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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.
Aims
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.
Method
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.
Results
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.
Conclusions
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.
There is currently little consensus as to how burnout is best defined and measured, and whether the syndrome should be afforded clinical status. The latter issue would be advanced by determining whether burnout is a singular dimensional construct varying only by severity (and with some level of severity perhaps indicating clinical status), or whether a categorical model is superior, presumably reflecting differing ‘sub-clinical’ versus ‘clinical’ or ‘burning out’ vs ‘burnt out’ sub-groups. This study sought to determine whether self-diagnosed burnout was best modelled dimensionally or categorically.
Methods:
We recently developed a new measure of burnout which includes symptoms of exhaustion, cognitive impairment, social withdrawal, insularity, and other psychological symptoms. Mixture modelling was utilised to determine if scores from 622 participants on the measure were best modelled dimensionally or categorically.
Results:
A categorical model was supported, with the suggestion of a sub-syndromal class and, after excluding such putative members of that class, two other classes. Analyses indicated that the latter bimodal pattern was not likely related to current working status or differences in depression symptomatology between participants, but reflected subsets of participants with and without a previous diagnosis of a mental health condition.
Conclusion:
Findings indicated that sub-categories of self-identified burnout experienced by the lay population may exist. A previous diagnosis of a mental illness from a mental health professional, and therefore potentially a psychological vulnerability factor, was the most likely determinant of the bimodal data, a finding which has theoretical implications relating to how best to model burnout.
The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification.
Aims
To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions.
Method
We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition.
Results
Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses.
Conclusions
Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions.
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