TY - JOUR
T1 - Analgesic effect of amitriptyline in chronic tension-type headache is not directly related to serotonin reuptake inhibition
AU - Ashina, Sait
AU - Bendtsen, Lars
AU - Jensen, Rigmor
N1 - Funding Information:
We thank Dr Inge Hindberg and our laboratory technician Mrs Hanne Andresen for skilful technical assistance. We also thank Professor Jes Olesen and Dr Peer Tfelt-Hansen for critical comments on the manuscript. The study was supported by the Pharmaceutical Foundation of 1991 (Apotekerfonden af 1991) and by the Lundbeck Foundation (145/91).
PY - 2004/3
Y1 - 2004/3
N2 - The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension-type headache (CTTH). However, it is not fully clarified whether the serotonin (5-HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5-HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline we investigated platelet 5-HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty-four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5-HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32-week, double-blind, placebo-controlled, three-way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5-HT was used as a measure of 5-HT reuptake inhibition and determined by high performance liquid chromatography. Area under the headache curve was 308 (157-715) (median with quartiles in parentheses) with amitriptyline and significantly lower than 377 (158-1121) with citalopram (P=0.04), and 441 (178-1408) with placebo (P=0.002). There was no difference between citalopram and placebo (P=0.23). Platelet 5-HT was 0.4 (0.3-0.7)×10-18mol/platelet with citalopram, which was significantly lower than 1.7 (1.2-2.4)×10-18mol/platelet with amitriptyline (P<0.001), and 3.5 (2.8-4.3)×10-18mol/ platelet with placebo (P<0.001). The lower platelet 5-HT during treatment with citalopram than amitriptyline indicates that 5-HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5-HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research.
AB - The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension-type headache (CTTH). However, it is not fully clarified whether the serotonin (5-HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5-HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline we investigated platelet 5-HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty-four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5-HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32-week, double-blind, placebo-controlled, three-way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5-HT was used as a measure of 5-HT reuptake inhibition and determined by high performance liquid chromatography. Area under the headache curve was 308 (157-715) (median with quartiles in parentheses) with amitriptyline and significantly lower than 377 (158-1121) with citalopram (P=0.04), and 441 (178-1408) with placebo (P=0.002). There was no difference between citalopram and placebo (P=0.23). Platelet 5-HT was 0.4 (0.3-0.7)×10-18mol/platelet with citalopram, which was significantly lower than 1.7 (1.2-2.4)×10-18mol/platelet with amitriptyline (P<0.001), and 3.5 (2.8-4.3)×10-18mol/ platelet with placebo (P<0.001). The lower platelet 5-HT during treatment with citalopram than amitriptyline indicates that 5-HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5-HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research.
KW - Amitriptyline
KW - Antidepressant
KW - Chronic pain
KW - Chronic tension-type headache
KW - Citalopram
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=1342321738&partnerID=8YFLogxK
U2 - 10.1016/j.pain.2003.12.012
DO - 10.1016/j.pain.2003.12.012
M3 - Article
C2 - 15109513
AN - SCOPUS:1342321738
SN - 0304-3959
VL - 108
SP - 108
EP - 114
JO - Pain
JF - Pain
IS - 1-2
ER -