- Email: [email protected]
ANTIDEPRESSANT ACTIVITY OF S-ADENOSYLMETHIONINE
904 insufficient dosage of bromocriptine since the daily dose in the unipolar group was, on average, more than twice that given to the bipolar group (see table).
DETAILS OF TREATMENT AND CONTROL GROUPS AND RESULTS
The clear-cut difference in response between the two groups which was significant at the end of the first week (t=3 . 5; p<0’01) would suggest that the- underlying abnormality in bipolar depressive illness is not the same as that in unipolar depression. The favourable response to a dopamine receptor agonist in all five bipolar patients, with two becoming manic, supports the view that bipolar depression is associated with a reduction in central dopaminergic neurotransmission, and mania with an increase. In keeping with this hypothesis is the observation that pimozide, a drug with a relatively selective dopamine receptor blocking action, is effective in the treatment of mania.9,10 Data
Academic Unit of Human Psychopharmacology, Medical College of St Bartholomew’s Hospital, London EC 1
as mean
(and range) or mean (±SD).
T. SILVERSTONE
between-group comparison was significant in favour of SAMe (p<0 001), for total score and for the depressive core (p<0. 005). No ANTIDEPRESSANT ACTIVITY OF S-ADENOSYLMETHIONINE
SIR,-Patients with rheumatoid arthritis often get depressed1 by their chronic pain and gradually declining function. When this depression is prolonged the patient may lose the motivation to designed to participate in treatment and rehabilitation Some clinical trials 3,4 strengthen muscles and restore have shown that S-adenosylmethionine (SAMe), a methyl donor occurring naturally in the central nervous system, has antidepressant effects, and Carney et al5 in an open study found that SAMe could reverse endogenous depression in six out of twelve patients treated for 14 days. The mechanism of action of SAMe is unknown. It may play an important role in the metabolism of the biogenic amines that are thought to participate in the modulation of affective disorders.4,6,7 Earlier results and the apparent safety of this physiological substance suggested the use of SAMe for the treatment of depressed rheumatoid patients who are often taking a lot of powerful drugs. Forty-nine patients (table) with classic or definite rheumatoid arthritis entered this double-blind study. They had moderate or severe depression, the mean Hamilton score being 43-6 6 ("no symptom" was scored 1). The patients were randomly allocated to receive treatment over a period of 21 days with either SAMe (200 mg intramuscularly in a single -daily dose) or placebo; antirheumatic treatment was unchanged throughout the study. Depression was rated (by means of twenty-one items on the Hamilton rating scale) on admission and at the end of the treatment, by two psychiatrists. Statistical evaluation was done by paired t and Wilcoxon signed rank tests for changes within the groups, while changes between the groups were evaluated by unpaired t and Mann-Whitney tests, calculated on basal-final differences. After 21 days’ treatment mean total scores had fallen from 45 - 0 to 33-6in the SAMe group (p<0-001), whereas no significant difference was observed in the placebo group. Similar results were also obtained for the depressive core (items 1, 2, 3, 7, and 8). The
function.rogrammes
9. Post RM, Jimerson DC, Bunney WE, Goodwin FK. Dopamine and mania: Behavioural and biochemical effects of the dopamine receptor blocker pimozide. Psychopharmacology 1980, 67: 297-305. 10 Cookson JC, Silverstone T, Wells B. A double-blind clinical trial of pimozide and chlorpromazine in mania: a test of the dopamine hypothesis. Acta Psychiatr Scand 1981; 64: 381-97. 1. Zaphiropoulos G, Burry HC. Depression in rheumatoid disease. Ann Rheum Dis 1974; 33: 132-35. 2. Baum J. A review of the psychological aspects of rheumatic disease. Semin Arthritis Rheum 1982; 11: 352-61. 3 Agnoli A, Andreoli V, Casacchia M, Cerbo R. Effect of S-adenosylmethionine (SAMe) J Psychiatr Res 1976, 13: 43-54. upon depressive symptoms. 4. Agnoli A, Andreoli V, Casacchia M, et al. Results and possible development of the clinical use of S-adenosyl-L-methionine (SAMe) in psychiatry. In: Andreoli V, Agnoli A, Fazio C, eds. Transmethylations and the central nervous system. New York, 1978. 5. Carney MWP, Martin R, Bottiglieri T, et al. Switch mechanism in affective illness and S-adenosylmethionine. Lancet 1983; i: 820-21. 6 Baldessarini RJ. The basis for amine hypotheses in affective disorders. Arch Gen
Psychiatry 1975, 32: 219-20. 7. Reynolds EH, Stramentinoli G. Folic acid, S-adenosylmethionine and affective disorders. Psychol Med 1983; 13: 705-10
side-effects were observed. This trial suggests that SAMe is active in the treatment of depression in patients with rheumatoid arthritis.
Rheumatology and Psychiatry Services, L. Sacco
Hospital, Milan, Italy
INNOCENZO CARUSO MARIO FUMAGALLI LAURA BOCCASSINI PIERCARLO SARZI PUTTINI GIOVANNI GINISELLI GIORGIO CAVALLARI
MALIGNANT MELANOMA IN PATIENT WHO RECEIVED NEUTRON BEAM THERAPY
SIR,—Neutron beam therapy has not been widely used until recently and it is not likely that all the adverse effects have yet been reported. I know of no reports on the induction of a melanocytic tumour as the result of this therapy; indeed, neutron beam therapy1,I has been used to treat malignant melanoma with some success. of melanoma of the skin describe here a case primary malignant in the of an irradiated field of neutron beam arising periphery therapy. A 32-year-old White woman noted a palmar mass on the right ulnar border 1 year before presenting to a physician. The mass was non-tender and had apparently gradually increased in size. 3 months after it first appeared, she experienced decreased motor strength and impairment of her ability to extend her wrist. At presentation the mass was 4 cm in diameter and extended radially. The range of motion of the right wrist was limited to 25° of extension. The patient had no gross sensory changes and the finger extension, finger flexion, and neurovascular examination were normal. At excisional biopsy the surgeon noted greyish loose "myxomatous" tissue over the hypothenar eminence extending radially where it was adherent to and infiltrating the carpal ligament. The pathological diagnosis was synovial sarcoma. Subsequent radiological and laboratory tests did not demonstrate metastatic disease. Almost immediately after this biopsy she received 2200 neutron rads over a 7 week period as an alternative to amputation (which she refused). Subsequently transient blistering of the skin developed with thick and dry blisters. Her skin also showed erythema and tanning. This reaction was followed by scaly and dry skin. 1 week after her last treatment her skin began to soften and become supple. Subsequently her skin retained a light tan and a small degree of puffiness until about 9 months after treatment. At that time a small blue-black lesion was first observed on the skin of the left hand, apparently at the periphery of the radiation field. This lesion was surgically excised and was diagnosed as superficial spreading malignant melanoma, level III (Clark) and 0’ 80 mm thick (Breslow). 1. Scherer
E, Bamberg M, Strotges MW, Muller RD, Welp R. The role of radiotherapy for interdisciplinary treatment of the malignant melanoma. Strahlentherapie 1982; 158: 131-38. 2. Tsunemoto H. Clinical evaluation of fast neutron therapy. Nippon Igaku Hoshasen Gakkai Zasshi 1982; 42: 823-47.
DETAILS OF TREATMENT AND CONTROL GROUPS AND RESULTS
The clear-cut difference in response between the two groups which was significant at the end of the first week (t=3 . 5; p<0’01) would suggest that the- underlying abnormality in bipolar depressive illness is not the same as that in unipolar depression. The favourable response to a dopamine receptor agonist in all five bipolar patients, with two becoming manic, supports the view that bipolar depression is associated with a reduction in central dopaminergic neurotransmission, and mania with an increase. In keeping with this hypothesis is the observation that pimozide, a drug with a relatively selective dopamine receptor blocking action, is effective in the treatment of mania.9,10 Data
Academic Unit of Human Psychopharmacology, Medical College of St Bartholomew’s Hospital, London EC 1
as mean
(and range) or mean (±SD).
T. SILVERSTONE
between-group comparison was significant in favour of SAMe (p<0 001), for total score and for the depressive core (p<0. 005). No ANTIDEPRESSANT ACTIVITY OF S-ADENOSYLMETHIONINE
SIR,-Patients with rheumatoid arthritis often get depressed1 by their chronic pain and gradually declining function. When this depression is prolonged the patient may lose the motivation to designed to participate in treatment and rehabilitation Some clinical trials 3,4 strengthen muscles and restore have shown that S-adenosylmethionine (SAMe), a methyl donor occurring naturally in the central nervous system, has antidepressant effects, and Carney et al5 in an open study found that SAMe could reverse endogenous depression in six out of twelve patients treated for 14 days. The mechanism of action of SAMe is unknown. It may play an important role in the metabolism of the biogenic amines that are thought to participate in the modulation of affective disorders.4,6,7 Earlier results and the apparent safety of this physiological substance suggested the use of SAMe for the treatment of depressed rheumatoid patients who are often taking a lot of powerful drugs. Forty-nine patients (table) with classic or definite rheumatoid arthritis entered this double-blind study. They had moderate or severe depression, the mean Hamilton score being 43-6 6 ("no symptom" was scored 1). The patients were randomly allocated to receive treatment over a period of 21 days with either SAMe (200 mg intramuscularly in a single -daily dose) or placebo; antirheumatic treatment was unchanged throughout the study. Depression was rated (by means of twenty-one items on the Hamilton rating scale) on admission and at the end of the treatment, by two psychiatrists. Statistical evaluation was done by paired t and Wilcoxon signed rank tests for changes within the groups, while changes between the groups were evaluated by unpaired t and Mann-Whitney tests, calculated on basal-final differences. After 21 days’ treatment mean total scores had fallen from 45 - 0 to 33-6in the SAMe group (p<0-001), whereas no significant difference was observed in the placebo group. Similar results were also obtained for the depressive core (items 1, 2, 3, 7, and 8). The
function.rogrammes
9. Post RM, Jimerson DC, Bunney WE, Goodwin FK. Dopamine and mania: Behavioural and biochemical effects of the dopamine receptor blocker pimozide. Psychopharmacology 1980, 67: 297-305. 10 Cookson JC, Silverstone T, Wells B. A double-blind clinical trial of pimozide and chlorpromazine in mania: a test of the dopamine hypothesis. Acta Psychiatr Scand 1981; 64: 381-97. 1. Zaphiropoulos G, Burry HC. Depression in rheumatoid disease. Ann Rheum Dis 1974; 33: 132-35. 2. Baum J. A review of the psychological aspects of rheumatic disease. Semin Arthritis Rheum 1982; 11: 352-61. 3 Agnoli A, Andreoli V, Casacchia M, Cerbo R. Effect of S-adenosylmethionine (SAMe) J Psychiatr Res 1976, 13: 43-54. upon depressive symptoms. 4. Agnoli A, Andreoli V, Casacchia M, et al. Results and possible development of the clinical use of S-adenosyl-L-methionine (SAMe) in psychiatry. In: Andreoli V, Agnoli A, Fazio C, eds. Transmethylations and the central nervous system. New York, 1978. 5. Carney MWP, Martin R, Bottiglieri T, et al. Switch mechanism in affective illness and S-adenosylmethionine. Lancet 1983; i: 820-21. 6 Baldessarini RJ. The basis for amine hypotheses in affective disorders. Arch Gen
Psychiatry 1975, 32: 219-20. 7. Reynolds EH, Stramentinoli G. Folic acid, S-adenosylmethionine and affective disorders. Psychol Med 1983; 13: 705-10
side-effects were observed. This trial suggests that SAMe is active in the treatment of depression in patients with rheumatoid arthritis.
Rheumatology and Psychiatry Services, L. Sacco
Hospital, Milan, Italy
INNOCENZO CARUSO MARIO FUMAGALLI LAURA BOCCASSINI PIERCARLO SARZI PUTTINI GIOVANNI GINISELLI GIORGIO CAVALLARI
MALIGNANT MELANOMA IN PATIENT WHO RECEIVED NEUTRON BEAM THERAPY
SIR,—Neutron beam therapy has not been widely used until recently and it is not likely that all the adverse effects have yet been reported. I know of no reports on the induction of a melanocytic tumour as the result of this therapy; indeed, neutron beam therapy1,I has been used to treat malignant melanoma with some success. of melanoma of the skin describe here a case primary malignant in the of an irradiated field of neutron beam arising periphery therapy. A 32-year-old White woman noted a palmar mass on the right ulnar border 1 year before presenting to a physician. The mass was non-tender and had apparently gradually increased in size. 3 months after it first appeared, she experienced decreased motor strength and impairment of her ability to extend her wrist. At presentation the mass was 4 cm in diameter and extended radially. The range of motion of the right wrist was limited to 25° of extension. The patient had no gross sensory changes and the finger extension, finger flexion, and neurovascular examination were normal. At excisional biopsy the surgeon noted greyish loose "myxomatous" tissue over the hypothenar eminence extending radially where it was adherent to and infiltrating the carpal ligament. The pathological diagnosis was synovial sarcoma. Subsequent radiological and laboratory tests did not demonstrate metastatic disease. Almost immediately after this biopsy she received 2200 neutron rads over a 7 week period as an alternative to amputation (which she refused). Subsequently transient blistering of the skin developed with thick and dry blisters. Her skin also showed erythema and tanning. This reaction was followed by scaly and dry skin. 1 week after her last treatment her skin began to soften and become supple. Subsequently her skin retained a light tan and a small degree of puffiness until about 9 months after treatment. At that time a small blue-black lesion was first observed on the skin of the left hand, apparently at the periphery of the radiation field. This lesion was surgically excised and was diagnosed as superficial spreading malignant melanoma, level III (Clark) and 0’ 80 mm thick (Breslow). 1. Scherer
E, Bamberg M, Strotges MW, Muller RD, Welp R. The role of radiotherapy for interdisciplinary treatment of the malignant melanoma. Strahlentherapie 1982; 158: 131-38. 2. Tsunemoto H. Clinical evaluation of fast neutron therapy. Nippon Igaku Hoshasen Gakkai Zasshi 1982; 42: 823-47.