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SSRIS: DO THEY CAUSE SUICIDE? Yolande Lucire PhD, MB BS DPM FRANZCP School of Rural Health, Albury NSW Forensic Psychiatrist. Woollahra Sydney Antidepressants form two major groupings: New SSRIs and older TCAs, which I’ll call Tricyclics SSRIs act on Serotonin and have profound effects. They are capable of changing people profoundly and not always for the best. Contrary to popular opinion, there is no scientific evidence that serotonin is abnormal in depression. Having more of it floating around makes for a lot of change. SSRIs (the Accused) TCAs (the Comparator) Prozac Zoloft Aropax Efexor Cipramil Lexapro Luvox Tryptanol Tofranil Prothiaden Sinequan For the purpose of a 20 minute presentation, I am grouping the drugs that act on serotonin together and calling them SSRIs, although some are SSRIs and some are SNRIs and others have mixed actions. For the purpose at hand, suicide induction or completed suicide they all have a similar profile, with the more energising ones possibly more heavily implicated. Suicide is the measurable tip of an iceberg of disturbance violence and disturbance, and may have come about in a variety of ways. Similarly the TCA are not only tricyclics but tetracyclics and some atypical ones, in general not having an action on serotonin. Caution: Do not stop taking an antidepressant without medical supervision. Complications occur on starting, stopping and with irregular dosing. Withdrawal can start up to four weeks after stopping the drug and can go on for three months Complications include agitation, mania, psychosis and self harm and suicide and violence and homicide. International Journal of Risk & Safety in Medicine 16 (2003/2004) 31–49 31 IOS Press Suicidality, violence and mania caused by selective serotonin reuptake inhibitors (SSRIs): A review and analysis * Peter R. Breggin 101 East State Street, No. 112, Ithaca, NY 14850, USA Abstract: Recognition of these adverse drug reactions and withdrawal from the offending drugs can prevent misdiagnosis and the worsening of potentially severe iatrogenic disorders. These findings also have forensic application in criminal, malpractice, and product liability cases. Evidence from many sources confirms that selective serotonin reuptake inhibitors (SSRIs) commonly cause or exacerbate a wide range of abnormal mental and behavioral conditions. These adverse drug reactions include the following overlapping clinical phenomena: a stimulant profile that ranges from mild agitation to manic psychoses, agitated depression, obsessive preoccupations that are alien. The possibility that a drug was causing the effects it was supposed to cure was unthinkable, especially by clinicians. But it is accepted: SSRI-induced akathisia is in the latest Diagnostic and Statistical Manual, the ever expanding list of mental disorders. DSM How common is it? A 2001: Yale: 8% of patients admitted ‘may suffer’ from SSRI-induced mania or psychosis. Higher levels of prescribing in OZ and including agitation, suicidal thoughts and attempts, its more like 20%. Preda A, MacLean RW, Mazure CM, Bowers MB (2001). Antidepressant associated mania and psychosis resulting in psychiatric admission. J Clinical Psychiatry 62, 30-33 I will give you Daubert competent science. Science that has passes 6 Daubert Hearings. Scientific (as opposed to opinion) evidence is the only kind of expert evidence admissible in American and Australian courts Scientific evidence that SSRIs cause: Suicidal thinking Suicidal acts Completed suicide. The 1993 US Supreme Court Decision in Daubert v. Merrell Dow Pharmaceuticals altered the criteria by which scientific testimony is admitted as evidence in court. The unanimous ruling states that the criterion of the scientific status of a theory is that it can be tested, refuted and falsified. Scientific method is based on generating a null hypothesis, a conjecture that something does not exist, and testing it to see if it you can prove the contrary. The unicorn does not exist. The prisoner is not guilty. These are respectively good science and good law Disproving the negative differentiates science from other forms of inquiry William Daubert, et ux., etc., et al., Petitioners v. Merrell Dow Pharmaceuticals, The null hypothesis is: SSRIs DO NOT CAUSE SUICIDE We need to watch two numbers RELATIVE RISK RR SUICIDE RATE /100,000 And the range, which is the CONFIDENCE INTERVAL CI indicating reliability A Relative Risk, RR, is how many more times SUICIDE and its precursors THINKING OF SUICIDE AND SUICIDAL ATTEMPTS occur in SSRI-TREATED PATIENTS over and above those treated with a Tricyclic or not treated at all. If a medicine saves some depressed patients from committing suicide, the RR between that medicine and no treatment should be less than 1. Tricyclics generally had an RR of 0.5 against no treatment, in “hospital” depressions, in which suicides were a known risk. Tricyclics halved the number of suicides in a seriously depressed population. Tricyclics were known to cause suicide by energising the depressed, but RR was still favourable. If the relative risk equals 1.0, the risk in treated individuals is the same as the risk in untreated ones. If the relative risk is more than 1.0, the risk in treated is greater than in untreated. As we are trying to prevent suicide, an RR of 1 would be ominous. Eli Lilly (Prozac) Pfizer (Zoloft) and GSK (Aropax) proposed in 1999, the cut off point of SIGNIFICANCE, Relative Risk, RR, be 2.0. Ridiculously HIGH by any standard. Corporate chutzpah. Exposure to asbestos is deemed contributory to cancer if the RR is only 1.2 which is 20% higher. Asbestos was never expected to PREVENT cancer. AN RR OF 2 IS FIVE TIMES THAT. The evidence for suicide induction can be found in many areas of research 1. 2. 3. 4. CLINICAL PSYCHIATRY Observations and mechanisms Challenge-Dechallenge-Rechallenge experiments Studies of NEW suicidal ideation, (Fava) SUICIDE EPIDEMIOLOGY SUICIDES BY PRESCRIBED DRUG JICK, UK DSRU DONOVAN POPULATION STUDIES , PRIMARY CARE HEALY AND BOARDMAN HEALTHY VOLUNTEER STUDIES RANDOM CONTROL TRIALS (RCTs) The evidence from all these sources is overwhelmingly supports a relative risk of CLINICAL PSYCHIATRY 1990 American Journal of Psychiatry. 147(2):207-10, 1990 Feb. Six developed intense, violent suicidal preoccupation after 2-7 weeks of Prozac which persisted 3 days to 3 months after Prozac was stopped. Abstract Teicher Glod and Cole. None had ever experienced a similar state . Drug companies called this ‘anecdotal’ and said “It’s the disease not the drug, doctor” Now scores of such reports, patients treated for anxiety, eating disorders,OCD and menstrual problems and children CLINICAL PSYCHIATRY Teicher and Cole (1993) delineate 9 “clinical mechanisms” by which SSRIs can induce or exacerbate suicidal tendencies by: (1) energizing depressed patients, (2) paradoxically worsening their depression , (3) inducing akathisia, (4) inducing panic attacks, (5) switching patients to mania or hypomania, (6) causing insomnia or interfering with sleep architecture (esp. with REM sleep), (7) inducing an organic obsessional state, (8) promoting personality disorder with borderline traits, (9) producing EEG or other neurological disturbances. Those at risk of suicide are agitated,in turmoil, nervous, sleepless, pacing, energized, almost manic, and they reject their obsessive suicidal thoughts as ‘strange’, ‘weird,’‘not me’. This can go on for weeks or can turn into suicide unpredictably in a matter of minutes. Teicher and Cole, 1993 Healy, Langmaak, and Savage, 1999; ’ • The traditional suicidogenic triumvirate of psychotropic drug reactions are 1) akathisia, (2) emotional blunting, also called psychic numbing “I cannot feel anything, do not care” and/or (3) psychotic decompensation Akathisia is turmoil, feeling numb as if nothing matters, and feeling one is going mad. It can happen over weeks or days, or very very quickly, in a matter of minutes. Teicher and Cole, 1993 Healy, Langmaak, and Savage, 1999; CLINICAL PSYCHIATRY 1991: Suicidal thinking (out of the blue) Fava and Rosenbaum found suicidal thinking developed in patients who had never been suicidal before, more on Prozac than on other drugs. Prozac v TCAs = RR = 2.7 Scores of reports Fava, M. & Rosenbaum, J. 1991. Suicide and 3 fluoxetine. Journal of Clinical Psychiatry, 52-5. CLINICAL PSYCHIATRY SUICIDAL ACTS 2 of 26 depressed patients overdosed in the first 2 weeks when Prozac was increased quickly. 7.6% is an extremely high rate. M. Muijen, et al., A Comparative Clinical Trial of Fluoxetine, Mianserin, and Placebo in Depressed Outpatients, Acta Psychiatrica Scandinavica, Vol. 78 (1988), pgs. 384-390). CLINICAL PSYCHIATRY Challenge-Dechallenge-Rechallenge CDR There are many Challenge-DechallengeRechallenge studies. Suicidality starts on drug, clears up when it is stopped and Reappears on re-exposure, even to another SSRI. SUICIDE EPIDEMIOLOGY: JICK Against concerns that Britain’s most popular TCA antidepressant, Prothiaden, dangerously toxic in overdose and being labeled as a ‘dirty drug by SSRI mfrs. Jick examined 172,598 persons and 1.2 million scripts for 10 antidepressants, old and new, general practice patients 143 had committed suicide. Jick S, Dean AD, Jick H (1995). Antidepressants and suicide. British Medical Journal 310: 215-218 SUICIDE EPIDEMIOLOGY : JICK Prothiaden turned out to be the safest as only 14% of suicides involved antidepressant overdose. RR of SUICIDE Prozac v all TCAs Prozac v Tofranil Prozac v Amitriptyline Prozac v Prothiaden Prozac v Lofepramine RR = RR = RR = RR = RR = 6.6 1.9 4.0 2.1 4.04 SSRI overdoses are not fatal. SSRI suicides tend to be violent: hanging, drowning, shooting, jumping, stabbing or cutting, dying on a railway, burning, electrocution, or deliberate road accidents. Jick Relative risks compared with Drug Dothiepin controls N= 823 Adj RR and CI dothiepin amitryptalin Clomipramin Cas e s N= 76 37 15 4 308 223 51 1.0 0.5 (0.3-1.0) 0.7 (0.2 to 2.0) Imipramine Flupenthixol Lofepramine Mianserin 4 6 1 5 56 49 36 41 0.5 (0.2 to 1.5) 0.9 (0.4 to 2.4) 0.2 (<0.1 to 1.7) 1.1 (0.4 to 3.2) Fluoxetine 3 18 2.1 (0.6 to 7.9) Doxepin Trazodone 1 0 19 12 0.5 (0.1 to 3.7) SUICIDE EPIDEMIOLOGY: JICK Jick was embarrassed and suggested that ‘selected’ patients may have been given Prozac, which had a high suicide rate attached. SUICIDE EPIDEMIOLOGY : DRUG SAFETY RESEARCH UNIT UK (50,000 pop.) The DSRU follows up drugs in the community it looked at completed suicides and what medicines they had been prescribed. Suicide rate on SSRIs = 219/100,000. Prozac 244/100,000 Aropax 269/100,000 Luvox 183/100,000 SUICIDE EPIDEMIOLOGY Table 8: Drug Drug Safety Research Un it Studies of SSRIs & Mirtazap ine in Primary Care in the United Kingdo m. No. Patients No. Suicides Fluoxetine Sertraline Seroxat/Paxil Fluvoxamin e 12692 12734 13741 10983 31 22 37 20 Suicides/ 100,000 Patients 244 (C.I. 168 – 340) 173 (C.I. 110 – 255) 269 (C.I. 192 – 365) 183 (C.I. 114 – 274) Total SSRIs 50150 110 219/100,000 Mirtaza pine 13,554 13 96 (C.I. 53 – 158) The suicide rate in UK prima ry care on thes e antidepressants is of the order of 200/100,000 patients. Boardman and Healy investigated 475,000 over 5 years counting all the mood disorders in all the private practices and suicide rates for these disorders SUICIDE EPIDEMIOLOGY Boardman &Healy North Staffs 467,000 X 5 Years Number of Suicides Primary Care Any Any Primary Disorder Affective Affective Primary Disorder Disorder Affective Disorder 212 180 115 41 Rate of Suicide 9/ 100,000 7.6/ 100,000 4.7/ 100,000 1.7/ 100,000 Suicide 30/ 68/ 48/ 27/ Prevalence 100,000 100,000 100,000 100,000 SUICIDE EPIDEMIOLOGY: Boardman &Healy PRIMARY CARE SUICIDE RATES All mental disorders < 27-67/100,000. Fits in with other primary care mood disorders suicide statistics Holland Sweden Antedating SSRIs Simon, von Korff Highest UK rate 30/100,000 0/100,000 30/100,000 68/100,000 Boardman AP, Healy D. Madeley suicide risk in primary care primary affective disorders. European Psychiatry. 2001; 16: 400-405. SUICIDE EPIDEMIOLOGY: DONOVAN again sought to establish the safety of SSRIs against TCAs which were toxic in overdose. Examined 222 COMPLETED SUICIDES, and the medicines they had been taking, and found SSRIs v TCA RR= 2 Donovan S, Kelleher MJ, Lambourn J, Foster R. The occurrence of suicide following the prescription of antidepressant drugs. Arch Suic Res. 1999; 5: 181-192. SUICIDAL ACTS: DONOVAN At the same time, DONOVAN looked at 2776 acts of DELIBERATE SELF HARM in 1954 persons presenting to emergency and what they were taking Aropax v Tryptanol (TCA) Prozac v Tryptanol (TCA) Zoloft v Tryptanol (TCA) Aropax v Tofranil (TCA) All SSRI v Tofranil (TCA) RR = 4.0 RR = 6.6 RR = 4.9 RR = 1.9 RR = 5.5 Donovan S, Clayton A, Beeharry M, Jones S, Kirk C, Waters K, Gardner D, Faulding J, Madely R. Deliberate self-harm and antidepressant drugs. Investigation of a possible link. Brit J Psychiatry. 2000; 177: 551-556 HEALTHY VOLUNTEERS Healy: 2 of 20 healthy volunteers suicidal on Zoloft. Healthy Volunteer Studies DRUG PUBLISHED DONE PROZAC 12 of 53 AROPAX 14 of 35 ZOLOFT 7 of 35 1 healthy volunteer suicide in an Aropax trial was not reported 2 healthy volunteers have suicided: 19 year old Traci Johnston, a healthy volunteer, suicided February 7th 2004 in a trial of Eli Lilly's new Serotonin drug - duloxetine, for incontinence aborting the trial Reported in Sydney Morning Herald Lilly had been doing clinical trials in Australia Result: You cannot set up a trial to see how many people kill themselves as a consequence of the drug you are testing It would be impossible to get insurance or ethics approval. Or informed consent? Have to make do with information we have. Emergence of antidepressant suicidality, published in 2000 in Primary Care Psychiatry (Vol. 6, No. 1). RANDOM CONTROLLED TRIALS (RCTs) SUICIDES AND SUICIDAL ACTS 2003, Khan et al. looked at BLIND CLINICAL TRIALS from 1986-90 Presented to the US Federal Drug Administration, to get SSRIs licensed. FOR 9 Serotonin ANTIDEPRESSANTS against comparators and placebos. Kahn found NO DIFFERENCE in suicides and suicidal acts between those on SSRIs or on COMPARATOR DRUGS or PLACEBOS 48,277 depressed patients participated in the trials,and 77 committed suicide. That’s a lot. Am J Psychiatry. 2003 Apr;160(4):790-2. RANDOM CONTROLLED TRIALS SSRIs had failed to demonstrate usefulness in hospital depressions. (We still give as much ECT as we ever did) so ‘hospital patients’ carrying suicide risk were not recruited into these trials. SSRIs were aimed at general practice. ‘Samples of convenience’ patients under stress, with minor disorders, The Valium using population of the 1970s With suicidal patients filtered out. In September of 2003, Healy and Whittaker re-evaluated the same, original FDA studies. They published a watershed paper in September 2003. Antidepressants and suicide: risk–benefit conundrums David Healy, MD; Chris Whitaker, MSc Healy — Department of Psychological Medicine, University of Wales College of Medicine, Hergest Unit; Whitaker — Department of Informatics, University of Wales Bangor, Bangor, United Kingdom. J Psychiatry Neurosci 2003;28(5):331-7 Whereas Kahn had coded as ‘placebo suicides’ those within 2 weeks of stopping an SSRI Healy and Whittaker recognised these 5 SUICIDES and MANY SUICIDAL ACTS AS ‘SSRI WITHDRAWAL SUICIDES’. Khan had counted suicides per number of patient years exposed to the drug, PEYs. Healy counted suicides per number of patients treated Healy argued that the risks of SSRIs resembled the risks of space travel which, mile for mile, was the safest form of transport available. But going up and coming down are the danger periods for both. But landing and re-entry occurs each time a dose is forgotten, not absorbed, taken with alcohol or if a co-prescribed medicine is added or removed. Incidence of Suicides and Attempts in Trials From FDA Medical Reviews Investigational Drug ZOLOFT Activ e comparator Placebo Placebo Was hout AROPAX Activ e comparator Placebo Placebo Was hout SERZONE Activ e comparator Placebo AVANZA Activ e comparator Placebo CIPRAMIL Placebo PROZAC Placebo Placebo Was hout EFFEXOR Placebo Patient No Suicide No Suicidal Act No Suicides & Acts as a % of Patient No 2,053 595 786 2 0 0 0 5 3 0 2 9 0 0 8 2 0 7 1 2 3 0.44% 0.17% 0.25% 40 12 3 2 1.52% 1.30% 0.54% 12 6 1 0.60% 0.63% 0.11% 1.53% 0.72% 0.61% 2.38% 1.59% 0.91% 0.00% 2,963 1151 554 3,496 958 875 2,425 977 494 4,168 691 1,427 370 3082 739 8 1 1 0 1 7 1 29 5 3 91 10 12 0 0 36 2 1.40% 0.41% Summary: Incidence of Suicides and Suicide Attempts (combined) in Antidepressant Trials From FDA Medical Reviews DRUG Suicides Suicide S/Acts Number Suicide Rate/ 100,000 Suicide and Acts % All Investigational drugs 21,556 43 232/100,000 1.28% All SSRIs 13,693 23 186/100,000 1.53% Active comparator 3,681 5 24/100,000 0.79% T otal Placebo 4,879 2 21/100,000 0.47% SSRI Trial Placebo 3,140 2 16/100,000 0.57% Healy D, Whitaker CJ (2003). Antidepressants and suicide; Risk-Benefit Conundrums. J Psychiatry & Neuroscience 28 (5) 331-339, with response by Y Lapierre 340-349. FDA TRIALS SUMMARY 26,000 subjects SUICIDE RATES ALL DRUGS SUICIDE SSRI SUICIDE PLACEBO SUICIDE = = = 232/100,000 186/100,000 64/100,000 RELATIVE RISK FDA TRIALS SUICIDE ON SSRI RR = 2.4 (CI 0.6-10.2) SUICIDAL ACT ON SSRIS RR = 2.2 (CI 1.4-3.5) S/ ACTS ON NEW ANTIDEPRESSANTS RR = 4.3 (CI 1.1-17.8) SUICIDE RATES DRUG SAFETY RESEARCH UNIT SSRI SUICIDE = 212/100,000 JICK PROZAC in first 30 days of treatment 274/100,000 PEYs PROZAC 93/100,000 SUICIDE EPIDEMIOLOGY: Boardman & Healy and many others Antedating SSRIs PRIMARY CARE SUICIDE RATES < 27-68/100,000 MAXIMUM ANY POPULATION STUDY 68/100,000 Boardman AP, Healy D. Madeley suicide risk in primary care primary affective disorders. European Psychiatry. 2001; 16: 400-405. Healy and Whittaker’s conclusion was modest: It is no longer possible to support the null hypothesis that SSRIs do not cause suicide The null hypothesis has been falsified. Any way you look at available information, clinical settings,emergency rooms, morgues, clinical trials, SSRIs as a general cause of suicide would pass the scientific standard of proof. The BMJ issued warnings on February 5 2004. FDA on March 23 Most manufacturers put on Websites on May 3, 2004. Only in USA. FDA Public Health Advisory March 22, 2004 Subject: WORSENING DEPRESSION AND SUICIDALITY IN PATIENTS BEING TREATED WITH ANTIDEPRESSANT MEDICATIONS Today the Food and Drug Administration (FDA) asked manufacturers of the following antidepressant drugs to include in their labeling a Warning statement that recommends close observation of adult and patients treated with these agents for worsening depression or the emergence of suicidality. The drugs that are the focus of this new Warning are: Prozac (fluoxetine); Zoloft (Sertraline); Paxil (paroxetine); Luvox (fluovoxamine); Celexa (citalopram); Lexapro (escitalopram); Wellbutrin (bupropion); Effexor (venlafaxine); Serzone (nefazodone); WARNING MAY 3 2004 … patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases. WARNING MAY 3 2004 Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and non-psychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers Unlike smallpox, depression has not been disappeared since a cure became available Potentially fatal complications of any treatment might be acceptable if the treated population were small, dangerously ill, at high risk the availability of a remedy has increased the diagnosis of depression a thousandfold. and lethal side effects have increased by the same multiplier. The drug manufacturers promote the medicalization of stress subsidize psychiatrists, journals, conferences. Encourage moral entrepreneurs of health who talk about cases undiagnosed, and so untreated John Merson calls this phenomenon ‘epistemic capture’: the control of knowledge by vested interests. 200/100,000 represents 1 death in 500 people treated with SSRIs in primary care. 68/100,000 v 200/100,000 A least 100 suicides per 100,000 over treatment with other drugs or non treatment. By 2003, over 28 million people had started Prozac since its launch in 1988. 6,664,960 prescriptions for SSRI written 2003 by Australian doctors. Twelve times the annual number studied by Donovan 40% of first prescriptions remain unfinished, because of side effects. PBS spends $160 million a year on SSRIs. Cui Bono? I in 500 too rare for clinicians to see. They need advice from suicide epidemiologists and statisticians. Opinion evidence is not admissible. ‘We are not convinced’ and ad hominem arguments do not get admitted as evidence. 1 in 500 is well above Rogers and Whittaker’s, 1 in 14,000 and demands a duty to warn of a catastrophic side effect. Someone has that duty. Who will tell the prescribing doctor? The manufacturers have not done so in Austrlalia. The Therapeutic Goods Administration has not issued warnings. The Federal Drug Administration in USA argues that its role is licensing drugs, not protecting the public. Psychiatrists, all clinicians, are ‘not convinced’. Some more alarming informataion has emerged from David Healy's re evaluation of the clinical trials of antipsychotic drugs presented to the FDA. It concerns commonly prescribed antipsychotic drugs The regulator, the FDA, just did not notice in the late 1980s that one in 208 or 12 in 2,500 clinical trial subjects committed suicide while Zyprexa was being trialled and only one on placebo and one on a comparator, most likely haloperidol did that. SUICIDAL ACTS IN ANTIPSYCHOTIC TRIALS DRUG PATIENT NO SUICIDES SUICIDAL ACTS Risperdal 2607 9 43 Comparator 601 1 5 Placebo 195 0 1 Zyprexa 2500 12 ?? Comparator 810 1 (2) ?? Placebo 236 0 (1) ?? Seroquel 2523 1 4 Comparator 426 0 2 Placebo 206 0 0 2194 5 20 Comparator 632 0 2 Placebo 290 0 1 Geodon 2993 6 ?? Comparator 951 1 ?? Sertindole Placebo The subject numbers are so small that relative risk cannot be calculated, but Zyprexa (Olanzepine) trials had the highest rate of suicide in clinical trial history. Suicidal Acts have not been reported Risperdal was not far behind Zyprexa. The mechanism is thought to be similar,through causing akathisia and doing these drugs synergistically with SSRIs. Doctors have not been warned. All Truth passes through Three Stages: First, it is Ridiculed... Second, it is Violently Opposed... Third, it is Accepted as being SelfEvident. Arthur Schopenhauer (1778-1860) In Friedson’s account, moral entrepreneurs in medicine are commonly part-time practitioners who crusade in health matters. The thrust of their activity is towards political power as they seek to implement measures designed to improve what they see as public health. They give press interviews and try to give testimony in court. They are often responsible for legislation. They want to place jurisdiction for their concerns in the hands of health professionals rather than leave them with society. Freidson identified lay interest groups, sometimes led by, and always including, prominent physicians, whom he described as ‘the most flamboyant moral entrepreneurs of health, untrammelled by professional dignity, crusading against the menace of a specially chosen disease, impairment or disease-producing agent’ Such moral entrepreneurs, essential players in any moral panic, are ubiquitous. Professional entrepreneurs are creating panics about the consequences of child sexual abuse, others about failing to have professionals attend immediately on persons involved in traumatic events and about depression which had become the greatest scourge of modern society. They advert to cases of undiagnosed and untreated post-traumatic stress disorder and depression, which medication would surely cure. They attribute to these evils a status of being important causes of personal failure and society’s epidemic ills. Physician moral entrepreneurs are likely to see the environment as more dangerous to health than does the layman, and to emphasise the seriousness of the health problem preoccupying them by estimating the cases probably undiagnosed and therefore untreated. They are disposed to see mental illness where the layman sees nervousness, to see illness where the layman sees variations within the broad range of normality, to see a serious problem where the layman sees only a minor one. They are biased towards the creation of sick roles and press their licence as physicians to manage the newly defined sick within their relevant speciality frameworks. In brief, the medical profession is more prone to see illness and the need for treatment than it is to see health and normality. This selective perception is both self-confirming and selfsustaining.