Postgrad Med J: first published as 10.1136/pgmj.60.710.881 on 1 December 1984. Downloaded from Postgraduate Medical Journal (December 1984) 60, 881-885 Psychotropic drugs G. W. HANKS B.Sc., M.B., M.R.C.P. The Royal Marsden Hospital, Fulham Road, London SW3 6JJ Introduction system-depressant effect ofthese drugs: by depressing the general level of arousal the central perception of The interaction between the cognitive component pain may be modified. (the perception ofnociceptive, or painful stimuli) and In this review the evidence for intrinsic analgesic the affective component of pain is reflected in the activity and overlap between the actions of anti-nociceptive the place of psychotropic drugs in the agents (analgesics) and mood-altering drugs (psycho- treatment of chronic pain are discussed in the light of tropics) when treating pain patients. Anxiety, depres- the published literature and recent clinical experi- sion, fear and sleeplessness may all respond to ence. psychotropic drugs, and this may result in a reduc- tion in pain or a greater ability to cope with it. This TABLE 1. The WHO classification of psychotropic drugs may enable a patient's pain to be controlled with a Neuroleptics by copyright. smaller dose of analgesic. In this sense psychotropic Anxiolytic sedatives drugs have an 'analgesic' effect but it is a misleading Antidepressants use of the word, and has been the source of much Psychostimulants misunderstanding. Psychodysleptics In the day-to-day management of pain problems the two groups of drugs do have well-defined indications. Acute pain is invariably associated with Neuroleptics nociception, and responds to analgesics or other Neuroleptics are antipsychotic agents of which the antinociceptive treatments. Chronic pain (except that prototype is chlorpromazine, a phenothiazine. Moore due to cancer or arthritis) is rarely associated with an and Dundee (1961) examined a range ofphenothiaz- identifiable nociceptive stimulus and frequently does ines for analgesic activity. They found apparent http://pmj.bmj.com/ not respond to simple antinociceptive measures. analgesic effects with trimeprazine, chlorpromazine Psychotropic drugs (Table 1) play an important part and promazine but algesic activity with prometha- in the management of chronic pain. Cancer pain is a zine, pecazine, prochlorperazine and others. The use special case. Loeser (1980) and others have proposed of an experimental pain technique in this study that chronic cancer pain should be characterized as means that it is not possible to extrapolate directly long-standing acute pain because it is associated with from these results to the clinical situation. In a a continuous nociceptive input and responds better to controlled clinical study, Houde and Wallenstein on September 25, 2021 by guest. Protected antinociceptive measures. Psychotropic drugs have a (1955) were unable to show any difference between lesser part to ptay in cancer pain than in other types intramuscular injections of morphine alone, and of chronic pain (Hanks, 1984). morphine combined with chlorpromazine. Twycross (1980) has suggested that chlorproma- The mode of action of psychotropic drugs in chronic zine may be useful in the management of rectal or pain bladder 'tenesmoid' pain in cancer. This effect is If relief ofpain is obtained with psychotropic drugs variable and needs to be explored further. There are there are three possible explanations. The pain relief no other cancer pain syndromes which appear to may be secondary to the amelioration of psychologi- respond preferentially to the phenothiazines. cal distress or disorder, which may be the primary problem or a result of the persistent pain. It may Methotrimeprazine. Interest has been shown in the represent some true intrinsic analgesic action. Or it analgesic action of methotrimeprazine (levomepro- may be a reflection of a non-specific central nervous mazine). Studies in postoperative patients (Lasagna Postgrad Med J: first published as 10.1136/pgmj.60.710.881 on 1 December 1984. Downloaded from 882 G. W. Hanks and DeKomfeld, 1961) and in a variety of other Antidepressants acute and chronic painful conditions (Montilla, Antidepressants are widely used in the treatment Frederik and Cass, 1963) have shown that when of chronic non-cancer pain (Table 2). Though they given by intramuscular or subcutaneous injection have been employed for this purpose for many years methotrimeprazine 15 mg and morphine 10 mg controversy still surrounds their use in this way. As appear to have equivalent analgesic activity. At these with the neuroleptics the results of animal studies doses sedation is more pronounced with methotri- have been conflicting, but there is evidence from meprazine. several different models of an antinociceptive and A recent study showed that, in mice, small non- opiate-potentiating action of the tricyclics (Saarni- sedative doses of methotrimeprazine potentiated the vaara and Mattila, 1974; Goldstein et al., 1982). analgesic action of morphine (Petts and Pleuvry, Antidepressants have never been shown to be effec- 1983). The same authors were unable to show a tive in the relief of acute pain in man or in similar effect in man using an experimental pain experimental pain. technique in healthy volunteers, though the dose they used (7 5 mg i.m.) caused significant sedation. Evidence of analgesic activity after oral adminis- TABLE 2. Chronic pain syndromes re- tration is unconvincing, and side effects, particularly ported to respond to treatment with sedation, are common (Hanks, 1984). There have antidepressants been no reliable controlled studies which show that, Cancer pain when given orally, methotrimeprazine has a useful Chronic rheumatic disorders effect. Migraine analgesic Tension headache Atypical facial pain Facial arthromyalgia (tempero- Haloperidol. Haloperidol was the first of the mandibular joint dysfunction butyrophenones to be synthesized, in 1957. It has syndrome) Low back pain since become one of the most widely used neurolep- Post-herpetic neuralgia by copyright. tics because it combines high potency and established Causalgia efficacy with low toxicity. It is chemically related to Phantom limb pain pethidine. There is some evidence that haloperidol Anaesthesia dolorosa enhances morphine analgesia in animal models (Head et al, 1979) and also that it binds to opiate receptors (Clay and Brougham, 1975) but there is There are numerous references in the literature to little clinical data to support these effects in man. the frequency of pain as a symptom in psychiatric A recent study in 34 patients undergoing surgery patients and to the common association of chronic failed to find any evidence of an analgesic or pain and depression (Sternbach, 1974). Certain analgesic-potentiating effect of haloperidol (Judkins chronic pain syndromes have been specifically re- http://pmj.bmj.com/ and Harmer, 1982). Our own experience in cancer garded as being manifestations of an underlying patients has been similar (Hanks et al., 1983). depressive illness and have been described as 'masked depression' or 'depressive equivalents' (Lo- pez-Ibor, 1972). Atypical facial pain (Lesse, 1974), Neuroleptic/antidepressant combinations. There facial arthromyalgia (Fine, 1971), and low back pain have been a number of reports of the use of with no identifiable organic cause (Forrest and combinations of phenothiazines with tricyclic antide- Wolkind, 1974) are the conditions which have most pressants in patients with difficult chronic pain often been described in these terms. These syndromes on September 25, 2021 by guest. Protected problems. Several series have produced apparently do respond favourably to treatment with antidepres- promising results (Merskey and Hester, 1972; Taub, sants (Lascelles, 1966; Feinmann, Harris and Cawley, 1973; Kocher, 1976; Clarke, 1981). However the 1984). validity of the data is often questionable (Hanks, Of the other conditions included in Table 2, some Evans and Lloyd, 1981). Many different drug combi- of the 'organic' disorders such as rheumatic pain and nations have been used. The choice of drugs and the headache (including migraine and tension headache) selection of patients does not appear to have been have also been shown in well-controlled studies to based on any clear rationale other than that the respond to antidepressants (Hanks, 1981). The effi- patients had usually failed to respond to more cacy of antidepressants in other varieties of chronic conventional measures. No controlled clinical trials pain is much more open to question. Post-herpetic have been carried out. This makes it difficult to draw neuralgia, post-traumatic neuralgia, causalgia, arach- any useful conclusions about the role and indications noiditis and phantom limb pain have all been the for using neuroleptics in this way. subject of extravagant claims. But clinical experience Postgrad Med J: first published as 10.1136/pgmj.60.710.881 on 1 December 1984. Downloaded from Psychotropic drugs 883 with antidepressants in such patients is often disap- chronic pain states. Particular attention has been pointing and clinical trial data are poor. An initial paid to drugs which have a predominant effect on 5- beneficial effect is often seen in these conditions but HT because this, of all the amine neurotransmitters, is rarely maintained and is partly (perhaps largely) seems to be important in anti-nociceptive mecha- explained by a placebo response. nisms. Studies with clomipramine and the more The potential magnitude of the placebo effect