Effects of electroconvulsive therapy on plasma vasopressin and oxytocin

BACKGROUND: Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients. METHODS: Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed. RESULTS: The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT (ps < .01-.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature. CONCLUSIONS: Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.     

Headache as a manifestation of myocardial infarction

A 33-year-old pregnant woman at 26 weeks gestation, who had a history of bipolar mood disorder, type I, was admitted to the hospital for hypomania and poorly controlled diabetes mellitus. The patient had had her first episode of affective illness at age 28, after the birth of her second child. After an initial postpartum depression, she had cycled into a manic state. She had subsequently been hospitalized seven times for acute mania. A combination of valproate and chlorpromazine had proven effective in managing most of her manic episodes, while her two most severe episodes had been successfully managed with bilateral ECT.     

Treatment of depression in bipolar disorder: new directions for research

The objective of the study was to review the clinical literature on the acute, somatic treatment of the depressed phase of bipolar disorder. We reviewed all available published studies of "standard" somatic treatments (lithium, antidepressant and anticonvulsant agents, and electroconvulsive therapy [ECT]) reporting three or more depressed bipolar patients who were not psychotic, rapid cycling, or previously treatment refractory. We also reviewed all studies of "nonstandard" pharmacologic treatments involving even a single case of a depressed bipolar patient. Data sources included the MEDLINE database and relevant references from articles obtained in this search and in major reviews. Five of seven studies comparing ECT with antidepressant agents find ECT more efficacious. Eight of nine controlled comparisons find lithium superior to placebo in depressed bipolar patients. Three controlled comparisons of lithium to tricyclic antidepressants suggest that lithium is equivalent to tricyclic drugs in such patients. Three double-blind, controlled studies indicate that carbamazepine is more effective than placebo. Limited data on other antidepressant classes suggest that monoamine oxidase inhibitors, bupropion, and serotonergic agents may offer some advantages over tricyclic antidepressants in this population. Some "nonstandard" treatments also show some potential in bipolar patients. The possibility of switching into a manic episode is an important consideration with many of the agents studied, although little remains known about spontaneous versus treatment-associated mood shifts. In contrast to the extensive literature on the acute treatment of the manic phase of bipolar disorder and on the prophylaxis of manic and depressive episodes, there are few studies of treatment of the depressed phase of bipolar disorder, and their results generally are limited or inconclusive. Lithium generated a revolution in psychiatric treatment, but the treatment of the depressed phase of bipolar disorder remains a relatively neglected corner of the field. Several study designs may help to augment knowledge in the treatment of bipolar depression.     

Dr Med. Alexander Rydzewski (obituary)]

Three patients with intractable thalamic pain unresponsive to a range of previous treatments received a course of six bilateral electroconvulsive therapy (ECT) treatments over 2 weeks. There was no evidence of any improvement in the intensity of the pain, pain relief or mood as measured on visual analogue scales and with standard measures. Propofol was used as the anaesthetic induction agent. Two patients showed wide changes in blood pressure during ECT but all three patients showed prompt recovery. In the light of the negative findings of this study and those of a previous study of the use of unilateral ECT in similar patients it is concluded that ECT is not an effective treatment for post-stroke thalamic pain.     

The manic syndrome: factors which may predict a patient's response to lithium, carbamazepine and valproate

Studies suggest that 80% to 90% of all patients in the manic state respond to lithium provided that they are relatively free of dysphoria ("pure mania"). In contrast, less than 40% of individuals in the manic state who cycle rapidly or are substantially dysphoric ("dysphoric mania") respond to lithium. These patients appear to be more responsive to carbamazepine and valproate. The authors conclude that carbamazepine and valproate are the drugs of choice if one desires to treat a rapidly cycling individual or patient with dysphoric mania with just one agent. However, they emphasize that a prospective study designed to identify the predictors of response of primary mania to lithium, carbamazepine and valproate is required. Studies assessing the relative value of lithium, carbamazepine or valproate as prophylactic agents in the care of patients with specific subtypes of mania are also needed. These studies would address the most important issues confronting researchers interested in the drug treatment of mania.     

Association of recurrent suicidal ideation with nonremission from acute mixed mania

OBJECTIVE: The authors' goal was to examine suicidality in relation to acute symptom remission in inpatients with mixed and pure bipolar disorder. METHOD: Using chart review of 184 adult inpatients with bipolar I disorder, the authors assessed patients' past and current suicidality, other psychopathology, treatment, and remission. RESULTS: Past, current, and recurrent suicidality were significantly more common among patients with mixed mania than among those with pure mania. The probability of remission declined by 49% for every suicide attempt made before the index manic episode. Mixed mania, multiple previous hospitalizations, and previous suicide attempts were significantly associated with current suicidality. CONCLUSIONS: Suicidality is linked with mixed manic states and may be a clinical marker for recurrent dysphoric mania. Multiple suicide attempts are associated with nonremission from mixed manic episodes.     

Excitotoxic damage of retinal glial cells depends upon normal neuron-glial interactions

BACKGROUND: It is unclear whether the serum prolactin (PRL) surge following electroconvulsive therapy (ECT) is a marker of optimal ECT administration. We investigated the relations among PRL surge, stimulus parameters, and outcome in major depressive disorder (MDD). METHODS: Seventy-nine patients with MDD were randomized in a double-blind trial to right unilateral (RUL) or bilateral (BL), and to low-dose (just above seizure threshold) or high-dose (2.5 x threshold) ECT. RESULTS: Change in PRL (delta PRL) varied among treatment groups, with significant effects of electrode placement (BL > RUL, p < .006), electrical dosage (high > low, p < .04), and gender (female > male, p < .005). There was no evidence that clinical improvement was associated with greater PRL surge. CONCLUSIONS: Although delta PRL varied with parameters impacting on response rates, these data indicate the PRL surge cannot serve as a useful index of clinically effective treatment. This finding does not support the view that diencephalic seizure propagation is necessary for ECT to exert therapeutic effects.     

Dexmedetomidine failed to block the acute hyperdynamic response to electroconvulsive therapy

BACKGROUND: Orally administered clonidine (0.2-0.3 mg) has been reported to decrease the acute hypertensive response to electroconvulsive therapy (ECT) without prolonging early recovery. This preliminary study was designed to evaluate the acute hemodynamic effects of the investigational alpha2-adrenergic agonist, dexmedetomidine, in patients undergoing a series of ECT treatments. METHODS: Six patients undergoing a series of three to six consecutive ECT treatments were studied according to a randomized, double-blind, placebo-controlled protocol All patients received either saline or dexmedetomidine, 0.5 or 1.0 microg/kg intravenously, 10-30 min before induction of anesthesia for ECT using a standardized anesthesia protocol. In addition to assessing the cardiovascular variables, the duration of seizure activity, degree of sedation, and time to discharge from the Phase I recovery unit were assessed. RESULTS: Although dexmedetomidine produced dose-related increases in the level of sedation before the ECT procedure, it failed to decrease the peak blood pressure and heart rate responses after the ECT treatment. The 0.5 and 1.0 microg/kg doses of dexmedetomidine prolonged the times to orientation and to discharge from the Phase I unit. CONCLUSIONS: The results of this pilot study suggest that dexmedetomidine (0.5-1.0 microg/kg given intravenously) is not beneficial in controlling the acute hyperdynamic response after ECT.     

ECT in the elderly

Depression is a common clinical problem in the elderly. Risk factors in this population include genetic vulnerability, psychosocial losses, medical comorbidity, cerebrovascular disease, and neurodegenerative disorders. Depression in the elderly may have severe consequences, including high rates of suicide, malnutrition or dehydration, high utilization of medical services, impaired recovery from medical illnesses, and inappropriate placement in residential care facilities. A significant number of older depressed patients may not respond to anti-depressant medications, suffer intolerable medication side effects, or have illnesses with symptoms or consequences so severe that it is not feasible to wait the time required for one or more antidepressant trials to work. For many of these patients ECT can be a dramatically effective treatment. With appropriate evaluation and monitoring, ECT can be performed with relative safety even for patients with serious concurrent medical illnesses. Serious adverse effects are rare, and cognitive consequences of ECT are generally circumscribed and of limited duration; there is no evidence of "brain damage" or permanent change in cognitive ability from ECT. After a recovery period memory function is often better than it was during the episode of depression. For patients who have been refractory to or intolerant of medication, maintenance ECT can be an effective strategy for preventing early relapse. Further research is needed, however, to clarify the optimum use of MECT schedules and pharmacotherapy combinations to most effectively and safely prevent relapse of depression in different elderly populations and to help predict who will best respond to which treatment modalities.     

Fitting the treatment to the patient: recent advances in the practice of electroconvulsive therapy

Traditionally it has been thought that a grand mal seizure is both necessary and sufficient for the maximum efficacy of ECT. Recent important research, however, has demonstrated that both the electrical dosage above the seizure threshold, i.e. the suprathreshold dosage, and the electrode placement (unilateral or bilateral) determine the efficacy of this treatment, as well as the degree of cognitive impairment. This article reviews the development of these significant concepts and suggests specific practical recommendations for incorporating these into contemporary ECT practice.     

Management of the depressive component of bipolar disorder

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.     

Obituary: Arthur Mourant (1904-1994)

Twenty patients with HIV infection and mania were grouped according to whether their first manic episode occurred when CD4 count was < 200 (late onset) or > or = 200 (early onset). The late-onset patients were less likely to have personal or family histories of mood disorder and more likely to have dementia or cognitive slowing. They also exhibited a different manic symptom profile. The different sociodemographic and symptom profiles associated with early-onset and late-onset mania may reflect differences in pathophysiology.     

GABA and mood disorders: a brief review and hypothesis

Considerable evidence implicates the neurotransmitter gamma-aminobutyric acid (GABA) in the biochemical pathophysiology of mood disorders. Animal models of depression show regional brain GABA deficits and GABA agonists have antidepressant activity in these models. Somatic treatments for depression and mania upregulate the GABAB receptor, similar to the effect of GABA agonists. Clinical data indicate that decreased GABA function accompanies depressed or manic mood states. GABA agonists are effective antidepressant and antimanic agents. Low GABA levels are found in brain, cerebrospinal fluid and plasma of patients with depression and in plasma of patients with mania. Plasma GABA levels, which reflect brain GABA, are not normalized with treatment and clinical remission in depression, suggesting low GABA is not a marker for mood state. Some somatic treatments, including valproic acid and electroconvulsive shock, reduced plasma GABA and response to these correlates with higher levels of baseline plasma GABA. From these data, a GABA hypothesis for mood disorders is formulated. Low GABA function is proposed to be an inherited biological marker of vulnerability for development of mood disorders. Environmental factors, including stress and excessive alcohol use, may increase GABA, causing symptoms of depression or mania. Treatment, or the passage of time, then returns GABA to its presymptomatic baseline as the symptoms remit. This hypothesis, applicable to a subset of mood disordered persons, is testable.     

A pharmacoeconomic model of divalproex vs. lithium in the acute and prophylactic treatment of bipolar I disorder

BACKGROUND: Divalproex and lithium are the two most rigorously studied pharmacologic treatments for acute mania in bipolar I disorder in randomized, controlled trials. The differences between the drugs in their time course of onset, predictors of response, and side effects have potentially important pharmacoeconomic implications. METHOD: Utilizing data from published studies, the University of Cincinnati Mania Project, and a consensus panel of psychiatrists, we developed a decision-analytic model to estimate the costs of treating patients with bipolar I disorder, acutely and prophylactically, for 1 year with divalproex or lithium. RESULTS: In the overall group of patients with bipolar I disorder, initial treatment with divalproex led to costs that were 9% lower than costs for initial treatment with lithium. Cost savings associated with divalproex were greatest for patients with mixed mania and rapid cycling, whereas cost savings for patients with classic mania were greater for lithium. CONCLUSION: According to the decision-analytic model developed in this study, divalproex, possibly because of a more rapid rate of antimanic activity associated with oral loading, is a less costly treatment than lithium in the acute and prophylactic treatment of patients with bipolar I disorder over 1 year.     

A study on thallium-201 SPECT in brain metastases of lung cancer: with special reference to tumor size and tumor to normal brain thallium uptake ratio

The activity of prolyl endopeptidase (PEP), a serine proteinase, has been found to be significantly lower in the blood of patients with major depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers. It also examines the effects of antidepressants, valproate, and neuroleptic drugs on plasma PEP activity. PEP activity was significantly lower in major depressed subjects than in normal volunteers and in patients with mania and schizophrenia. In depressed subjects, plasma PEP activity was significantly increased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizophrenic subjects compared with normal volunteers. In manic subjects, short-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activity could be found in the schizophrenic patients. The results support the hypothesis that lower PEP activity could play a role in the pathophysiology of major depression, while increased PEP activity may be related to psychotic conditions, such as mania and schizophrenia.     

Temporary results only in electroconvulsive therapy in therapy-resistant depression; retrospective study

OBJECTIVE: To evaluate the use and efficacy of electroconvulsive therapy (ECT) in refractory major depression according to DSM-III-R criteria, and to look for factors predicting response in the acute phase and the occurrence of relapse or recurrence after recovery. DESIGN: Retrospective. SETTING: University Hospital Rotterdam, The Netherlands. METHODS: Of all patients who received ECT between January 1988 and July 1993 data were collected by study of clinical records and of information by treating physicians after discharge. Every patient was visited once, or received an outpatient department appointment, to obtain informed consent, take a follow-up history and evaluate social functioning by scoring Global Assessment of Functioning and Sickness Impact Profile rating scales. RESULTS: 35 patients received ECT. In clinical practice, the guidelines of the Netherlands Psychiatric Association were not violated; most patients had received adequate pharmacological pretreatment before the decision to start ECT was made. Two patients died in hospital (not from ECT). In the acute phase 25 of the 33 patients still alive upon discharge showed good recovery. Seven of these suffered relapse within six months. The number of patients with a return of depressive symptoms rose to 12 by the end of the first year of follow-up. Sociodemographic variables and treatment characteristics did not appear to influence the result of treatment in the acute phase, nor the occurrence of relapse or recurrence. With less intensive pre- and post-ECT drug treatment the chances of relapse were increased. CONCLUSIONS: ECT is an effective treatment in the acute phase of a depression. Results after a longer period of follow-up are less satisfactory.     

Rating scales for mania: is self-rating reliable?

This commentary addresses the issue of whether self-rating mania scales are reliable. After a brief introduction, several newly developed self-rating mania scales are described and critically reviewed. Among the issues discussed are: the practical utility of self-assessment in patients with mania; the influence of severity of illness on ability to self-report; and, the extent to which the presence of psychosis or the absence of insight significantly interferes with a patients' ability to reliably complete self-rating measures. Data from recent studies suggests that self-rating mania scales are both reliable and valid for patients with manic symptoms, including those with psychotic features and those having little or no insight into their illness. The merits of including self-rating measures in the assessment of mania are discussed in terms of their value for both clinical and research purposes.     

New perspectives in the treatment of acute mania: a single case report

1. There is increasing evidence that standard treatment of mania with lithium or neuroleptics fails in many subtypes of mania, e.g. dysphoric mania or rapid cycling, and new strategies are needed. 2. This single case report reports on possibilities and pitfalls in alternative attempts to tackle a severe manic syndrome successfully. 3. In this patient, lamotrigine and valproate, the latter only in an i.v. formulation, led to a relief from mania. 4. It is concluded that the success of this treatment may be due to a common underlying mechanism of action of these drugs, most likely on the level of ion channel regulation, and that further experience with alternative formulations of standard treatments such as valproate i.v. should be collected.     

The effects of electroconvulsive therapy on human learning and memory.

Reviews the effects of ECT on human learning and memory in terms of treatment variables (including number and frequency of treatments, characteristics of the convulsive agent, and different electrode placements), test procedures and task specific characteristics, and temporal parameters. Differences between the effects of bilateral and unilateral ECT may be due to the balance of verbal symbolic and nonverbal imaginal processes evoked by the range of stimuli used. Results have implications for the understanding of human brain–behavior relationships, and for the cost–benefit evaluation of electrically induced convulsions as a form of psychiatric treatment. (French summary) (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)