There have been many hundreds of studies which have examined the efficacy of different forms of treatment of psychiatric disorders over the past 40 years. This paper presents some background to these studies for statisticians, illustrating and discussing some of the difficult problems which arise in this specialty of medicine. It also demonstrates a major requirement for statisticians to influence both the design and presentation of clinical trials and provides some suggestions about how this may be done.
Get full access to this article
View all access options for this article.
References
1.
1 Sargant W. Antidepressant drugs [Letter]. British Medical Journal1965; i: 1495-1495.
2.
2 Report to the Medical Research Council by its Clinical Psychiatry Committee. Clinical trial of the treatment of depressive illness. British Medical Journal1965; i: 881-886.
3.
3 Sargant W. On chemical tranquilizers. British Medical Journal1956; i: 939-943.
4.
4 West ED, Fernandes da Fonseca A. Controlled trial of meprobamate. British Medical Journal1956; ii: 1206-1209.
5.
5 Hill AB. Reflections on the controlled trial. Annals of Rheumatic Diseases1966; 25: 107-113.
6.
6 Staudt VM, Zubin J. A biometric evaluation of the somatotherapies in schizophrenia. Psychological Bulletin1957; 54: 171-196.
7.
7 Cole JO, Ross S, Bouthilet L. Improvement of clinical drug evaluation reports. In: Kline NS ed. Psychopharmacology frontiers. London: Churchill, 1959: 217-231.
8.
8 Letemendia FJJ. Clinical trials in psychiatry. In: Richter D ed. Aspects of psychiatric research. London: Oxford University Press, 1962: 384-400.
9.
9 Sainsbury P, Kreitman N eds. Methods of psychiatric research: an introduction for clinical psychiatrists, 2nd edition. London: Oxford University Press, 1975.
10.
10 Tyrer P. The basis of drug treatment in psychiatry. In: Hill P, Thorley A, Murray R eds. Essentials of postgraduate psychiatry. London: Academic Press, 1979: 627-647.
11.
11 Metzler CM, Schooley GL. Design and analysis of clinical trials of psychoactive drugs. In: Buncher CR, Tsay J-Y eds. Statistics in the pharmaceutical industry. New York: Marcel Dekker, 1981: 157-187.
12.
12 Tyrer P. Clinical trials. In: Bean P ed. Mental illness: changes and trends. Chichester: John Wiley, 1983: 179-193.
13.
13 King PR. Methodological guidelines for reading drug-evaluation research. Canadian Journal of Psychiatry1984; 29: 575-582.
14.
14 Hirsch SR, Macrae KD. Essential elements in the design of clinical trials. In: Bradley PB, Hirsch SR eds. The psychopharmacology and treatment of schizophrenia. Oxford: Oxford Universty Press, 1986.
15.
15 Kraemer HC, Pruyn JP, Gibbons RD, Greenhouse JB, Grochocinski VJ, Waternaux C, Kupfer DJ. Methodology in psychiatric research: report on the 1986 MacArthur Foundation Network I Methodology Institute. Archives of General Psychiatry1987; 44: 1100-1106.
16.
16 Newcombe RG. Evaluation of treatment effectiveness in psychiatric research. British Journal of Psychiatry1988; 152: 696-697.
17.
17 Hirsch SR, Barnes TRE. Testing the efficacy of new neuroleptic drugs. In: Benkert O, Maier W, Rickels K eds. Methodology of the evaluation of psychotropic drugs. Berlin: Springer, 1990: 26-36.
18.
18 Streiner DL. Sample size and power in psychiatric research. Canadian Journal of Psychiatry1990; 35: 616-620.
19.
19 Leber P. The future of controlled clinical trials. Psychopharmacology Bulletin1991; 27: 3-8.
20.
20 Kraemer HC. To increase power in randomized clinical trials without increasing sample size. Psychopharmacology Bulletin1991; 27: 217-224.
21.
21 Freeman C, Tyrer P eds. Research methods in psychiatry: a beginner's guide, 2nd edition. London: Royal College of Psychiatrists, 1992.
22.
22 Fava M, Rosenbaum JR eds. Research designs and methods in psychiatry. New York: Elsevier, 1992.
23.
23 Fava M. Traditional and alternative research designs and methods in clinical pediatric psychopharmacology. Journal of the American Academy of Child and Adolescent Psychiatry1996; 34: 1292-1303.
24.
24 Piper WE. Psychotherapy research in the 1980s: defining areas of consensus and controversy. Hospital and Community Psychiatry1988; 39: 1055-1063.
25.
25 Stephenson J, Imrie J. Why do we need randomised controlled trials to assess behavioural interventions?British Medical journal1998; 316: 611-613.
26.
26 Loeb C, Gandolfo C. Methodological problems of clinical trials in multi-infarct dementia. Neuroepidemiology1990; 9: 223-227.
27.
27 Swash M, Brooks DN, Day NE, Frith CD, Levy R, Warlow CP. Clinical trials in Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry1991; 54: 178-181.
28.
28 Berrios GE, Freeman H eds. 150 Years of British psychiatry, 1841-1991. London: Royal College of Psychiatrists, 1991.
29.
29 Stafford-Clark D. Psychiatry to-day, 2nd edition. Harmondsworth: Penguin, 1963.
30.
30 Edwardson, PL.Psychiatry. In: Microsoft encarta 96 encyclopedia. Seattle, WA: Microsoft Corporation, 1993-95.
31.
31 Blashfield RK, Draguns JG. Toward a taxonomy of psychopathology: the purpose of psychiatric classification. British Journal of Psychiatry1976; 129: 574-583.
32.
32 Sara G, Raven P, Mann A. A comparison of DSM-III-R and ICD-10 personality disorder criteria in an out-patient population. Psychological Medicine1996; 26: 151-160.
33.
33 Kendell RE. The classification of depressions: a review of contemporary confusion. British Journal of Psychiatry1976; 129: 15-28.
34.
34 Maj M. Critique of the DSM-IV operational diagnostic criteria for schizophrenia. British Journal of Psychiatry1998; 172: 458-460.
35.
35 World Health Organisation. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization, 1992.
36.
36 World Health Organization. The ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. Geneva: World Health Organization, 1993.
37.
37 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). Washington, DC: American Psychiatric Association, 1994.
38.
38 American Psychiatric Association. Quick reference to the diagnostic criteriafrom DSM-IV. Washington, DC: American Psychiatric Association, 1994.
39.
39 Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur RA, Munoz R. Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry1972; 26: 57-63.
40.
40 Spitzer RL, Endicott J, Robins E. Research diagnostic criteria: rationale and reliability. Archives of General Psychiatry1978; 35: 773-782.
41.
41 Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study. Lancet1997; 349: 1269-1276.
42.
42 Murray CJL, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet1997; 349: 1436-1442.
43.
43 Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet1997; 349: 1498-1504.
44.
44 ABC of mental health. British Medical journal. Common mental health problems in primary care 1997; 314: 1609-12; Common mental health problems in hospital 1997; 314: 1679-81; Mental health emergencies 1997; 314: 1740-42; Community mental health services 1997; 314: 1817-20; Anxiety 1997; 314: 1886-89; Depression 1997; 315: 43-46; Schizophrenia 1997; 315: 108-11; Disorders of personality 1997; 315: 176-79; Psychosexual problems 1997; 315: 239-42; Addiction and dependence–I: illicit drugs 1997; 315: 297-300,–II: alcohol 1997; 315: 358-60; Mental health in old age 1997; 315: 413-17; Mental health in a multiethnic society 1997; 315: 473-76; Mental health on the margins 1997; 315: 536-39; Mental health and the law 1997; 315: 590-592.
45.
45 Weatherall DJ, Ledingham JGG, Warrell DA eds. Oxford textbook of medicine, 3rd edition. Oxford: Oxford University Press, 1996.
46.
46 Gelder MG, Gath DH, Mayou R. Oxford textbook of psychiatry, 3rd edition. Oxford: Oxford University Press, 1996.
47.
47 Marholin D, Phillips D. Methodological issues in psychopharmacological research: chlorpromazine–a case in point. American Journal of Orthopsychiatry1976; 46: 477-495.
48.
48 Pathare SR, Paton C. ABC of mental health: psychotropic drug treatment. British Medical journal1997; 315: 661-664.
49.
49 Blackwell B. Treatment adherence. British Journal of Psychiatry1976: 129: 513-531.
50.
50 Richardson P. ABC of mental health: psychological treatments. British Medical journal1997; 315: 733-735.
51.
51 Tillett R. Psychotherapy assessment and treatment selection. British Journal of Psychiatry1996; 168: 10-15.
52.
52 Conte HR, Plutchik R, Wild KV, Karasu TB. Combined psychotherapy and pharmacotherapy for depression. Archives of General Psychiatry1986; 43: 471-479.
53.
53 Tibbetts RW, Hawkings JR. The placebo response. Journal of Mental Science1956; 102: 60-66.
54.
54 Black AA. Factors predisposing to a placebo response in new out-patients with anxiety states. British Journal of Psychiatry1966; 112: 557-567.
55.
55 Brody H. Placebos and the philosophy of medicine: clinical, conceptual, and ethical issues. Chicago, IL: University of Chicago Press, 1980.
56.
56 Sanford RL, Schmitz TH. The wonders of placebo. In: Buncher CR, Tsay J-Y eds. Statistics in the pharmaceutical industry. New York: Marcel Dekker, 1981: 231-250.
57.
57 Grunbaum A. The placebo concept in medicine and psychiatry. Psychological Medicine1986; 16: 19-38.
58.
58 Shepherd M. The placebo: from specificity to the non-specific and back. Psychological Medicine1993; 23: 569-578.
60 Brown WA. The placebo effect. Scientific American1998; 278: 68-73.
61.
61 Gribbin M. Placebos: cheapest medicine in the world. New Scientist1981; 8 Jan: 64-65.
62.
62 Senn S. Regression to the mean. Statistical Methods in Medical Research1997; 6: 99-183.
63.
63 McDonald CJ, Mazzuca SA. How much of the placebo effect is really regression to the mean. Statistics in Medicine1983; 2: 417-427.
64.
64 Ernst E, Resch KL. Concept of true and perceived placebo effects. British Medical journal1995; 311: 551-553.
65.
65 de Craen AJM, Roos PJ, de Vries AL, Kleijnen J. Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness. British Medicaljournal1996; 313: 1624-1626.
66.
66 Streiner DL, Norman GR. Health measurement scales: a practical guide to their development and use, 2nd edition. Oxford: Oxford University Press, 1995.
67.
67 Royal College of Psychiatrists. Psychiatric instruments and rating scales: a select bibliography. Occasional Paper OP23. London: Royal College of Psychiatrists, 1994.
68.
68 McDowell I, Newell C. A guide to rating scales and questionnaires, 2nd edition. Oxford: Oxford University Press, 1996.
69.
69 Hamilton M. The role of rating scales in psychiatry. Psychological Medicine1976; 6: 347-349.
70.
70 Garside RF. The comparative value of types of rating scale. British Journal of Clinical Pharmacology1976; supplement: 61-67.
71.
71 Moller H-J. Outcome criteria in antidepressant drug trials: self-rating versus observer-rating scales. Pharmacopsychiatry1991; 24: 71-75.
72.
72 Lader M. The clinical assessment of depression. British Journal of Clinical Pharmacology1981; 1: 5-14.
73.
73 Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry1960; 23: 56-62.
74.
74 Hamilton M. Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology1967; 6: 278-296.
75.
75 Hedlund JL, Vieweg BW. The Hamilton rating scale for depression: a comprehensive review. Journal of Operational Psychiatry1979; 10: 149-165.
76.
76 Snaith RP. Present use of the Hamilton depression rating scale: observations on method of assessment in research of depressive disorders. British Journal of Psychiatry1996; 168: 594-597.
77.
77 Foulds GA. Clinical research in psychiatry. Journal of Mental Science1958; 104: 259-265.
78.
78 Laties VG, Weiss B. A critical review of the efficacy of meprobamate (miltown, equanil) in the treatment of anxiety. Journal of Chronic Diseases1958; 7: 500-519.
79.
79 Heilizer F. A critical review of some published experiments with chlorpromazine in schizophrenic, neurotic, and normal humans. Journal of Chronic Diseases1960; 11: 102-148.
80.
80 Fox B. The investigation of the effects of psychiatric treatment. Journal of Mental Science1961; 107: 493-502.
81.
81 Glick BS, Margolis R. A study of the influence of experimental design on clinical outcome in drug research. American Journal of Psychiatry1962; 118: 1087-1096.
82.
82 Glick BS. Inadequacies in the reporting of clinical drug research. Psychiatry Quarterly1963; 17: 234-244.
83.
83 Wechsler H, Grosser GH, Greenblatt M. Research evaluating antidepressant medications on hospitalized mental patients: a survey of published reports during a five-year period. Journal of Nervous and Mental Disease1965; 141: 231-239.
84.
84 Smith A, Traganza E, Harrison G. Studies on the effectiveness of antidepressant drugs. Psychopharmacology Bulletin1969; 40(suppl): 1-21.
85.
85 Solomon K, Hart R. Pitfalls and prospects in clinical research on antianxiety drugs: benzodiazepines and placebo–a research review. Journal of Clinical Psychiatry1978; 39: 823-831.
86.
86 Dubois-Brillet AM, Guelfi JD. Essais therapeutiques en psychiatrie: evolution recente de la methodologie en France. La Nouvelle Presse Medicale1979; 8: 677-682.
87.
87 Tweardy DJ, Bishop YMM, Donner AP et al. Critique of randomized trials: lithium maintenance therapy of manic depressive disorder. In: Rosenoer VM, Rothschild M eds. Controversies in clinical care. New York: Spectrum, 1981: 25-36.
88.
88 Kane JM, Lieberman J. The efficacy of amoxapine, maprotiline, and trazodone in comparison to imipramine and amitriptyline: a review of the literature. Psychopharmacology Bulletin1984; 20: 240-249.
89.
89 Edlund MJ, Overall JE, Rhoades HM. Beta, or type II error in psychiatric controlled clinical trials. Journal of Psychiatric Research1985; 19: 563-567.
90.
90 Gerson SC, Plotkin DA, Jarvik LF. Antidepressant drug studies, 1964 to 1986: empirical evidence for aging patients. Journal of Clinical Psychopharmacology1988; 8: 311-322.
91.
91 Ekstrom MA, Quade D, Golden RN. Statistical analysis of repeated measures in psychiatric research. Archives of General Psychiatry1990; 47: 770-772.
92.
92 King PR. Appraising the quality of drugevaluation research: II. A methodological review procedure for prophylactic treatment trials. Journal of Clinical Psychopharmacology1990; 10: 22-26.
93.
93 Collins EJ, Hogan TP, Nuttall SE. Methodological standards in schizophrenia research: a critical survey of clinical trials. International Journal of Methods in Psychiatric Research1992; 2: 111-116.
94.
94 Stern RG, Schmeidler J, Davidson M. Limitations of controlled augmentation trials in schizophrenia. Biological Psychiatry1997; 42: 138-143.
95.
95 Bielski RJ, Friedel RO. Prediction of tricyclic antidepressant response: a critical review. Archives of General Psychiatry1976; 33: 1479-1489.
96.
96 Overall JE, Hollister LE, Dalal SN. Psychiatric drug research. Archives of General Psychiatry1967; 16: 152-161.
97.
97 Freiman JA, Chalmers TC, Smith H, Kuebler R. The importance of beta, the type II error and sample size, in the design and interpretation of the randomized trial. New England Journal of Medicine1978; 299: 690-694.
98.
98 Pulver AE, Bartko JJ, McGrath JA. The power of analysis: statistical perspectives: part 1. Psychiatry Research1988; 23: 295-299.
99.
99 Hemminki E, Falkum E. Psychotropic drug registration in the Scandinavian countries: the role of clinical trials. Social Science and Medicine1980; 14A: 547-559.
100.
100 May PRA. Treatment of schizophrenia: I. A critique of reviews of the literature. Comprehensive Psychiatry1974; 15: 179-185.
101.
101 May PRA, Van Putten T. Treatment of schizophrenia: II. A proposed rating scale of design and outcome for use in literature surveys. Comprehensive Psychiatry1974; 15: 267-275.
102.
102 May PRA. Schizophrenia: evaluation of treatment methods. In: Freedman AM, Kaplan HI, Sadock BJ eds. Comprehensive textbook of psychiatry, 2nd edition. Baltimore, MD: Williams & Wilkins, 1975: 955-982.
103.
103 Hokanson JA, Bryant SG, Gardner R, Luttman DJ, Guernsey BG, Bienkowski AC. Spectrum and frequency of use of statistical techniques in psychiatric journals. American Journal of Psychiatry1986; 143: 1118-1125.
104.
104 Ling W, Charuvastra C, Kaim SC, Klett CJ. Methadyl acetate and methadone as maintenance treatments for heroin addicts. Archives of General Psychiatry1976; 33: 709-720.
105.
105 Lipman RS, Covi L, Rickels K et al. Imipramine and chlordiazepoxide in depressive and anxiety disorders. Archives of General Psychiatry1986; 43: 68-77.
106.
106 Roth M, Mountjoy CG, Amrein R and the International Collaborative Study Group. Moclobemide in elderly patients with cognitive decline and depression. British Journal of Psychiatry1996; 168: 149-157.
107.
107 Sass H, Soyka M, Mann K, Zieglgansberger W. Relapse prevention by acamprosate. Archives of General Psychiatry1996; 53: 673-680.
108.
108 Thase ME, Fava M, Halbreich U et al. A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. Archives of General Psychiatry1996; 53: 777-784.
109.
109 Zohar J, Judge R and the OCD Paroxetine Study Investigators. Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. British Journal of Psychiatry1996; 169: 468-474.
110.
110 Peuskens J on behalf of the Risperidone Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multinational, multi-centre, double-blind, parallelgroup study versus haloperidol. British Journal of Psychiatry1995; 166: 712-726.
111.
111 Hopkins CE. Psychiatry, science, and statistics–a review of current trends. Psychiatric Quarterly1956; 30: 1-14.
112.
112 Altman DG. The scandal of poor medical research. British Medical Journal1994; 308: 283-284.
113.
113 White SJ. Statistical errors in papers in the British Journal of Psychiatry. British journal of Psychiatry1979; 135: 336-342.
114.
114 McGuigan SM. The use of statistics in the British Journal of Psychiatry. British journal of Psychiatry1995; 167: 683-688.
115.
115 Altman DG, Gore SM, Gardner MJ, Pocock SJ. Statistical guidelines for contributors to medical journals. British Medical Journal1983; 286: 1489-1493.
116.
116 Begg C, Cho M, Eastwood S et al. Improving the quality of reporting of randomized controlled trials: the CONSORT statement. Journal of the American Medical Association1996: 276: 637-639.
117.
117 Greenfield T ed. Research methods: guidance for postgraduates. London: Arnold, 1996.
118.
118 Everitt BS. The analysis of repeated measures: a practical review with examples. The Statistician1995; 44: 113-135.
