Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: an open-label clinical trial

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.

There is increasing evidence for the efficacy of neuromodulation in the treatment of resistant mood disorders and emerging data supporting the use of neuromodulation in cognitive disorders. A significant minority of depressed elders do not respond to pharmacotherapy and/or psychotherapy. This has led clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in the treatment of medication-resistant or life-threatening geriatric depression. Multiple studies have supported the safety and efficacy of ECT in the elderly, yet ECT is associated with side effects including cardiovascular and cognitive side effects. Neuromodulation therapies have the potential for providing effective treatment for treatment-resistant older adults with reduced side effects and this review will outline the risks and benefits of neuromodulation treatment in geriatric psychiatry. There is also emerging evidence of the efficacy of neuromodulation devices in the treatment of cognitive disorders. Pharmacotherapy has been largely ineffective in changing the course of neurodegenerative diseases causing dementia and other treatments are clearly needed. This review will outline the available evidence for neuromodulation in the treatment of mood and cognitive disorders in the elderly.

Extracorporeal shock wave therapy for the treatment of poststroke plantar-flexor muscles spasticity: a prospective open-label study.

OBJECTIVES: To assess the use of extracorporeal shock wave therapy (ESWT) for the treatment of equinus foot after stroke and to correlate the ESWT effect on spastic plantar-flexor muscles with echo intensity on the Heckmatt scale. METHODS: The prospective open-label study examined 23 patients with poststroke lower limb spasticity. Adults with spastic equinus foot after stroke received one ESWT session on hypertonic plantar-flexor muscles. The effect on spasticity, degree of passive ankle dorsiflexion, and neurophysiological values were evaluated. Before treatment, participants underwent a sonography evaluation of calf muscles to identify echo intensity on the Heckmatt scale. RESULTS: Immediately after the session, ESWT induced a statistically significant reduction in muscle tone, increasing passive ankle dorsiflexion motion. At 30 days of follow-up, the effect persisted only in patients with echo intensity of spastic plantar-flexor muscles graded I, II, or III on the Heckmatt scale without any action related to spinal excitability. Mild adverse events were reported after the treatment but were resolved in a few days. CONCLUSIONS: ESWT is safe and efficacious for the treatment of poststroke plantar-flexor muscles spasticity, reducing muscle tone and improving passive ankle dorsiflexion motion. The effect was long lasting in subjects with echo intensity of calf muscles graded I, II, or III but was brief for echo intensity graded IV on the Heckmatt scale. The ESWT effect did not appear to be related to spinal excitability.

The seizure, not electricity, is essential in convulsive therapy: the flurothyl experience.

BACKGROUND: For more than 50 years, research in convulsive therapy has been focused on the impact of electricity and seizures on memory and not on brain chemistry or neurophysiology. Brief pulse and ultra-brief pulse currents replaced sinusoidal currents. Electrode placements were varied, energy dosing was altered, and electricity was replaced by magnetic currents. METHOD: The published experiences and archival records of seizures induced by camphor, pentylenetetrazol, and flurothyl are reviewed and compared with the changes induced by electricity. FINDINGS: The clinical efficacy of chemically induced seizures is equal to that of electrical inductions. Seizure durations are longer, and impairment of cognition and memory is less. Electroconvulsive therapy replaced chemical treatments for ease of use, not for greater efficacy or safety. CONCLUSIONS: The brain seizure, not the method of induction, is the essential element in the efficacy of convulsive therapy. Seizure induction with chemicals avoids the direct effects of electricity on brain functions with lesser effects on cognition. Reexamination of chemical inductions of seizures as replacements for electricity is encouraged.

Insulinoterapia em pacientes com doença arterial coronariana e diabetes do tipo 2 / Insulin therapy in patients with coronary artery disease and type 2 diabetes mellitus

O diabetes melito do tipo 2 vem ganhando crescente importância entre os fatores de risco para desenvolvimento e piores desfechos das doenças cardiovasculares. Apesar de ter sido demonstrada, por diversos estudos epidemiológicos, a relação da doença arterial coronariana com a hiperglicemia, o controle glicêmico adequado persistente nem sempre é mantido nos portadores de diabetes melito do tipo 2. Para esses pacientes, a introdução de insulinoterapia é imperativa. Considerando a possível persistência de reserva de insulina pancreática e a comum resistência dos pacientes em aceitar o uso de medicaçõe injetáveis, costuma-se iniciar a insulinoterapia com a introdução de injeção de insulina de ação ao deitar, em complementação ao uso diurno de antidiabéticos orais. Caso seja obtido controle glicêmico adequado, é indicada a substituição dos antidiabéticos orais pela insulinização intensiva basal...

No risk of diabetes after insulin-shock treatment.

Prophylactic insulin treatment is effective in preventing diabetes in animal models of insulin-dependent diabetes mellitus (IDDM) but the safety of such preventive treatment in prediabetic human subjects remains unclear; insulin is a potential autoantigen that could accelerate beta-cell decompensation and onset of IDDM. We have investigated whether insulin treatment of non-diabetic subjects increases the risk of subsequent development of diabetes in a retrospective study of Danish patients who received insulin-shock treatment for psychiatric disorders. Mean age of the 481 patients at insulin-shock treatment was 32.6 (range 12.9-69.6) years. The patients received 59 (6-200) injections of 78 (16-261) IU bovine/porcine insulin. Hospital records provided an average of 22.0 (0.6-51.2) years' observation. During the observation time, IDDM developed in only 1 patient; 1.3 cases would be expected from Danish incidence data (p = 0.75). Similarly, there was no significant difference between the observed number of cases of non-insulin-dependent diabetes mellitus (NIDDM) and the number expected from Danish prevalence data (12 vs 10.2; p = 0.45). We collected blood samples from 27 of the patients. All but 2 (who had previously diagnosed NIDDM) had normal fasting blood glucose and plasma insulin concentrations, none had islet-cell antibodies, and only 2 had detectable insulin antibodies. Thus, the risk of diabetes was not increased by the use of many insulin injections in these non-diabetic subjects. We conclude that clinical trials on prevention of IDDM by prophylactic insulin treatment can be regarded as safe.

[Revival of convulsive therapy]. / Revival della terapia convulsivante.

After a brief review of the history of convulsive therapy, the paper criticises the denigratory campaign which was directed against this form of therapy for many years in Italy and later abroad. It stresses that convulsive therapy is now used worldwide, in spite of a few justifiable restrictions, for these indications and that the risks involved in the therapy itself, which are minimum, have been reduced. The Authors complain that this revival, which is now spreading internationally, has been hardly felt in Italy, especially in university circles.

[A reduced variant of convulsive therapy with ammonium chloride in patients with neurotic depression]. / Redutsirovannyi variant sudorozhnoi terapii khloristym ammoniem bol'nykh nevroticheskoi depressiei.

Results of ammonium convulsive therapy (ACT) in 203 patients with neurotic depressive states of various nosological origin are presented. In the total population subjected to 4-20 sessions of ACT, a full recovery or a good remission were attained in 89% of patients. The remission starts after 2 to 4 sessions with the improvement of basic mood and reducing of anxiety. Later continuous activation of the behavior may be seen. The best results were attained in patients with depressive, hypochondriac and neurasthenic neuroses, especially when astheno-, anxious-depressive or astheno-hypochondriac syndromes predominated. ACT is well tolerated by patients with no marked side effects. ACT can be recommended as a safe and effective treatment method in patients with moderate depression.

Insulin coma therapy in the treatment of early schizophrenia.

The results of the insulin therapy of early schizophrenia patients in the Department of Psychiatry at the Medical Academy of Lublin are summarized in the article. The clinical data of 236 patients hospitalized in 1950-1983 was analysed with the use of standardized methods. The analysis showed that insulin therapy, is a relatively safe method of treatment. The antipsychotic effects of insulin therapy were substantial and comparable with the antipsychotic effectiveness of contemporary agents.

[Effect of psychopharmacotherapy on the course of forced insulin-coma treatment of patients with paranoid schizophrenia]. / Vliianie psikhofarmakoterapii na khod forsirovannogo insulinokomatoznogo lecheniia bol'nykh paranoidnoi shizofreniei.

The course of forced insulin-coma therapy in cases of preliminary employment of psychotropic drugs (mainly derivatives of phenothiazine or leponex) may be attended by variable forms of deviations including serious complications whereas they are not encountered in cases of treatment with haloperidol and pharmacologically similar long-acting drugs. These findings justify the employment, when necessary, of the above drugs in combination with forced insulin-coma therapy.

The persistence of electroconvulsive therapy-induced changes in the electroencephalogram.

The literature concerning the effects of electroconvulsive therapy (ECT) upon the EEG is reviewed with respect to the degree and persistence of abnormalities. The most common electrophysiological dysfunction consists of generalized regular and irregular slow wave activity. This slowing typically disappears by a few weeks to a few months following completion of the ECT course but in rare cases may persists for longer periods. Patients given large numbers of ECT treatments tend to show more prolonged alterations. Possible correlations of these EEG changes with a variety of parameters are discussed.