Is Conduct of Research in Electroconvulsive Therapy Ethical?

INTRODUCTION: Controversy surrounding ECT creates skepticism about the ethics of conducting ECT research. This paper discusses the ethical conduct of clinical research and then focus on the ethics as applied to ECT. METHODS: PubMed was searched for articles related to the ethical conduct of research and that of ECT research published in English. RESULTS: ECT research is ethically justified and should always continue to be conducted with the highest ethical standards. ECT research entails few ethical peculiarities such as involving multiple sessions were capacity to consent can change. It would be unethical not to conduct ECT research. CONCLUSION: ECT research must be based on sound hypotheses in the presence of a clinical equipoise in well-designed studies. ECT studies must select a fair and non-biased sample of participants. It is important that participants represent the broad population of the people that would be receiving ECT for that specific indication. ECT research is ethical; and more research in this field could help decrease stigma and barriers to treatment, and/or reduce side effects and improve efficacy of a potentially life-saving intervention.

Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a safe and effective treatment for major depression. We describe quality of life (QOL) outcomes from acute treatment with TMS, and describe the durability of benefit across 24-weeks. METHODS: Three hundred and one medication-free patients with pharmacoresistant major depression were randomized to active or sham TMS in a 6-week controlled trial. Nonresponders to the 6-week blinded phase of the study were enrolled in a 6-week open-label study without unblinding the prior treatment assignment. Responders and partial responders to both the blinded (active or sham treatment) or open acute treatment phases were tapered off TMS over three weeks, while initiating maintenance antidepressant medication monotherapy. These subjects entered the 24-week study to examine the durability of response to TMS. The Medical Outcomes Study-36 Item Short Form (SF-36) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to measure overall function and QOL. During the 24-week durability of effect study, QOL assessments were done at study entry and at the end of 24-weeks. RESULTS: Statistically significant improvement in both functional status and QOL outcomes was observed in patients treated with active TMS compared with sham TMS during the acute phase of the randomized, sham-controlled trial. Similar benefits were observed in patients who entered the open-label extension study. These improvements were sustained across the 24-week follow up study. CONCLUSIONS: Acute treatment with TMS improved functional status and QOL outcomes in patients with major depression. This clinical effect was durable in long-term follow up.

A prospective study of religion/spirituality and depressive symptoms among adolescent psychiatric patients.

OBJECTIVE: Previous research has uncovered relationships between religion/spirituality and depressive disorders. Proposed mechanisms through which religion may impact depression include decreased substance use and enhanced social support. Little investigation of these topics has occurred with adolescent psychiatric patients, among whom depression, substance use, and social dysfunction are common. METHOD: 145 subjects, aged 12-18, from two psychiatric outpatient clinics completed the Beck Depression Inventory-II (BDI-II), the Fetzer multidimensional survey of religion/spirituality, and inventories of substance abuse and perceived social support. Measures were completed again six months later. Longitudinal and cross-sectional relationships between depression and religion were examined, controlling for substance abuse and social support. RESULTS: Of thirteen religious/spiritual characteristics assessed, nine showed strong cross-sectional relationships to BDI-II score. When perceived social support and substance abuse were controlled for, forgiveness, negative religious support, loss of faith, and negative religious coping retained significant relationships to BDI-II. In longitudinal analyses, loss of faith predicted less improvement in depression scores over 6 months, controlling for depression at study entry. LIMITATIONS: Self-report data, clinical sample. CONCLUSIONS: Several aspects of religiousness/spirituality appear to relate cross-sectionally to depressive symptoms in adolescent psychiatric patients. Findings suggest that perceived social support and substance abuse account for some of these correlations but do not explain relationships to negative religious coping, loss of faith, or forgiveness. Endorsing a loss of faith may be a marker of poor prognosis among depressed youth.

A comparison of placebo and no-treatment during a hypnotic clinical trial.

OBJECTIVE: Sleep parameters commonly improve during placebo treatment in insomnia clinical trials. We examined whether the improvement seen with placebo was related to taking pills or other non-specific factors. METHOD: 95 insomniacs took either a placebo pill (pill+) or no pill (pill-) on nights of their choosing over 12 weeks. RESULTS: Pills were consumed on about half of the nights. Consistent improvement was seen with reduced reported sleep latency, wakefulness after sleep onset, number of awakenings, and total sleep time over the 12 weeks for both the pill+ and pill condition. A difference between pill+ and pill- was detected only for total sleep time, and this difference favored pill+. CONCLUSIONS: This study suggests that improvement seen during placebo treatment is more related to non-specific factors of participating in clinical trial than to pill taking behavior.

Sleep histories are seldom documented on a general medical service.

BACKGROUND: Sleep disorders are common, but the frequency of sleep history documentation in hospitalized patients is unknown. METHODS: We reviewed 442 initial histories and physical examinations recorded by 122 house officers and 47 medical students in 208 consecutive general medicine ward patients. RESULTS: Any reference to sleep was recorded in only 18 patients (9%), including 12 of 141 (9%) with conditions associated with obstructive sleep apnea. Sleep histories were recorded more often in women (13% vs 4%) and less often than histories of cigarette smoking or alcohol use. Medical students recorded such histories more often than did house officers. Patients with sleep histories more often had pulse oximetry (78% vs 37%), pulmonary function testing (11% vs 1%), arterial blood gas analysis (67% vs 30%), or electrocardiograms (78% vs 49%). CONCLUSIONS: Sleep histories are documented infrequently in hospitalized patients. Patients with a recorded sleep history more often have tests that suggest increased concerns about cardiorespiratory risk and/or a different process of care.

Electroconvulsive therapy in the era of modern psychopharmacology.

Fifty years of advances in the pharmacotherapy of major depression (MDE), mania, schizophrenia, and other severe and persistent psychiatric disorders have neither made ECT obsolete nor unnecessary. However, advances in pharmacotherapy have radically changed the practice of ECT. ECT is rarely a first-line treatment of mental disorder, unless the clinical situation is desperate. Otherwise, ECT is most often offered to persons who have failed to respond to pharmacotherapy, thus defining a relatively treatment-refractory population for ECT. The physician who refers patients for ECT, as well as the ECT provider, must be able to judge at what point a patient is deemed "medication resistant", implying expertise in pharmacotherapy for both the referring physician and the ECT provider. Authoritative sources from 20 years ago quoted antidepressant response rates > or = 90% for ECT, but the antidepressant response rate in medication-resistant MDE may be only 60%. Improvements in the safety of ECT have resulted in the referral of large numbers of older persons for ECT. High relapse rates after ECT are perhaps the biggest problem presently facing patients and providers. High relapse rates are not surprising given that (i) most patients are medication resistant, and (ii) ECT is usually withdrawn at the moment it becomes effective. Although continuation/maintenance ECT is an option in preventing relapse, it may not be a practical solution for persons still in their productive years, and it is resource-intensive. Still, continuation/maintenance ECT is the only method to prevent relapse and recurrence of severe psychiatric disorder for some persons.

A psychiatric perspective on insomnia.

Insomnia is a cardinal symptom for many psychiatric disorders, especially depressive disorders. Treatment of the underlying psychiatric disorder may be sufficient to relieve the accompanying insomnia. If the insomnia fails to respond, then consideration should be given to the possibility of inadequate treatment of the primary psychiatric disorder, iatrogenic insomnia, insomnia related to a medical disorder, or learned/habit insomnia. Persistent insomnia should be aggressively pursued, since it has been associated with a variety of adverse outcomes in samples of depressed patients. The physician should always inquire about and encourage healthy sleeping behaviors, even if hypnotic medication is contemplated. Benzodiazepines and nonbenzodiazepine benzodiazepine receptor agonists (BzRAs) have the best evidence for efficacy as hypnotics, although sedating antidepressants are popularly prescribed. Although all benzodiazepine hypnotics and nonbenzodiazepine BzRAs are comparably efficacious in inducing sleep, they vary markedly in their potential for residual side effects.

Practice parameters for the treatment of narcolepsy: an update for 2000.

Successful treatment of narcolepsy requires an accurate diagnosis to exclude patients with other sleep disorders, which have different treatments, and to avoid unnecessary complications of drug treatment. Treatment objectives should be tailored to individual circumstances. Modafinil, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, selegiline, pemoline, tricyclic antidepressants, and fluoxetine are effective treatments for narcolepsy, but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness, but naps seldom suffice as primary therapy. Regular follow up of patients with narcolepsy is necessary to educate patients and their families, monitor for complications of therapy and emergent of other sleep disorders, and help the patient adapt to the disease.

Reliability of telepsychiatry assessments: subjective versus observational ratings.

Geriatric patients in underserved areas could benefit from the use of telecommunications to expand access to mental health services. It is important to determine the clinical limitations of using videoconferencing for psychiatric assessments, particularly in the elderly. The goal of this study was to test the hypothesis that videoconferencing ratings based on visual observations of behavior would be less reliable than ratings based on patients' verbal reports of symptoms. Videoconferencing assessments of 30 geriatric patients using low-bandwidth (ISDN) equipment were compared to gold standard face-to-face assessments. The Brief Psychiatric Rating Scale (BPRS) was dichotomized into subjective items based on patients' verbal reports and observational items based on visual ratings of behavior. Reliability of the BPRS subjective items was consistently higher than for the observational items. Future studies should emphasize the accuracy of telemedicine ratings that require visual observation of behavior, which is crucial to clinical assessment of psychogeriatric conditions.

Social support increases in the year after inpatient treatment of depression.

High levels of social support are reported to protect against major depressive episode (MDE), but little is known about how social support changes during MDE. In this study, we measured total social support and four subtypes of social support in 75 psychiatric inpatients at the time of admission and one year later. The four subtypes of social support were tangible support, affectionate support, positive social interaction, and emotional/informational support. The majority of the sample were women (81%) with a mean age of 53.7+/-14.9 years. The severity of depressive symptoms improved over the year and was accompanied by a significant increase in two types of social support -- positive social interaction, and emotional/informational support. There was no significant change in tangible support or affectionate support. Linear regression showed that changes in all four subtypes were correlated with changes in depressive severity after adjustment for age, gender, and baseline clinical characteristics. While Instrumental Activities of Daily Living (IADL) scores also improved throughout the period of observation, and while the change in IADL scores were significantly associated with changes in social support, change in IADL scores were no longer significantly associated with change in social support after adjustment for change in depression severity. These results suggest that supportive relationships improve after psychiatric hospitalization for MDE, and these changes are best explained by reduction in depression severity.

The outcome of 369 ECT consultations.

OBJECTIVE: The components of a pre-ECT consultation have been well-described, but the outcome has not been described. We describe the outcome of 369 consecutive ECT consultations. METHODS: We performed a retrospective review of ECT consultations performed at Wake Forest University School of Medicine between January 23, 1992, and October 22. 1998. Each consultation was coded as either recommending against ECT, unenthusiastic about ECT, or recommending ECT. RESULTS: Thirteen percent of the patients at their first consultation needed clarification of their capacity to consent to ECT. Additional testing was recommended in 34%, and additional medical consultation was recommended for 11% of the patients. The ECT consultation recommended against ECT for 4% of patients, was unenthusiastic for an additional 15% of patients, and was enthusiastic for 81%. Likelihood of receiving ECT was strongly influenced by the consulting physician's level of enthusiasm for ECT. Enthusiasm for ECT, in turn, was highly related to diagnosis. CONCLUSIONS: The recommendations from an ECT consultation appeared influential in the likelihood of receipt of ECT. The consultation's enthusiasm for ECT, in turn, was related to the patient's diagnosis. Furthermore, the consultation revealed the need for additional testing, medical consultation, or clarification of capacity to consent in a substantial number of patients.

Electroconvulsive therapy is associated with superior symptomatic and functional change in depressed patients after psychiatric hospitalization.

BACKGROUND: Major depressive episode is associated with quality of life (QOL) deficits, and QOL improves following remission of depression. We conducted an observational study of the relationship between depressive symptoms and QOL for 1 year after psychiatric hospitalization, and compared QOL in patients who received ECT against those who did not. METHODS: We examined 88 patients with major depressive disorder (53.4+/-15.4 years old; 69 women) upon admission, with repeated measurements at discharge, 1, 3, 6, and 12 months after discharge. Depression severity was measured with the Beck Depression Inventory. QOL measurements encompassed ADLs, IADLs, performance in major roles, and satisfaction with relationships. Treatment for depression was at the discretion of the respective physicians. RESULTS: Depression severity dropped dramatically by discharge, and changed little thereafter. QOL measures showed improvement at the first month, with additional improvement at the third month. Improvement in QOL was closely tied to improvement in depression severity. ECT during the index hospitalization was associated with greater improvement in depressive symptoms and in most measures of QOL. LIMITATIONS: The results of this study may not apply to the treatment of outpatients, and the large number of statistical comparisons may have resulted in some spurious associations. CONCLUSIONS: Inpatient treatment of depression is followed by improvement in QOL. Novel findings in this study include evidence that maximum improvement in QOL does not occur until an average of 3 months after discharge, and that ECT-treated patients had superior outcomes.

Seizure threshold rise during electroconvulsive therapy in schizophrenic patients.

A rise in seizure threshold during a course of electroconvulsive therapy (ECT) has been demonstrated in patients with depression and mania, but no information has been available as to whether the same result occurs in schizophrenia. Ninety-three patients with schizophrenia underwent estimation of the seizure threshold by the dose-titration method, at the first and second, seventh, fourteenth, and twentieth treatments over an index ECT course. The 3-week stabilization period was used as a response criterion. Eighty-six patients (92%) showed a rise in threshold. The magnitude of increment was 269+/-244%. The rise in seizure threshold could be predicted by the number of treatments, initial seizure threshold and EEG seizure duration, and these factors explained 42% of the variance.

Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects.

BACKGROUND: The antidepressant and cognitive side effects of right unilateral (RUL) electroconvulsive therapy (ECT) are reported to depend on the magnitude of the electrical stimulus relative to the seizure threshold. The stimulus doses explored in previous clinical trials of RUL ECT have generally been limited to 1 to 2.5 times the convulsive threshold and the antidepressant efficacy has been low compared with bilateral (BL) ECT. The present study compares the antidepressant and cognitive side effects of 2 RUL dosing strategies: titrated moderately suprathreshold and fixed high dose. METHODS: Seventy-two adult patients with major depression were randomized to either titrated RUL ECT at 2.25 times initial seizure threshold (mean dose, 136 millicoulombes [mC]), or RUL ECT at a fixed dose of 403 mC. Primary outcome measures were antidepressant response and cognitive status 1 or 2 days after the course of ECT. RESULTS: The 2 treatment groups were comparable in demographic and clinical characteristics prior to ECT. Both groups received a mean of 5.7 sessions of RUL ECT. Patients receiving fixed-dose ECT were more likely to have an antidepressant response at the end of the protocol (n = 49 [67%]) compared with those receiving titrated dosing (n = 28 [39%]). Furthermore, the likelihood of both antidepressant response and cognitive deficits increased as stimulus dose increased relative to initial seizure threshold, up through 8 to 12 times the threshold. CONCLUSIONS: The antidepressant efficacy and cognitive side effects of RUL ECT are dependent on the magnitude of the stimulus dose relative to the seizure threshold, and a dose-response relationship extends through at least 12 times the seizure threshold.

Subjective measurement of insomnia and quality of life in depressed inpatients.

Insomnia and major depressive episodes (MDE) have each been associated with quality of life (QOL) deficits. In this study we examined insomnia as an independent predictor of QOL deficits during MDE, and used a secondary analysis of cross-sectional data. The study was based at the inpatient psychiatric ward and included 88 adults (mean age 53; 78% women). We assessed insomnia severity with the 21-item Hamilton Rating Scale for Depression (HRSD) and the Beck Depression Inventory (BDI). Measurements of QOL in the week prior to admission included activities of daily living (ADLs), instrumental ADLs (IADLs), daily living and role functioning, and relation to self and colleagues (the last two both subscales of the Basis 32). Linear regression models used the insomnia items as independent variables and the QOL measures as the dependent variables, after adjusting for age and nonsleep related depression severity. The results showed that 93% of patients endorsed insomnia on the observer-rated HRSD, and 97% endorsed sleep disturbance in the self-rated BDI. However, the insomnia items on the HRSD and BDI showed poor concurrent validity. Increasing severity of insomnia on the HDRS was associated with better QOL, while increasing severity of insomnia on the BDI was associated with worse QOL. We conclude that the BDI and HRSD do not produce equivalent measures of insomnia severity in depressed inpatients, and each insomnia measure has a unique relationship with QOL.

Pretreatment differences in specific symptoms and quality of life among depressed inpatients who do and do not receive electroconvulsive therapy: a hypothesis regarding why the elderly are more likely to receive ECT.

Electroconvulsive therapy (ECT) is among the most commonly performed medical procedures requiring general anesthesia in the United States. Nevertheless, very little is known about the characteristics of depressed patients who receive ECT and how they differ from depressed patients receiving psychotropic medication. We conducted a detailed examination of demographic, clinical, and quality-of-life (QOL) measurements in a group of 90 depressed inpatients, and we then used these measurements to contrast the 31 patients who received ECT with the 59 who received alternative therapies. The ECT group did not differ from the non-ECT group in gender composition, marital status, race, education, employment status, overall severity of depression, chronicity of depression, adequacy of prehospitalization antidepressant treatment, extent of physical illness, or extent of social support. The ECT group was older. Furthermore, the ECT group had greater weight loss, worse functioning in activities of daily living (ADLs), and worse functioning in instrumental activities of daily living (IADLs). The differences in weight loss, ADL, and IADL scores disappeared after age adjustment. However, statistical adjustment for age revealed that the ECT group reported worse capacity in their daily living and role functioning than did the non-ECT group. We conclude that the decision to pursue ECT is based in part on the perceived effect of the depression on QOL, as well as the severity of specific symptoms such as weight loss. The elderly seem particularly vulnerable to depression-related functional deficits and weight loss, and this may explain why prior studies showed a differential use of ECT in the elderly.

Bright light therapy: improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods.

Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.