Ketamine: stimulating antidepressant treatment?

Summary: The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations.

The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.

Objective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.

Insight in bipolar disorder: relationship to episode subtypes and symptom dimensions.

Background: The study of insight in bipolar disorder has received limited attention, despite its potential impact on treatment compliance and prognosis. In the current study we compare insight levels during different phases of bipolar disorder, and consider its relationship to symptoms dimensions and epidemiologic variables.

Methods: Insight ratings obtained from 156 bipolar subjects in any phase of bipolar disorder were compared.

Anxiety as a symptom of mixed mania: implications for DSM-5.

The recently released preliminary proposal for the DSM-5 diagnostic system includes modification of the mixed mania diagnosis symptom set. That definition includes the long-overdue exclusion of nonspecific signs and symptoms, as well as the inclusion of psychomotor retardation. Anxiety is specifically excluded from the definition.

Combined catecholamine and indoleamine depletion following response to ECT.

The mechanism of action of electroconvulsive therapy (ECT) in treating major depression is unknown. We studied two candidate mechanisms through inhibiting simultaneously the synthesis of noradrenaline and serotonin in patients immediately after successful treatment with ECT using a randomised, placebo-controlled, double-blind crossover design. There were no significant changes in depression scores under any experimental conditions, or between the amine-depleted and placebo groups despite reductions of 61% in serum homovanillic acid, 47% in 3-methoxy-4-hydroxyenylethyleneglycol, and 89% in serum tryptophan.

The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments.

Objectives: Safety monitoring is an important aspect of bipolar disorder treatment, as mood-stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost-effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder.

Gray and white matter brain volumes in older adults with bipolar disorder.

Objectives: Structural magnetic resonance imaging (MRI) studies have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder. Most studies have not found difference in total gray or white matter in bipolar patients compared with controls, but there have been several studies suggesting that regional abnormalities are present. These have predominately been located in the frontal and temporal lobes.

Antidepressant response to electroconvulsive therapy is sustained after catecholamine depletion.

Although the antidepressant mechanism of ECT is unknown, there are data to support noradrenergic involvement. Patients who had been recently successfully treated with ECT for major depression were studied in a randomized double-blind cross-over design comparing catecholamine depletion using alpha-methyl-para-tyrosine to a placebo procedure. Mean MADRS scores at baseline (4.

Concordance of self-rated and observer-rated dysphoric symptoms in mania.

Objectives: High rates of some depressive symptoms occur in both mixed and pure manic episodes. This study examined whether manic subjects identify these depressive symptoms by self-report consistently with observer ratings, whether dysphoric symptoms are self-rated differently in mixed compared to pure manic episodes, and whether discriminative self-rated dysphoric symptom sets agree with those established by observer ratings.

Methods: Ninety-four inpatients meeting DSM-IV criteria for mania were classified as in pure or mixed episodes.

Stressful life events in older bipolar patients.

Objective: Theories about the impact of stressful life events (SLE) in bipolar disorder have focused on their role early in the disease. Few studies have examined SLE in older bipolar patients. We wanted to assess the impact of SLE in late life bipolar disorder

Methods: We evaluated negative SLE experienced by older bipolar subjects compared with younger bipolar subjects and older controls for number, type, and their association with phase of illness, age of onset, and previous episodes.

Pure and mixed manic subtypes: a review of diagnostic classification and validation.

Objective: To review issues surrounding the diagnosis and validity of bipolar manic states.

Methods: Studies of the manic syndrome and its diagnostic subtypes were reviewed emphasizing historical development, conceptualizations, formal diagnostic proposals, and validation.

Results: Definitions delineating mixed and pure manic states derive some validity from external measures.

Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report.

The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Cortical white matter microstructural abnormalities in bipolar disorder.

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri.

Hippocampal volume measurement in older adults with bipolar disorder.

Objective: Decreased hippocampal volumes have been noted in unipolar depressed subjects, especially in elderly patients and those with cognitive impairment. Initial studies of mixed-aged bipolar subjects and controls have had conflicting findings, with most noting no difference; however this region has not been examined in older bipolar subjects.

Methods: The authors examined the hippocampal volumes of 36 older bipolar subjects (mean age: 58 years) and 29 older normal-comparison (NC) subjects (mean age: 61), using logistic-regression analyses to control for age and gender.

Caudate volume measurement in older adults with bipolar disorder.

Background: Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects.

Methods: We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences.

Social support in elderly patients with bipolar disorder.

Objective: The role of social support in bipolar disorder is poorly understood. It is known that young and middle-aged patients with impaired social support are more likely to be treatment resistant and have increased hospitalization. However, the role of social support in elderly patients with bipolar disorder has not been studied.

An open label trial of C-1073 (mifepristone) for psychotic major depression.

Background: The rationale for treating patients with psychotic major depression (PMD) with glucocorticosteroid receptor (GR) antagonists is explained.

Methods: Thirty patients with PMD, with Hamilton Rating Scale for Depression (HAMD-21) scores of 18 or greater, were assigned in an open label trial to receive 50 mg, 600 mg, or 1200 mg of mifepristone for 7 days.

Results: All the subjects completed the protocol; there were no dropouts.