Daniel M. Bennett

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients’ mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging “hyperconnectivity hypothesis” in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.

A comparison of ECT dosing methods using a clinical sample

BACKGROUND Several methods have been used to determine ECT dose based on formulae, protocols or fixed-dosing. This study aims to explore the relative utility of these ECT dosing methods. METHODS A sample of ECT patients from Aberdeen was analysed. Seizure thresholds derived empirically were used to calculate the proportions of patients who would have had a therapeutic stimulus had Half-Age or a fixed-dosing method (200 mC for those <65 years old and 250 mC for those >65 years old) been used. RESULTS 62 patients were included. Initial seizure threshold varied 6 fold across the sample. Using the Half Age method 19.4% would have had a therapeutic seizure at first stimulation compared with 61.3% using an age based fixed protocol and 0% using the Royal College recommended dose titration method. Half Age and Fixed Dosing would have significantly (p<.0001) reduced the number of stimulations, the cumulative electrical dose delivered, the complexity of the procedure and the number of treatment sessions required. LIMITATIONS This study applies only to patients receiving bilateral ECT for a major depressive episode. It uses a pragmatic design to explore a common clinical issue. This allows the feasibility of further work to be explored as this would be precluded by ethical concerns otherwise. It also uses ECT parameters which are common in UK practice which may limit its applicability internationally. CONCLUSIONS Age based fixed-dosing would simplify the ECT process and result in more patients receiving effective treatment at first stimulation.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial.

Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT.

Anticonvulsant Mechanisms of Electroconvulsive Therapy and Relation to Therapeutic Efficacy.

Background Electroconvulsive therapy (ECT) is held to confer anticonvulsant effects, although the role of rise in seizure threshold upon clinical effect is uncertain. This study investigated the relationship in a large, consecutive, retrospective sample of patients receiving ECT in Aberdeen. We have tested the hypotheses of previous authors to further examine the relationship between seizure and therapeutic effect as well as discuss the potential underlying neurobiological mechanisms. Methods All patients receiving ECT at the Royal Cornhill Hospital between 2000 and the end of 2008 were identified from the Scottish ECT Accreditation Network. Electroconvulsive therapy was administered twice weekly with a bifrontotemporal electrode placement using routine dosage schedules. Data were gathered from the Scottish ECT Accreditation Network and case notes regarding ECT course and clinical effect. Results The seizure threshold increased in 219 (94.4%) patients, stayed the same in 13 (5.6%) patients, and decreased in 0 patient (n = 232). No significant relationship was present between change in seizure threshold and change in Montgomery-Asberg Depression Rating Scale score (P = 0.39; Kendall &tgr; b r = 0.047; n = 182), although responders did display greater increase in seizure threshold than nonresponders. Conclusions Electroconvulsive therapy confers anticonvulsant effects in a consecutive sample of real-life patients. Neither initial seizure threshold nor magnitude of seizure threshold increase is a predictor of clinical response to ECT. A rise in seizure threshold is not essential for therapeutic effect but may represent an important marker of underlying neuronal state. The evidence reviewed in this article supports a link between neuroplastic effects of ECT and the evidenced rise in seizure threshold.

Differences in Cognitive Outcomes After ECT Depending on BDNF and COMT Polymorphisms.

Objective The study aimed to explore cognitive outcomes after electroconvulsive therapy (ECT) depending on which version of common single nucleotide polymorphisms the patient expressed for brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT). Methods A total of 87 patients from the clinical ECT service in Aberdeen, Scotland, were included in the study. Cognitive function testing (using Spatial Recognition Memory task from the Cambridge Neuropsychological Test Automated Battery and Mini–Mental State Examination) and mood ratings (Montgomery-Åsberg Depression Rating Scale) were performed before ECT, after 4 treatments, at the end of ECT and 1 and 3 months after the end of treatment. These scores were compared depending on BDNF and COMT variant at each time point using the Student t test and using a time series generalized least squares random effects model. Results No differences were found between the val and met versions of the BDNF or COMT polymorphism in either cognitive or mood outcomes at any time point during ECT treatment or up to 3 months of follow-up. Conclusions This study did not detect significant differences in cognitive or mood outcomes between patients who have the val66val or met versions of the BDNF polymorphism. Our results suggest that these polymorphisms will not be helpful in clinical practice for predicting cognitive outcomes after ECT.

Assessing the Association Between Electrical Stimulation Dose, Subsequent Cognitive Function and Depression Severity in Patients Receiving Bilateral Electroconvulsive Therapy for Major Depressive Disorder.

Objective To assess the relationship between electrical stimulation administered to patients undergoing bilateral electroconvulsive therapy (ECT) and subsequent measures of cognitive function and depression severity. Methods Stimulus dose titrated patients receiving bilateral ECT were assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Recognition Memory test and Montgomery Asberg Depression Rating Scale (MADRS) at baseline, after 4 ECT treatments and on course completion. Changes in CANTAB and MADRS scores were assessed in relation to electrical dosage, initial stimulus dose, and demographic variables using linear mixed models. Results Data pertained to 143 patients (mean age, 56.85 [SD, 14.94], 43% male). Median change in CANTAB score was −10% (−20% to 5%) after 4 ECT treatments and −10% (−20% to 5%) at course completion. Median change in MADRS score was −22 (−33 to −13) after 4 ECT treatments and −14 (−25 to −7) at course completion. Electrical dosage had no effect on CANTAB or MADRS change scores either after 4 treatments or course completion. Improvement in CANTAB score at end of course was associated with female sex (P < 0.05), higher intelligence quotient (P = 0.01), and age. After 4 treatments, improvement in CANTAB score was associated with younger age (P < 0.001) and higher intelligence quotient (P < 0.01). Improved MADRS score at course completion was associated with older age (P < 0.001 at end of course and after 4 treatments). Conclusions Electroconvulsive therapy has significant antidepressant and cognitive effects which are not associated with the total electrical dose administered. Other, unalterable variables, such as age and sex, have an influence on these effects.

The UN Convention on the Rights of Persons with Disabilities and UK mental health legislation

The editorial by Kelly[1][1] was thought-provoking for two reasons: the implication that the United Nations Convention on the Rights of Persons with Disabilities might prevent the detention and treatment of patients who are ill, and that there was a ‘UK’ Mental Health Act 1983 modified in 2007

Appeals against detention in conditions of excessive security in Scotland

The Mental Health (Care and Treatment)(Scotland) Act 2003 introduced the provision for patients to appeal against being treated in conditions of excessive security for the first time. In this article, we examine the first 100 patients to appeal using this new provision. We compared the clinical, demographic and legal factors of these patients depending upon the outcome of the appeal. Forty-four per cent of appeals were successful compared with 22% which were rejected. There was no difference on any clinical factors studied between these groups. The main difference between the groups was that those patients who had the support of their Responsible Medical Officer and were already on the transfer list were significantly more likely to succeed p .000. We have demonstrated that legislation is an important mechanism to drive change in any forensic mental health system such as the development of medium and low secure services in Scotland.

The density and abundance of juvenile Varanus exanthematicus (Sauria: Varanidae) in the coastal plain of Ghana

The density and abundance of Varanus exanthematicus was measured by single searches and markrecapture studies at sites in the Great Accra Region of Ghana. One hour search effort yielded a mean of 0.42 lizards in August/September 1994 and 0.87 lizards in March/April 1996. Mark-recapture results indicated a density of 357 juveniles per km 2 in mixed farmland and grassland habitats.

Appeals against detention in excessive security (outcomes of appeals against detention in conditions of excessive security in Scotland)

The Mental Health (Care and Treatment) (Scotland) Act 2003 introduced the right for patients in high-security psychiatric care to appeal against detention in conditions of excessive security. A previous study examined the first 100 patients to appeal under this provision. In this study we compare them with the next cohort of 110 patients to lodge an appeal, finding, contrary to expectations, no change in patient characteristics or the outcome of their appeals. The clinical, legal and demographic features of successful and unsuccessful appellants, who made up 38% and 27% of the 110 patients, respectively, were also compared. Those patients with the support of their responsible medical officer and those already included on a transfer list had a significantly better chance of success (p = 0.00). It was also found that a history of excessive alcohol consumption was associated with successful appeals (p = 0.002). A diagnosis of learning disability was associated with unsuccessful appeals (p = 0.018), though the sub-sample was very small. These findings are important given the forthcoming extension of this right of appeal to other levels of security.