101 MONOAMINE
METABOLITES,
AS MEAN
(AND S.E.) IN DELUSIONAL
SERUM-PROLACTIN BEFORE AND AFTER TREATMENT
AND NON-DELUSIONAL UNIPOLAR DEPRESSIVES
*Non-parametric Mann-Whitney U test, because of variance in some sample distributions.
heterogeneity
of
delusional group (see table). c.s.F. 5-H.I.A.A. did not differ in the two groups. M.H.P.G.H.V.A. ratios were significantly lower in the delusional group. The groups did not differ significantly in c.s.F. probenecid concentrations, age, or severity of depression or agitation (rated daily by nurses). These data support the view that delusional depression may be a clinical state accompanied by alteration in brain systems mediated by’both dopamine and noradrenaline. Such findings may provide a neurochemical rationale for clinical use of antipsychotic-antidepressant drug combinations to treat delusional depression.9.,o The data also support hypotheses from animal" and clinicap2 studies regarding interactions between dopamine and noradrenaline (i.e., that functionally decreased noradrenergic activity may facilitate the "release" of dopaminemediated behaviour). Studies of monoamine interactions may be increasingly important for the further understanding of the neurobiological substrate of psychopathology.
Clinical Research Ward,
Department of Psychiatry, Yale University, New Haven, Connecticut 06508, U.S.A.
DONALD SWEENEY CRAIG NELSON MALCOLM BOWERS JAMES MAAS GEORGE HENINGER
HYPERPROLACTINÆMIA IN CHRONIC ALCOHOLICS TREATED WITH PROMAZINE
SIR,-Long-acting phenothiazines have been proposed as a form of drug therapy for alcohol-dependence syndrome.1,2 Alcoholism causes hyperprolactinsemia. I record here prolactin values found in three groups of chronic alcoholics-namely, 5 with hyperprolactinsemia on admission (group A), S treated with non-depot promazine (group B), and 5 not treated with promazine (group C). Serum-prolactin was estimated by radioimmunoassay on admission in all three groups and repeated immediately after completion of treatment in groups B and C. The table shows that hyperprolactinxmia may be a problem in alcoholics on admission or in those with normal admission serum-prolactin concentrations who are treated with promazine. There -may be serious consequences for the patient since hyperprolactinsemia may lead to impotence, hypogonadism, and gynaecomastia in men and galactorrhoea, and amenorrhcea in women.3 The promazine-treated patients were given ’Sparine’ 100 mg daily for 6 days and in all of them serum-prolactin levels rose after treatment, post-treatment values being above the normal range in three. Phenothiazines are known to raise serum-prolactin by blocking dopaminergic receptors in the hypothalamus and thus blocking prolactin-inhibiting factor.’’ In the patients not given promazine (group C) serum-prolactin levels dropped after treatment. The relevance of these findings 9. Extein, I., Bowers, M. B. Comprehens. Psychiat. 1975, 16, 427. 10. Nelson, J. C., Bowers, M. B. Archs gen. Psychiat. (in the press). 11. Antelman, S. M., Caggiula, A. R. Science, 1977, 195, 646. 12. Sweeney, D R., Pickar, D., Redmond, D. E., Jr., Maas, J. W. Lancet, 1978.
I, 872. 1
Q. Jl. Stud Alcohol, 1966, 27, 510
2. Kinnel, H G. Lancet, 1977, ii, 659. 3. Majumdar, S K., Thomson, A. D., Shaw, G. K. Br. med. J. 1978, 4. Thorner, M O. Lancet, 1975, i, 662.
i,
409.
*Mean is.D. and range. Normal up to 500 VII.
the use of slow-release injectable phenothiazines is not known. I have seen three male alcoholics with clinical features of hypogonadism in this unit during the past year, and all of them were hyperprolactinaemic on admission. Depressive psychosis may also be associated with raised prolactin secretion,5 and depressive symptoms and suicide are common in alcoholics.6 to
Elmdene Alcoholic Treatment Unit,
Bexley Hospital, Bexley, Kent DA5
2BW
SISIR K. MAJUMDAR
FAILURE OF METHYL-C.C.N.U. AND 5-FLUOROURACIL IN COLORECTAL CANCER
SIR,-A report from the Sidney Farber Cancer Institute’ on combination chemotherapy with 5-fluorouracil and methvl
chloroethyl-cyclohexyl-nitrosourea
(methyl-c.c.N.U.)
in
advanced colorectal cancer has failed to confirm the results obtained in earlier studies.2.3 However, these drugs are still widely used and believed to be effective. We report here the results of treatment in a group of 49 patients-37 with advanced colorectal cancer, 11 with carcinoma of the pancreas, and 1 with metastases from an cesophageal primarywho were treated with similar combination chemotherapy. There were 27 males and 22 females aged 30-74. Criteria for entry the study were histological confirmation of carcinoma, measurable disease, and progressive disease which could not be treated by radiotherapy or surgery. 7 patients had had previous chemotherapy, 11 previous radiotherapy, and 3 a combination of both. 4 received concomitant radiotherapy for local problems. 35 patients had liver metastases. The treatment schedule was methyl-c.c.N.U. orally 150 mg/m2 on day 1 with 5-F.U. i.v. 325 mg/m2 and dacarbazine (D.T.I.C.) i.v. 75 mg/m2 on days 1-5. Patients with pancreatic carcinoma were treated with mitomycin C (3 mg/m2) on days 1-5 instead of D.T.I.C. These courses were repeated every 6 weeks. Response was assessed at 10 weeks and at 6 months as "complete response" (disappearance of all measurable disease), "partial response" (50% reduction in all measurable lesions), "no change" (no evidence of progression), or "progression" (new lesions, increasing size of indicator lesions, with or without rising carcinoembryonic antigen levels and biochemical abnormalities. 22 patients received one course only, 13 received two courses, and 14 more than two courses. 4 patients with panto
creatic carcinoma had known residual disease after surgery. Of the patients with measurable disease 11 were unassessable because of insufficient follow-up data or change of chemotherapy (though this reflected clinical evidence of progression of disease). 25 out of 49 patients had progression of disease by 10 weeks, 10 patients shows no change, and 3 showed partial 5. Horrobin, D. F. Br. J Psychiat. 1974, 124, 456. 6. Merry, J., Renolds, M. C., Bailey, J., Coppen, A. Lancet, 1976,
ii, 481.
1. Lokich, J. J., Skarin, A. T., Mayer, R. J., Frei, E., III Cancer, 1977, 40, 2792. 2. Kisner, D., Schein, P., Cohen, L., Smythe, T., Duvall, C. Am. Soc. clin. Oncol. 1976, 17, 264. 3. Moertel, C. G., Schutt, A. J., Hahn, R. G., Reitemeier, R. J. J nat. Cancer Inst. 1975, 54, 69.
METABOLITES,
AS MEAN
(AND S.E.) IN DELUSIONAL
SERUM-PROLACTIN BEFORE AND AFTER TREATMENT
AND NON-DELUSIONAL UNIPOLAR DEPRESSIVES
*Non-parametric Mann-Whitney U test, because of variance in some sample distributions.
heterogeneity
of
delusional group (see table). c.s.F. 5-H.I.A.A. did not differ in the two groups. M.H.P.G.H.V.A. ratios were significantly lower in the delusional group. The groups did not differ significantly in c.s.F. probenecid concentrations, age, or severity of depression or agitation (rated daily by nurses). These data support the view that delusional depression may be a clinical state accompanied by alteration in brain systems mediated by’both dopamine and noradrenaline. Such findings may provide a neurochemical rationale for clinical use of antipsychotic-antidepressant drug combinations to treat delusional depression.9.,o The data also support hypotheses from animal" and clinicap2 studies regarding interactions between dopamine and noradrenaline (i.e., that functionally decreased noradrenergic activity may facilitate the "release" of dopaminemediated behaviour). Studies of monoamine interactions may be increasingly important for the further understanding of the neurobiological substrate of psychopathology.
Clinical Research Ward,
Department of Psychiatry, Yale University, New Haven, Connecticut 06508, U.S.A.
DONALD SWEENEY CRAIG NELSON MALCOLM BOWERS JAMES MAAS GEORGE HENINGER
HYPERPROLACTINÆMIA IN CHRONIC ALCOHOLICS TREATED WITH PROMAZINE
SIR,-Long-acting phenothiazines have been proposed as a form of drug therapy for alcohol-dependence syndrome.1,2 Alcoholism causes hyperprolactinsemia. I record here prolactin values found in three groups of chronic alcoholics-namely, 5 with hyperprolactinsemia on admission (group A), S treated with non-depot promazine (group B), and 5 not treated with promazine (group C). Serum-prolactin was estimated by radioimmunoassay on admission in all three groups and repeated immediately after completion of treatment in groups B and C. The table shows that hyperprolactinxmia may be a problem in alcoholics on admission or in those with normal admission serum-prolactin concentrations who are treated with promazine. There -may be serious consequences for the patient since hyperprolactinsemia may lead to impotence, hypogonadism, and gynaecomastia in men and galactorrhoea, and amenorrhcea in women.3 The promazine-treated patients were given ’Sparine’ 100 mg daily for 6 days and in all of them serum-prolactin levels rose after treatment, post-treatment values being above the normal range in three. Phenothiazines are known to raise serum-prolactin by blocking dopaminergic receptors in the hypothalamus and thus blocking prolactin-inhibiting factor.’’ In the patients not given promazine (group C) serum-prolactin levels dropped after treatment. The relevance of these findings 9. Extein, I., Bowers, M. B. Comprehens. Psychiat. 1975, 16, 427. 10. Nelson, J. C., Bowers, M. B. Archs gen. Psychiat. (in the press). 11. Antelman, S. M., Caggiula, A. R. Science, 1977, 195, 646. 12. Sweeney, D R., Pickar, D., Redmond, D. E., Jr., Maas, J. W. Lancet, 1978.
I, 872. 1
Q. Jl. Stud Alcohol, 1966, 27, 510
2. Kinnel, H G. Lancet, 1977, ii, 659. 3. Majumdar, S K., Thomson, A. D., Shaw, G. K. Br. med. J. 1978, 4. Thorner, M O. Lancet, 1975, i, 662.
i,
409.
*Mean is.D. and range. Normal up to 500 VII.
the use of slow-release injectable phenothiazines is not known. I have seen three male alcoholics with clinical features of hypogonadism in this unit during the past year, and all of them were hyperprolactinaemic on admission. Depressive psychosis may also be associated with raised prolactin secretion,5 and depressive symptoms and suicide are common in alcoholics.6 to
Elmdene Alcoholic Treatment Unit,
Bexley Hospital, Bexley, Kent DA5
2BW
SISIR K. MAJUMDAR
FAILURE OF METHYL-C.C.N.U. AND 5-FLUOROURACIL IN COLORECTAL CANCER
SIR,-A report from the Sidney Farber Cancer Institute’ on combination chemotherapy with 5-fluorouracil and methvl
chloroethyl-cyclohexyl-nitrosourea
(methyl-c.c.N.U.)
in
advanced colorectal cancer has failed to confirm the results obtained in earlier studies.2.3 However, these drugs are still widely used and believed to be effective. We report here the results of treatment in a group of 49 patients-37 with advanced colorectal cancer, 11 with carcinoma of the pancreas, and 1 with metastases from an cesophageal primarywho were treated with similar combination chemotherapy. There were 27 males and 22 females aged 30-74. Criteria for entry the study were histological confirmation of carcinoma, measurable disease, and progressive disease which could not be treated by radiotherapy or surgery. 7 patients had had previous chemotherapy, 11 previous radiotherapy, and 3 a combination of both. 4 received concomitant radiotherapy for local problems. 35 patients had liver metastases. The treatment schedule was methyl-c.c.N.U. orally 150 mg/m2 on day 1 with 5-F.U. i.v. 325 mg/m2 and dacarbazine (D.T.I.C.) i.v. 75 mg/m2 on days 1-5. Patients with pancreatic carcinoma were treated with mitomycin C (3 mg/m2) on days 1-5 instead of D.T.I.C. These courses were repeated every 6 weeks. Response was assessed at 10 weeks and at 6 months as "complete response" (disappearance of all measurable disease), "partial response" (50% reduction in all measurable lesions), "no change" (no evidence of progression), or "progression" (new lesions, increasing size of indicator lesions, with or without rising carcinoembryonic antigen levels and biochemical abnormalities. 22 patients received one course only, 13 received two courses, and 14 more than two courses. 4 patients with panto
creatic carcinoma had known residual disease after surgery. Of the patients with measurable disease 11 were unassessable because of insufficient follow-up data or change of chemotherapy (though this reflected clinical evidence of progression of disease). 25 out of 49 patients had progression of disease by 10 weeks, 10 patients shows no change, and 3 showed partial 5. Horrobin, D. F. Br. J Psychiat. 1974, 124, 456. 6. Merry, J., Renolds, M. C., Bailey, J., Coppen, A. Lancet, 1976,
ii, 481.
1. Lokich, J. J., Skarin, A. T., Mayer, R. J., Frei, E., III Cancer, 1977, 40, 2792. 2. Kisner, D., Schein, P., Cohen, L., Smythe, T., Duvall, C. Am. Soc. clin. Oncol. 1976, 17, 264. 3. Moertel, C. G., Schutt, A. J., Hahn, R. G., Reitemeier, R. J. J nat. Cancer Inst. 1975, 54, 69.
