Evaluating Ineffective Treatments: A Proposed Model for Discussing Futility in Psychiatric Illness.

BACKGROUND: Treatment futility and terminality discussions arise rarely in psychiatric practice, frequently instilling apprehension, as there is little written that defines these terms in relation to mental illness. It therefore remains uncertain how to deal with cases that are refractory to multimodal interventions and that demonstrate limited improvement or even a worsening trajectory. Any viable solution needs to respect patient autonomy and maintain both beneficence and nonmaleficence, while taking into account the strained resources of the mental health care system as a whole. OBJECTIVE: This article reviews historical conflicts surrounding the notion of futility in psychiatric disorders, and proposes and elaborates a set of six criteria that psychiatrists can use in working through these difficult cases. Given the potential controversy involving futility in psychiatry, it proves helpful to understand its similarity to the notion of futility in standard medical contexts. This article also works through some of the common concerns or objections regarding the application of futility in psychiatric contexts. CONCLUSIONS: Futility in psychiatric illness is a concept that the psychiatric community needs to understand and address, given the limited treatment options available to our field, as well as the limitations of health care resources. The proposed framework allows for ethically appropriate treatment decisions for treatment-resistant patients-respecting their individual wishes while ensuring appropriate care.

Characteristics of Successful Transitions From Inpatient to Outpatient Electroconvulsive Therapy.

OBJECTIVES: The purpose of this study was to identify clinical and psychosocial factors involved in transitioning hospitalized patients receiving electroconvulsive therapy (ECT) from the inpatient to the outpatient setting and to propose an algorithm to guide clinicians with this process. METHODS: A retrospective chart review was completed for adult patients discharged from a psychiatric hospital from 2002 to 2012 who had an acute course of ECT that was initiated in the hospital and completed as an outpatient. We reviewed demographic and clinical information and outcomes, including ECT treatments. RESULTS: Among the 277 patients who were identified, the mean age was 52.2 years, 60% were women, and 66% were married. The mean length of hospital stay was 12.9 days, and the mean number of ECT treatments was 4.9 as an inpatient and 3.1 as an outpatient. The most frequent primary diagnosis was depression. Most patients (81%) had a responsible adult at home. Patients had good cognitive functioning at both baseline and discharge, and showed improved functional status at discharge (P<0.001 for change in scores on the Global Assessment of Functioning from admission to discharge). CONCLUSIONS: Factors such as improved cognitive and functional status from admission to discharge, a medically uncomplicated course, and a responsible adult at home were observed among patients transitioned from inpatient to outpatient ECT. On the basis of these study results, a review of the literature, and clinical experience, an algorithm to assist clinical decisions for ECT transitioning was developed.

Development of a bipolar disorder biobank: differential phenotyping for subsequent biomarker analyses.

BACKGROUND: We aimed to establish a bipolar disorder biobank to serve as a resource for clinical and biomarker studies of disease risk and treatment response. Here, we describe the aims, design, infrastructure, and research uses of the biobank, along with demographics and clinical features of the first participants enrolled. METHODS: Patients were recruited for the Mayo Clinic Bipolar Biobank beginning in July 2009. The Structured Clinical Interview for DSM-IV was used to confirm bipolar diagnosis. The Bipolar Biobank Clinical Questionnaire and Participant Questionnaire were designed to collect detailed demographic and clinical data, including clinical course of illness measures that would delineate differential phenotypes for subsequent analyses. Blood specimens were obtained from participants, and various aliquots were stored for future research. RESULTS: As of September 2014, 1363 participants have been enrolled in the bipolar biobank. Among these first participants, 69.0 % had a diagnosis of bipolar disorder type I. The group was 60.2 % women and predominantly white (90.6 %), with a mean (SD) age of 42.6 (14.9) years. Clinical phenotypes of the group included history of psychosis (42.3 %), suicide attempt (32.5 %), addiction to alcohol (39.1 %), addiction to nicotine (39.8 %), obesity (42.9 %), antidepressant-induced mania (31.7 %), tardive dyskinesia (3.2 %), and history of drug-related serious rash (5.7 %). CONCLUSIONS: Quantifying phenotypic patterns of illness beyond bipolar subtype can provide more detailed clinical disease characteristics for biomarker research, including genomic-risk studies. Future research can harness clinically useful biomarkers using state-of-the-art research technology to help stage disease burden and better individualize treatment selection for patients with bipolar disorder.

Management of psychiatric symptoms in anti-NMDAR encephalitis: a case series, literature review and future directions.

Anti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007, has been increasingly identified as a significant cause of autoimmune and paraneoplastic encephalitis. Approximately 80% of the patients are females. The characteristic syndrome evolves in several stages, with approximately 70% of the patients presenting with a prodromal phase of fever, malaise, headache, upper respiratory tract symptoms, nausea, vomiting and diarrhoea. Next, typically within two weeks, patients develop psychiatric symptoms including insomnia, delusions, hyperreligiosity, paranoia, hallucinations, apathy and depression. Catatonic symptoms, seizures, abnormal movements, autonomic instability, memory deficits may also develop during the course of the disease. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis, which also should prompt a thorough search for an underlying tumor. Age, gender, and ethnicity may all play a role, as black females older than 18 years of age have an increased likelihood of an underlying tumor. Treatment is focused on tumor resection and first-line immunotherapy [corticosteroids, plasma exchange, and intravenous immunoglobulin]. In non-responders, second- line immunotherapy [rituximab or cyclophosphamide or combined] is required. More than 75% of the patients recover completely or have mild sequelae, while the remaining patients end up demonstrating persistent severe disability or death. There is a paucity of literature on the management of psychiatric symptoms in this population. Given the neuropsychiatric symptoms in the relatively early phase of the illness, approximately 77 % of the patients are first evaluated by a psychiatrist. Earlier recognition of this illness is of paramount importance as prompt diagnosis and treatment can potentially improve prognosis. We describe two patients diagnosed with NMDAR encephalitis presenting with two different psychiatric manifestations. The first patient presented with psychotic mania and catatonic symptoms, while the second suffered from depression with psychotic and catatonic features refractory to psychotropic medications. We review of the use of psychotropic medications and ECT to address insomnia, agitation, psychosis, mood dysregulation and catatonia in NMDAR encephalitis.

Serial infusions of low-dose ketamine for major depression.

BACKGROUND: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. METHODS: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. RESULTS: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. CONCLUSIONS: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

Catatonia as a manifestation of tacrolimus-induced neurotoxicity in organ transplant patients: a case series.

Tacrolimus has been associated with severe neurotoxicity in organ transplant patients. Catatonia can be a rare manifestation of tacrolimus-induced neurotoxicity as we report two cases of catatonia in solid organ transplant patients on tacrolimus. Catatonic symptoms completely resolved in these patients after reducing the tacrolimus dosage or switching it to alternative immunosuppressants. Catatonia symptoms in organ transplant patients should alert clinicians to look for tacrolimus-induced neurotoxicity despite normal serum tacrolimus levels and neuroimaging findings.

Successful use of ECT in post-stroke depression.

Post-stroke depression is a potentially persistent complication of stroke. Electroconvulsive therapy (ECT) is an effective treatment for depression, but with limited data regarding safety in stroke patients. We report the case of a 30-year-old woman with a history of stroke and antiphospholipid syndrome, who became depressed and suicidal. Neurologic and Internal Medicine consults did not reveal any contraindications to ECT, but stroke risk factor management was identified as an important measure for patient safety. The patient tolerated ECT well, reporting improvement of mood and abatement of hopelessness. This case suggests that ECT may be a safe and well-tolerated treatment for post-stroke depression.

An updated review of implantable cardioverter/defibrillators, induced anxiety, and quality of life.

Despite overall favorable acceptance of implantable cardioverter-defibrillators (ICDs), patients may experience discharges as frightening and painful. The authors reviewed ICD-induced psychopathology in 2005. During the past 2 years the number of studies examining psychopathology and quality of life after ICD implantation has increased dramatically, warranting this update of that review. Variables assessed have included recipient age, gender, social support network, perception of control and predictability of shocks, and personality style. Now the picture of what is known is, if anything, cloudier than it was 2 years ago, with little definitive and much contradictory data emerging in most of these categories.

Electroconvulsive therapy-responsive catatonia in a medically complicated patient.

BACKGROUND: Profoundly depressed states of awareness classified as either catatonia or akinetic mutism have been reported in patients with various general medical conditions including encephalitis, frontal lobe tumors, or paraneoplastic limbic encephalitis. Catatonic features are often difficult to apprise in this context. This can result in electroconvulsive therapy (ECT) discontinuation, although it remains the most effective treatment of catatonia. CASE REPORT: We describe the case of a patient with a history of unresectable right retroorbital squamous cell carcinoma, status poststereotactic radiation and cisplatin, and subsequent pneumococcal meningitis of the temporal lobe with abscess formation who became catatonic after receiving 3 bitemporal treatments with ECT for severe depression and whose catatonia improved with continued ECT. Furthermore, she demonstrated progressive improvement in mood, interactivity, and overall neurologic function after ECT treatment was completed. CONCLUSIONS: The search for an etiology of a profound catatonic state should include the probability of underlying medical disorder. Although lorazepam may be helpful in some cases, ECT deserves early consideration in catatonia, especially in cases where the underlying cause seems to be uncertain, even if the catatonia begins in the midst of treatment.

An updated review of implantable cardioverter/defibrillators, induced anxiety, and quality of life.

During the past 2 years the number of studies examining psychopathology and quality of life after ICD implantation has increased dramatically. Variables assessed have included recipient age, gender, and social support network. How recipients respond to having the device, particularly after experiencing firing, has been evaluated in light of new depression and anxiety disorder diagnoses as well as premorbid personality structure. Now the picture of what is known is, if anything, cloudier than it was 2 years ago, with little definitive and much contradictory data emerging in most of these categories. It still seems clear that in a significant minority of ICD recipients the device negatively affects quality of life, probably more so if it fires. Education about life with the device before receiving it remains paramount. Reports continue to appear of patients developing new-onset diagnosable anxiety disorders such as panic and posttraumatic stress disorder. Until recently the strongest predictors of induced psychopathology were considered to be the frequency and recency of device firing. It now seems that preimplantation psychologic variables such as degree of optimism or pessimism and an anxious personality style may confer an even greater risk than previously thought. Certainly many variables factor into the induction of psychopathology in these patients. Among these factors are age, gender, and perception of control of shocks, as well as the predictability of shocks and psychologic attributions made by the patient regarding the device. Another source of variability is this population's medical heterogeneity. Some patients receive ICDs after near-death experiences; others get them as anticipatory prophylaxis. Some have longstanding and entrenched heart disease; others were apparently healthy before sudden dangerous arrhythmias. Diagnoses as diverse as myocardial infarction in the context of advanced coronary artery disease and dilated cardiomyopathy after acute viral infection may warrant ICD placement. Moreover the course of cardiac disease after ICD placement may vary from relative stability to continuing disease progression and severe functional compromise. Unless these and other pre- and postimplantation differences are taken into account, it is almost impossible to make meaningful comparisons between studies. Ideally, future research would consist either of large-scale, randomized, prospective studies using validated structured-interview tools to supplement a literature dominated by self-report measures, unstructured assessments, and anecdotal reports, or of smaller studies designed to focus on particular diagnostic subsets. As ICDs become the standard of care for potentially life-threatening arrhythmias, the rate of implantations continues to increase. Because negative emotions have been linked to an increased incidence of arrhythmias, and untreated or unrecognized psychiatric illness can interfere with adaptation to an ICD, assessing and managing both pre-existing and induced psychiatric disorders becomes even more critical. Greater research attention should be paid to determining which patients meet criteria for anxiety disorders before and after implantation and what premorbid traits predispose to postimplantation psychopathology. The authors predict that psychiatrists will be involved increasingly in caring for this population, offering insights into treatment options that increase the likelihood of successful ICD acceptance and decrease the psychosocial costs of these devices.