Effects of antidepressant mirtazapine on fibromyalgia symptoms
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Roczniki Akademii Medycznej w Białymstoku · Vol. 49, 2004 ·Effects
Annalesof Academiae
antidepressant mirtazapine
Medicae on fibromyalgia symptoms
Bialostocensis 265
Effects of antidepressant mirtazapine
on fibromyalgia symptoms
Samborski W1, Leańska-Szpera M2, Rybakowski JK2
1
Department of Physiotherapy and Rheumatology, University of Medical Sciences, Poznań, Poland
2
Department of Adult Psychiatry, University of Medical Sciences, Poznań, Poland
Abstract the reduction on all four main symptoms of FS suggests
a common pathophysiology of depression and symptoms of
Purpose: Fibromyalgia syndrome (FS) is a form of non- fibromyalgia. The data thus far obtained indicate the block-
articular rheumatism. The main criteria are the widespread ade of 5-HT2 and 5-HT3 receptors with mirtazapine as an
musculoskeletal pain and tender points at multiple charac- effective and promising method in FS.
teristic sites which are associated with several vegetative Conclusions: Further double-blind placebo-controlled
and functional symptoms. Depression is the most frequent study are required to confirm our results.
psychiatric concomitant of FS. Etiology is unknown, con-
nection between disturbances of serotonin metabolism
and pathogenesis is postulated. Pharmacological therapy Key words: fibromyalgia, blockade of 5-HT2 and 5-HT3
with analgetic and nonsteroidal antiinflammatory drugs is receptors, mirtazapine.
not very effective. Positive effects were reported in some
patients treated with antidepressant drugs, especially sero-
tonergic agents. Introduction
Material and methods: In the study a novel antidepres-
sant drug mirtazapine was used characterized by selective Fibromyalgia syndrome (FS) is a form of non-articular
blockade of 5-HT2 and 5-HT3 receptors. In an open trial rheumatism. Widespread musculoskeletal pain is the dominant
participated 29 patients with FS, who met 1990 ACR cri- symptom, and tender points at multiple characteristic sites can be
teria for fibromyalgia. All were treated with mirtazapine demonstrated in most instances [1,2]. FS is frequently associated
for 6 weeks. Intensity of pain, sleep disturbances, fatigue with chronic fatigue, poor sleep, irritable bowel, headaches,
and other symptoms were measured using visuale analogue dysmenorrhea and other vegetative symptoms [3-5]. All studies
scale, severity of depression was evaluated with HDRS and confirm the female preponderance as well as the chronicity
BDI. of symptoms in this syndrome [6,7]. Muscle biopses reveal no
Results: An open trial completed 26 patients, the major- inflammatory processes and basic laboratory tests are normal
ity of them experienced a clinical improvement at the end [8,9]. Depression is the most frequent psychiatric concomitant
of the study as a consequence of 40% reduced intensity of FS and observed association between FS and depression has
of fibromyalgia symptoms as well as reduced severity of been considered in several ways: is FS a variant of depression
depression. The significant correlation between reduction (somatized depression) or are the symptoms of depression
in depression after 6 weeks of mirtazapine treatment with secondary to disturbances in the process of coping with chronic
and painful disease? Another possibility is that depression and
FS share common aspects of their pathophysiology [10,11].
ADDRESS FOR CORRESPONDENCE: Several studies have shown that central serotonin
Samborski W
abnormality may be connected with an increased pain
Department of Physiotherapy and Rheumatology
University of Medical Sciences sensitivity, sleep disturbance and depression [12]. Because these
ul. 28 czerwca 1956 r 135/147 symptoms are prominent in FS, an association between FS and
61-545 Poznań, Poland
disturbed serotonin (5-HT) metabolism has been postulated
Tel: +061-8-310-244
[13]. There is some evidence supporting this hypothesis such as
Received 1.07.2003 8.06.2004 showing a decrease in both serum concentration of 5-HT and266 Samborski W, et al.
plasma concentration of tryptophan (5-HT precursor) in FS. Figure 1. Intensity of pain and fatigue in the courses of mirtazap-
ine treatment. (VAS score)
A relationship exists between the 5-HT serum concentration
and the intensity of pain as well as the number of specific
score
“tender points” [14-16]. A presence of antibodies against 5-HT 10
in patients with FS has been also demonstrated [17,18].
8
Pharmacological therapy of FS is mostly unsatisfactory.
fatigue
Analgetic agents and nonsteroidal antiinflammatory drugs are 6
pain
not very effective. On the other hand, a favorable therapeutic 4
response was observed to antidepressant drugs. Positive
2
effects were reported in some FS patients treated with tricyclic
antidepressants – imipramine and amitriptyline [19,20], with 0
Visit 1 Visit 2 Visit 3 Visit 4
selective serotonin reuptake inhibitors – citalopram and
fluoxetine [21,22], and also with the novel antidepressant
venlafaxine [23]. Influencing serotonergic system makes an
important element of mechanism of each of these drugs. A recent exceeding 2 g/day. The patients were treated with mirtazapine
meta-analysis of fibromyalgia treatment with antidepressant for 6 weeks (42 days), the first week with 15 mg in the evening,
drugs suggests a significant effect of such treatment on sleep, the next 5 weeks the dose could be increased to 30 mg in the
fatigue, pain and well-being of patients. However, it is not clear evening. All patients were examined by the rheumatologist and
whether this effect is related to antidepressant action [24,25]. psychiatrist before enrolling into the study (visit 1), after 7 days
Apart from antidepressant drugs, some effect in FS was (visit 2), after 21 days (visit 3) and after 42 days (visit 4).
also observed with serotonergic agents, e.g. selective blockers
of serotonergic receptors. In the study with ketanserine, the Assessment
drug blocking serotonin 5-HT2 receptors, it was found that Intensity of pain, sleep disturbances, fatigue and other
quality of sleep in FS was improved [26]. Also, a therapy with symptoms: cold extremities, dryness of mouth, perfuse sweating,
tropisetron or ondansetron, the selective 5-HT3 receptor dizziness, gastric problems, headache or migraine, irregular
antagonists reduced pain intensity in about half of FS patients breathing, arrhythmia, paresthesia and urinary urgency was
whereas no change in pain level was seen in the other half. The measured using visual analogue scale (VAS) where 0 = no
lack of uniform pattern of responsiveness to these agents may symptom and 10 = extreme intensity of symptoms [31]. The
suggest a heterogeneity of pathogenic background in relation to duration of morning stiffness was measured in minutes.
serotonergic system in FS patients [27-29]. The severity of depression was measured using the Hamilton
Mirtazapine is a novel antidepressant drug characterized, Depression Rating Scale (HDRS) – 17 item version [32] and
among others, by selective blockade of both 5-HT2 and 5-HT3 Beck Depression Inventory [33].
receptors. In view of previous moderately promising studies with Patient was considered improved, if he/she obtained the
selective serotonin receptor antagonists, we hypothesized that reduction of 40% of the following main symptoms: pain,
this drug may be useful in the treatment of fibromyalgia. In this fatigue, sleep disturbances and depression.
study we present the results of an open trial of mirtazapine in
FS patients. Statistics
For the statistical analysis, the Wilcoxon-Test, the Mann-
Whithney U Test and ANOVA procedure were used.
Materials and methods
Subjects Results
The study group consisted of 29 patients with FS (25 female
and 4 male) with mean age 45.6 years (range 20 - 64). All Among 26 patients who completed an open trial with
patients met the 1990 American College of Rheumatology mirtazapine, the majority experienced a clinical improvement at
diagnostic criteria for FS [30]. Each patient underwent routine the end of the study as a consequence of 40% reduced intensity
clinical examination, radiographic and laboratory investigation of fibromyalgia symptoms. In 13 patients (50%), the reduction
to establish the diagnosis (excluding other inflammatory, of pain and fatigue level was observed. The decrease of intensity
rheumatic, metabolic, endocrine disease associated with muscle of these symptoms in whole group of patients with subsequent
pain). They all gave written consent to the study which was visits is depicted in Fig. 1.
also approved by the Ethics Committee, University of Medical The improvement of the sleep quality with significant
Sciences, Poznań. reduction on VAS was noted in 19 patients (73%), what was also
supported by the decrease of intensity on HDRS sleep subscale
Procedure (items 4-6). This is shown in Fig. 2.
The patients were free from all antidepressant medication The reduced severity of depressive symptoms 40% on
for at least 7 days before the administration of mirtazapine. HDRS scale was observed in 18 patients (69%) and on BDI
Throughout the study, no other drugs were permitted with the scale in 16 subjects (61%). The mean intensity of depressive
exception of paracetamol, if required by the patient, but not symptoms during subsequent visits in shown in Fig. 3.Effects of antidepressant mirtazapine on fibromyalgia symptoms 267
Figure 2. Sleep disturbances in the course of mirtazapine treat- Figure 3. Intensity of depression (HDRS and BDI scores) in the
ment (VAS score and HDRS sleep subscale) course of mirtazapine treatment
points points
10 25
8 20
6 15
4 10 BDI
VAS HDRS
2 5
0 HDRS 0
Visit 1 Visit 2 Visit 3 Visit 4 Visit 1 Visit 2 Visit 3 Visit 4
Table 1. Intensity of fibromyalgia symptoms before and after Table 2. Correlation between reduction of depression (HDRS
therapy with mirtazapine in patients with fibromyalgia (n=26) and BDI scales) and reduction of main fibromyalgia symptoms
after 6 weeks of mirtazapine treatment
Symptoms n=26
VAS I II p< Reduction in HDRS Reduction in BDI
Pain 7.92 5.0 0.0005 Pain 0.72** 0.63**
Morning stiff. ( min) 67.9 48.7 0.0005 Sleep disturbances 0.46* 0.42*
Fatigue 8.4 5.7 0.0005 Fatigue 0.77** 0.69**
Sleep disturbances 8.2 2.7 0.0001 Morning stiffness 0.64** 0.53*
Cold extremities 7.3 4.7 0.0005 * p268 Samborski W, et al.
Table 3. Intensity of fibromyalgia symptoms before and after therapy with mirtazapine
(Group A: patients with 18 pts in HDRS; group B: patients withEffects of antidepressant mirtazapine on fibromyalgia symptoms 269
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