1189

TRYPTOPHAN AND ALLOPURINOL IN THETREATMENT OF DEPRESSION

Sm,—The hypothesised deficiency of brain serotonin in

depressed patients’ inevitablyz led to "precursor-load" treat-ment with L-tryptophan. Earlier reports of drug efficacy3 4

have not been substantiated. 6 L-tryptophan probably acti-vates liver pyrrolase, and animal studies suggest that pretreat-ment with the xanthine-oxidase inhibitor allopurin017 preventsthis effect and increases brain tryptophan levels.8 Combinedtryptophan/allopurinol would thus seem to be a rational poly-pharmacy for treating depression in man.Under conditions of informed consent, eight male out-

patients with a history of gout have received combined L-tryp-tophan/allopurinol treatment for an acute recurrence of anendogenous depressive episode. The results of this uncontrolledtrial are shown in the table. The treatment design was as fol-lows : 3 weeks after starting allopurinol, patients were rated(baseline) using a revised N.LM.H.-P.R.B. 21-item Hamiltondepression scale9 and a clinical global rating. L-tryptophan wasthen added, and patients were rated weekly for each of 3weeks, then biweekly for 4 weeks (total of 7 weeks on com-bined treatment). L-tryptophan tablets contained 500 mgL-tryptophan, 5 mg pyridoxine hydrochloride, and 10 mgascorbic acid (’Optimax’).The results of this open trial are encouraging but must be

cautiously interpreted. As a group, the eight patients showeda significant improvement in depression ratings at the end oftreatment (Wilcoxon test p<0-01). However, whilst scores fortwo patients fell by more than 50% both remained quali-tatively depressed with some functional impairment andanhedonia. Another patient showed no improvement. Totalsymptom remission was recorded in five patients; three re-

sponded within the first 2 weeks, another at the 2-week inter-val, and the fifth during week 3. It is thus the rapidity of re-sponse which appears striking and characterises the

antidepressant effects. Even patients 2 and 4 who failed toshow total remission were nevertheless rated as much im-

proved during the 3rd to 4th weeks of treatment.Behavioural side-effects’" included a syndrome of anger,

hostility, irritability, and temper outbursts in patients 3 and 6;this coincided with the hypomanic state induced in patient 3.

1. Lapin, I. P., Oxenkrug, G F. Lancet, 1969. i, 132.2. Moir, A. T. B., Eccleston, D. J. Neurochemistry, 1968, 15, 1093.3. Coppen, A., Shaw, D. M., Herzberg, B., Maggs, R. Lancet, 1967, ii, 1178.4. Broadhurst, A. D. ibid. 1970, 10, 126.5. Carrol, B. J, Mowbray, R. M., Davies, B. ibid. 1970, i, 967.6 Bunney, W E., Jr, Brodie, H. K. H., Murphy, D. L., Goodwin, F. K. Am.

J. Psychiat. 1971, 127, 872.7 Badaway, A. A - B, Evans, M Biochem. J. 1973, 133, 585.8. Curzon, G. Am. J. clin. Nutr. 1971, 24, 830.9. Early Clinical Drug Evaluation Unit. Assessment Battery for Psychophar-

macology National Institute of Mental Health, PsychopharmacologyResearch Branch, 1974.

10. Cole, J. O. in Drugs and Behaviour (edited by L. Uhr and J. G. Miller); p.375. New York, 1960.

Other (physical) side-effects were infrequent and similar to

those published previously; they did not interfere withtreatment response.The data are sufficiently encouraging to justify controlled

trials in depressed patients of both sexes. The findingsconverge with other work by our department" 12 to implicatea role for serotonin in the symptomatic relief of "endogenous"depression.

Department of Psychiatry,New York University Medical Center,New York, N.Y. 10016, U.S.A. BARON SHOPSIN

THREE-DIMENSIONAL SHAPES

SIR,-We have developed a system for measuring surfaceshapes, extending into three dimensions a technique thought tohave been used previously only for the measurement of pointsin two dimensions on a plane. The system is used in the studyof scoliotic deformities, and provides a method for measuringand recording changes in external body shape which is both

simple and accurate.The position of a point in space is most commonly expressed

within a cartesian frame of reference. Measurement systemsoften follow this convention for the very good reason thatlinear displacements can generally be measured with greateraccuracy than small angular displacements, which are neces-sary for direct measurement in spherical or cylindrical coor-dinate systems. Nevertheless, even cartesian-based measure-ment systems must maintain a high degree of orthogonality inorder to preserve accuracy, and this can greatly increase theircomplexity. However, there is a scheme in which all measure-ments may be taken from linear displacements and in whichangular accuracy at sliding joints is not a consideration. Thisscheme is used in the device described below.

Geometrically, the system is very simple and is shown in fig.1. The point whose position needs to be determined is "trian-gulated" by measuring its distance from three points whosepositions are known: (ex, p, o), (y, 8, o), and (E, &Agrave;, o). Themoduli of the vectors joining the three known points to the un-known are denoted p, o, and 1:. The unknown point, expressedas (x, y, z) in a cartesian system is defined by the equations:

x ot)2+(y h’)Z+ZZ-N2-O 0(X-I )2+(y-&otilde;)l+Z2_(J2=O(X-E)2+(y-&Agrave;)2+ Z2_,2=0 0

from which x and y may be found uniquely. z may also befound, but there is an ambiguity of sign corresponding to a re-flexion of the point (x, y, z) in the plane z=o. In most situ-ations this ambiguity is easily resolved.

11. Shoptin, B., Friedman, E., Goldstein, M., Gershon, S. Psychopharmac.Commun. 1975, 1, 239.

12. Friedman, E., Shopsin, B., Gershon, S. J. Pharm. Pharmac. 1974, 26, 995.

RESPONSE TO COMBINED TRYPTOPHAN-ALLOPURINOL TREATMENT IN ENDOGENOUSLY DEPRESSED MALES S

I =1 13- Wpolar depressive.’hnp.nrcj hmcomn .<nd dnhedol1ld are mandatory cntena for acceptance along with a Hamilton score of at least 30;(,J"I1," ’eBenlB’ rating m Ildbc type 0=nu disease, 7=border[me ))),2=m)ldty tll, 3=moderately ilt, 4=severely 111.