Serial blood serotonin levels in a randomized controlled trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in patients with chronic tension-type facial pain

Abstract

Patients often present with chronic facial pain despite normal nasal endoscopy and sinus computerized tomography. Such pain has increasingly been recognized as being of neurological origin with one of the commonest underlying causes being mid-facial segmental tension-type pain (MFP) which is a version of tension headache in the face. Descending serotonergic neuronal projections are known to modulate pain and intra-platelet serotonin levels are an accepted model reflecting central intra-neuronal serotonin. 1.To determine whether low-dose amitriptyline significantly changes whole blood serotonin compared to a surrogate placebo in patients with chronic MFP 2. To determine whether the addition of pindolol, a beta blocker with serotonin receptor blocking properties further alters blood serotonin. Sixty-two patients were randomized to three treatment groups a) amitriptyline , b) amitriptyline with pindolol, and c) loratadine as surrogate placebo. Whole blood serotonin was taken before and after 8 weeks of treatment. Serotonin was also measured in 40 age-matched healthy controls. There was a significant reduction in blood serotonin levels in the amitriptyline with pindolol group. A non-significant reduction was seen in the amitriptyline group, with no change in serotonin levels in the surrogate placebo group. A comparison of change in serotonin with change in pain frequency and intensity scores is presented. Women in the control group had significantly higher serotonin levels than men. Women with tension-type facial pain who failed to respond to treatment had significantly lower blood serotonin than women in the control group. When linked to the clinical response this study provides evidence that the serotonergic system is involved in the modulation of chronic MFP. Serotonin levels are sex-dependent and related to treatment response.