Archives of General Psychiatry

Avery, David;Winokur, George

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090019001pmid: 962487

Abstract • The treatments of 519 depressed patients hospitalized from 1959 to 1969 were compared in a three-year follow-up study with particular reference to mortality. The electroconvulsive therapy (ECT) group had a significantly lower mortality than the inadequate antidepressant treatment group (P <.05) and the group that received neither ECT nor antidepressants (P <.025). Although the adequate antidepressant treatment group had a low mortality, statistically significant differences between this and other treatment groups could not be documented. Nonsuicidal deaths (P <.005), and particularly myocardial infarctions (P <.01), were significantly more frequent in the inadequately treated group compared to the adequately treated group. The superiority of adequate treatment is especially striking among men and among the older age groups. The results underscore the importance of adequate treatment of depression, especially in the older man. References 1. ødegaard O: The excess mortality of the insane . Acta Psychiatr Scand 27:353-367, 1952.Crossref 2. Malzberg B: Mortality among patients with involutional melancholia . Am J Psychiatry 93:1231-1238, 1937. 3. Huston PE, Locher LM: Involutional psychosis: Course when untreated and when treated with electric shock . Arch Neurol Psychiatry 59:385-394, 1948.Crossref 4. Stenstedt A: A study in manic-depressive psychosis . Acta Psychiatry Scand 79( (suppl) ):1-111, 1952. 5. Norris V: Mental Illness in London: A Statistical Inquiry into Admissions to Mental Hospitals . Maudsley Monograph Series, London, Chapman & Hall, 1959. 6. Helgason T: Epidemiology of mental disorders in Iceland . Acta Psychiatr Scand 173( (suppl) ):1-258, 1964. 7. Bratfos O, Haug JO: The course of manic-depressive psychosis . Acta Psychiatr Scand 44:89-112, 1968.Crossref 8. Ziskind E, Somerfeld-Ziskind E, Ziskind L: Metrazol and electroconvulsive therapy of the affective psychoses . Arch Neurol Psychiatry 53:212-217, 1945.Crossref 9. Huston PE, Locher LM: Manic-depressive psychosis: Course when treated and untreated with electric shock Arch Neurol Psychiatry 60:37-48, 1948.Crossref 10. Karagulla S: Evaluation of electric convulsive therapy as compared with conservative methods of treatment in depressive states . J Ment Sci 96:1060-1091, 1950. 11. Slater ET: Evalution of electric convulsive therapy as compared with conservative methods of treatment . J Ment Sci 17:567-569, 1951. 12. ED: Results of treatment in psychoses with a control series . Am J Psychiatry 110:881-887, 1954. 13. Rogers SC, Clay PM: A statistical review of controlled trials of imipramine and placebo in the treatment of depressive illness . Br J Psychiatr 127:599-603, 1975.Crossref 14. Morris JB, Beck AT: The efficacy of antidepressant drugs . Arch Gen Psychiatry 30:667-676, 1974.Crossref 15. Medical Research Council: Clinical trial of the treatment of depressive illness . Br Med J 1:881-886, 1965.Crossref 16. Greenblatt M, Grosser GH, Wechsler H: Differential response of hospitalized depressed patients to somatic therapy . Am J Psychiatry 120:935-943, 1964. 17. Hordern A, Burt CG, Holt NF: Depressive States . Springfield, Ill, Charles C Thomas Publisher, 1975. 18. Slater ET, Roth M: Clinical Psychiatry . Baltimore, Williams & Wilkins Co, 1969. 19. Jefferson J: A review of the cardiovascular effects and toxicity of tricyclic antidepressants . Psychosom Med 37:160-179, 1975.Crossref 20. Moir DC, Cornwell WB, Dingwall-Fordyce I, et al: Cardiotoxicity of amitryptyline . Lancet 2:561-564, 1972.Crossref 21. Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 26:57-63, 1972.Crossref 22. Malzberg B: Rates of Mortality Among Patients With Mental Diseases . Albany, NY, Research Foundation for Mental Hygiene Inc, 1968. 23. Dalgard OS: Mortality in patients with functional psychoses . Nord Med 16:680-684, 1966. 24. Alström CH: Mortality in mental hospitals . Acta Psychiatr Neurol , (suppl 24) , 1942. 25. Watts CAH: The incidence and prognosis of endogenous depression . Br Med J 1:1392-1397, 1956.Crossref 26. Pederson AM, Barry DJ, Babigian HM: Epidemiological considerations of psychotic depression . Arch Gen Psychiatry 27:193-197, 1972.Crossref 27. Kessell A, Holt NF: Depression: An analysis of a follow-up study . Br J Psychiatry 11:1143-1153, 1965.Crossref 28. Fuller RG: Expectation of hospital life and outcome for mental patients on first admission . Psychiatr Q 4:295-323, 1930.Crossref 29. Fuller RG: What happens to mental patients after discharge from hospital . Psychiatr Q 9:95-104, 1935.Crossref 30. Bond ED, Braceland FJ: Prognosis in mental disease . Am J Psychiatry 94:263-274, 1937. 31. Roth M: The natural history of mental disorder in old age . J Ment Sci 101:281-301, 1955. 32. Hastings DW: Follow-up results in psychiatric illness . Am J Psychiatry 114:1057-1066, 1958. 33. Seager CP: A comparison between the results of unmodified and modified electroplexy . J Ment Sci 104:206-220, 1958. 34. Seager CP: Controlled trial of straight and modified electroplexy . J Ment Sci 105:1022-1028, 1959. 35. Guze SB, Robins E: Suicide and primary affective disorders . Br J Psychiatry 117:437-438, 1970.Crossref 36. Malzberg B: Mortality from cancer among patients with mental disease in the New York civil state hospitals . Psychiatr Q , (suppl 124) , 1950. 37. Babigian HM, Odoroff CL: The mortality experiences of a population with psychiatric illness . Am J Psychiatry 124:470-479, 1969. 38. Kerr TA, Schapira TA, Roth M: The relationship between premature death and affective disorders . Br J Psychiatry 115:1277-1283, 1969.Crossref 39. Fras I, Litin EM, Bartholomew LG: Mental symptoms as an aid in the early diagnosis of carcinoma of the pancreas . Gastroenterol 55:191-198, 1968. 40. Fras I, Litin EM, Pearson JS: Comparison of psychiatric symptoms in carcinoma of the pancreas with those in some other intra-abdominal neoplasms . Am J Psychiatry 123:1553-1561, 1967. 41. Dreyfuss F, Asberg H, Assael MI: The relationship of myocardial infarction to depressive illness . Psychother Psychosom 17:73-81, 1969.Crossref 42. Wynn A: The recognition of coronary proneness . Med J Aust 1:350-353, 1967. 43. Boston Collaborative Drug Surveillance Program: Adverse reactions to the tricyclic-antidepressant drugs . Lancet 1:529-531, 1972. 44. Klein DF, Davis JM: Diagnosis and Drug Treatment of Psychiatric Disorders . Baltimore, Williams & Wilkins Co, 1969. 45. Kotin J, Post PM, Goodwin FK: Drug treatment of depressed patients referred for hospitalization . Am J Psychiatry 130:1139-1141, 1973. 46. Willcox DRC, Gilan R, Hare EH: Do psychiatric outpatients take their drugs . Br Med J 2:790-792, 1965.Crossref 47. Jaaskelainen J, Viukari NMA: Do tricyclic antidepressants work? Lancet 1:424, 1976.Crossref 48. Hessø R, Retterstøl NT: Suicid i Norske Psykiatriske Sykehas . Nor Laegeforen 95:1571-1574, 1975. 49. Kay DWK, Bergmann K: Physical disability and mental health in old age . J Psychosom Res 10:3-12, 1966.Crossref

Carroll, Bernard J.;Curtis, George C.;Mendels, Joseph

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090029002pmid: 962488

Abstract • The regulation of hypothalamopituitary-adrenal (HPA) function in depressed patients was studied by a midnight dexamethasone suppression test. By using an observation period of 24 hours postadministration of dexamethasone, a graded series of abnormal test responses was identified. Depressed patients show abnormal early escape from suppression rather than absolute resistance to HPA suppression by dexamethasone. With increasing severity of depression, this escape occurs progressively more early on the day after administration of dexamethasone. These abnormalities were strongly related to the presence of HPA hyperactivity before dexamethasone was given. The essential disturbance of neuroendocrine regulation in depression is a failure of the normal brain inhibitory influence on the HPA system. This disinhibition of HPA activity suggests that there is an abnormal limbic system drive on the HPA axis in primary depressive illness. References 1. Michael RP, Gibbons JL: Interrelationships between the endocrine system and neuropsychiatry , in Pfeiffer C, Smythies J (eds): International Review of Neurobiology . New York, Academic Press Inc, 1963, vol 5, pp 243-292. 2. Rubin R, Mandell A: Adrenal cortical activity in pathological emotional states: A review . Am J Psychiatry 123:387-400, 1966. 3. Martini L, Ganong WF (eds): Neuroendocrinology . New York, Academic Press Inc, 1966-1967. 4. Carroll BJ: The hypothalamic-pituitary-adrenal axis: Functions, control mechanisms and mehods of study , in Davies B, Carroll BJ, Mowbray RM (eds): Depressive Illness: Some Research Studies . Springfield, Ill, Charles C Thomas Publisher, 1972, pp 23-68. 5. Carroll BJ, Mendels J: Neuroendocrine regulation in affective disorders , in Sachar EJ (ed): Hormones, Behavior and Psychopathology . New York, Raven Press, 1976, pp 193-224. 6. Carroll BJ, Martin FIR, Davies BM: Resistance to suppression by dexamethasone of plasma 11-OCHS levels in severe depressive illnesses . Br Med J 3:285-287, 1968.Crossref 7. Carroll BJ, Davies BM: Clinical associations of 11-hydroxycorticosteroid suppression and non-suppression in severe depressive illnesses . Br Med J 1:789-791, 1970.Crossref 8. Stokes P: Studies on the control of adrenocortical function in depression, in Williams TA, Katz MM, Shield JA Jr (eds): Recent Advances in the Psychobiology of the Depressive Illnesses. US Government Printing Office, 1972, pp 199-220. 9. Platman SR, Fieve RR: Lithium carbonate and plasma cortisol response in the affective disorders . Arch Gen Psychiatry 18:591-594, 1968.Crossref 10. Butler PWP, Besser GM: Pituitary-adrenal function in severe depressive illness . Lancet 2:1234-1236, 1968.Crossref 11. Bridges PK: Methods of assessing patients for psychosurgery and their outcome after operation . Psychiatr Neurol Neurochir 76:335-344, 1973. 12. Endo M, Endo J, Nishikubo M, et al: Endocrine studies in depression , in Hatotani N (ed): Psychoneuroendocrinology . Basel, Switzerland, Karger, 1974, pp 22-31. 13. Gibbons JL, Fahy TJ: Effect of dexamethasone on plasma corticosteroids in depressive illness . Neuroendocrinology 1:358-363, 1966.Crossref 14. Shopsin B, Gershon S: Plasma cortisol response to dexamethasone suppression in depressed and control patients . Arch Gen Psychiatry 24:320-326, 1971.Crossref 15. Carpenter WT Jr, Bunney WE Jr: Adrenal cortical activity in depressive illness . Am J Psychiatry 128:31-40, 1971. 16. Verghese A, Matthew J, Mathai G, et al: Plasma cortisol in depressive illness . Indian J Psychiatry 15:72-79, 1973. 17. Carroll BJ: Control of plasma cortisol levels in depression: Studies with the dexamethasone suppression test , in Davies BM, Carroll BJ, Mowbray RM (eds): Depressive Illness: Some Research Studies . Springfield, Ill, Charles C Thomas Publisher, 1972, pp 87-148. 18. Krieger D, Allen W, Rizzo F, et al: Characterization of the normal temporal pattern of plasma corticosteroid levels . J Clin Endocrinol Metab 32:266-284, 1971.Crossref 19. McHardy-Young S, Harris PWR, Lessoff MH, et al: Single-dose dexamethasone suppression test for Cushing's syndrome . Br Med J 1:740-744, 1967.Crossref 20. Mendels J, Frazer A: Intracellular lithium concentration and clinical response: Towards a membrane theory of depression . J Psychiatr Res 10:9-18, 1973.Crossref 21. Sachar EJ, Hellman L, Roffwarg H, et al: Disrupted 24-hour patterns of cortisol secretion in psychotic depression . Arch Gen Psychiatry 28:19-24, 1973.Crossref 22. Hellman L, Nakada F, Curti J, et al: Cortisol is secreted episodically by normal man . J Clin Endocrinol Metab 30:411-422, 1970.Crossref 23. Curtis GC, Fogel ML: Circadian periodicity of plasma cortisol levels: Effect of random living schedule in man . Space Life Sci 3:125-134, 1971. 24. Hellman L, Weitzman E, Roffwarg H, et al: Cortisol is secreated episodically in Cushing's syndrome . J Clin Endocrinol Metab 30:686-689, 1970.Crossref 25. Nugent CA, Nichols T, Tyler FH: Diagnosis of Cushing's syndrome: Single dose dexamethasone suppression test . Arch Intern Med 116:172-176, 1965.Crossref 26. Pavlatos FC, Smilo RP, Forsham PH: A rapid screening test for Cushing's syndrome . JAMA 193:720-723, 1965.Crossref 27. Cope CL, Black EG: The reliability of some adrenal function tests . Br Med J 2:1117-1122, 1959.Crossref 28. Carroll BJ, Curtis GC, Davies BM, et al: Urinary free cortisol excretion in depression . Psychol Med 6:43-50, 1976.Crossref 29. Sachar EJ, Mackenzie J, Binstock W, et al: Corticosteroid responses to psychotherapy of depressions: I. Evalutions during confrontation of loss . Arch Gen Psychiatry 16:461-470, 1967.Crossref 30. Rabhan NB: Pituitary-adrenal suppression and Cushing's syndrome after intermittent dexamethasone therapy . Ann Intern Med 69:1141-1148, 1968.Crossref 31. Haque N, Thrasher K, Werk E Jr, et al: Studies of dexamethasone metabolism in man: Effect of diphenylhydantoin . J Clin Endocrinol Metab 34:44-50, 1972.Crossref 32. Hichens M, Hogans A: Radioimmunoassay for dexamethasone in plasma . Clin Chem 20:266-271, 1974. 33. Meikle A, Lagerquist L, Tyler F: A plasma dexamethasone radioimmunoassay . Steroids 22:193-202, 1973.Crossref 34. DeKloet E, Van der Vies J, DeWied D: The site of the suppressive action of dexamethasone on pituitary-adrenal activity . Endocrinology 94:61-73, 1974.Crossref

Carroll, Bernard J.;Curtis, George C.;Mendels, Joseph

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090041003pmid: 962489

Abstract • Forty-two patients with endogenomorphic depression (ED) and 42 patients with other psychiatric disorders received an overnight dexamethasone test of hypothalamopituitary-adrenal (HPA) suppressibility. Plasma and urinary cortisol measures showed that the ED patients had significantly greater HPA activity before dexamethasone and less complete HPA suppression after dexamethasone. High cortisol values after dexamethasone correlated strongly with spontaneous HPA disinhibition, as indicated by high baseline midnight plasma cortisol levels. Criteria for defining normal suppression responses were developed. All patients with depressive neuroses and most patients with other nondepressive disorders had completely normal responses to dexamethasone. About half of the ED patients had abnormal responses, whether or not they were receiving other drugs at the time of the test. Drug-free patients with depressive neuroses or other disorders showed no abnormal responses to dexamethasone. The effects of psychotropic drugs on the test require further study. Patients with two or more abnormal cortisol values after administration of dexamethasone were identified correctly as ED at confidence levels close to100%. dexa-methasone suppression test may be of value as a laboratory aid in the diagnosis of "endogenous" depression. References 1. Klein DF: Endogenomorphic depression . Arch Gen Psychiatry 31:447-454, 1974.Crossref 2. Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 26:57-63, 1972.Crossref 3. Jubiz W, Meikle AW, Levinson RA, et al: Effect of diphenylhydantoin on the metabolism of dexamethasone . N Engl J Med 283:11-14, 1970.Crossref 4. Brooks SM, Werk EE, Ackerman SJ, et al: Adverse effects of pheno-barbital on corticosteroid metabolism in patients with bronchial asthma . N Engl J Med 286:1125-1128, 1972.Crossref 5. Mason JW, Sachar EJ, Fishman JR, et al: Corticosteroid responses to hospital admission . Arch Gen Psychiatry 13:1-8, 1965.Crossref 6. Murphy BEP: Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay . J Clin Endocrinol Metab 27:973-990, 1967.Crossref 7. Murphy BEP: Clinical evaluation of urinary cortisol determination by competitive protein-binding radioassay . J Clin Endocrinol Metab 28:343-348, 1968.Crossref 8. Hsu TH, Bledsoe T: Measurement of urinary free corticoids by competitive protein-binding radioassay in hypoadrenal states . J Clin Endocrinol Metab 30:443-448, 1970.Crossref 9. Beardwell CG, Burke CW, Cope CL: Urinary free cortisol measured by competitive protein-binding . J Endocrinol 42:79-89, 1968.Crossref 10. Carroll BJ: The hypothalamus-pituitary-adrenal axis in depression , in Davies B, Carroll BJ, Mowbray RM (eds): Depressive Illness: Some Research Studies . Springfield, Ill, Charles C Thomas Publisher, 1972, pp 23-201. 11. Asfeldt VH: Simplified dexamethasone suppression test . Acta Endocrinol 61:219-231, 1969. 12. Hellman L, Nakada F, Curti J, et al: Cortisol is secreted episodically by normal man . J Clin Endocrinol Metab 30:411-422, 1970.Crossref 13. Krieger DT, Allen W, Rizzo F, et al: Characterization of the normal temporal pattern of plasma cortisol levels . J Clin Endocrinol Metab 32:266-284, 1971.Crossref 14. Gaddum JH: Log-normal distributions . Nature 156:463-466, 1945.Crossref 15. Heath DF: Normal or log-normal: Appropriate distributions . Nature 213:1159-1160, 1967.Crossref 16. Burke CW, Beardwell CG: Cushing's Syndrome: An evaluation of the clinical usefulness of urinary free cortisol and other urinary steroid measures in diagnosis . Q J Med 42:175-204, 1973. 17. Mattingly D: Plasma steroid levels as a measure of adrenocortical activity . Proc R Soc Med 56:717-720, 1963. 18. Doe RP, Vennes JA, Flink EB: Diurnal variation of 17-hydroxycorticosteroids, sodium, potassium, magnesium and creatinine in normal subjects and in cases of treated adrenal insufficiency and Cushing's Syndrome . J Clin Endocrinol Metab 20:253-265, 1960.Crossref 19. Carpenter WT, Bunney WE: Adrenal cortical activity in depressive illness . Am J Psychiatry 128:31-40, 1971. 20. Sachar EJ, Hellman L, Roffwarg HP, et al: Disrupted 24-hour patterns of cortisol secretion in psychotic depression . Arch Gen Psychiatry 28:19-24, 1973.Crossref 21. Zumoff B, Fukushima DK, Weitzmann ED, et al: The sex difference in plasma cortisol concentration in man . J Clin Endocrinol Metab 39:805-808, 1974.Crossref 22. Curtis GC, Fogel ML: Circadian periodicity of plasma cortisol levels: Effect of random living schedule in man . Space Life Sci 3:125-134, 1971. 23. McHardy-Young S, Harris PWR, Lessof MH, et al: Single-dose dexamethasone suppression test for Cushing's Syndrome . Br Med J 1:740-744, 1967.Crossref 24. Carroll BJ, Curtis GC, Davies BM, et al: Urinary free cortisol excretion in depression . Psychol Med 6:43-50, 1976.Crossref 25. Greaves AR, West HF: Relation of free corticosteroids in urine to steroid dosage . Lancet 1:368, 1960.Crossref 26. Rosner JM, Cos JJ, Biglieri EG, et al: Determination of urinary unconjugated cortisol by glass fiber chromatography in the diagnosis of Cushing's syndrome . J Clin Endocrinol Metab 23:820-827, 1963.Crossref 27. Beisel WR, Cos JJ, Horton R, et al: Physiology of urinary cortisol excretion . J Clin Endocrinol Metab 24:887-893, 1964.Crossref 28. Cope CL, Black EG: The reliability of some adrenal function tests . Br Med J 2:1117-1122, 1959.Crossref 29. Eddy RL, Jones AL, Gilliland PF, et al: Cushing's Syndrome: A prospective study of diagnostic methods . Am J Med 55:621-630, 1973.Crossref 30. Carroll BJ: Limbic system-pituitary-adrenal regulation in depression and schizophrenia . Psychosom Med 38:106-121, 1976.Crossref 31. Blumenfield M, Rose L, Richmond LH, et al: Dexamethasone suppression in basic trainees under stress . Arch Gen Psychiatry 23:299-304, 1970.Crossref 32. Robins E, Hartman BK: Biochemical theories of mental disorders , in Albers RW, Siegel GJ, Katzman R, et al (eds): Basic Neurochemistry . Boston, Little Brown & Company, 1972, pp 607-644. 33. Krieger DT, Krieger HP: The effect of short-term administration of CNS-acting drugs on the circadian variation of the plasma 17-OHCS in normal subjects . Neuroendocrinology 2:232-246, 1967.Crossref 34. Sachar EJ: Evidence for neuroendocrine abnormalities in the major mental illnesses , in Freedman DX (ed): Biology of the Major Psychoses . New York, Raven Press, 1975, vol 54, pp 347-358. 35. Stokes PE: Studies on the control of adrenocortical function in depression, in Williams TA, Katz MM, Shield JA (eds): Recent Advances in the Psychobiology of the Depressive Illnesses, No. (HSM) 70-9053. US Department of Health, Education and Welfare, 1972, pp 199-220. 36. Kiloh LG, Andrews G, Neilson M, et al: The relationship of the syndromes called endogenous and neurotic depression . Br J Psychiatry 121:183-196, 1972.Crossref 37. Sachar EJ, Hellman L, Fukushima DK, et al: Cortisol production in depressive illness: A clinical and biochemical clarification . Arch Gen Psychiatry 23:289-298, 1970.Crossref 38. Bunney WE, Mason JW, Hamburg DA: Correlations between behavioral variables and urinary 17-hydroxycorticosteroids in depressed patients . Psychosom Med 27:299-308, 1965.Crossref 39. Jacobs HS, Nabarro JDN: Plasma 11-hydroxycorticosteroid and growth hormone levels in acute medical illnesses . Br Med J 2:595-598, 1969.Crossref 40. Connolly CK, Gore MBR, Stanley N, et al: Single-dose dexamethasone suppression in normal subjects and hospital patients . Br Med J 2:665-667, 1968.Crossref 41. Connolly CK, Wills MR: Plasma "cortisol" levels in right and left ventricular failure . J Clin Pathol 22:598-601, 1969.Crossref 42. Alleyne GAO, Young VH: Adrenocortical function in children with severe protein-calorie malnutrition . Clin Sci 33:189-200, 1967. 43. Bethge H, Nagel AM, Solbach HG, et al: Zentrale Regulationsstorung der Nebennierenrindenfunktion beider Anorexia Nervosa . Mater Med Nordmark 22:204-214, 1970. 44. Smith SR, Bledsoe T, Chhetri MK: Cortisol metabolism and the pituitary-adrenal axis in adults with protein-calorie malnutrition . J Clin Endocrinol Metab 40:43-52, 1975.Crossref 45. Burke CW: Biologically active cortisol in plasma of oestrogen-treated and normal subjects . Br Med J 2:798-800, 1969.Crossref 46. Burke CW, Roulet F: Increased exposure of tissues to cortisol in late pregnancy . Br Med J 1:657-659, 1970.Crossref 47. Rosenthal HE, Slaunwhite WR, Sandberg AA: Transcortin—a corticosteroid-binding protein of plasma: X. Cortisol and progesterone interplay and unbound levels of these steroids in pregnancy . J Clin Endocrinol Metab 29:352-367, 1969.Crossref

Himmelhoch, Jonathan M.;Mulla, Dawood;Neil, John F.;Detre, Thomas P.;Kupfer, David J.

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090052004pmid: 962490

Abstract • The simultaneous existence of manic and depressive symptoms in a manic-depressive patient was first described by Kraepelin.1 This so-called mixed state has come to have much theoretical significance in recent hypotheses about the nature of bipolar affective disorders. In this investigation a mixed state is shown to be the initial episode in 31% of 84 manic-depressive outpatients. Moreover, the presence of "mixed" features does not correlate with severity of illness or mood circularity, but does correlate with sedative abuse and poor response to psychopharmacologic treatment. These results suggest that the "continuum hypothesis" and its satellite theories represent viable conceptualizations of the nature of manic-depressive illness. References 1. Kraepelin E: Lectures on Clinical Psychiatry , a facsimile of the 1904 edition. New York, Hafner Publishing Co Inc, 1968. 2. Court J: The continuum model as a resolution of paradoxes in manicdepressive psychosis . Br J Psychiatry 120:133-141, 1972.Crossref 3. Bunney W, Murphy D, Goodwin F, et al: The "switch process" in manic depressive illness: I. A systematic study of sequential behavior change . Arch Gen Psychiatry 27:295-302, 1972.Crossref 4. Court J: Manic-depressive psychosis: An alternative conceptual model . Br J Psychiatry 114:517, 1523-1530, 1968.Crossref 5. Feighner JP, Robins E, Guze B, et al: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 26:57-63, 1972.Crossref 6. Kupfer D, Detre T: Development and application of the KDStm-1 in inpatient and outpatient settings . Psychol Rep 29:607, 1970.Crossref 7. Kupfer D, Detre T: Once more—On the extraordinary side effects of drugs . Clin Pharmacol Ther 12:575-582, 1971. 8. Woodruff R, Goodwin D, Guze S: Psychiatric Diagnosis . New York, Oxford University Press Inc, 1974. 9. Coppen A: Mineral metabolism in affective disorders . Br J Psychiatry 111:1133-1142, 1965.Crossref 10. Dunner D, Cohn C, Gershon E, et al: Differential catechol-o-methyltransferase activity in unipolar and bipolar illness . Arch Gen Psychiatry 25:348-353, 1971.Crossref 11. Sachar E, Finkelstein J, Hellman L: Growth hormone responses in depressive illness . Arch Gen Psychiatry 25:263-269, 1971.Crossref 12. Sachar E, Hellman L, Fukushima D, et al: Cortisol production in depressive illness: A clinical and biochemical clarification . Arch Gen Psychiatry 23:289-298, 1970.Crossref 13. Winokur G: Genetic findings and methodological considerations in manic depressive disease . Br J Psychiatry 117:267-274, 1970.Crossref 14. Buchsbaum M, Goodwin F, Murphy D, et al: AER in affective disorders . Am J Psychiatry 128:19, 1971. 15. Court JH, Mai JH: A double-blind intensive crossover design trial of methysergide in mania . Med J Aust 2:526-529, 1970. 16. Beigel A, Murphy D: Unipolar and bipolar affective illness: Differences in clinical characteristics accompanying depression . Arch Gen Psychiatry 24:215-220, 1971.Crossref 17. Rosenfield H: Notes on the psychopathology and psychoanalytic treatment of depressive and manic-depressive patients , in Azima H, Glueck BC (eds): Psychotherapy of Schizophrenic and Manic-Depressive States , psychiatric research report 17. Washington, DC, American Psychiatric Association, 1973. 18. Prange A Jr: The use of drugs in depression: Its theoretical and practical basis . Psychiatr Ann 3:2, 1973. 19. Dyson W, Mendels J: Recurrent depressions and the lithium ion . Am J Psychiatry 125:544-548, 1968. 20. Mendels J, Frazer A: Intracellular lithium concentration and clinical response: Towards a membrane theory of depression . J Psychiatr Res 10:9-18, 1973.Crossref 21. Elizur A, Shopsin B, Gershon S, et al: Intra: Extracellular lithium ratios and clinical course in affective states . Clin Pharmacol Ther 13:947-952, 1972. 22. Janowsky D, El-Yousef M, Davis J: Acetylcholine and depression . Psychosom Med 36:248-256, 1974.Crossref 23. Winokur G, Clayton P, Reich T: Manic-Depressive Illness . St Louis, CV Mosby Co, 1969. 24. Dunner D, Goodwin F, Gershon E, et al: Excretion of 17-OHCS in unipolar and bipolar depressed patients . Arch Gen Psychiatry 26:360-363, 1972.Crossref 25. Himmelhoch J, Kupfer D, Detre T, et al: Agitated psychotic depression associated with severe hypomanic episodes: A rare syndrome . Am J Psychiatry , to be published. 26. Dunner DL: Clinical characteristics of lithium prophylaxis failure . Arch Gen Psychiatry 30:229-233, 1974.Crossref 27. Prien RF, Caffey EM Jr, Klett CJ: Factors associated with treatment success in lithium carbonate prophylaxis . Arch Gen Psychiatry 31:189-192, 1974.Crossref 28. Klerman G, Cole J: Clinical pharmacology of imipramine and related antidepressant compounds . Pharmacol Rev 17:2, 1965. 29. Klein D, Davis L: Diagnosis and Drug Treatment of Psychiatric Disorders . Baltimore, Williams & Wilkins, 1969. 30. Hollister L: Antidepressant drugs , in Palma D Jr (ed): Drill's Pharmacology in Medicine . New York, McGraw-Hill Book Co Inc, 1971. 31. Caldwell J, Sever P: The biochemical pharmacology of abused drugs . Clin Pharmacol Ther 16:737-749, 1974. 32. Zarcone V Jr, Hoddes E: Effects of 5-hydrozytryptophan on fragmentation of REM sleep in alcoholics . Am J Psychiatry 132:74-76, 1975. 33. Ellsworth R, Foster L, Childres B, et al: Hospital and community adjustment as perceived by psychiatric patients, their families, and staff . J Consult Clin Psychol 32( (suppl) ):1-41, 1968. 34. Kahn E: The Emil Kraepelin memorial lecture , in Epidemiology of Mental Disorders , publication 60. Washington, DC, American Association for the Advancement of Science, 1959.

Wetzel, Richard D.

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090059005pmid: 962491

Abstract • One hundred fifty-four suicide attempters, threateners, and psychiatric controls were rated on suicide intent scales and given tests to assess hopelessness, depression, and self-rated suicide risk. Ninety-four subjects were retested one month later. Both hopelessness and depression were significantly greater in suicidal subjects. In threateners, hopelessness and depression scores differed significantly between high and low suicide intent subjects. In attempters ranked by suicide intent at time of testing, more and less suicidal subjects differed significantly in hopelessness and depression scores. Both depression and hopelessness were sensitive to changes in suicide risk during the one-month follow-up. In all analyses, hopelessness correlated more highly with suicide intent than did depression. The data were regarded as supporting the hypothesis that hopelessness is more closely related to suicide intent than is depression. References 1. Beck AT: Thinking and depression: I. Idiosyncratic content and depression . Arch Gen Psychiatry 9:324-333, 1963.Crossref 2. Farber M: Theory of Suicide . New York, Funk and Wagnalls, 1968. 3. Kobler AL, Stotland E: The End of Hope . London, Glencoe Free Press, 1964. 4. Beck AT, Weissman A, Lester D, et al: The measurement of pessimism: The hopelessness scale . J Consult Clin Psychol 42:861-865, 1974.Crossref 5. Minkoff K, Bergman E, Beck AT, et al: Hopelessness, depression and attempted suicide . Am J Psychiatry 130:455-459, 1973. 6. Taylor MA: Schneiderian first-rank symptoms and clinical prognostic factors in schizophrenia . Arch Gen Psychiatry 26:64-67, 1972.Crossref 7. Beck AT, Herman I, Schuyler D: Development of suicidal intent scales , in Beck AT, Resnik HLP, Lettieri D (eds): The Prediction of Suicide . New York, Charles Press, 1974. 8. Beck RW, Morris JB, Beck AT: Cross-validation of the suicide intent scale . Psychol Rep 34:445-446, 1974.Crossref 9. Bruning JL, Kintz BL: Computational Handbook of Statistics . Glenview, Ill, Scott Foresman & Co, 1968, pp 112-116. 10. Stengel E, Cook NG: Attempted Suicide: Its Social Significance and Effects . London, Chapman and Hall, 1958. 11. Farberow NL: Personality patterns of suicidal mental hospital patients . Genet Psychol Monogr 42:3-79, 1950. 12. Braaten LJ, Darling CD: Suicidal tendencies among college students . Psychiatr Q 36:665-692, 1962.Crossref 13. Devries AG, Farberow NL: A multivariate profile analysis of MMPI's of suicidal and non-suicidal neuropsychiatric patients . J Projective Techniques 31:81-84, 1967. 14. Farberow NL, Devries AG: An item differentiation analysis of MMPI's of suicidal neuropsychiatric hospital patients . Psychol Rep 20:607-617, 1967.Crossref 15. Silver MA, Bohnert M, Beck AT, et al: Relation of depression of attempted suicide and seriousness of intent . Arch Gen Psychiatry 25:573-576, 1971.Crossref

Stokes, Peter E.;Kocsis, James H.;Arcuni, Orestes J.

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090070006pmid: 17642108

Abstract • Three separate lithium chloride doses, calculated according to body weight, and a placebo were administered under doubleblind conditions to 68 manic inpatients. The relationship of lithium chloride treatment dose to steady-state serum lithium levels (day 7 to 10 of treatment) and clinical response were examined. High (0.72 mEq/kg/day) and medium (0.5 mEq/kg/day) lithium chloride doses were more efficacious than placebo (P <.001 and p <.05, respectively), as determined by decrements in global mania ratings (day 7 to 10 of treatment). A low dose (0.24 mEq/kg/day) was not found to be more efficacious than placebo. The proportion of patients with improved manic ratings increased markedly as a function of increased steady-state serum lithium level (x2 for trend in proportions, 17.91; p <.001). References 1. Stokes PE, Shamoian CA, Stoll PM, et al: Efficacy of lithium as acute treatment of manic depressive illness . Lancet 1:1319-1325, 1971.Crossref 2. Maggs R: Treatment of manic illness with lithium carbonate . Br J Psychiatry 109:56-65, 1963.Crossref 3. Gershon S: Lithium salts in the management of the manic-depressive syndrome . Annu Rev Med 23:439-452, 1972.Crossref 4. Bunney W, Goodwin FK, Davis JM, et al: A behavioral-biochemical study of lithium treatment . Am J Psychiatry 125:499-512, 1968. 5. Schou M, Juel-Nielsen N, Strömgren E, et al: The treatment of manic psychoses by the administration of lithium salts . J Neurol Neurosurg Psychiatry 17:250-257, 1954.Crossref 6. Goodwin F, Murphy DL, Bunney WE Jr: Lithium carbonate treatment in depression and mania . Arch Gen Psychiatry 21:486-496, 1969.Crossref 7. Spring G, Schweld D, Gray C, et al: A double-blinded comparison of lithium and chlorpromazine in the treatment of manic states . Am J Psychiatry 126:1306-1310, 1970. 8. Prien RF, Caffey EM Jr, Klett CJ: A comparison of lithium carbonate and chlorpromazine in the treatment of excited schizo-affectives . Arch Gen Psychiatry 27:82-89, 1972.Crossref 9. Noyes AP, Kolb LC: Psychotic disorders: Affective reactions , in Modern Clinical Psychiatry , ed 7. Philadelphia, WB Saunders, 1968. 10. Prien RF, Caffey EM Jr, Klett CJ: Relationship between serum lithium level and clinical response in acute mania treated with lithium . Br J Psychiatry 120:409-414, 1972.Crossref

Neil, John F.;Himmelhoch, Jonathan M.;Licata, Sandra M.

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090080007pmid: 962492

Abstract • In a patient with recurrent episodes of severe mania, classical manifestations of myasthenia gravis developed for the first time during treatment with lithium carbonate. Four episodes were recorded in which the appearance of progressive weakness coincided with subacute or long-term lithium carbonate administration during periods of psychiatric remission. In each instance, neurologic symptoms were ameliorated or disappeared shortly after the drug was discontinued or its dosage was reduced. There was no evidence of lithium carbonate toxicity or electrolyte disturbances at any time during treatment. Based on a literature review of animal studies and related clinical reports, a mechanism of peripherally mediated neuromuscular cholinergic insufficiency is proposed. In addition, the differential diagnosis of muscle weakness during lithium carbonate administration is discussed. References 1. Schou M, Baastrup PC, Grof P, et al: Pharmacological and clinical problems of lithium prophylaxis . Br J Psychiatry 116:615-619, 1970.Crossref 2. Vacaflor L: Lithium side effects and toxicity: The clinical picture , in Johnson FN (ed): Lithium Research and Therapy . London, Academic Press Inc, 1975, pp 212-214. 3. Borden H, Clark MT, Katz H: The use of pancuronium bromide in patients receiving lithium carbonate . Can Anaesth Soc J 21:79-82, 1974. 4. Girke W, Krebs FA, Muller-Oerlinghausen B: Effects of lithium on electromyographic recordings in man: Studies in manic-depressive patients and normal volunteers . Int Pharmacopsychiatry 10:24-36, 1975. 5. Kelly JS: The antagonism of Ca++ by Na++ and other monovalent ions at the frog neuromuscular junction . J Exp Physiol 53:239-249, 1968. 6. Onodera K, Yamakawa K: The effects of lithium on the neuromuscular junction of the frog . Jap J Physiol 16:541-550, 1966.Crossref 7. Vizi ES, Illes P, Ronai A, et al: The effect of lithium on acetylcholine release and synthesis . Neuropharmacology 11:521-530, 1972.Crossref 8. Vizi ES: Lithium and acetylcholine metabolism , in Johnson FN (ed): Lithium Research and Therapy . London, Academic Press Inc, 1975, pp 391-408. 9. Himmelhoch JM, Detre TP, Kupfer DJ, et al: Treatment of previously intractable depressions with tranylcypromine and lithium . J Nerv Ment Dis 155:216-220, 1972.Crossref 10. Helmchen H, Hoffmann I, Kanowski S: Paroxysmale Muskelschwäche bei Lithiumtherapie . Pharmakopsychiatry 4:269-273, 1969.Crossref 11. Shopsin B, Johnson G, Gershon S: Neurotoxicity with lithium: Differential drug responsiveness . Int Pharmacopsychiatry 5:170-182, 1970. 12. Kupfer DJ, Detre TP: Development and application of the KDS-1 in inpatient and outpatient settings . Psychol Rep 29:607-617, 1971.Crossref 13. Kupfer DJ, Detre TP, Amdur MJ: The KDS-1 scale for symptom discrimination Psychol Rep 30:915-919, 1972.Crossref 14. Kupfer DJ, Detre TP: Once more... On the extraordinary side effects of drugs . Clin Pharmacol Ther 12:575-582, 1971. 15. Kupfer DJ, Detre TP: Psychopharmacologic management of patients: A method for recording treatment decisions . Am J Psychiatry 132:186-188, 1975. 16. Merritt HH: A Textbook of Neurology , ed 5. Philadelphia, Lea & Febiger Publishers, 1973, pp 536-537. 17. Detre TP, Jarecki HG: Modern Psychiatric Treatment . Philadelphia, JB Lippincott Co, 1971, pp 185-187. 18. Kupfer DJ, Detre TP, Himmelhoch JM: Classification of depressions: A guide for the clinician. Read before the Rutgers Medical School, College of Medicine and Dentistry of New Jersey, New Brunswick, 1973. 19. Shopsin B: Effects of lithium on thyroid function. (A review) . Dis Nerv Syst 31:204-211, 1970. 20. Eaton LM: A warning concerning the use of curare in convulsive shock treatment with psychiatric disorders who may have myasthenia gravis . Proc Mayo Clin 22:4-7, 1947.

Simpson, George M.;Lee, J. Hillary;Cuculic, Zarko;Kellner, Robert

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090083008pmid: 786204

Abstract • Fifty-one newly hospitalized depressed patients participated in a double-blind comparison of two dosage levels of imipramine hydrochloride (150 mg vs 300 mg daily). Although some patients were suffering from neurotic depressions, they, together with the endogenous depressives, were a severely depressed group who required hospitalization. Improvement occurred with both dosage regimens, although a greater and more consistent improvement was noted in the 300-mg group than in the 150-mg group. There were a few differences between the response of the endogenous and that of the neurotic depressives, as assessed by the physician and self-rating scales. However, endogenous depressives who received 150 mg were overrepresented in the treatment failure group. A comparison of the response of deluded and nondeluded depressives indicated that the deluded patients responded less well than the nondeluded depressives, although half of the delusional group did respond to the treatment. References 1. Morris JB, Beck AT: The efficacy of antidepressant drugs: A review of research (1958 to 1972) . Arch Gen Psychiatry 30:667-674, 1974.Crossref 2. Nodine JH, Siegler PE, Bodi T, et al: A variable dose phase 3, human bioassay of nortriptyline . Am J Med Sci 250:443-447, 1965.Crossref 3. Nies A, Robinson DS, Lamborn D, et al: The efficacy of the MAO inhibitor phenelzine: Dose effects and prediction of response. Read before the Ninth Congress of the Collegium Internationale Neuropsychopharmacologicum, Paris, 1974. 4. Hamilton M: Development of a rating scale for primary depressive illness . Br J Soc Clin Psychiatry 6:278-296, 1967.Crossref 5. Zung WWK: A self-rating depression scale . Arch Gen Psychiatry 12:63-70, 1965.Crossref 6. Kellner R, Sheffield BF: A self-rating scale of distress . Psychol Med 3:88-100, 1973.Crossref 7. Winer BJ: Statistical Principles and Experimental Design , ed 2. New York, McGraw-Hill Book Co Inc, 1971, p 564. 8. Clinical trial of the treatment of depressive illness, Medical Research Council . Br Med J 1:881-886, 1965.Crossref 9. Friedman C, Mowbray MS, Hamilton VJ: Imipramine (Tofranil) in depressive states . J Ment Sci 107:948-953, 1961. 10. Hordern A, Holt NF, Burt CG, et al: Amitriptyline in depressive states: Phenomenology and prognostic considerations . Br J Psychiatry 109:815-825, 1963.Crossref 11. Glassman AH, Kantor SJ, Shostak M: Depression, delusions and drug response . Am J Psychiatry 132:716-719, 1975.

Sathananthan, Gregory L.;Gershon, Samuel;Almeida, Manny;Spector, Neil;Spector, Sidney

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090099009pmid: 962493

Abstract • This study measured the levels of imipramine hydrochloride and desipramine hydrochloride (desmethylimipramine) in the plasma and cerebrospinal fluid (CSF) in 11 depressed patients. The oral doses correlated significantly with the plasma levels irrespective of different diagnostic categories. The CSF levels varied significantly. In the endogenous depressive group the CSF levels were significantly higher in responders as compared to nonresponders. The CSF levels of the nonresponders in the endogenous depressive group, and of both responders and nonresponders in the schizo-affective groups, were similar. References 1. Yates CM, Todrick A, Tait AC: Aspects of clinical chemistry of desmethylimipramine in man . J Pharm Pharmacol 15:432-439, 1963.Crossref 2. Walters CJS: Clinical significance of plasma imipramine levels . Proc R Soc Med 64:282-285, 1971. 3. Asberg M, Cronholm B, Sjoqvist F, et al: Correlation of subjective side effects of plasma concentration of nortriptyline . Br Med J 4:18-21, 1970.Crossref 4. Asberg M, Cronholm B, Sjoqvist F, et al: Relationship between plasma level and therapeutic effect of nortriptyline . Br J Med 3:331-334, 1971.Crossref 5. Kragh-Sorensen P, Hansen CE, Asberg M: Plasma levels of nortriptyline in treatment of endogenous depression . Acta Psychiatr Scand 49:444-456, 1973.Crossref 6. Braithwaite RA, Goulding R, Theano G, et al: Plasma concentration of amitriptyline and clinical response . Lancet 1:1279-1300, 1972. 7. Burrows GD, Davis B, Scoggins BA: Plasma concentration of nortriptyline and clinical response in depressive illness . Lancet 2:619-623, 1972.Crossref 8. Glassman AH, Hurwic MJ, Perel JM: Plasma binding of imipramine and clinical outcome . Am J Psychiatry 130:1367-1369, 1973. 9. Moody JP, Tait AC, Todrick A: Plasma levels of imipramine and desmethylimipramine during therapy . Br J Psychiatry 113:183-193, 1967.Crossref 10. Slater E, Roth M: Clinical Psychiatry , ed 3. London, Baillere Tindall & Cassell Ltd, 1969. 11. Spector S, Almeida M, Spector N: Radioimmunoassay for desmethylimipramine . Psychopharmacol Commun 1:421-429, 1975. 12. Winer BJ: Statistical Principles in Experimental Design . New York, McGraw-Hill Book Co Inc, 1962.

Weissman, Myrna M.;Bothwell, Sallye

1976 Archives of General Psychiatry

doi: 10.1001/archpsyc.1976.01770090101010pmid: 962494

Abstract • Current emphasis on early case finding, outpatient care, and on longitudinal studies of asymptomatic patients has focused attention on the community adjustment of psychiatric patients. Thus, simple and inexpensive methods such as self-report scales, which allow the routine assessment of patient adjustment, are potentially useful. The derivation and testing of such a method, the Social Adjustment Scale Self-Report, is described. This scale covers the patient's role performance, interpersonal relationships, friction, feelings and satisfaction in work, and social and leisure activities with the extended family, as a spouse, parent, and member of a family unit. Self-report results based on 76 depressed outpatients were comparable to those obtained from relatives as well as by a rater who interviewed the patient directly. References 1. Weissman MM, Paykel ES: The Depressed Woman: A Study of Social Relationships . Chicago, University of Chicago Press, 1974. 2. Gurland BJ, Yorkston NJ, Stone AR, et al: The Structured and Scaled Interview to Assess Maladjustment (SSIAM): I. Description, rationale, and development . Arch Gen Psychiatry 27:259-264, 1972.Crossref 3. Gurland BJ, Yorkston NJ, Goldberg K, et al: The Structured and Scaled Interview to Assess Maladjustment (SSIAM): II. Factor analysis, reliability, and validity . Arch Gen Psychiatry 27:264-267, 1972.Crossref 4. Katz MM, Itil TM: Video methodology for research in psychopathology and psychopharmacology . Arch Gen Psychiatry 31:204-210, 1974.Crossref 5. Shopsin B, Gershon S, Thompson H, et al: Psychoactive drugs in mania: A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol . Arch Gen Psychiatry 32:34-42, 1975.Crossref 6. Klerman GL: Clinical research in depression . Arch Gen Psychiatry 24:305-319, 1971.Crossref 7. Weissman MM, Klerman GL, Paykel ES, et al: Treatment effects on the social adjustment of depressed patients . Arch Gen Psychiatry 30:771-778, 1974.Crossref 8. Weissman MM: The assessment of social adjustment: A review of techniques . Arch Gen Psychiatry 32:357-365, 1975.Crossref 9. Katz MM, Lyerly SB: Methods of measuring adjustment and social behavior in the community: I. Rationale, description, discriminating validity and scale development . Psychol Rep 13:503-535, 1963.Crossref 10. Clark AW: The personality and social network adjustment scale . Hum Relations 21:85-96, 1968.Crossref 11. Burnes AJ, Roen SR: Social roles and adaptation to the community . Community Ment Health J 3:153-158, 1967.Crossref 12. Ellsworth RB, Clayton W: Measurement of improvement in mental illness . J Consult Clin Psychol 23( (suppl 1) ):15-20, 1959.Crossref 13. Rice CE, Berger DG, Sewall LG, et al: Measuring social restoration performance of public psychiatric hospital . Public Health Rep 76:437-446, 1961.Crossref 14. Paykel ES, Weissman M, Prusoff BA, et al: Dimensions of social adjustment in depressed women . J Nerv Ment Dis 152( (suppl 3) ):158-172, 1971.Crossref 15. Wiggins JS: Personality and Prediction: Principles of Personality Assessment . Boston, Addison-Wesley Publishing Co Inc, 1973, p 290. 16. Hogarty J: Informant rating of community adjustment, in Waskow IE, Parloff MB (eds): Psychotherapy Change Measures: Report of Clinical Research Branch, National Institute of Mental Health, Outcome Measures Project, publication 8DM74-120. US Government Printing Office, 1973.