Newer Antidepressants in Combination With Pregabalin for Fibromyalgia Syndrome
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background: The investigator hypothesized that the combined use of pregabalin and paroxetine
      would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and higher tolerability
      than amitriptyline or venlafaxine.

      Methods: After ethical approval, 75 patients with diagnosed fibromyalgia who were receiving
      pregabalin 75 mg/day, were randomly allocated to receive amitriptyline 25 mg/day (n = 24),
      venlafaxine 75 mg/day (n = 25), or paroxetine 25 mg/day (n = 26). All patients were assessed
      bi-monthly for consequent six months for the changes in the SSS-8, Center for Epidemiological
      Studies Depression Scale (CESDS), life satisfaction, mood, sleep quality, fatigue and
      medication tolerability and adverse effects.
    

Detailed description: 
      Fibromyalgia is a common cause of chronic widespread disabling pain affecting 2-5% of the
      young to middle-aged women in developed countries. The American College of Rheumatology has
      been established new diagnostic criteria for fibromyalgia in 2010 included a widespread pain
      index (WPI) and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and
      number of somatic symptoms. The definite pathophysiology of chronic pain in fibromyalgia
      remains unclear.

      Fibromyalgia is usually associated with depression, anxiety, and alexithymia increasing over
      age which contribute significantly to reduced patient wellbeing. These may be due to
      alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal
      axis, and disturbances in the dopaminergic and serotonergic systems. Thus the European League
      Against Rheumatism (EULAR) recommends the use of serotonin and noradrenaline reuptake
      inhibitors (SNRIs) for the treatment of fibromyalgia, to reduce pain and improve function.

      However, few patients achieve satisfactory pain relief with the sole use of SNRIs. A recent
      Cochrane review demonstrated only modest improvement in relieving pain without reducing of
      sleep disturbances, fatigue, or the poor quality of life with the use of duloxetine and
      milnacipran than placebo in patients with fibromyalgia. More patients experienced adverse
      events like as nausea, dry mouth, constipation, headache, somnolence, dizziness and insomnia
      leading to stopping medications. Whereas, the evidence from clinical studies shows that
      combined use of pregabalin and SNRIs such as duloxetine has potential efficacy and better
      tolerability during the treatment of improvement of pain, fatigue, and sleep disorders in
      patients with fibromyalgia.

      The use of the second-generation antidepressants like as paroxetine (a selective serotonin
      reuptake inhibitors (SSRIs)) and venlafaxine (SNRIs) may be associated with more tolerability
      and reduce pain in patients with major depressive disorder.

      To the best of the investigator's knowledge, the comparison of the long-term efficacy,
      tolerability, and safety of the combined use of pregabalin with one of the three
      antidepressants, namely, amitriptyline, venlafaxine, or paroxetine for the treatment of
      fibromyalgia has not yet been studied.

      The investigators hypothesized that the combined use of pregabalin and paroxetine would be
      associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological
      Studies Depression scales (CESD) and higher tolerability than the use of pregabalin with
      either amitriptyline or venlafaxine.
    

Intervention name(s): Amitriptyline; Venlafaxine; Paroxetine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Amitriptyline 25 mg/day; Venlafaxine 75 mg/day; Paroxetine 25 mg/day
Intervention MeSH terms: Amitriptyline; Paroxetine; Venlafaxine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Pregabalin; Fibromyalgia