Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is a debilitating disorder with prominent symptoms of malaise, fatigue, myalgia, arthralgia, and impaired concentration. The symptoms of CFS may often overlap those of Major Depressive Disorder (MDD). Treatment of CFS has generally been disappointing. We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression.

METHODS: 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks. Outcome measures of CFS included the Chalder Fatigue Questionnaire (CFQ), the multi-dimensional Fatigue Impact Scale (FIS), the CFS symptom rating (CFS-SR) 100 mm visual analogue scale, and the clinical global impressions severity (CGI/S) and change (CGI/C) ratings. Secondary outcomes of MDD included the Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and the CGI/S and CGI/C ratings of MDD.

RESULTS: We observed reductions in the mean CFQ score (p<0.0005), FIS score (p<0.0005), and CGI/S (p<0.0005) and CGI/C (p<0.0005) ratings over time. There was a significant improvement in 5 of the 8 CFS-SR symptoms: post-exertion malaise (p=0.001), headaches (p<0.0005), un-refreshing sleep (p<0.0005), and impaired memory and concentration (p<0.0005). There was also a reduction in mean HAM-D (p<0.0005), BDI (p<0.0005), CGI/S (p=0.001) and CGI/C (p<0.0005) ratings of MDD.

LIMITATIONS: The sample size was limited and the study design was not double-blind or placebo controlled.

CONCLUSION: We observed a significant reduction in both CFS and co-morbid MDD symptom severity ratings, and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy.

 

Source: Amsterdam JD, Shults J, Rutherford N. Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):100-6. Epub 2007 Aug 3. https://www.ncbi.nlm.nih.gov/pubmed/17804135

 

Psychological symptoms in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently complain of psychological symptoms including depression, anxiety, and neuropsychological impairment. In addition, patients with CFS have been reported to be more likely to have psychiatric diseases such as major depressive disorder, panic disorder, generalized anxiety disorder, and personality disorder.

In the present review article, psychological symptoms and psychiatric comorbidity in CFS patients were introduced. In addition, differentiation between CFS and psychiatric disorders were discussed, because there have been few studies on comorbidity and differentiation between CFS and undifferentiated somatoform disorder although there has been heated debate about the existence of CFS itself.

 

Source: Yoshiuchi K. Psychological symptoms in chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1023-7. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561692

 

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects.

No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies.

Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).

 

Source: Robertson MJ, Schacterle RS, Mackin GA, Wilson SN, Bloomingdale KL, Ritz J, Komaroff AL. Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression. Clin Exp Immunol. 2005 Aug;141(2):326-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809442/ (Full article)

 

Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression

Abstract:

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients.

Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms ofchronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear.

Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.

 

Source: Wheatland R. Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65(2):287-95. http://www.ncbi.nlm.nih.gov/pubmed/15885924

 

Subjective quality of life in patients with chronic fatigue syndrome

Abstract:

The aim of this study was to (1) assess Subjective Quality of Life (SQOL) of patients with Chronic Fatigue Syndrome (CFS) using a generic concept and to compare the findings with those in groups with mental disorders and healthy subjects, and (2) investigate whether and, if so, to what extent socio-demographic and clinical variables predict SQOL in CFS patients.

Seventy-three patients diagnosed with CFS were randomly selected and interviewed from two specialised clinics. CFS was diagnosed using the Oxford Criteria. SQOL was assessed on the Manchester Short Assessment of Quality of Life (MANSA) and Health-Related Quality of Life (HRQOL) on the Medical Outcome Study Short-Form 36 (MOS) SF-36. A battery of mood and symptom questionnaires, including the Symptom Checklist Questionnaire (SCL-90-R), was administered to assess various aspects of symptomatology as potential predictor variables.

Multiple regression analyses were conducted to identify predictors of SQOL. Overall, SQOL was low in CFS patients and less favourable than in groups with mental disorders and healthy subjects. Satisfaction was particularly low with life as a whole, leisure activities and financial situation. Whilst SQOL was only moderately correlated with HRQOL, the SCL-90-R score, especially SCL-90-R Depression scale score, was the best predictor of SQOL explaining 35% of the variance. HRQOL and generic SQOL appear distinct despite some overlap.

The findings underline that SQOL is significantly disrupted in CFS patients. Depressive symptoms are statistically the strongest ‘predictor’ of SQOL, although the direction of the relationship is not established. These data suggest that treatment of depression associated with CFS, regardless of causation, could help to improve SQOL in CFS patients.

 

Source: Rakib A, White PD, Pinching AJ, Hedge B, Newbery N, Fakhoury WK, Priebe S. Subjective quality of life in patients with chronic fatigue syndrome. Qual Life Res. 2005 Feb;14(1):11-9. http://www.ncbi.nlm.nih.gov/pubmed/15789937

 

Neuropsychiatric sequelae of Nipah virus encephalitis

Abstract:

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome.

Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

 

Source: Ng BY, Lim CC, Yeoh A, Lee WL. Neuropsychiatric sequelae of Nipah virus encephalitis. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):500-4. http://www.ncbi.nlm.nih.gov/pubmed/15616178

 

Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care

Abstract:

OBJECTIVE: Unexplained fatigue syndromes, such as chronic fatigue syndrome and neurasthenia, are strongly associated with depression, but the temporal nature of this association is not clear.

METHODS: The authors examined this issue by using data from the World Health Organization collaborative study of psychological problems in general health care. Three thousand two hundred one subjects from 15 primary care centers in 14 countries were followed up for 12 months. The Composite International Diagnostic Interview was the main instrument used. Odds ratios and their 95% confidence intervals (CI) were calculated using logistic regression models adjusted for sociodemographic variables, physical morbidity and intercenter variability.

RESULTS: Cases of depression were found to have an increased risk of developing a new episode of unexplained fatigue at follow-up with an adjusted odds ratio of 4.15 (95% CI = 2.64-6.54). Similarly, cases of unexplained fatigue were found to have an increased risk of developing a new episode of depression at follow-up with an adjusted odds ratio of 2.76 (95% CI = 1.32-5.78). Further adjustment for subthreshold symptoms at baseline weakened the reported associations, especially between fatigue and development of a new episode of depression, but these remained significant.

CONCLUSIONS: The findings support the view that unexplained fatigue and depression might act as independent risk factors for each other.

 

Source: Skapinakis P, Lewis G, Mavreas V. Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care. Psychosom Med. 2004 May-Jun;66(3):330-5. http://www.ncbi.nlm.nih.gov/pubmed/15184691

 

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

Abstract:

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones.

A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI).

Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05).

Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.

 

Source: Gur A, Cevik R, Nas K, Colpan L, Sarac S. Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.  Arthritis Res Ther. 2004;6(3):R232-8. Epub 2004 Mar 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416440/ (Full article)

 

Post-traumatic stress disorder among patients with chronic pain and chronic fatigue

Abstract:

BACKGROUND: Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD).

METHOD: Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined for their relationship with PTSD.

RESULTS: The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3.4, 95% CI 2.0-5.8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a three-fold increase in the prevalence of PTSD (95% CI 1.5-7.1); conversely, FM patients without MDD showed no increase in PTSD (OR=1.3, 95% CI 0.5-3.2). The components of the CFS criteria were not significantly associated with PTSD.

CONCLUSION: Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.

 

Source: Roy-Byrne P, Smith WR, Goldberg J, Afari N, Buchwald D. Post-traumatic stress disorder among patients with chronic pain and chronic fatigue. Psychol Med. 2004 Feb;34(2):363-8. http://www.ncbi.nlm.nih.gov/pubmed/14982142

 

Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome

 Abstract:

Chronic fatigue syndrome (CFS) is a controversial entity whose cause is unknown. In this study we have explored the possibility that progesterone metabolites may be involved. Plasma levels of the progesterone precursor pregnenolone, progesterone itself, and five ring A-reduced metabolites of progesterone were measured in 20 women with CFS and in 13 age-matched controls.

To minimize the contribution of the ovary, women were either post-menopausal or in the follicular phase of the menstrual cycle (day 4-8), and progesterone levels were all well within the expected range (< or = 3.5 nmol/l). Mean values for progesterone and all of its metabolites were higher in CFS patients, the most marked being a 2.3-fold elevation in isopregnanolone (3beta,5alpha-tetrahydroprogesterone; p < or = 0.001). Progesterone levels were correlated with those of its metabolites, but even after controlling for progesterone by ANCOVA, isopregnanolone levels were still elevated (p < or = 0.001). These elevated levels of isopregnanolone could not be attributed to medications (antidepressants and anxiolytics).

When the CFS patients were divided into two groups according to their Hamilton depression scale ratings, mean (+/-SD) isopregnanolone levels were higher (274+/-160 vs 197+/-119 pmol/l) in the less depressed group (ratings 2-14) than in the more depressed group (ratings 17-28), although this difference did not reach significance. Progesterone levels were negatively correlated with Hamilton depression rating scores (r=-0.56; p<0.01). These results suggest that increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS, and that the pathophysiology of CFS is unlikely to be due to depression.

 

Source: Murphy BE, Abbott FV, Allison CM, Watts C, Ghadirian AM. Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Feb;29(2):245-68. http://www.ncbi.nlm.nih.gov/pubmed/14604604