New approaches in managing bipolar depression

Historically, the pharmacologic treatment of bipolar depression has not been well studied. New data are beginning to emerge regarding the efficacy of new medications and the use of combinations of mood stabilizers and antidepressants in acute and long-term treatment of bipolar depression. We reviewed data from recent randomized, controlled trials of mood stabilizers and antidepressants in the treatment of bipolar depression and naturalistic studies examining the risk of switching and depressive relapse with ongoing antidepressant treatment.     

New approaches to the treatment of refractory depression

Although the majority of patients with depression respond well to their initial pharmacologic treatment, as many as 30% to 45% fail to achieve an adequate response. In addition to the more traditional lithium and thyroid hormone augmentation strategies, a number of new pharmacotherapeutic approaches are currently being used to help manage refractory depression, including the addition of another agent or a switch to another antidepressant. Augmentation and switching strategies are often selected in order to obtain a different neurochemical effect (e.g., adding a relatively noradrenergic agent to a relatively serotonergic antidepressant). In particular, several studies have suggested that depressed patients refractory to treatment with selective serotonin reuptake inhibitors (SSRIs) may show a good response to newer agents that have a pharmacologic profile distinct from the SSRIs. Furthermore, preliminary studies have shown that the addition of SSRIs to either noradrenergic drugs such as the tricyclic antidepressants (TCAs) or dopaminergic agents may be efficacious, even though concerns about drug-drug interactions and tricyclic cardiac toxicity have limited the use of TCA-SSRI combinations. The introduction of reboxetine, a relatively selective norepinephrine reuptake inhibitor, may increase the use of the latter therapeutic approach because of its improved safety profile compared with the TCAs. The review of treatment options for refractory depression that follows will outline the advantages, disadvantages, and level of support for a number of new treatment strategies.     

Breaking the myths: new treatment approaches for chronic depression.

BACKGROUND: Chronic depressive disorders are common, accounting for approximately one-third of all cases of depression and posing a major public health problem. In the past, chronic depression has been thought to be treatment-resistant, and evidence suggests that it is currently underdiagnosed, misdiagnosed, and suboptimally treated. OBJECTIVES: To review the subtypes of chronic depression and the evidence-base concerning their optimal treatment and to discuss some key clinical issues and areas of future research. METHODS: We identified key studies and randomized controlled trials (RCTs) by systematically searching electronic databases and hand searching specialist journals and bibliographies. RESULTS: Chronic depressive disorders respond well to standard pharmacologic interventions in the acute and maintenance phases of treatment. Standard psychotherapies alone may not be efficacious for chronic depression (especially dysthymia). Recent evidence suggests that treatment combining psychotherapy and medications may be superior to either treatment alone. CONCLUSIONS: Chronic depressive disorders are amenable to treatment, provided that intervention is both thorough and intensive. Although our knowledge about the optimal treatment of chronic depression has developed rapidly, changes in clinical practice have been slower to evolve. Further research is required to assess the effectiveness of multimodal interventions for chronic depression in more naturalistic settings.     

New approaches to managing psychotic depression

Major depression with psychotic features, while fairly common, is frequently misdiagnosed. Symptoms seen in these patients are those of an overall severe depressive disorder with psychomotor impairment (retardation or agitation), guilt, suicidal preoccupation, and neuropsychological impairment. A number of biological characteristics and behavioral symptoms are specific to patients suffering from psychotic depression and differ significantly from those of nonpsychotic depression. Psychotic depression is seen in patients of all ages, and it has a high short-term morbidity and risk of suicide. Data support the use of antipsychotics in combination with antidepressants for major depression with psychotic features, but other treatments may have as great or greater efficacy for the disorder. This article focuses on recognizing the features of psychotic depression, the success of current treatment options, and new treatments under investigation.     

Actual approaches to post-psychotic depression]

Clinical features of post-psychotic depression in schizophrenia have been described since the beginning of the century. However, international nosographies mention this concept only since the ICD 10 and the DSM IV. In clinical practice, post-psychotic depression is a real challenge. Currently, the exact prevalence remains undetermined and is estimated about 25%, varying from 7 to 70% in the literature. The diagnostic criteria nowadays available will encourage searchers to determine the exact prevalence of post-psychotic depression. This is surely due to difficulties in the diagnostic approach. The clinical picture resembles that of major depression. However, there are confounding factors such as negative symptoms and extrapyramidal symptoms. With regard to psychometrics, two specific rating scales are thought to measure depressive symptoms in schizophrenia: the Calgary Depression Scale (CDS) and the Psychotic Depression Scale (PDS). Nonetheless, the scales are not specific for post-psychotic depression. Prognosis of an acute schizophrenia is linked among other factors with the emergence of a post-psychotic depression that is in turn influences suicidal risk and quality of life. Genetic, therapeutic, psychodynamic and psychological factors have been invoked in the etiopathogenesis of post-psychotic depression. In clinical practice, post-psychotic depression can be successfully treated with antidepressive medication. Some antidepressants have shown their efficacy.     

Treatment-resistant depression: critique of current approaches

The aim of the present study was to critically appraise current conceptual approaches; demographic, neurobiological and clinical correlates; and management strategies of treatment-resistant depression (TRD), especially in light of recent research findings. To this end, a review of the relevant English-language literature was undertaken using Medline, Embase and Psychinfo. TRD has been defined in conceptually restrictive terms as symptomatic non-response to physical therapies alone, with little systematic study of aetiology made. It is likely that a range of sociodemographic (such as higher socioeconomic status), genetic (such as variation in functional monoamine polymorphisms) and clinical variables (such as signal hyperintensities seen on structural neuroimaging scans) are responsible for non-response in individuals. There is insufficient evidence to suggest that TRD is associated with specific subtypes of depression, physical comorbidity, personality or chronicity. The large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and other studies have suggested that a structured psychotherapy such as cognitive behaviour therapy may be as effective as medication in initial drug non-responders. Also conventional alternatives such as the use of older antidepressant classes, pharmacological augmentation or electroconvulsive therapy in established cases of TRD are not as effective as traditionally thought. There is insufficient preliminary evidence to make formal recommendations about the use of novel brain stimulation techniques in TRD. TRD should be re-defined as the failure to reach symptomatic and functional remission after adequate treatment with physical and psychological therapies. Treatment resistance may be more usefully conceived within the context of well-defined cohorts such as patients with specific subtypes of depression. Although neurobiological markers such as gene polymorphisms, which are potentially predictive of medication tolerance and efficacy, may be used in the future, it is likely that sociocultural variables such as beliefs about depression, and evidence-based treatments for it, will also determine treatment resistance.     

Alternative approaches to refractory depression in bipolar illness

This article is a U.S. government work, and, as such, is in the public domain in the United States of America.     

Transcranial and deep brain stimulation approaches as treatment for depression.

Given that a considerable portion of depressed patients does not respond to or remit during pharmacotherapy, there is increasing interest in non-pharmacological strategies to treat depressive disorders. Several brain stimulation approaches are currently being investigated as novel therapeutic interventions beside electroconvulsive therapy (ECT), a prototypic method in this field with proven effectiveness. These neurostimulation methods include repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), deep brain stimulation (DBS) and transcranial direct current stimulation (tDCS). It is via different neuroanatomically defined "windows" that the various approaches access the neuronal networks showing an altered function in depression. Also, the methods vary regarding their degree of invasiveness. One or the other method may finally achieve antidepressant effectiveness with minimized side effects and constitute a new effective treatment for major depression.     

Current approaches to management of depression in Parkinson's Disease.

Depression is a common problem in patients affected by Parkinson's Disease (PD). In many cases, treatment with antidepressants is necessary, and the choice of the most suitable drug is often controversial, as many factors need to be considered that may complicate the development of the disease, including potential side effects of antidepressant therapy. Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs) are the two major categories of antidepressants used. Tricyclics have been shown to be effective in most cases, but some side effects (orthostatic hypotension, sedation, cognitive and anticholinergic effects) may present problems. In contrast, SSRI appear to be better tolerated, but some reports indicate a potential worsening of the parkinsonism. Other recently introduced medications need further investigation. The main therapeutic strategies, as reported in the international literature according to efficacy and tolerability, interactions with antiparkinsonian or concomitant drugs and possible effects on worsening of PD, are presented.     

Temporal segmentation of response speed in depression: neuro-electrophysiological approaches

1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event-related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to 'stimulus evaluation time', was found to be slower but within normal range in depressed patients.     

奎硫平治疗抑郁发作的对照研究

目的:探讨奎硫平对抑郁发作的疗效和安全性。方法:收集抑郁发作或复发性抑郁的患者60例,分为奎硫平组和5-羟色胺再摄取抑制剂(SSRIs)组各30例,疗程8周。使用Montgomery-As-berg抑郁量表(MADRS)、汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评定疗效,以治疗中出现的症状量表(TESS)评定不良反应。结果:治疗8周两组MADRS、HAMD和HAMA量表减分值相仿(P均>0.05),治疗1周末奎硫平组即显示疗效优于SSRIs组(P均<0.05);奎硫平组MADRS量表失眠障碍因子减分值大。治疗8周奎硫平组有效率为25例(83.3%),SSRIs组为26例(86.7%)。奎硫平组无转躁患者,而SSRIs组转躁3例。奎硫平组头晕、口干、便秘的发生率明显多于SSRIs组。结论:奎硫平单药治疗抑郁发作的疗效与SSRIs相当,可改善患者失眠和焦虑症状,头晕、口干、便秘等不良反应较多见。     

Impulse control disorders and depression

This study assessed the frequency of impulse control disorders (ICDs) and their association with bulimia, compulsive buying, and suicide attempts in a population of depressed inpatients. We investigated ICDs using the Minnesota Impulsive Disorders Interview. Patients answered the Zuckerman Sensation-Seeking Scale and the Barratt Impulsivity Rating Scale. Among the 31 depressed patients who met criteria for ICD (ICD+ group), we found 18 cases of intermittent explosive disorder, three cases of pathological gambling, four cases of kleptomania, three cases of pyromania, and three cases of trichotillomania. Patients with co-occurring ICDs were significantly younger (mean age = 37.7 versus 42.8 years). Patients with kleptomania had a higher number of previous depressive episodes (5.7 versus 1.3), and patients with pyromania had a higher number of previous depressions (3.3 versus 1.3, p =.01). Bipolar disorders were more frequent in the ICD+ group than in the ICD- group (19% versus 1.3%, p =.002), whereas antisocial personality was not (3% versus 1%, p = ns). Bulimia (42% versus 10.5%, p =.005) and compulsive buying (51% versus 22%, p =.006) were significantly more frequent in the ICD+ group. Patients from the ICD+ group had higher scores of motor impulsivity assessed with the Barratt Impulsivity rating scale (p =.01).     

Dopaminergic control of TSH secretion in endogenous depression

To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to a reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 micrograms i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TRH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.     

女性单相抑郁症对照研究

目的:了解女性单相抑郁症临床特征,包括共病情况与患病风险。方法:采用复合国际诊断访谈与自评式问卷调查方式,入组100例女性单相抑郁症患者与100例正常女性对照。结果:女性单相抑郁症与广泛性焦虑障碍、惊恐障碍、心境恶劣共病率较高,与对照组相比,抑郁症患者家族史阳性率高,艾森克人格问卷神经质维度评分高,生活应激明显。结论:女性单相抑郁症共病较多。神经质、家族史阳性、生活应激事件可能是患病风险因素。     

Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches

Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models: (1) “the avoidance model”; (2) “the intolerance of uncertainty model”; (3) “the meta-cognitive model”; (4) “the emotion dysregulation model”; and (5) “the acceptance based model”. For depression, the following theoretical models are explicated: (1) “the cognitive model”; (2) “the behavioral activation model”; and (3) “the interpersonal model”. Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines (BZDs) are an important “bridging strategy” to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a “stacking approach” not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.