Pierpaolo Medda

Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy

There is an increasing evidence that the Brain-Derived Neurotrophic Factor (BDNF) could be involved in the mode of action of antidepressants and, perhaps, of ECT. This study aimed to investigate whether the clinical course of medication-resistant depressed patients following a course of ECT might be associated with changes of plasma BDNF concentrations. Our findings showed that at T0 (baseline) plasma BDNF levels of patients were significantly lower than those of control subjects, and that at T2 (after ECT) were significantly increased in parallel with the decrease of the Hamilton Rating Scale for Depression (HRSD) total score. However, only remitter patients who showed higher baseline BDNF levels than non-remitters reached normalized BDNF levels after ECT. These findings would suggest the potential usefulness of baseline plasma BDNF levels as predictors of response to ECT in treatment-resistant depressed patients.

Response to ECT in bipolar I, bipolar II and unipolar depression

OBJECTIVES A significant body of evidence indicates the efficacy of electroconvulsive therapy (ECT) in unipolar depression but mixed results have been reported in bipolar depression. We explored difference of response to ECT in unipolar (UP), bipolar I (BP I) and bipolar II (BP II) depression, in a sample of patients resistant to pharmacological treatment. METHODS One hundred and thirty depressive patients (17 with Major Depression (UP), 67 with bipolar disorder II (BP II) and 46 with bipolar disorder I (BP I) according to DSM-IV criteria) were included in the study and treated with bilateral ECT, on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score), using the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Improvement (CGI). RESULTS The three groups (UP, BP II, BP I) showed a significant improvement after the ECT course. Global response rate (CGI<2) was 94.1% for UP, 79.1% for BP II and 67.4% for BP I. Concerning depressive symptomatology, the remission rate (HAM-D <8) was respectively 70.5 for UP, 56.7% for BP II and 65.3% for BP I. The best results were achieved by UP patients, while BP I group showed the worst results with a lower remission rate and higher scores in YMRS and BPRS psychotic cluster at the final evaluation. CONCLUSION ECT turns out to be a viable option for the treatment of both unipolar and bipolar depressive patients resistant to pharmacological treatment. Nevertheless, while the UP group showed the best response and clinical outcomes, the BP I patients tended to exhibit residual manic and psychotic symptomatology.

Comparative response to electroconvulsive therapy in medication-resistant bipolar I patients with depression and mixed state.

Objectives: We compared the response with electroconvulsive therapy (ECT) of bipolar I patients resistant to pharmacological treatment, who presented depression or mixed state (MS). Methods: Ninety-six bipolar I patients according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition were included in the study (46 with major depressive episode and 50 with MS). Bilateral ECT was delivered using a brief pulse stimulator Mecta 5000Q (Mecta Corp, Lake Oswego, Ore) on a twice-a-week schedule. The patients were evaluated before ECT (baseline) and a week after the ECT course (final score), using the Hamilton Rating Scale for Depression (HAM-D), Mania Rating Scale, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Improvement (CGI). Results: Global response rate (CGI ≤2) was similar in bipolar depression and MS (67.4% and 76.0%, respectively); no difference was found in global remission rate (CGI ≤1) between depression (41.3%) and MS (34.8%). The response rate of depressive symptoms (HAM-D ≤50% was 69.6% for bipolar depression and 66.0% for MS; remission rate (HAM-D ≤8) was 26.1% and 30.0%, respectively. At the end of the ECT course, CGI-Severity, HAM-D total, Young Mania total, BPRS total, and psychotic cluster scores showed a progressive reduction in both groups. A significant group effect was present for Young mania total score, BPRS total score, and psychotic cluster. Limitations: With the exception of anticonvulsants, concomitant psychotropic medications were permitted during ECT course, based on the physicians decision. Conclusions: Electroconvulsive therapy should be considered a viable treatment alternative in bipolar I patients with depression or MS who do not respond to conventional pharmacologic management. The only difference is that MS may present more residual agitation or psychotic features in comparison with depressive patients.

Clinical subtypes of severe bipolar mixed states.

OBJECTIVE The aim of the present study was to identify different clinical subtypes in severe, treatment resistant bipolar mixed state (MS). METHOD The sample comprised 202 Bipolar I patients currently in MS referred for an Electro-convulsive Therapy (ECT) trial and evaluated in the first week of hospitalization and one week after the ECT course. Principal component factor analysis (PCA) followed by Varimax rotation was performed on 21 non-overlapping items selected from Hamilton rating-scale for depression (HAMD) and from Young mania rating-scale (YMRS) at baseline evaluation. Cluster subtypes derived from the factor scores were compared in clinical variables and final HAMD, YMRS, Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. RESULTS The principal-component analysis extracted 6 interpretable factors explaining 55.9% of the total variance. Cluster analysis identified four groups, including respectively 63 (31.2%) subjects with Agitated-Irritable Mixed-Depression, 59 (29.2%) with Psychotic Mixed-Mania, 17 (8.5%) with Anxious-Irritable-Psychotic Mixed-Mania, and 63 (31.2%) with Retarded-Psychotic Mixed-Depression. The four clusters were statistically distinct and did not show significant overlap in the main symptomatological presentation. Cluster subtypes reported differences in number of past mood episodes, duration of the current episode, suicide attempts, lifetime comorbidity with panic and eating disorders, baseline and final rating-scale scores and rate of remission after ECT trial. CONCLUSIONS Our study indicates that, at least in severe treatment resistant MS, multiple depressive and manic subtypes can be observed with substantial differences in terms of clinical presentation, course, associated comorbidities and treatment response.

The mood-stabilizing effects of electroconvulsive therapy.

Abstract The “ideal” mood stabilizer has been defined as an agent displaying demonstrated efficacy for the acute treatment and long-term prevention of both mania and depression. On the basis of a selective and an extensive review of the existing literature primarily focused on prospective and controlled studies, we discuss the potential mood-stabilizing effects of electroconvulsive therapy (ECT) and its efficacy for the acute treatment of bipolar depressive and mixed-manic states and the prevention of all types of recurrences of bipolar disorder (BD). We conclude that ECT should be considered an effective acute treatment for the depressive and manic-mixed states of BD, as ECT displays response and remission rates superior to those of other treatment approaches, even in severe and treatment-resistant cases. From this point of view, its clinical mood-stabilizing effects are clearly superior compared with other pharmacological approaches because most treatments that alleviate bipolar depression can cause mania, hypomania, mood instability, or rapid cycling and treatments that can control mania can induce or precipitate depressive symptoms or episodes. The ECT-induced mania is rare, and there are no data suggesting possible long-term mood destabilization, including cycle induction or acceleration. Conversely, several case reports and open trials reported a significant reduction in morbidity among patients experiencing rapid-cycling BD. Regarding relapse prevention, c-ECT and m-ECT are considered as appropriate therapies for treatment-resistant patients exhibiting high rates of depressive or mixed relapse. Further investigation is necessary to identify the frequency and duration of continued treatment after a successful index course of ECT.

Catatonia in 26 patients with bipolar disorder: clinical features and response to electroconvulsive therapy

We describe the clinical characteristics and short‐term outcomes of a sample of inpatients with bipolar disorder with severe catatonic features resistant to pharmacological treatment.

Long-term naturalistic follow-up of patients with bipolar depression and mixed state treated with electroconvulsive therapy.

Objective The aim of the present study was to evaluate the long-term outcome in a sample of patients with bipolar disorder with severe depression or mixed-state resistant to pharmacological treatment who have responded to electroconvulsive therapy (ECT). Method The study involved 36 patients with major depression (5 patients with bipolar I depression, and 14 patients with bipolar II depression) or mixed state (17 patients) treated with bilateral ECT delivered using a brief pulse stimulator Mecta 5000 Q on a twice-a-week schedule. The patients were evaluated before ECT (baseline) and 1 week after the ECT course (final score) using the Hamilton Depression Rating Scale, Mania Rating Scale, Brief Psychiatric Rating Scale, and Clinical Global Improvement. The Longitudinal Interval Follow-up Evaluation was administered every 16 weeks to assess time to relapse (defined as LIFE scores ≥5 for at least 2 consecutive weeks or as the need for hospitalization) and periods of response and remission. Results The mean duration of follow-up was 55.3 ± 30.4 weeks (range, 24–160 weeks). Thirteen patients (36.1%) showed a depressive relapse during the follow-up; the mean time (length) of depressive relapse was 20.4 ± 21.8 weeks (range, 2–60 weeks). Twenty-nine patients (80.5%) fulfilled the criteria for a full remission from depressive symptoms after 6.7 ± 7.9 weeks from the last ECT. Seventeen patients (47.2%) were in remission for more than 70% of the time. No manic episodes occurred during the follow-up, only 1 patient had a mixed episode, and 11 patients had a hypomanic episode. Conclusion Electroconvulsive therapy showed a positive impact on the clinical course of severe and treatment-resistant patients with bipolar disorders, as suggested by the high number of weeks spent in remission during the follow-up period. In our study, the duration of depressive episode was related to early relapse during follow-up period.

The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features

Objective: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. Method: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. Results: Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤2) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. Conclusion: ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a “last resort”.

A case of deep venous thrombosis following protracted catatonic immobility recovered with electroconvulsive therapy: the relevance for an early intervention

Catatonic patients often experience prolonged inactivity and dehydration, thus being prone to venous stasis leading to life-threatening thrombosis and pulmonary embolism (PE). When this occurs, the prescription of electroconvulsive therapy (ECT), actually irreplaceable in most life-threatening cases, remains controversial essentially due to an increased risk for PE and cerebral haemorrhage, with timing clinical decisions being as crucial as difficult to take. We report the case of a catatonic patient affected by malnutrition, deep venous thrombosis, severe pressure ulcers and septic syndrome resulting from previous untimely management, successfully treated with 16 well-tolerated ECT applications upon intensive supportive care. Although anecdotal, cases like this remind the relevance of early ECT to reduce the risk for potentially life-threatening complications due to prolonged catatonic inactivity, especially to those clinicians substantially disregarding this practice.

Plasma Amyloid-β Levels in Drug-Resistant Bipolar Depressed Patients Receiving Electroconvulsive Therapy

Aims: Alterations of plasma amyloid-β (Aβ) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aβ peptides (Aβ40, Aβ42) and the Aβ40/Aβ42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course. Methods: Aβ40 and Aβ42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale. Results: Plasma Aβ levels and the Aβ40/Aβ42 ratio were similar at T0 and T1. The Aβ40/Aβ42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aβ40/Aβ42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aβ40/Aβ42 ratio at T0 than nonremitters. Conclusion: The present data suggest that a low Aβ40/Aβ42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment.