Treatment Of Severe Mood Disorders Research Articles

Electroconvulsive Therapy for the Treatment of Severe Mood Disorders During Adolescence: A Retrospective Chart Review.

Objective: Electroconvulsive therapy (ECT) is a well-recognized treatment of refractory mood disorders in adults. However, relatively little is known about its use for similar conditions in adolescents. Based on a chart review, we describe its use and outcome in a sample of adolescents with severe, refractory mood disorders (unipolar or bipolar disorder) hospitalized in an academic medical center. Methods: The sample was drawn from referrals to an adolescent psychiatry service. After obtaining approval from the ethics board, medical records of 54 adolescents with refractory mood disorder were examined. Participants (males 24, females 30; mean age 15.8 ± 1.5 years) had received their first course of ECT before the age of 18 years during the period 1996-2010. Response to treatment was examined after the initial treatment and during a 1-year follow-up. Results: Following the index course of ECT (mean number of treatments = 13.7 ± 6.3), a 52.8% response rate (defined as a Clinical Global Impressions [CGI] score ≤2) was noted, while 15.1% achieved remission (CGI = 1). The response rate was 82.4% after a 1-year follow-up with a remission rate of 23.5%. The Children's Depression Rating scores declined significantly from pre-ECT to the end of the index course (70.7 ± 16.4 to 52.5 ± 18; p ≤ 0.00). A reduction in suicidal ideation and self-injurious behaviors along with increased school attendance was noted. Cognition, monitored by the Mini-Mental State Examination, did not decline significantly. Minor side effects were limited to the day of the treatment. Prolonged seizures (>2 minutes) were common during ECT (74% of subjects experienced one or more). The only side effect noted at the 1-year follow-up was self-reported memory loss involving events during and around the index treatment course. Conclusions: In this severely impaired sample of adolescents, ECT was found to decrease suicidal behavior, reduce depressive symptoms, and improve overall functioning, as indexed by school attendance at follow-up after 1 year. Prospective studies using large samples are needed to determine its effectiveness and safety in refractory mood disorders in adolescents.

Comparison of the ex vivo receptor occupancy profile of ketamine to several NMDA receptor antagonists in mouse hippocampus

NMDA receptor antagonists, particularly these targeting the GluN2B subunit are of therapeutic interest for the treatment of severe mood disorders. The receptor occupancy profiles of several NMDA receptor antagonists (30mg/kg, s.c.) were compared in mouse hippocampus by ex vivo autoradiography using [3H]MK-801, a non-selective NMDA channel blocker, and [3H]ifenprodil a selective GluN2B antagonist. Subcutaneous administration of ketamine ((RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone) and memantine (3,5-dimethyladamantan-1-amine) inhibited [3H]MK-801 but not [3H]ifenprodil binding in mouse hippocampus. Ketamine reached maximal occupancy of [3H]MK-801 binding sites after 15min and rapidly cleared from the brain with no significant level of occupancy measured at the 1h time point. Memantine significantly occupied [3H]MK-801 binding sites throughout the 6h time course. The selective GluN2B antagonist CP101,606 ((1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol) and Ro 25-6981 ((αR,βS)-α-(4-Hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidinepropanol maleate) inhibited [3H]ifenprodil but not [3H]MK-801 binding and significant levels of occupancy (above 50%) were measured throughout the 6h time course. These data highlight the unique quick pulse target engagement profile of ketamine compared to other NMDA receptor antagonists.

P03-399 - Somatization disorder treated with electro convulsive therapy

Electroconvulsive therapy (ECT) is predominantly being recommended for treatment of severe mood disorders and of catatonia. We report improvement with ECT in a patient suffering from somatization disorder.The patient, a 55-year-old man, suffered from intractable somatization disorder for more than thirty years. Numerous diagnostic and several futile surgical procedures had been performed in the past. On admission there had been no psychopharmacological therapy for one month. Subsequently treatment trials with duloxetine, mirtazapine, and venlafaxine were performed, but remained ineffective. Pregabalin lead to only slight amelioration of anxiety and no improvement of pain symptoms. After 3 months of unsuccessful clinical treatment, including pharmacotherapy, cognitive behavioral therapy, and regularly scheduled interdisciplinary medical consultations, ECT was first considered. A trial of right unilateral ECT was initiated. After five sessions the course had to be terminated due to severe ECT-related hypertension. During and following the ECT course, the patient reported rapid and significant improvement of somatic symptoms. In order to evaluate the effects of ECT the patient passed an assessment before and after the ECT (Hamilton Depression Rating Scale, Whiteley-Index, Quantification Inventory for Somatoform Syndroms, and an observer-rated version of the Screening for Somatoform Disorders). Assessment scores were in line with our clinical impression. Follow-up examination four months later showed no further change.Though somatic anxiety and hypochondriasis have been described to be negative predictors of successful remission with ECT, in our patient ECT has been particularly effective with regard to somatic symptoms of somatization disorder.

Case report of treatment of severe mood disorder in an inpatient setting: When less is more

Abstract Inpatient treatment of severe and chronic mood disorders can be challenging as clinicians are often under pressure to stabilize mood symptoms in a short period of time with limited resources. However, a multipronged team approach can help in fairly rapid resolution of symptoms. The case presented illustrates that this is both practical and beneficial.

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

A growing body of data suggests that the glutamatergic system may be involved in the pathophysiology and treatment of severe mood disorders. Chronic treatment with the antimanic agents, lithium and valproate, resulted in reduced synaptic expression of the AMPA(-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit GluR1 in the hippocampus, while treatment with an antidepressant (imipramine) enhanced the synaptic expression of GluR1. The anticonvulsants, lamotrigine (6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine) and riluzole (2-amino-6-trifluoromethoxybenzothiazole), have been demonstrated to have efficacy in the depressive phase of bipolar disorder. We therefore sought to determine the role of these anticonvulsants, compared to that of the predominantly antimanic anticonvulsant valproate, on AMPA receptor localization. We found that the agents with a predominantly antidepressant profile, namely lamotrigine and riluzole, significantly enhanced the surface expression of GluR1 and GluR2 in a time- and dose-dependent manner in cultured hippocampal neurons. By contrast, the predominantly antimanic agent, valproate, significantly reduced surface expression of GluR1 and GluR2. Concomitant with the GluR1 and GluR2 changes, the peak value of depolarized membrane potential evoked by AMPA was significantly higher in lamotrigine- and riluzole-treated neurons, supporting the surface receptor changes. Phosphorylation of GluR1 at the PKA (cAMP-dependent protein kinase) site (S845) was enhanced in both lamotrigine- and riluzole-treated hippocampal neurons, but reduced in valproate-treated neurons. In addition, lamotrigine and riluzole, as well as the traditional antidepressant imipramine, also increased GluR1 phosphorylation at GluR1 (S845) in the hippocampus after chronic in vivo treatment. Our findings suggest that regulation of GluR1/2 surface levels and function may be responsible for the different clinical profile of anticonvulsants (antimanic or antidepressant), and may suggest avenues for the development of novel therapeutics for these illnesses.

Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications

Although mood disorders have traditionally been regarded as good prognosis diseases, a growing body of data suggests that the long-term outcome for many patients is often much less favorable than previously thought. Recent morphometric studies have been investigating potential structural brain changes in mood disorders, and there is now evidence from a variety of sources demonstrating significant reductions in regional CNS volume, as well as regional reductions in the numbers and/or sizes of glia and neurons. In this perspective paper, we discuss the preclinical and clinical evidence that lithium has neuroprotective and neurotrophic effects, and furthermore, show that these effects may have great relevance for the optimal treatment of severe mood disorders. Lithium has been noted to have neuroprotective effects in cell culture, and in animal models of neurodegeneration such as stroke, Huntington's disease and Alzheimer's disease. This may be due to the findings that lithium regulates the expression and/or activity of numerous molecules and enzymes involved in neuroplasticity, neuroprotection and mitochondrial function including bcl-2, GSK-3 and the ERK/MAP kinase pathway. Emerging clinical evidence additionally suggests that lithium may have similar effects in patients; these findings include an increase in N-acetyl aspartate (NAA) and gray matter in patients following long-term lithium treatment. Together, the data has implications not only for the optimal treatment of severe mood disorders, but potentially also for the treatment of other, more classical, neurodegenerative disorders.

Cellular plasticity and resilience and the pathophysiology of severe mood disorders

Recent advances in the identification of the neural circuits, neurochemicals, and signal transduction mechanisms involved in the pathophysiology and treatment of mood disorders have led to much progress toward understanding the roles of genetic factors and psychosocial stressors. The monoaminergic neurotransmitter systems have received the most attention, partly because of the observation that effective antidepressant drugs exert their primary biochemical effects by regulating intrasynaptic concentrations of serotonin and norepinephrine. Furthermore, the monoaminergic systems are extensively distributed throughout the network of limbic, striatal, and prefrontal cortical neuronal circuits thought to support the behavioral and visceral manifestations of mood disorders. Increasing numbers of neuroimaging, neuropathological, and biochemical studies indicate impairments in cellular plasticity and resilience in patients who suffer from severe, recurrent mood disorders. In this paper, we describe studies identifying possible structural, functional, and cellular abnormalities associated with depressive disorders, which are potentially the cellular underpinnings of these diseases. We suggest that drugs designed to enhance cellular plasticity and resilience, and attenuate the activity of maladaptive stress-responsive systems, may be useful for the treatment of severe mood disorders.

The impact of a history of childhood abuse on hospital outcome of affective episodes.

Despite increased awareness of the prevalence of a history of childhood abuse among adults with psychiatric disorders, the implications for treatment and outcome are generally unknown. This study examined the impact of childhood sexual abuse (in some cases combined with physical abuse) on the hospital treatment of severe mood disorders. A chart review was conducted of 110 cases of consecutively admitted adult inpatients with affective disorders. The abused and nonabused groups were compared in terms of demographic variables, severity of illness, treatment history, duration of hospitalization, and outcome of the hospital treatment episode. A history of childhood abuse was associated with younger age, comorbid personality disorders, and shorter duration of hospitalization. Other measures, such as level of functioning at discharge and recidivism, were not related to abuse status. The results suggest that childhood abuse may be associated with earlier onset of affective episodes and personality disorders but is not strongly associated with other clinical and outcome measures in the acute treatment setting.

Half a century of ECT use in young people.

Pharmacological treatments for certain psychiatric disorders in young people are often ineffective and may cause major side effects; thus, it is important to investigate other treatments. This article reviews the literature on the efficacy and safety of ECT in this age group and examines the evidence for the suggestion that it may be used inappropriately. All studies published in English and other languages on the use of ECT in persons 18 years of age or younger were obtained. The reports were systematically reviewed and rated according to the quality of the information in several domains, yielding an overall quality score for each study. Individual cases from each report were then examined and grouped according to diagnosis and response to ECT. Sixty reports describing ECT in 396 patients were identified; most (63%) were single case reports. The overall quality was poor but improved in the more recent studies. There were no controlled trials. Rates of improvement across studies were 63% for depression, 80% for mania, 42% for schizophrenia, and 80% for catatonia. Serious complications were very rare, whereas minor, transient side effects appeared common. ECT in the young seems similar in effectiveness and side effects to ECT in adults. However, this conclusion is qualified by the lack of systematic evidence. More research and education of professionals and the public are needed. It is suggested that ECT registers be set up, that surveys and controlled trials be conducted, and that seizure thresholds, the optimal anesthetic, effects of concurrent medications, and cognitive consequences of ECT in the young be investigated.

Relapse and recurrence following a course of ECT: Reasons for concern and strategies for further investigation

Patients treated with electroconvulsive therapy (ECT) have a more severe illness. This severity is evidenced in the clinical profile of the illness, in the course of the illness, in the resistance to pharmacotherapy, and in the high relapse and recurrence rates after the course of ECT. In this article the authors explore some of the issues, particularly those of biological correlates of severe mood disorders and the continuation of treatment after ECT, which may be factors in this increased severity. The authors propose avenues for the investigation and treatment of severe mood disorders treated with ECT.