nature and degree remains to be clarified fully. In these circumstances it is useful for clinicians to have guidance regarding what to tell patients and how to monitor these side-effects clinically.

Trinucleotide repeats have been associated with schizophrenia, but the evidence, based on cross-sectional clinical information, is equivocal.

To examine the relationship between genomic CAG/CTG repeat size and premorbid development in schizophrenia.

Early development and premorbid functioning of 22 patients with DSM-IV diagnosis of schizophrenia were assessed by parental interviews. Repeat expansion detection (RED) technique was used to measure genomic CAG/CTG repeat size, and PCR for CAG repeat size at the ERDA-1 and CTG 18.1 loci.

There was an inverse association between CAG/CTG size and perinatal complications. Patients with speech and motor developmental delay had larger repeats. The results were not due to expansion in the ERDA-1 and CTG 18.1 genes.

CAG/CTG repeat expansion is associated with speech and motor developmental delay in schizophrenia. We propose that the developmental model may be useful for research into the genetics of schizophrenia.

The Treatment Algorithm Group (TAG) was supported logistically by Servier who provided financial assistance with travel and accommodation for those TAG members travelling interstate or overseas to attend the meeting in Sydney (held on 18 November 2017). None of the committee were paid to participate in this project and Servier have not had any input into the content, format or outputs from this project.