There are two systematic reviews [13, 14] on the use of antidepressants which used data from three RCT to suggest that they may be effective in atypical facial pain [14-17]. There is also a systematic review that looks at all types of pharmacologic treatments for this condition . Only the larger studies will be included here.
Lascelles  used phenelzine in 40 atypical facial pain patients in a cross-over study and found it to be effective. The study by Feinmann & Harris  involving 93 patients with mixed chronic facial pain assessed the effect of dothiepin (dosulepin) versus placebo using a dose titration. At 9 weeks, 71% were pain free but withdrawal of drug at 6 months led to relapse in some patients. There was a high drop-out rate and it is not possible to separate out the patients with different types of pain. The largest study was by Harrison et al.  which included 178 patients with mixed chronic facial pain who were divided into four groups: fluoxetine, placebo, cognitive behavioral treatment (CBT) with placebo, CBT with fluoxetine, and followed up for 3 months. Fluoxetine reduced pain at 3 months compared to placebo. CBT on its own was not effective in reducing pain but did improve patients' control of their lives. These improvements were maintained when drug therapy ceased.
Sharav et al.  showed the effectiveness of low-or high-dose amitriptyline 25 mg or 100 mg but their patients had a mixture of chronic idiopathic facial pain, TMD pain and even neuropathic pain.
Forsell et al.  used venlafaxine versus placebo in 30 patients in a double-blind cross-over RCT. Ten patients did not complete - eight due to adverse side effects and two due to noncompliance. There was no difference between placebo and active drug in terms of pain intensity although there was more significant improvement in pain relief scores in the active treatment group. There were no differences in terms of anxiety and depression. Efficacy of this drug was only modest but this could be due to small sample size as the study itself was of high quality.
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