Tag: Hickie

A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome is characterized by prolonged and disabling fatigue and a range of neuropsychiatric symptoms including depressed and/or irritable mood. To date, no medical or psychotropic therapies have provided clear symptomatic benefit.

METHOD: Ninety patients with chronic fatigue syndrome, diagnosed with our system that approximates CDC criteria, participated in a randomized, placebo-controlled, double-blind trial of 450 to 600 mg/day of moclobemide, a novel reversible inhibitor of monoamine oxidase-A.

RESULTS: Fifty-one percent (24/47) of patients receiving moclobemide improved compared with 33% (14/43) of patients receiving placebo (odds ratio = 2.16, 95% confidence interval [CI] = 0.9 to 5.1). Drug response was best characterized symptomatically by an increase in the subjective sense of vigor and energy rather than a reduction in depressed mood. The effect of moclobemide on subjective energy was detectable within the first 2 weeks of treatment and increased across the course of the study. The greatest reduction in clinician-rated disability was in patients with concurrent immunologic dysfunction (mean difference in standardized units of improvement = 0.8, 95% CI = 0.03 to 1.6).

CONCLUSION: Moclobemide produces some improvement in key symptoms experienced by patients with chronic fatigue syndrome. This effect is not dependent on the presence of concurrent psychological distress and is likely to be shared with other monoamine oxidase inhibitors.

 

Source: Hickie IB, Wilson AJ, Wright JM, Bennett BK, Wakefield D, Lloyd AR. A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome. J Clin Psychiatry. 2000 Sep;61(9):643-8. http://www.ncbi.nlm.nih.gov/pubmed/11030484

 

Prolonged fatigue, anxiety and depression: exploring relationships in a primary care sample

Abstract:

OBJECTIVE: While prolonged fatigue states are frequently comorbid with other forms of distress, they are now the subject of independent aetiological and treatment research. The objective of this study was to use principal component analysis to clarify the relationships between proposed measures of prolonged fatigue and anxiety and depression in data obtained from patients attending primary care.

METHOD: Self-report measures of prolonged fatigue and psychological distress (anxiety and depression) were administered to consecutive ambulatory care patients attending primary care.

RESULTS: Data from 1593 subjects were obtained. A two-factor principal component solution (varimax rotation) demonstrated a clear separation between fatigue-related items (Cronbach’s alpha = 0.81) as compared with those items describing anxiety and/or depression (Cronbach’s alpha = 0.95). A four-factor solution produced similar results with two factors describing general psychological distress (contrasting anxiety and depression), with two other factors describing the profiles of mental and physical fatigue.

CONCLUSIONS: The results lend weight to the argument that prolonged fatigue states can be measured independently of conventional notions of anxiety and depression in patients attending primary care. Epidemiological, aetiological and treatment research in psychiatry may need to focus greater attention on such prolonged fatigue states.

Comment in: Response to: ‘Prolonged fatigue, anxiety and depression: exploring relationships in a primary care sample‘. [Aust N Z J Psychiatry. 2000]

 

Source: Koschera A, Hickie I, Hadzi-Pavlovic D, Wilson A, Lloyd A. Prolonged fatigue, anxiety and depression: exploring relationships in a primary care sample. Aust N Z J Psychiatry. 1999 Aug;33(4):545-52. http://www.ncbi.nlm.nih.gov/pubmed/10483850

 

Fatigue and psychiatric disorder: different or the same?

Abstract:

BACKGROUND: Fatigue and psychiatric symptoms are common in the community, but their association and outcome are sparsely studied.

METHOD: A total of 1177 patients were recruited from UK primary care on attending their general practitioner. Fatigue and psychiatric disorder was measured at three time points with the 12-item General Health Questionnaire and the 11-item Fatigue Questionnaire.

RESULTS: Total scores for fatigue and psychiatric disorder did not differ between the three time points and were closely correlated (r around 0.6). The association between non-co-morbid (‘pure’) fatigue and developing psychiatric disorder 6 months later was the same as that for being well and subsequent psychiatric disorder. Similarly, having non-co-morbid psychiatric disorder did not predict having fatigue any more than being well 6 months previously. Between 13 and 15% suffered from non-co-morbid fatigue at each time point and 2.5% suffered from fatigue at two time points 6 months apart. Less than 1% of patients suffered from non-co-morbid fatigue at all three time points.

CONCLUSIONS: The data are consistent with the existence of ‘pure’ independent fatigue state. However, this state is unstable and the majority (about three-quarters) of patients become well or a case of psychiatric disorder over 6 months. A persistent, independent fatigue state lasting for 6 months can be identified in the primary-care setting, but it is uncommon of the order of 2.5%. Non-co-morbid (pure) fatigue did not predict subsequent psychiatric disorder.

 

Source: van der Linden G, Chalder T, Hickie I, Koschera A, Sham P, Wessely S. Fatigue and psychiatric disorder: different or the same? Psychol Med. 1999 Jul;29(4):863-8. http://www.ncbi.nlm.nih.gov/pubmed/10473313

 

The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care

Abstract:

BACKGROUND: Depression, anxiety and fatigue are among the most common symptoms presented in primary care. Whether such symptoms indicate discrete psychological syndromes or whether they result from a common vulnerability is not clear. This study examined longitudinally the patterns of co-morbidity between prolonged fatigue and other forms of psychological distress in patients attending general practitioners.

METHODS: Adults attending primary care completed questionnaires designed to detect cases of prolonged fatigue and psychological distress at presentation and 12 months later.

RESULTS: Of 652 patients, the prevalence rates of ‘prolonged fatigue’ alone, ‘psychological distress’ alone, ‘prolonged fatigue + psychological distress’ and ‘no disorder’ were 7%, 19%, 15% and 59% respectively at initial assessment. Of those patients with any prolonged fatigue syndrome initially, 58% still reported fatigue 12 months later (representing 13% of the total sample). Most importantly, the risk of developing prolonged fatigue was not increased in patients who initially had psychological distress (OR = 0.95; 95% CI 0.2-3.6), neither was the risk of developing psychological distress increased in patients who initially had prolonged fatigue (OR = 1.4; 95% CI 0.6-3.4).

CONCLUSIONS: This study indicates that prolonged fatigue is a persistent diagnosis over time. The longitudinal patterns of co-morbidity with psychological distress do not support an aetiological model that proposes a common vulnerability factor for these disorders. Psychiatric classification systems may be better served by treating prolonged fatigue and psychological distress as independent disorders.

 

Source: Hickie I, Koschera A, Hadzi-Pavlovic D, Bennett B, Lloyd A. The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care. Psychol Med. 1999 Jul;29(4):855-61. http://www.ncbi.nlm.nih.gov/pubmed/10473312

 

Nefazodone for patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) present with a variety of musculoskeletal, neurocognitive, sleep disturbance and mood symptoms. An open evaluation of the clinical utility of the novel antidepressant compound, nefazodone, was completed.

METHOD: Ten patients with CFS presenting for assessment by a specialist psychiatrist were treated with nefazodone. Patients treated within this specialist service are also advised to engage in appropriate behavioural and sleep-wake cycle strategies to improve their level of functioning.

RESULTS: Of the 10 patients, eight (80%) reported at least some improvement in the key symptom of fatigue, with four (40%) reporting moderate or marked symptom relief. Additionally, sleep disturbance and mood were both moderately or markedly improved in seven (70%) and eight (80%) of the patients, respectively. Five of the patients (50%) achieved at least a moderate improvement in overall functional outcome and were able to return to work or their previous level of role function. The mean dose of nefazodone was 370 mg/day (range = 200-800 mg), with a strong preference for nocturnal dosing. Seven of the patients had previously failed to respond to moclobemide, while seven had previously failed to respond to conventional antidepressant therapy.

CONCLUSION: Nefazodone appears to be worthy of further systematic investigation in patients with CFS. Given its effects on sleep, mood and anxiety symptoms, it may have particular advantages in patients with this disorder.

 

Source: Hickie I. Nefazodone for patients with chronic fatigue syndrome. Aust N Z J Psychiatry. 1999 Apr;33(2):278-80. http://www.ncbi.nlm.nih.gov/pubmed/10336228

 

Unique genetic and environmental determinants of prolonged fatigue: a twin study

Abstract:

BACKGROUND: Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression.

METHODS: To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age.

RESULTS: Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ:DZ ratios of 2.12-2.69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0.67-0.79) and higher than that between fatigue and psychological distress (0.38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25-60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor.

CONCLUSION: This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.

 

Source: Hickie I, Kirk K, Martin N. Unique genetic and environmental determinants of prolonged fatigue: a twin study. Psychol Med. 1999 Mar;29(2):259-68. http://www.ncbi.nlm.nih.gov/pubmed/10218917

 

Chronic fatigue syndrome: an immunological perspective

Abstract:

OBJECTIVE: The aim of this study is to review research examining an immunological basis for chronic fatigue syndrome (CFS) and to discuss how a disturbance in immunity could produce central nervous system (CNS)-mediated symptoms.

METHOD: Data relevant to the hypothesis that abnormal cytokine release plays a role in the pathogenesis of CFS are reviewed as well as recent evidence relating to potential mechanisms by which immune products may enter the brain and produce a disturbance in CNS processes.

RESULTS: Examinations of cytokine levels in patients with CFS have produced inconclusive results. Recent evidence suggests that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms.

CONCLUSION: Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines. This possibility is discussed in the context of unresolved issues in the pathogenesis of CFS.

 

Source: Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D. Chronic fatigue syndrome: an immunological perspective. Aust N Z J Psychiatry. 1998 Aug;32(4):523-7. http://www.ncbi.nlm.nih.gov/pubmed/9711366

 

Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) report neuro-psychological symptoms as a characteristic feature. We sought to assess cognitive performance in patients with CFS, and compare cognitive performance and subjective workload experience of these patients with that of two disease comparison groups (non-melancholic depression and acute infection) and healthy controls.

METHOD: A computerized performance battery employed to assess cognitive functioning included tests of continuous attention, response speed, performance accuracy and memory. Severity of mood disturbance and subjective fatigue were assessed by questionnaire.

RESULTS: All patient groups demonstrated increased errors and slower reaction times, and gave higher workload ratings than healthy controls. Patients with CFS and non-melancholic depression had more severe deficits than patients with acute infection. All patient groups reported more severe mood disturbance and fatigue than healthy controls, but patients with CFS and those with acute infection reported less severe mood disturbance than patients with depression.

CONCLUSIONS: As all patients demonstrated similar deficits in attention and response speed, it is possible that common pathophysiological processes are involved. The differences in severity of mood disturbance, however, suggest that the pathophysiological processes in patients with CFS and acute infection are not simply secondary to depressed mood.

 

Source: Vollmer-Conna U, Wakefield D, Lloyd A, Hickie I, Lemon J, Bird KD, Westbrook RF. Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression. Br J Psychiatry. 1997 Oct;171:377-81. http://www.ncbi.nlm.nih.gov/pubmed/9373430

 

Is there a postinfection fatigue syndrome?

Abstract:

Prolonged fatigue syndromes are common in general practice. Most of these syndromes are secondary to other common medical or psychological disorders. It appears, however, that some specific infectious illnesses are associated with prolonged recovery. Theories as to the mechanisms for such post infection fatigue syndromes include a range of immunological, psychological and neurobiological processes. Current evidence suggests disruption of fundamental central nervous system mechanisms, such as the sleep-wake cycle and the hypothalamic-pituitary-adrenal axis, may underpin the clinical features of this disorder. Treatment should focus on the provision of continuous medical care, physical rehabilitation and adjunctive psychological therapies.

 

Source: Hickie I, Lloyd A, Wakefield D, Ricci C. Is there a postinfection fatigue syndrome? Aust Fam Physician. 1996 Dec;25(12):1847-52. http://www.ncbi.nlm.nih.gov/pubmed/9009004

 

Chronic fatigue syndrome: current perspectives on evaluation and management

Abstract:

OBJECTIVE: To describe clinical and laboratory guidelines for assessment and management of patients presenting with chronic fatigue syndrome(CFS).

DATA SOURCES: Relevant international consensus diagnostic criteria and research literature on the epidemiology, pathophysiology, concurrent medical and psychological disturbance and clinical management of CFS.

CONCLUSIONS: Medical and psychiatric morbidity should be carefully assessed and actively treated, while unnecessary laboratory investigations and extravagant treatment regimens should be avoided. No single infective agent has been demonstrated as the cause of CFS, and immunopathological hypotheses remain speculative. The aetiological role of psychological factors is debated, but they do predict prolonged illness. The rate of spontaneous recovery appears to be high. Effective clinical management requires a multidisciplinary approach, with consideration of the medical, psychological and social factors influencing recovery.

Comment in: Chronic fatigue syndrome: is total body potassium important? [Med J Aust. 1996]

 

Source: Hickie IB, Lloyd AR, Wakefield D. Chronic fatigue syndrome: current perspectives on evaluation and management. Med J Aust. 1995 Sep 18;163(6):314-8. http://www.ncbi.nlm.nih.gov/pubmed/7565238