Old age liaison psychiatry during COVID-19; an audit of pre- and mid-pandemic service provision.

Older adults in acute hospitals are uniquely vulnerable to mental illness during the COVID-19 pandemic. We describe two eighteen-week periods of specialised liaison psychiatry for older inpatients in a large teaching hospital, pre- and mid-pandemic. Service delivery went from almost completely via face-to-face consultation in the Routine period, to majority remote work in the Pandemic period. During the Routine period, 195 patients were assessed, and patients received a mean number of 2.6 consultations (range 1-15). In the Pandemic period, 197 patients were assessed and received 3.1 consultations on average (range 1-19). Patient age trended toward older in the Pandemic period, mean 77 years (SD 6.9) vs 78 years (SD 1.32) in the Routine period. There were more referrals for behavioural disturbance and confusion during the Pandemic period, and more diagnoses of Behavioural and Psychological Symptoms of Dementia, Delirium and Adjustment Disorder during the Pandemic period vs the Routine period.

Decision-making Capacity for Treatment After Electroconvulsive Therapy for Depression.

OBJECTIVES: Depression can impair decision-making capacity (DMC) for health care decisions. However, it is unclear whether DMC improves after treatments for depression such as electroconvulsive therapy (ECT). There is limited evidence available on DMC for treatment in patients with depression referred for ECT, and it is unknown whether ECT has any impact on DMC. We hypothesized that ECT will improve DMC in severely depressed patients and that this change will be associated with reduced depressive symptom severity. METHODS: Using the MacArthur Competence Assessment Tool-Treatment, 4 abilities related to DMC were evaluated: Understanding, Appreciation, Reasoning, and Expressing a choice. This prospective study compared DMC abilities, depression severity, and cognition scores in 24 patients hospitalized with a major depressive episode before and 3 to 5 days after a course of ECT. RESULTS: Although Understanding scores significantly improved after ECT (P = 0.004, r = 0.41), there was no change in other abilities related to DMC or cognition scores. As expected, there was a large improvement in mood ratings after ECT, but the change in DMC abilities was not associated with change in depressive symptoms. CONCLUSIONS: To our knowledge, this is the first study to provide data on the effects of ECT on DMC in patients with depression. Abilities related to DMC that may be affected in this group before treatment include Understanding and Reasoning. Findings indicate that DMC to consent to treatment mostly does not change after a course of ECT and some aspects can improve in patients with depression.

PBMC telomerase activity in depression and the response to electroconvulsive therapy.

Telomerase, the DNA polymerase responsible for maintaining telomere length, has previously been implicated in depression and the response to antidepressant drugs. In this study, we aimed to compare telomerase activity in peripheral blood mononuclear cells between patients with severe depression recruited as part of the KEEP-WELL Trial (Ketamine for Depression Relapse Prevention Following ECT; NCT02414932) and age- and sex-matched healthy volunteers both at baseline/pre-ECT and at follow-up 1 month later for controls or in patients after a course of ECT. We found no differences in telomerase activity between patients with depression (n = 20) compared to healthy controls (n = 33) at baseline/pre-ECT, or between patients treated with ECT compared to controls at follow-up. In patients, telomerase activity was not associated with mood, as assessed by the 24-item Hamilton Rating Scale for Depression, or the duration of the current depressive episode. Additionally, we found no significant relationship between telomerase activity and exposure to recent or childhood adversity in either the patient or control groups. Overall, our results suggest that telomerase activity is not associated with depression, the therapeutic response to ECT, or exposure to adversity.

Ketamine Versus Midazolam for Depression Relapse Prevention Following Successful Electroconvulsive Therapy: A Randomized Controlled Pilot Trial.

OBJECTIVE: Depression relapse after electroconvulsive therapy (ECT) is common (40% at 6 months). Ketamine has a robust antidepressant effect, but there are no reported studies of ketamine for depression relapse prevention. This pilot trial (NCT02414932) was designed to assess feasibility of the proposed trial protocol, including examining reasons for nonrecruitment, nonrandomization, and dropout. METHODS: Patients with unipolar depression referred for ECT were monitored weekly for therapeutic response, using the 24-item Hamilton Rating Scale for Depression (monitoring phase). Those who met standard response criteria were invited to be randomized to a course of 4 once-weekly infusions of ketamine (0.5 mg/kg) or the active comparator, midazolam (0.045 mg/kg), over 40 minutes to examine trial processes (treatment phase). Participants were followed up for 6 months after ECT to assess for relapse. RESULTS: One hundred seventy-five referrals were screened over 18 months, and 68% of eligible participants (n = 43) were recruited to the monitoring phase; 60.5% of participants met ECT response criteria (n = 26), but only 26% (6) of these consented to take part in the treatment phase. These were randomized (3 to ketamine and 3 to midazolam), and no participant completed the 4-week treatment protocol. Information was gathered on reasons for nonrecruitment, nonrandomization, and dropout, which included practical aspects of infusions and lack of interest in further treatment after response to ECT. CONCLUSIONS: The proposed treatment protocol is not suitable for a definitive trial in our center. Information collected on reasons for dropout may inform future clinical trials of intravenous ketamine. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02414932.

Peripheral blood SIRT1 mRNA levels in depression and treatment with electroconvulsive therapy.

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+) dependent enzymes that regulate cellular functions through deacetylation of protein targets. They have roles in both the periphery and central nervous system and have been implicated in depression biology. A recent genome-wide association study has identified a locus for major depression in the Sirtuin1 gene (SIRT1) and lower blood levels of SIRT1 mRNA in patients with depression have also been observed in two studies. To our knowledge, no studies have examined the effect of treatment on SIRT1 levels in patients with depression. We therefore examined SIRT1 mRNA levels in a well characterised group of patients with depression, compared to healthy controls, and characterised the effects of a course of electroconvulsive therapy (ECT) on peripheral blood SIRT1 mRNA. Depressed patients (n = 91) were matched to healthy controls (n = 85) on the basis of age and sex. In line with previous studies, blood SIRT1 mRNA levels were lower in depressed patients in comparison to controls (p = 0.005). However, ECT had no effect on SIRT1 levels (p = 0.67). There was no relationship between baseline pre-ECT SIRT1 levels and depression severity, change in mood scores, suicidality, depression polarity, presence of psychosis, or response to treatment. There was a trend for a negative association between an increase in SIRT1 mRNA and a decrease in HAM-D24 scores in ECT responders and remitters. These results indicate that reduced peripheral blood SIRT1 mRNA could be a trait feature of depression.

Involuntary and voluntary electroconvulsive therapy: A case-control study.

BACKGROUND: It is not known whether results of clinical research in ECT can be used to guide treatment decisions for those having involuntary ECT, who are not represented in trial populations. OBJECTIVE: We aimed to compare courses of involuntary ECT with matched voluntary ECT courses in terms of clinical and demographic factors, treatment requirements, and outcomes. METHOD: We performed a retrospective case-control study examining a five-year sample of involuntary ECT courses and an age-, gender- and time-matched voluntary ECT control sample. RESULTS: We examined 48 involuntary and 96 control voluntary ECT courses. While groups differed at baseline in terms of diagnosis, illness severity and illness characteristics, there were no differences in treatment outcomes after ECT or six-month readmission rates. CONCLUSION: Our findings suggest that research on capacitous ECT patients is applicable to those having involuntary ECT.

Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial).

BACKGROUND: Major depressive disorder is a common debilitating illness that is the second leading contributor to the global burden of disease. Unfortunately, about 30 % of patients do not respond to adequate trials of antidepressants and/or psychotherapies. About 45-60 % of such treatment-resistant patients will remit with electroconvulsive therapy (ECT). However, relapse rates are high following ECT-38 % after 6 months. There is a need for better relapse prevention strategies. One possibility is to use ketamine, a competitive glutamate receptor antagonist used for anaesthesia. A recent paradigm shift in treating depression and understanding its biology has been the finding that ketamine has a robust, rapid-onset, though short-lived, antidepressant effect that is possibly mediated through neuroplastic effects. However, ketamine has not previously been reported on for relapse prevention. METHODS/DESIGN: The main objective of this study is to conduct a randomised controlled pilot trial (n = 40) of a 4-week course of once-weekly ketamine infusions for relapse prevention following ECT for depression to assess trial procedures that will inform a future definitive trial. Participants with unipolar depression will be recruited prior to commencing ECT and be assessed weekly during the ECT course using the primary clinical outcome, the 24-item Hamilton Rating Scale for Depression (HRSD-24). Those who meet standard response criteria will be invited, on completing ECT, to be randomised in a 1:1 ratio to a course of four once-weekly infusions of ketamine or an active comparator midazolam, which mimics some of the effects of ketamine and may improve blinding over inactive placebo. Participants will be followed up over 6 months using the HRSD-24 to assess for relapse. DISCUSSION: This is the first registered trial (NCT02414932, https://clinicaltrials.gov/ct2/show/NCT02414932) of ketamine for depression relapse prevention, an important possible use of this agent. The primary focus of the pilot trial is on feasibility. However, a 95 % confidence interval will be determined for the difference between ketamine and midazolam groups in 6-month relapse rates to help inform a future definitive trial. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT02414932 Secondary Identifying numbers: EudraCT number: 2014-000339-18 Sponsors' Reference, Sponsor: St. Patrick's Mental Health Services: 05/14 Research Ethics Committee Reference, Joint REC of St James' and Tallaght Hospitals, Dublin: 2014-08-19.

Socioeconomic status at birth and risk for first episode psychosis in rural Ireland: Eliminating the features of urbanicity in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: There is a paucity of research on the relationship between social environment at birth and risk for psychosis in rural settings. This study examined the relationship between individual- and neighbourhood-level socioeconomic indicators proximal to the time of birth and risk for a first psychotic episode in a rural context using a prospective dataset of unusual epidemiological completeness. METHODS: A matched case-control design was used. 186 cases were identified from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) and 679 age- and sex-matched controls from the same rural setting were identified and analysed for relationships with individual and neighbourhood-level socioeconomic indicators at the level of Electoral Divisions. RESULTS: While neither the distribution nor the ordinal scale of parental social class differed between cases and controls, logistic regression revealed both parental social class III and increasing level of rurality to be associated (p≤0.05) with reduced risk for affective psychosis. There was a prominent relationship (p<0.001) between lower parental social class and older age at first presentation [mean age at first presentation for all psychoses: social class I, 22.8; social class VI, 44.3]. CONCLUSIONS: These findings indicate modest effects of individual- and neighbourhood-level socioeconomic indicators and risk for psychosis by place at birth within a rural environment. Thus, these factors are not confined to large urban settings and apply across the urban-rural continuum. The substantive finding in relation to age at first presentation may indicate that a gradient of socioeconomic position is influential on delay in presentation to mental health services.