An Open and Double-Blind Cross-Over Study on the Efficacy of Clomipramine (Anafranil®) in Patients with Painful Mono- and Polyneuropathies

Abstract

82 patients with chronic pain resulting from mononeuropathy were treated with psychotropic drugs in an open therapeutic study. In this study we found that treatment with a combination of clomipramine (Anafranil®) and small doses of neuroleptics was significantly superior to therapy with neuroleptics alone. In a subsequent double-blind study, it was attempted for the first time to determine the efficacy of clomipramine compared to that of acetylsalicylic acid in 48 patients with painful mono- and polyneuropathies. The test was carried out in a cross-over trial with two sequence groups. We evaluated assessments of pain by both patients and doctors, and were able to prove statistically that clomipramine possesses a significantly greater efficacy compared to that of acetylsalicylic acid. By taking into account recent anatomical, biochemical and pharmacological studies, it can be concluded that clomipramine probably has - in addition to the action on peripheral receptors - a direct effect upon pain modulation systems. It seems possible that clomipramine activates serotonin-containing neurons of the endorphin-mediated analgesia system that control pain transmission in the CNS.

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

“…They have significant side effects and even in neuropathic pain they are increasingly being supplanted by gabapentin and pregabalin. 80 Antidepressants have been used to treat pain in a number of populations 81 and have been shown to have some benefit in conditions such as neuropathic pain and fibromyalgia but not low back pain; however, only a limited number of studies have examined their use in post-SCI pain. Tricyclic antidepressants (TCA) have been shown to be partially effective in some SCI patients with neuropathic pain although it is still uncertain whether this is due to an antinociceptive effect or whether the diminished reports of pain are related to the antidepressant effect.…”

Effect of pertussis toxin on morphine, diphenhydramine, baclofen, clomipramine and physostigmine antinociception

“…To this end, drugs modulating cholinergic, serotoninergic and histaminergic systems were investigated since they not only represent central analgesic compounds effective in both animals (Harris et al, 1969;Sacerdote et al, 1978;Rumore and Schlichting, 1985) and humans (Hood et al, 1995;Langohr et al, 1982;Campos and Solis, 1980), but also they interact with G-protein-coupled receptors (Birnbaumer, 1990). The effect of intracerebroventricular injection of pertussis toxin on the antinociception induced by administration of the t~-~ opioid receptor agonist morphine, the GABA B agonist baclofen, the tricyclic antidepressant clomipramine, the cholinesterase inhibitor physostigmine and the histamine H~ receptor antagonist diphenhydramine was, therefore, evaluated in mice.…”

The Future for Antidepressants: Treatment of Pain

“…In studies comparing relative effectiveness of various antidepressant drugs [18,23,25,26,28,32], no single antidepressant drug has been shown to be more effective than the others for chronic pain. Some physicians have advocated the use of antidepressant drugs in combination with phenothiazines [20,22,59,73,76,78,82,83,88], antiepi leptic drugs [75], lithium [ 16], or minor tran quilizers [71], However, these assertions are based on case studies; the effectiveness of antidepressant drugs in combination with these other agents is presently not known. Given the potential for the development of tardive dyskinesia with long-term use of neu roleptic drugs, and the lack of superior effect of combination therapy over antidepressant agents alone, use of neuroleptic drugs in chronic pain patients should be limited.…”

“…Two out of four controlled studies [52,55,88,90] have shown antidepressant agents to be more effective than placebo in pain reduction. It is difficult to interpret the results, since these studies included patients with varied pain syndromes who were not matched for severity of symptoms.…”

“…[52] doxepin1 150 0 Johanssen and von Knorring [90] zimelidine1 200 P Pilowsky et al [55] amitriptyline1 150 0 Singh and Verma [25] imipramine P amitriptyline P chlordiazepoxide 0 Duthie [84] amitriptyline trifluoperazine 75 67 Magni ct al. [85] amitriptyline 75 75 Montastruc et al [86] clomipramine 150 67 Castaigne et al [87] clomipramine 50-200 93 Langohr et al [88] clomipramine + 75-150 68 neuroleptic neuroleptic 45 Langohr et al [88] clomipramine1 150 P Blunter and Heilbronn [89] various HCAs 89 p = Drug significantly more effective than placebo or other comparison drug. 1 Controlled study.…”