Anticonvulsants during electroconvulsive therapy: review and recommendations

OBJECTIVES: To review the literature on the concurrent use of electroconvulsive therapy (ECT) and anticonvulsant drugs (AC) and to provide recommendations to guide clinical practice. METHODS: A MEDLINE search (1985-2006) was performed, using the terms "electroconvulsive therapy," "anticonvulsants," "epilepsy," "carbamazepine," "gabapentin," "lamotrigine," "topiramate," and "valproate," supplemented by manual searches of guidelines and textbooks on ECT. RESULTS: To date, no prospective, randomized and controlled trials examining outcome and safety of the AC-ECT combination have been published. Existing data are from case reports on the use of ECT for psychiatric conditions that are simultaneously treated with AC, and from case reports of patients treated with ECT and AC for epilepsy or for psychiatric conditions with comorbid epilepsy. Apart from an occasional difficulty in eliciting seizures, no severe adverse effects or complications are reported. CONCLUSIONS: The literature that is currently available indicates that ECT can be safely and effectively administered to patients treated with various AC. There is, however, no evidence to combine the 2 treatment modalities to augment therapeutic efficacy.     

Serious psychiatric and neurological adverse effects of herbal medicines -- a systematic review

OBJECTIVE: Psychiatric and neurological patients frequently try herbal medicines often under the assumption that they are safe. The aim of this systematic review was to provide a summary of recent data on severe psychiatric and neurological adverse effects of herbal remedies. METHOD: Computerized literature searches were carried out to identify all reports of psychiatric and neurological adverse effects associated with herbal medicines. These data were subsequently extracted, validated and summarized in narrative and tabular form. RESULTS: Numerous case reports comprise a diverse array of adverse events including cerebral arteritis, cerebral oedema, delirium, coma, confusion, encephalopathy, hallucinations, intracerebral haemorrhage, and other types of cerebrovascular accidents, movement disorders, mood disturbances, muscle weakness, paresthesiae and seizures. Several fatalities are on record. They are caused by improper use, toxicity of herbal ingredients, contamination and adulteration of preparations and herb/drug interactions. CONCLUSION: Herbal medicines can cause serious psychiatric and neurological adverse effects.     

The Current Clinical Practice of Herbal Medicine in Psychiatry in Mainland China: A Review of Literature

Abstract: The current clinical psychiatric practice of herbal medicine in the People's Republic of China was explored by reviewing the literature. The results found in many of the articles were lacking methodological strictness. Some reliable articles reported that certain herbal medicines were effective for psychiatric conditions, and that a combination treatment of modern drugs with herbs was useful for the enhancement of the efficacy and the reduction of both recovery time and side effects. It is suggested that more sophisticated investigations are necessary to corroborate any conclusions concerning the value for herbal medicine in the psychiatric field.     

Herbals and botanicals in geriatric psychiatry.

There is high prevalence of herbal medicine use among elderly people. Most patients do not reveal their herbal use to their physicians and pharmacists. The authors describe some commonly used herbal remedies in terms of their potential benefits and known adverse effects. The review also highlights the potentially serious risk of herb-drug interactions and discusses communication issues and regulatory concerns associated with use of herbal medicines. Health practitioners should remember to include herbal use history in their routine drug histories and remain informed of the beneficial and harmful effects of these treatments.     

The current clinical practice of herbal medicine in psychiatry in mainland China: a review of literature.

The current clinical psychiatric practice of herbal medicine in the People's Republic of China was explored by reviewing the literature. The results found in many of the articles were lacking methodological strictness. Some reliable articles reported that certain herbal medicines were effective for psychiatric conditions, and that a combination treatment of modern drugs with herbs was useful for the enhancement of the efficacy and the reduction of both recovery time and side effects. It is suggested that more sophisticated investigations are necessary to corroborate any conclusions concerning the value for herbal medicine in the psychiatric field.     

A meta-analysis of Chinese herbal medicines for vascular dementia

OBJECTIVE: To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. DATA RETRIEVAL: We retrieved publications from Cochrane Library (2004 to July 2011), PubMed (1966 to July 2011), the Chinese Science and Technique Journals Database (1977 to July 2011), the China National Knowledge Infrastructure (1979 to July 2011), Google Scholar (July 2011), and the Chinese Biomedical Database (1977 to July 2011) using the"Chinese medicine OR Chinese herbal medicine" and "vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia". SELECTION CRITERIA: Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l’Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers’ Handbook 5.0. MAIN OUTCOME MEASURES: Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. RESULTS: We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants (1 605 patients took Chinese medicine decoctions (treatment group); 1 263 patients took western medicine or placebo). The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention (relative risk (RR)=1.27; 95% confidence interval (CI): 1.18-1.38, P<0.01). Mini-Mental State Examination scores were higher in patients taking Chinese herbal medicines than in those in the control group (weighted mean difference (WMD)=2.83; 95%CI: 2.55-3.12, P<0.01). Patients in the treatment group showed better disease amelioration than those in the control group (Hasegawa Dementia Scale scores; WMD=2.41, 95%CI: 1.48-3.34, P<0.01). There were also considerably fewer adverse reactions among those in the treatment group compared with those in the control group (RR=0.20, 95%CI: 0.08-0.47, P<0.01). CONCLUSION: Chinese herbal medicine appears to be safer and more effective than control measures in the treatment of vascular dementia. However, the included trials were generally low in quality. More well-designed, high-quality trials are needed to provide better evidence for the assessment of the efficacy and safety of Chinese medicines for vascular dementia.     

Insights from molecular investigations of traditional Chinese herbal stroke medicines: implications for neuroprotective epilepsy therapy

Traditional Chinese herbal medicine is the most widely practiced form of herbalism worldwide. It is based on a sophisticated system of medical theory and practice that is distinctly different from orthodox Western scientific medicine. Most traditional therapeutic formulations consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic efficacy by facilitating synergistic actions and ameliorating or preventing potential adverse effects while at the same time aiming at multiple targets. Orthodox drug therapy has been subject to critical analysis by the "evidence-based medicine" movement, and demands have been made that herbal medicine should be subject to the same kind of scrutiny. However, evaluation of the effectiveness of herbal medicines can be challenging, as their active components are often not known. Accordingly, it may be difficult to ensure that an herbal preparation used in clinical trials contains the components underlying its purported therapeutic effect. We reasoned that the identification of actions of herbal medicines at well-defined molecular targets and subsequent identification of chemical compounds underlying these molecular effects might serve as surrogate markers in the hypothesis-guided evaluation of their therapeutic efficacy. A research program was initiated to characterize in vitro molecular actions of a collection of 58 traditional Chinese drugs that are often used for the treatment of stroke. The results indicate that these drugs possess activity at disparate molecular targets in the signaling pathways involved in N-methyl-d-aspartate (NMDA) receptor-mediated neuronal injury and death. Each herbal drug contains diverse families of chemical compounds, where each family comprises structurally related members that act with low affinity at multiple molecular targets. The data appear to support the multicomponent, multitarget approach of traditional Chinese medicine. Glutamate release and excessive stimulation of NMDA receptors cause status epilepticus-induced neuronal death and are involved in epileptogenesis. Therefore, these results are also relevant to the development of antiepileptogenic and neuroprotective therapy for seizures. The combination of principles of modern molecular medicine with certain ideas of traditional empirical Chinese medicine may be beneficial in translational medicine in general.     

Recent advances in optimizing electroconvulsive therapy

This review aims to summarize and critically evaluate the evidence for recent advances and alternative approaches in electroconvulsive therapy (ECT) technique. Novel developments in ECT research are also mentioned. An EMBASE literature search was undertaken of clinical trials, case reports and research updates on novel and alternative approaches in ECT practice and research, including alternative electrode placements, variations in stimulus configuration, and novel developments (magnetic seizure therapy, focal electrical stimulation). The evidence for these approaches is reviewed, and implications for the optimizing of ECT in clinical practice are discussed. Evidence from studies suggests that unilateral ECT be given at substantially suprathreshold doses (at least 6 times seizure threshold) for maximizing efficacy, while bilateral ECT is likely to be effective at doses of 1.5-2.5 times seizure threshold. There is some evidence to support the use of bifrontal ECT, although further research is required to establish its efficacy and side-effects relative to standard unilateral and bilateral electrode placements. Other alternative electrode placements have been minimally studied. More advantageous efficacy side-effect outcomes may be achieved by reducing the pulse width and/or frequency of the ECT stimulus. Lastly, novel developments using alternative means of seizure induction (magnetic fields, focal electrical stimulation) may hold promise for the future. Clinical practice should be guided by a careful appraisal of the available evidence for alternative approaches in ECT technique.     

The use of herbal alternative medicines in neuropsychiatry. A report of the ANPA Committee on Research

Growing numbers of people throughout the United States (40% in 1998) are using various forms of alternative therapies. A MEDLINE literature search of journals from the past three decades and an Internet database query were performed to determine the types and frequency of alternative therapies used, with special attention given to the herbal medicines used in neuropsychiatric disorders. Clinical effects, mechanisms of action, interactions, and adverse reactions of the herbal treatments are detailed. Objective controlled trials will be needed to establish safety and efficacy of herbal supplements. Knowledge of the properties of these therapies can improve the care of neuropsychiatric patients.     

Neuromodulation techniques for status epilepticus: A review

BackgroundElectroconvulsive therapy (ECT), Vagal Nerve Stimulation (VNS), Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) are neuromodulation therapies that have been used to treat Status Epilepticus (SE).ObjectiveReview the literature about the efficacy and safety of neuromodulation therapies in SE in humans.MethodsWe searched studies in PubMed, Scopus, Google Scholar and Science Direct (inception to June 2018). Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, Oxford and GRADE scales, and Murad et al., 2018 methodological quality and synthesis of case series and case reports.ResultsWe analyzed 27 articles (45 patients) with 4 different neuromodulation therapies. In ECT we found 80% rate of disruption of SE and 5% of adverse events was reported. Using iVNS 15/16 (93.7%) patients resolved the SE. All patients who underwent TMS and DBS aborted SE, however, 50% of patients with DBS had severe adverse events.ConclusionsCase series and case reports suggest that neuromodulation therapies can abort SE in 80–100% of patients (Oxford scale and GRADE were level 4 and D) with a wide range of adverse effects, which claims for prospective studies on the relationship be-tween efficacy and safety.     

Combined ECT and Antidepressant Drug Therapy

The current literature on the interaction between antidepressant drugs and electroconvulsive therapy (ECT) is reviewed. Tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors are discussed. The efficacy of combinations and possible adverse effects (mainly cardiovascular and seizure threshold effects) are considered. Many previous studies on the efficacy of combinations used inadequate methods, and the safety data consist largely of anecdotes and small case series. Additional studies are needed to assess the safety and efficacy of the combined use of antidepressants and ECT.     

Herbal medicine and epilepsy: proconvulsive effects and interactions with antiepileptic drugs

The use of complementary and alternative medicine is on the rise, including among patients with epilepsy. Herbal medicine, one of the most popular forms of CAM, is considered to be both safe and effective by most consumers. Yet many herbs may increase the risk for seizures, through intrinsic proconvulsant properties or contamination by heavy metals, as well as via effects on the cytochrome P450 enzymes and P-glycoproteins, altering antiepileptic drug (AED) disposition. Herb-drug interactions may be difficult to predict, especially since the quality and quantity of active ingredients are often unknown. Since most patients do not inform their physicians that they are taking herbal medicines, health care professionals must initiate a dialogue in order to prevent complications with the combined regimen. At the same time, further research is required regarding the effect of herbs on seizure activity and interactions with AED treatment.     

Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases.

OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse effect of neuroleptic medication, with no satisfactory treatment currently available. Electroconvulsive therapy (ECT) has been anecdotally reported to be effective in its treatment. We review 45 published case reports of ECT for NMS and describe nine new cases, to examine its effectiveness, the likelihood of adverse reactions, and the theoretical implications of such treatment. METHOD: The authors used Medline to identify reports in the English literature where ECT was used in cases of suspected NMS. In addition, the charts of patients referred to the second author for treatment of NMS were reviewed and cases in which ECT used were identified. RESULTS: The case reports suggest that ECT is effective in many individuals with NMS, even when drug therapy has failed. The response is usually apparent after a few treatments, generally up to six. The response is not predictable on the basis of age, gender, psychiatric diagnosis or any particular feature of NMS including catatonia. Electroconvulsive therapy is a relatively safe treatment in NMS, although the risk of cardiovascular complications should be considered. Malignant hyperthermia due to the anaesthesia associated with ECT has not been reported in patients with NMS, and succinylcholine has been used safely with the exception of one report of fever and raised creatine kinase levels and another report of hyperkalemia. CONCLUSIONS: Electroconvulsive therapy is the preferred treatment in severe NMS, cases where the underlying psychiatric diagnosis is psychotic depression or catatonia, and in cases where lethal catatonia cannot be ruled out. The effectiveness of ECT for the treatment of NMS has theoretical implications for the relationship between NMS and catatonia, and the possible pathophysiological mechanisms that underlie these disorders.     

What do psychiatrists mean by medication resistance as an indication for electroconvulsive therapy?

OBJECTIVES: Resistance to antidepressant medication is the commonest stated indication for electroconvulsive therapy (ECT) by psychiatrists, but what this means in practice has not been described. Our aims were to survey what antidepressant drug treatment had been prescribed to patients before they underwent ECT and to what extent this treatment would satisfy operational criteria for adequate antidepressant drug treatment used in ECT research. METHODS: The survey was conducted prospectively among 37 depressed patients referred for a new course of bilateral ECT and where antidepressant medication resistant was identified as the indication for ECT. RESULTS: Only half the sample had been prescribed more than one antidepressant drug, and only 38% had been prescribed any augmentation compound. Although the majority of patients were resistant to medication when rated by the older operational criteria, only half the sample met contemporary criteria for medication resistance. CONCLUSIONS: The findings suggest a lack of agreement between clinicians and researchers in what constitutes medication resistance as a possible indication for ECT. It will take some time to establish if the revised UK Royal College of Psychiatrists ECT Handbook will encourage more intensive medical treatment of depressive illness before the use of ECT.     

Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.

OBJECTIVE: Despite the widespread use of benzodiazepines during pregnancy and lactation, little information is available about their effect on the developing fetus and on nursing infants. The authors review what is currently known about the effects of benzodiazepine therapy on the fetus and on nursing infants. METHODS: A MEDLINE search of the literature between 1966 and 2000 was conducted with the terms "benzodiazepines," "diazepam," "chlordiazepoxide," "clonazepam," "lorazepam," "alprazolam," "pregnancy," "lactation," "fetus," and "neonates." RESULTS: Currently available information is insufficient to determine whether the potential benefits of benzodiazepines to the mother outweigh the risks to the fetus. The therapeutic value of a given drug must be weighed against theoretical adverse effects on the fetus before and after birth. The available literature suggests that it is safe to take diazepam during pregnancy but not during lactation because it can cause lethargy, sedation, and weight loss in infants. The use of chlordiazepoxide during pregnancy and lactation seems to be safe. Avoidance of alprazolam during pregnancy and lactation would be prudent. To avoid the potential risk of congenital defects, physicians should use the benzodiazepines that have long safety records and should prescribe a benzodiazepine as monotherapy at the lowest effective dosage for the shortest possible duration. High peak concentrations should be avoided by dividing the daily dosage into two or three doses. CONCLUSIONS: Minimizing the risks of benzodiazepine therapy among pregnant or lactating women involves using drugs that have established safety records at the lowest dosage for the shortest possible duration, avoiding use during the first trimester, and avoiding multidrug regimens.     

Electroconvulsive therapy in patients taking steroid medication: should supplemental doses be given on the days of treatment?

Patients who take chronic steroid medication are often prescribed extra "stress doses" before procedures involving general anesthesia. The rationale for this practice is that the chronic steroid use has suppressed the ability of the endogenous hypothalamic-pituitary-adrenal steroid stress-reactivity system to handle the systemic stress of surgery. Whether the stress of treatments is sufficient enough to warrant this practice in electroconvulsive therapy (ECT) has not been broached in the literature. In this case series, we describe our experience treating 27 ECT patients taking prednisone. We conclude that use of "stress doses" of extra steroid medication is unnecessary in ECT practice and recommend that patients receive their usual morning dose of steroid before ECT treatments.     

ECT in mental retardation: a review.

The use of electroconvulsive therapy (ECT) in patients with mental retardation and a psychiatric disorder seems to be infrequent, and controlled studies are not available. We reviewed the literature on the use of ECT in mental retardation, using Medline, Embase, and the Cochrane Library. References were checked and ECT experts consulted. The reported case studies were examined on patients' characteristics and illness, treatment, and outcome variables. Forty-four patients, mostly with a diagnosis of psychotic depression, were found. In 84% (n = 37) of them, ECT was effective and without important side effects. However, relapse occurred frequently, in 48% (n = 21) of the patients. In 16% (n = 7), side effects and/or no improvement were noted. The reported case studies suggest that ECT may be of value in treating severe psychiatric disorders in mentally retarded patients, with similar indications as in general psychiatry. However, the lack of strong scientific evidence, besides complicated psychiatric assessment as well as ethical and legal issues, probably cause an unnecessarily limited use of ECT in these patients. Further controlled trails are needed to firmly establish the efficacy and safety of ECT in mental retardation.     

The first-line use of electroconvulsive therapy in major affective disorders

Although electroconvulsive therapy (ECT) has generally been reserved for patients refractory to other forms of treatment, its use as a first-line treatment, prior to the use of other biologic approaches, has occasionally been mentioned in the literature on the treatment of affective disorders and, when indicated, can prove rapidly effective and even life saving. The present study retrospectively reviewed 27 cases treated over the span of a decade in which ECT was chosen as the first treatment of an affective episode. In none of these cases was antidepressant medication or other biologic approaches used for the current episode. A clinical global rating scale was employed to measure improvement. Although the majority of such patients were treated with ECT first based upon the severity of their depressive illness, 13 received ECT because of their obtunded condition and these patients, initially diagnosed as catatonic on admission, were suspected of having a bipolar condition, as revealed on their discharge diagnosis. In addition, ECT was recommended preferentially in 4 patients because they were pregnant and in another 4 because it had worked well in the past; an additional patient received ECT first because of his fragile medical condition. Almost all patients recovered and none suffered serious adverse effects. Sample case histories are provided along with tentative guidelines for the consideration of first-line use of ECT in clinically difficult cases.     

Epilepsy in The Alienist and Neurologist, 1880-1920

PURPOSE: To study the history of epilepsy from 1880 to 1920. METHODS: We reviewed all 40 volumes of The Alienist and Neurologist and identified articles concerning primarily epilepsy. We analyzed three of these articles in greater detail. RESULTS: The Alienist and Neurologist published "Original Contributions,"Selections," (abstracts from other journals written by the editorial board), "Editorials," and (book) "Reviews." Of 258 epilepsy articles, there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15 Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17 other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case studies; 28 social/legal articles; and 13 autopsy or pathology articles. CONCLUSIONS: Analysis of The Alienist and Neurologist provides a unique and valuable perspective on the clinical practice and academic world of epileptology during the decades around the turn of the twentieth century.     

ECT and intracranial vascular masses

In 1990, the APA Task Force on ECT cited no "absolute" contraindications to ECT but "Substantial Risk" to be associated with ECT for patients with space occupying or other cerebral lesions with increased intracranial pressure and with bleeding or otherwise unstable vascular aneurysm or malformation. These findings indicate that patients with intracranial vascular masses are at increased risk for serious morbidity and mortality. Several authors have reported performing ECT in patients with intracranial vascular masses without adverse events by monitoring blood pressure both with and without pharmacologic intervention. Given the relatively recent change in practice of considering ECT for patients with intracranial vascular masses and the few number of cases thus far reported, we present a review of the existing literature and two additional cases of ECT performed with good result and no adverse events. With the cases we have presented, the literature now contains eight cases of ECT performed in patients with intracranial vascular masses, none of which had adverse outcomes. While such numbers do not establish unequivocal safety in this population, and the individual ECT practitioner must continue to make a risk/benefit analysis on a case-by-case basis, this report adds to the growing literature on the safety and efficacy of ECT for such patients.