Showing papers on "Treatment-resistant depression published in 2001"

The definition and meaning of treatment-resistant depression.

Abstract: Most patients treated for an episode of unipolar or bipolar major depression are treatment resistant in the sense that the majority do not achieve full remission with the first somatic or psychosocial treatment they receive. Little attention has been given to formalizing criteria for evaluating the nature and extent of treatment resistance, even though determining the adequacy and outcome of prior treatment trials is key in clinical decision making about subsequent treatment. Furthermore, determining the adequacy of prior treatment is essential since substantial evidence indicates that large numbers of depressed patients are undertreated, resulting in prolonged episodes and the appearance of "pseudoresistance." Adequacy of antidepressant treatment trials should be defined in terms of thresholds for the dosage and duration of medication, adherence, and clinical outcome. The Antidepressant Treatment History Form is presented as one method to formalize the evaluation of treatment adequacy and treatment resistance.

Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression.

Abstract: Multiple definitions have been used to characterize the outcome of treatments for depression. Beyond the simple criterion of a statistically significant improvement in depression rating scale scores, researchers have had to use more clinically relevant categorical outcomes: response (without remission), remission, nonresponse, partial response, relapse, recurrence, recovery, and, more recently, depressive breakthrough. This article reviews the definitions of these terms and their relevance for the study of treatment-resistant depression.

The burden of disease for treatment-resistant depression.

Abstract: Assessing the consequences of specific diseases on global, national, and individual levels is complex. The Global Burden of Disease Study was launched in 1992 to develop objective measures of the burden of disease. Two measures have become widely accepted: disability-adjusted life-years (DALYs) assesses years of life lost due to a disease plus years lived with the disability due to that disease, and years lived with disability (YLDs) is a related measure with greater relevance for diseases that do not routinely produce earlier mortality. When DALYs and YLDs were compared world-wide for 100 disorders, they revealed a huge burden of disease for depression. Indeed, the findings were startling. Neuropsychiatric conditions are by far the world's leader in YLDs, accounting for almost 30%. Unipolar major depressive disorder alone accounted for 11% of global YLDs. The disability of major depressive disorder produces its greatest burden upon women and starts early in life. No separate disability assessments have been compiled for treatment-resistant depression, but of individuals with major depressive disorder, the most severely disabled are those with treatment-resistant depression. The contributions to the morbidity associated with major depressive disorder and treatment-resistant depression include widespread prevalence; relatively early symptom onset; severe underdiagnosis and undertreatment; genetic vulnerabilities and precipitation or accentuation by relatively unavoidable stressors; a longitudinal pattern of frequent recurrences with increasing frequency, severity, and consequences unless treated with maintenance strategies; inadequate prioritization of recurrence prevention among clinicians; and possible suppression of brain neurogenesis, neuronal atrophy, cell death, hippocampal dysfunction, and magnetic resonance imaging changes for those with chronic treatment-resistant depression. Since the patterns of recurrences, cycle acceleration, and increasing severity of treatment-resistant depression are key reasons for its high burden, reducing the burden requires an entire paradigm shift, including emphasis on the prevention of recurrences. Only then will this prevalent, disabling yet treatable disorder lose its ignominious status as a world leader in disease burden.

Clinical features of treatment-resistant depression.

Abstract: As many as 30% to 40% of patients with major depressive disorder are unresponsive to a trial of antidepressant medication. Many patients labeled with treatment-resistant depression actually have pseudoresistance, in that they have been inadequately treated or are misdiagnosed. Others may have unrecognized comorbid psychiatric or general medical conditions that contribute to treatment resistance. Variables such as gender, family history, age at onset, severity, and chronicity have also been evaluated as possible risk factors for treatment-resistant depression. This article reviews the current literature regarding the clinical characteristics of treatment-resistant depression, with particular attention to the relevance of these factors for clinical decision making.

Augmentation and combination strategies in treatment-resistant depression.

Abstract: A substantial proportion of depressed patients show only partial or no response to antidepressants, and even among responders to antidepressant treatment, residual symptoms are rather common. When depressions do not respond adequately to treatment with an antidepressant, clinicians may choose to keep the same antidepressant and add another "augmenting" compound. Such augmentation strategies involve the use of a pharmacologic agent that is not considered to be a standard antidepressant but may boost or enhance the effect of an antidepressant. Alternatively, clinicians may choose combination strategies, in which they combine the antidepressant that did not produce adequate response with another antidepressant, typically of a different class. There are only a few controlled clinical trials of these 2 strategies among patients with treatment-resistant depression or among patients who have only partially benefited from antidepressant treatment. Most of the time, clinicians' decisions are, therefore, guided by anecdotal reports, case series, and by some relatively smaller, uncontrolled clinical trials. These augmentation and combination strategies appear to be relatively safe and effective approaches to treatment-resistant depressions, although there is a relative paucity of controlled studies to support their efficacy. These strategies typically aim at obtaining a different neurochemical effect than the one obtained with the antidepressant that has not produced adequate response. While drug-drug interactions may limit the use of some of these strategies, the potential loss of partial benefit from the failed drug inherent in switching may increase the acceptability of augmentation and combination strategies among partial responders. Further studies are clearly needed to evaluate the comparative efficacy and tolerability of these different approaches in treatment-resistant depressions.

The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression.

Abstract: Background Chronic vagus nerve stimulation (VNS) is effective in the management of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has clinically significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes. However, limited information regarding the effects of VNS on neurocognitive performance exists. Objective The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration. Method A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS. Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor function, language, attention, memory, and executive function. Results No evidence of deterioration in any neurocognitive measure was detected. Relative to baseline, improvement in motor speed (finger tapping), psychomotor function (digit-symbol test), language (verbal fluency), and executive functions (logical reasoning, working memory, response inhibition, or impulsiveness) was found. For some measures, improved neurocognitive performance correlated with the extent of reduction in depressive symptoms, but VNS output current was not related to changes in cognitive performance. Conclusions Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function, primarily among patients who show clinical improvement. Controlled investigation is needed to rule out the contribution of practice effects.

Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.

Abstract: The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.

Management of treatment-resistant depression: psychotherapeutic perspectives.

Abstract: Treatment-resistant depression is a heterogeneous condition that occurs within a psychosocial milieu. The impact of prior pharmacologic interventions may have been adversely affected by a poor therapeutic alliance, low social support, life stress, or chronic adversity and cognitive or personality factors such as neuroticism or pessimism. This article considers the psychosocial factors that predispose to treatment-resistant depression and the psychotherapeutic principles thought to be helpful in both shorter- and longer-term treatment plans. We focus on the interpersonal, cognitive, and behavioral forms of treatment that constitute the depression-focused psychotherapies, which have been studied in major depressive disorder. Also discussed are modifications in treatment planning necessary to take into account the complexity of treatment-resistant depression.

Treatment resistant depression and axis I co-morbidity.

Abstract: Background. Treatment resistant depression (TRD) continues to present a formidable challenge to clinicians, accounts for over half of the annual costs associated with treatment for depression and causes great frustration to patients. Although there have been studies attempting to define TRD, little information is available as to the cause of TRD. One suggestion is that patients with TRD have a greater frequency of co-morbid psychiatric disorders, which explains their resistance to standard antidepressant treatments. The objective of this study was to compare the co-morbidity of Axis I disorders between a sample of TRD patients and a sample of non-TRD patients.Methods. TRD and non-TRD patients, recruited from two separate antidepressant treatment studies, were assessed for Axis I co-morbidity using the SCID-P for the DSM-III-R. Patients for the two samples were then matched for baseline HAM-D-17 total score and gender.Results. Results reveal that non-TRD patients had a higher rate of both lifetime and current generalized anxiety disorder co-morbidity than did the TRD patients. No other statistically significant differences in Axis I co-morbidity were found.Conclusions. These findings do not support the idea that current or lifetime Axis I co-morbidity is more common in TRD than non-TRD patients. In fact, the only statistical difference showed non-TRD patients with higher co-morbidity rates.

The need for clinically relevant research on treatment-resistant depression.

Abstract: Posternak and Zimmerman reported on a series of 74 outpatients with depressive disorders who were treated in their group practice at the Rhode Island Hospital between 1996 and 1999. All of the patients had either failed to respond to or relapsed after responding to an adequate trial of antidepressant medication. The treating psychiatrists either switched the patients to another antidepressant (N = 38) or added a second medication to augment the first antidepressant (N = 36). The relatively even number of patients treated with each strategy was not by design. Rather, it may be viewed as a behavioral indicator of the psychiatrists’ belief that augmenting and switching strategies are comparably useful for antidepressant nonresponders. Forty-five patients (61%) were taking a selective serotonin reuptake inhibitor (SSRI) at the time of the decision to switch or augment. Fifteen patients were taking other newer antidepressants (bupropion, N = 5; venlafaxine, N = 5; nefazodone, N = 4; and mirtazapine, N = 1). Among the remainder, 12 patients were treated with tricyclic antidepressants (TCAs), and 2 patients were taking monoamine oxidase inhibitors (MAOIs) (phenelzine and moclobemide, 1 each). The selection of antidepressants appears to be representative of contemporary psychiatric practice, although moclobemide is not approved for general use in the United States. The Need for Clinically Relevant Research on Treatment-Resistant Depression

Using treatment algorithms for the effective management of treatment-resistant depression.

Abstract: Increasingly, clinicians are looking to evidence-based medicine for information about treatment options. Treatment algorithms have been used with a variety of psychiatric disorders to assist physicians in making treatment decisions. The direct, prescriptive nature of algorithms also makes them suitable for use in treatment-resistant depression. Two major projects, the Texas Medication Algorithm Project and Sequenced Treatment Alternatives to Relieve Depression, have begun to address the questions of sequenced treatment options. Future directions for algorithm development and implementation are discussed.

Are atypical antipsychotic drugs also atypical antidepressants

Abstract: Objective: To report a case series and review the psychopharmacology of the neuroleptic drugs to suggest that the atypical antipsychotic drugs may have an antidepressant action, at least for those patients with the melancholic subtype.Method: We note the literature suggesting that the older (or typical) antipsychotic drugs were established as having antidepressant activity, describe an open study of some two dozen patients with a treatment-resistant melancholic depression, describe rapid resolution of depression and augmentation benefits associated with commencing an atypical antipsychotic drug in a percentage of subjects, and then review relevant psychopharmacological studies to consider whether there is a rationale for use of antipsychotic drugs to treat depression.Results: Of some two dozen patients treated with an atypical antipsychotic drug, almost immediate improvement was noted in four patients, and evidence of augmentation benefit obtained in another three patients.Conclusions: Impressions from th...

Intractable depression or psychosis.

Abstract: Objective: Some patients with treatment resistant depression may have a difficult to recognize and therefore untreated thought disorder. Even a subtle disorder may significantly impact patients' lives. This case illustrates a mechanism for identifying and treating this subgroup of patients. Method: The treatment of a 67-year-old female with intractable depression is described. Results: The Rorschach Exner Comprehensive System identified the presence of a thought disorder with four out of five conditions positive on the Schizophrenia Index and five out of seven conditions positive on the Depression Index. Low-dose risperidone was added to the patient's medications with excellent results. Post-testing indicated that the Schizophrenia and Depression Indices were no longer positive. Conclusion: A subgroup of patients with intractable depression may have an underlying thought disorder that can be identified with the Rorschach and successfully treated with low-dose antipsychotic medication.

Lamotrigine in the treatment of mental disorders

Abstract: BACKGROUND: Bipolar and other mood disorders often do not respond satisfactorily to lithium, valproate, carbamazepine or antidepressants. MATERIAL AND METHODS: On the basis of six years of clinical experience with lamotrigine in the treatment of psychiatric disorders, supplemented by three case reports and a comprehensive literature review of empirical studies, we discuss the possible indications for lamotrigine in psychiatric disorders. RESULTS: Lamotrigine seems to have a stronger antidepressant effect in bipolar 1 disorders than gabapentine, carbamazepine and valproate, but a weaker effect on manic symptomatology than the latter two. Lamotrigine may be of value in the treatment of bipolar 2 disorders in which chronic treatment resistant depression is often a complication, including rapid cycling and, in the unipolar version of rapid cycling, brief recurrent depression. We have also used to good effect the neuroprotective effects of lamotrigine in prophylactic treatment of neurodegenerative disorders (e.g. Huntington's chorea). INTERPRETATION: Lamotrigine is an anticonvulsant with an efficacy profile in psychiatric disorders different from those of valproate, carbamazepine and gabapentine. The drug represents an important supplement to the treatment options in chronic recurrent mood and neuropsychiatric disorders.