Acute treatment of tension-type headache has been investigated in episodic tension-type headache, and in prophylactic treatment of chronic tension-type headache, antidepressant drugs and botulinum toxin have been investigated.
Aspirin and paracetamol are the analgesics used most commonly in the treatment of acute tensiontype headache . In the most recent RCT, 452 patients treated episodes of tension-type headache with aspirin (500 mg or 1000 mg), paracetamol (500 mg or 1000 mg) or placebo. Headache relief after 2 hours was 76% after aspirin 1000 mg and 71% after paracetamol 1000 mg. Both were superior to placebo despite a high placebo response of 55%. The following NSAID were superior to placebo in RCT on the treatment of acute tension-type headache: ibupro-fen , ketoprofen [78, 112] naproxen [79, 80] and diclofenac . Caffeine has long been used as an analgesic adjuvant . In a RCT the combination of aspirin and caffeine was superior to paracetamol and placebo ; in another RCT, the combination of caffeine and ibuprofen was superior to ibuprofen and placebo . The combination of caffeine, aspirin and paracetamol was more effective than the single substances in one large RCT.
Antidepressants are the drugs most commonly used in chronic tension-type headache . Amitriptyline was superior to placebo in most RCT [82-86] but in the largest RCT there was no effect of amitriptyline and amitriptylinoxide . Mirtazapine 15-30 mg daily was superior to placebo in one RCT  whereas the the selective serotonin reuptake inhibitor (SSRI) citalopram was not more effective than placebo .
After positive open studies, botulinum toxin has been studied in chronic tension-type headache but the conclusion of these RCT is that botulinum toxin is not more effective than placebo .Thus in the most recent large RCT including 298 randomized patients, botulinum toxin A admistered in doses from 50 U to 150 U was not different from placebo .
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