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The aims of this study were to examine whether pindolol, a serotonin (5-hydroxytryptamine [5-HT])-1A receptor antagonist, and mianserin, a 5-HT2A/C and alpha2-adrenoceptor (alpha2-AR) antagonist, may augment the clinical efficacy of fluoxetine, a selective serotonin reuptake inhibitor, and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression (TRD). Ten days after admission to the hospital, 31 major depressed patients were randomly assigned using a double-blind, controlled design to receive fluoxetine 20 mg daily, fluoxetine 20 mg daily plus pindolol 7.5 mg daily, or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks. The 17-item Hamilton Rating Scale for Depression (HAM-D) score was the primary outcome measure. Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint. It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone. Using an outcome measure of 50% reduction in the HAM-D, a 60% response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9% response rate in patients treated with fluoxetine alone. The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone. The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin, but not pindolol, may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine.

There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of 24-h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post-traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24-h UC excretion. The aim of the present study was to examine 24-h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24-h UC excretion than normal controls and fibromyalgia patients. At a threshold value of > or = 240 micrograms/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24 h UC excretion with a specificity of 100%. There were no significant differences in 24-h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24-h UC excretion and the HDRS score. In fibromyalgia, no significant correlations were found between 24-h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24-h UC excretion and severity of either depression-avoidance or anxiety-arousal symptoms. In conclusion, this study found increased 24-h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.

Background: The aims of the present study were to examine serum activities of peptidases, i.e. prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), in patients with fibromyalgia and to examine the effects of subchronic treatment with sertraline on these variables., Method: Serum PEP and DPP IV activity were measured in 28 normal volunteers and 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Tenderness at tender points was evaluated by means of dolorimetry. Fibromyalgia patients had repeated measurements of serum PEP and DPP IV both before and after repeated administration of sertraline or placebo for 12 weeks., Results: Patients with fibromyalgia had significantly lower serum PEP activity than normal volunteers. There were significantly negative correlations between serum PEP activity and severity of pressure hyperalgesia and the non-somatic, cognitive symptoms of the Hamilton Depression Rating Scale. Fibromyalgia patients with severe pressure hyperalgesia had significantly lower PEP activity than normal controls and fibromyalgia patients with less severe hyperalgesia. Fibromyalgia patients with severe non-somatic depressive symptoms had significantly lower serum PEP activity than normal volunteers. There were no significant changes in serum DPP IV activity in fibromyalgia. There were no significant effects of repeated administration of sertraline on serum PEP and DPP IV activity in patients with fibromyalgia., Conclusions: The results show that fibromyalgia, and aberrant pain perception and depressive symptoms in fibromyalgia are related to lower serum PEP activity. It is hypothesized that lower serum PEP activity may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides.

Background: Some studies have shown disturbances in auditory event related potentials (AERPs) in patients with major depression., Methods: In this exploratory study, the late AERP components, N100 (latency), P200 (amplitude and latency) and P300 (amplitude and latency) were recorded in 68 subjects, i.e. 39 major depressed subjects, with (n=4) or without (n=35) cognitive deterioration, 18 patients with Alzheimer's dementia (SDAT) and 11 normal volunteers. Twenty-five major depressed patients had repeated measurements of AERPs both before and after treatment with antidepressants., Results: Major depressed subjects without cognitive deterioration had significantly higher P300 latency and P200 amplitude than normal volunteers. SDAT patients and major depressed patients with cognitive impairment had a significantly higher P300 latency than depressed patients without cognitive impairment. In the latter, no significant alterations in any of the AERP components upon subchronic treatment with antidepressants were recorded. Nonresponders to antidepressant therapy had significantly higher pretreatment P300 latency and P200 amplitude than responders to treatment (P=0.006) and normal volunteers (P=0.0004)., Conclusions: The findings may suggest that delayed P300 latency as well as increased P200 amplitude accompany major depression and may predict a nonresponse to subsequent antidepressive therapy.

Background: There is a high degree of comorbidity between fibromyalgia and major depression. The latter is characterized by signs of immune activation, whereas the immune status in fibromyalgia is not yet elucidated. The aims of the present study were to examine (i) neopterin and biopterin excretion in 24-h urine of patients with fibromyalgia compared with normal volunteers and patients with major depression; and (ii) the effects of subchronic treatment with sertraline (11 weeks) on the urinary excretion of neopterin and biopterin., Methods: Measurements of neopterin, biopterin, pseudouridine, creatinine and uric acid in 24-h urine were performed by means of HPLC in 14 fibromyalgia and ten major depressed patients and 17 normal volunteers., Results: There were no significant differences in urine excretion of the above five analytes between patients with fibromyalgia and normal volunteers. Patients with major depression showed significantly higher urinary neopterin excretion than normal volunteers and fibromyalgia patients. Patients with fibromyalgia and major depression had a significantly increased neopterin/creatinine ratio. Fibromyalgia patients had significantly lower urinary excretion of creatinine than patients with major depression. In fibromyalgia patients, there were no significant effects of sertraline treatment on any of the urine analytes., Conclusions: The findings suggest that fibromyalgia, in contrast to major depression, may not be accompanied by activation of cell-mediated immunity., Limitation: Other immune markers should be measured in fibromyalgia before drawing definite conclusions., Clinical Relevance: Increased urinary excretion of neopterin can be used as a marker for major depression, but not fibromyalgia.

Serum total tryptophan and the five competing amino acids (CAA), i.e., valine, leucine, tyrosine, phenylalanine, and isoleucine were determined in 35 major depressed subjects of whom 27 with treatment resistant depression (TRD), and 15 normal controls. Twenty-five of the depressed subjects had repeated measurements of the amino acids both before and after antidepressive treatment. The following immune-inflammatory variables were assayed in the above subjects: serum zinc (Zn), total serum protein (TSP), albumin (Alb), transferrin (Tf), iron (Fe), high-density lipoprotein cholesterol (HDL-C), number of peripheral blood leukocytes, and the CD4+/CD8+ T cell (T-helper/T-suppressor) ratio. Serum tryptophan and the tryptophan/CAA ratio were significantly lower in major depressed subjects than in normal controls. The tryptophan/CAA ratio was significantly lower in patients with TRD than in patients without TRD and normal controls. There were no significant alterations in any of the amino acids upon successful therapy. There were significant correlations between serum tryptophan and serum Zn, TSP, Alb, Tf, Fe, and HDL-C (all positive), and number of leukocytes and the CD4+/CD8+ T-cell ratio (all negative). The tryptophan/CAA ratio was significantly and negatively related to the number of leukocytes and the CD4+/CD8+ T-cell ratio. The results suggest that (a) TRD is characterized by lower availability of serum tryptophan; (b) the availability of tryptophan may remain decreased despite clinical recovery; and (c) the lower availability of tryptophan is probably a marker of the immune-inflammatory response during major depression.

Strong evidence has recently been reported that major depression is accompanied by an acute phase response (APR), characterized by elevated levels of positive acute phase proteins (APPs) and decreased levels of negative APPs. The APR is also reflected in lowered total serum protein (TSP) and specific changes in the major electrophoretically separated protein fractions. The present study examined pretreatment and posttreatment serum TSP and the concentrations and percentages of the major electrophoretically separated serum protein fractions in 37 major depressed subjects, of whom 29 had treatment-resistant depression (TRD), and in 29 normal controls. We found that TSP and the percentage and concentration of serum albumin (Alb) and gamma-globulin fraction were significantly lower in major depression and TRD than in normal controls. Serum beta-globulin concentrations were significantly lower in major depressed and TRD subjects than in normal controls. The percentages of the alpha 1- and alpha 2-globulin fractions were significantly higher in major depressed subjects than in normal controls. There were no significant effects of subchronic treatment with antidepressants on TSP, the percentage or concentration of the major electrophoretically separated protein fractions, i.e. alpha 1-, alpha 2- and beta-globulin. There was a significant increase in percentage of the gamma-globulin fraction after subchronic treatment with antidepressants. The results support the hypothesis that major depression and TRD are accompanied by a chronic APR.