TREATMENT OF PAIN DUE TO POSTHERPETIC NEURALGIA WITH TRAMADOL - RESULTS OF AN OPEN PILOT-STUDY VS CLOMIPRAMINE WITH OR WITHOUT LEVOMEPROMAZINE

To date, no universally applicable recommendations are available for t he treatment of patients with postherpetic neuralgia. A mixture of cli nical anecdotes, experimental findings and observations from clinical trials form the basis of the medical arsenal for this condition. Tricy clic antidepressants are commonly used, and clinical experience and se veral investigations have documented their effectiveness. Today, singl e entity antidepressants, which can be combined with neuroleptics to i ncrease analgesia, are,generally recommended for the treatment uf post herpetic neuralgia. Some authors also recommend the additional adminis tration of an opioid if analgesia is inadequate, Just over a decade ag o, opioids were considered ineffective for the treatment of neuropathi c pain; however, more recent Investigations relating to the use of opi oids, primarily in thp treatment of nontumour-related chronic pain, ha ve led to a revision of their use in neuropathic pain, Nevertheless, t he use of opioid therapy for neurogenic pain remains controversial. Tr amadol is a synthetic, centrally acting analgesic with both opioid and nonopioid analgesic activity. The nonopioid component is related to t he inhibition of noradrenaline (norepinephrine) reuptake and simulatio n of serotonin (5-hydroxytryptamine; 5-HT) release al the spinal level . In this regard, there are parallels with antidepressants, which are believed to potentiate the effect of biogenic amines in endogenous pai n-relieving systems. Then is evidence that in tramadol, both mechanism s act synergistically with respect to analgesia. The aim of this pilot study was to investigate, for the first time, the analgesic efficacy and tolerability of tramadol, compared with the antidepressant clomipr amine,; in the treatment of postherpetic neuralgia. If necessary, clom ipramine was used in combination with the neuroleptic tevomepramazine. The study allowed individualised dosages at predetermined intervals u p tit a maximum daily dose of tramadol 600mg and clomipramine 100mg, c lomipramine 100mg with or without levomepromazine 100mg. 21 (60%) of 3 5 randomised patients (greater than or equal to 65 years) received the study medication over the 6-week. period [tramadol n = 10; clomiprami ne (with or without levomepromazine) n = 11]. After 3 weeks' treatment the dosage in both groups remained almost constant for the rest of th e 6-week treatment phase (mean daily dose: tramadol 250 to 290mg; clom ipramine 59.1 to 63.6mg). Only 3 patients required the combination of clomipramine and levomepromazine. At the outset, both groups recorded an average pain level of 'moderate' to 'very severe'. In correlation w ith increasing the study medication, this had decreased to 'slight' by the end of the treatment, when 9 of 10 patients in the tramadol group and 6 of Il patients in the clomipramine group retrospectively rated their analgesia as excellent, good or satisfactory. The psychological/ physical condition of the patients did not change significantly during tramadol treatment. Sensitivity and depression parameters decreased i n the clomipramine group. The incidence of adverse events for all pati ents was similar in both groups (tramadol 76.5%; clomipramine with or without levomepromazine 83.3%). In conclusion, tramadol would appear t o be an interesting therapeutic alternative for pain relief in posther petic neuralgia, particularly in patients who are not depressed. In cl inical practice, tramadol and clomipramine can best be used differenti ally. For example, tramadol could be the drug of first choice in patie nts with obvious cardiovascular disease (not an uncommon problem in th e greater than or equal to 65 year age group) in whom antidepressants are contraindicated, and similarly in patients in whom an antidepressa nt effect is not required. On the other hand, patients presenting with both postherpetic neuralgia and clinical depression but no obvious ca rdiovascular disease may benefit from the addition of an antidepressan t. In order to achieve clinical success, individual dose titration is necessary. After the third week of treatment, the relationship between pain intensity and dose of study medication remained nearly stable (i .e. pain intensities remained almost constant for the remaining 3 week s, and there was no further increase in dose after the third week).