Why were doctors so slow to recognise antidepressant discontinuation problems? D B Double

Defeat depression campaign Five-year national campaign launched Jan 1992 by Royal College of Psychiatrists in association with Royal College of General Practitioners

Defeat depression campaign Five-year national campaign launched Jan 1992 by Royal College of Psychiatrists in association with Royal College of General Practitioners To educate health professionals and public and reduce stigma

Defeat depression campaign Door-to-door survey of public opinion before the campaign started

Defeat depression campaign Door-to-door survey of public opinion before the campaign started Most of the sample (78%) thought that antidepressants were addictive

Defeat depression campaign Patients should be informed clearly when antidepressants are first prescribed that discontinuing treatment in due course will not be a problem

Warning in British National Formulary since 1990 Symptoms may occur if an antidepressant is stopped suddenly after regular administration for 8 weeks or more.

Warning in British National Formulary since 1990 Symptoms may occur if an antidepressant is stopped suddenly after regular administration for 8 weeks or more. Case reports of discontinuation reactions have appeared since antidepressants were first introduced

Serotonin specific reuptake inhibitors (SSRIs) New class of antidepressants introduced into the market in 1987

Serotonin specific reuptake inhibitors (SSRIs) New class of antidepressants introduced into the market in 1987 Discontinuation symptoms only recognised after the SSRIs had been in widespread clinical use for several years

Recognition of antidepressant discontinuation reactions Consensus meeting sponsored by Eli Lilly in Phoenix, Arizona, at end of 1996

Recognition of antidepressant discontinuation reactions Consensus meeting sponsored by Eli Lilly in Phoenix, Arizona, at end of 1996 Preventable and simple to treat (BMJ editorial 1998)

Recognition of antidepressant discontinuation reactions Discontinuation symptoms are common (Letter to Lancet 2000)

Recognition of antidepressant discontinuation reactions Discontinuation symptoms are common (Letter to Lancet 2000) GlaxoSmithKline dropped its insistence that paroxetine is not addictive in 2003

NICE guideline for depression 2004 All patients prescribed antidepressants should be informed that discontinuation/ withdrawal symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug.

Nature of antidepressant discontinuation reactions No accepted definition of an antidepressant discontinuation syndrome

Nature of antidepressant discontinuation reactions No accepted definition of an antidepressant discontinuation syndrome Commonly seen as related to re-regulation of receptors and transporters

Psychological dependence Negative affect experienced in absence of the drug

Psychological dependence Negative affect experienced in absence of the drug People may form attachments to their medications more because of what they mean to them than what they do

Psychological dependence Patients often stay on medications, maybe several at once, even though their actual benefit is questionable

Psychological dependence Patients often stay on medications, maybe several at once, even though their actual benefit is questionable Any change threatens an equilibrium related to a complex set of meanings that their medications have acquired

Doctor does not know best A drug which is thought to improve mood is likely to be habit forming, so however much the medical profession may declare that antidepressants are not primarily reinforcing like psychostimulants, the public understands that there may be problems discontinuing antidepressants

Reasons for defensiveness about discontinuation problems (1) Doctors concentrate on short-term rather than long-term treatment

Reasons for defensiveness about discontinuation problems (1) Doctors concentrate on short-term rather than long-term treatment (2) Doctors focus on neurobiological rather than psychosocial factors

Reasons for defensiveness about discontinuation problems (1) Doctors concentrate on short-term rather than long-term treatment (2) Doctors focus on neurobiological rather than psychosocial factors (3) Doctors are biased about the effectiveness of medication

(1) Doctors concentrate on short- term rather than long-term treatment Medication is often prescribed in life crises reinforcing defensive mechanisms against overwhelming anxiety

(1) Doctors concentrate on short- term rather than long-term treatment Medication is often prescribed in life crises reinforcing defensive mechanisms against overwhelming anxiety Power of placebo should be recognised

(1) Doctors concentrate on short- term rather than long-term treatment We all want a simple, quick, cheap, painless, and complete cure.

(1) Doctors concentrate on short- term rather than long-term treatment We all want a simple, quick, cheap, painless, and complete cure. People express reluctance to take drugs, but an inability to be free of them

(1) Doctors concentrate on short- term rather than long-term treatment There is nothing men will not do … to recover their health and save their lives. They have submitted to be half drowned in water, … half choked with gases, … buried up to their chins in earth, … seared with hot irons like galley slaves, … have needles thrust into their flesh, and bonfires kindled on their skin, to swallow all sorts of abominations, and to pay for all this, as if blisters were a blessing and leeches were luxury. What more can be asked to prove their honesty and sincerity? Oliver Wendell Holmes (1842)

(1) Doctors concentrate on short- term rather than long-term treatment Mean duration of trials in NICE analysis of SSRIs vs placebo = 6.75 weeks

(1) Doctors concentrate on short- term rather than long-term treatment Mean duration of trials in NICE analysis of SSRIs vs placebo = 6.75 weeks Episodic nature of depression means that episodes seem easy to treat

(1) Doctors concentrate on short- term rather than long-term treatment Discontinuation trials of antidepressants have a substantial relapse rate (92% to 36%)

(1) Doctors concentrate on short- term rather than long-term treatment Discontinuation trials of antidepressants have a substantial relapse rate (92% to 36%) Long term prognosis in depression is not good – only 1 / 5 th recovered after 15 years

(1) Doctors concentrate on short- term rather than long-term treatment Distinguishing discontinuation reaction from true relapse is not always clear-cut

(1) Doctors concentrate on short- term rather than long-term treatment Distinguishing discontinuation reaction from true relapse is not always clear-cut Expectations are as likely to play a role in discontinuing medication, producing a nocebo reaction

(1) Doctors concentrate on short- term rather than long-term treatment Some evidence that people treated without antidepressants may do better over the long term

(1) Doctors concentrate on short- term rather than long-term treatment Some evidence that people treated without antidepressants may do better over the long term Could antidepressants create a vulnerability to relapse?

(2) Doctors focus on neurobiological rather than psychosocial factors Commonly believed that mental illness is due to chemical imbalance

(2) Doctors focus on neurobiological rather than psychosocial factors Commonly believed that mental illness is due to chemical imbalance No rigorous corroboration of the serotonin theory of depression, and a significant body of contradictory evidence

(2) Doctors focus on neurobiological rather than psychosocial factors [No] discernible pathological lesions … that in or of themselves serve as reliable or predictive markers of mental disorder

(2) Doctors focus on neurobiological rather than psychosocial factors [No] discernible pathological lesions … that in or of themselves serve as reliable or predictive markers of mental disorder BUT mental disorders will eventually be proven to represent disorders of intercellular communication or disrupted neural circuitry APA (2003)

(2) Doctors focus on neurobiological rather than psychosocial factors People are able to understand that the “chemical imbalance theory” is only a theory

(2) Doctors focus on neurobiological rather than psychosocial factors People are able to understand that the “chemical imbalance theory” is only a theory What they may find more difficult to appreciate is why they are told that this theory has been proven, when this is not the case

(2) Doctors focus on neurobiological rather than psychosocial factors Chemical imbalance theory is used as a means of persuading patients to take medication

(2) Doctors focus on neurobiological rather than psychosocial factors Chemical imbalance theory is used as a means of persuading patients to take medication People require the expertise of doctors to make sense of the information available to them

(2) Doctors focus on neurobiological rather than psychosocial factors Insanity is "a corporeal disease". … I have never been able to conceive … a disease of the mind.

(2) Doctors focus on neurobiological rather than psychosocial factors Insanity is "a corporeal disease". … I have never been able to conceive … a disease of the mind. [T]he various and discordant opinions, which have prevailed in this department of knowledge, have led me to disentangle myself as quickly as possible from the perplexity of metaphysical mazes. Haslam (1798)

(2) Doctors focus on neurobiological rather than psychosocial factors View that the phenomena of human existence can be understood in exclusively biological terms is obviously attractive

(2) Doctors focus on neurobiological rather than psychosocial factors View that the phenomena of human existence can be understood in exclusively biological terms is obviously attractive It is legitimate to question whether an understanding of human nature can take the same form as the laws of natural science

(2) Doctors focus on neurobiological rather than psychosocial factors Biomedical hypothesis is so fundamental to the edifice of psychiatry that “chemical imbalance” theory is still believed despite contrary evidence

(2) Doctors focus on neurobiological rather than psychosocial factors Biomedical hypothesis is so fundamental to the edifice of psychiatry that “chemical imbalance” theory is still believed despite contrary evidence At its most extreme, biomedical psychiatry reduces the person to a brain that needs its biology cured.

(2) Doctors focus on neurobiological rather than psychosocial factors Suggesting mental illness has a physical basis serves as the justification for psychiatric interventions and institutions

(2) Doctors focus on neurobiological rather than psychosocial factors Suggesting mental illness has a physical basis serves as the justification for psychiatric interventions and institutions In the UK prescriptions for antidepressants almost tripled in the 11 years up to 2002

(2) Doctors focus on neurobiological rather than psychosocial factors Patients may want antidepressant prescription, but doctors do not appreciate how much they may not

(2) Doctors focus on neurobiological rather than psychosocial factors Patients may want antidepressant prescription, but doctors do not appreciate how much they may not Doctors should not deceive their patients

(3) Doctors are biased about the effectiveness of medication Results of thousands of studies of antidepressants are not nearly as conclusive as they are often claimed to be

(3) Doctors are biased about the effectiveness of medication Results of thousands of studies of antidepressants are not nearly as conclusive as they are often claimed to be About a third of published studies show no difference between antidepressants and placebo

(3) Doctors are biased about the effectiveness of medication Negative studies of antidepressants may not be published

(3) Doctors are biased about the effectiveness of medication Negative studies of antidepressants may not be published Even in the trials that are published, outcomes are not always reported, particularly if the findings are negative

(3) Doctors are biased about the effectiveness of medication Conclusions in trials funded by drug companies tend to be more positive

(3) Doctors are biased about the effectiveness of medication Conclusions in trials funded by drug companies tend to be more positive Better quality studies are associated with less treatment effect

(3) Doctors are biased about the effectiveness of medication Mean drug–placebo difference in improvement scores of 1.8 points on the Hamilton Rating Scale of Depression

(3) Doctors are biased about the effectiveness of medication Mean drug–placebo difference in improvement scores of 1.8 points on the Hamilton Rating Scale of Depression Statistically significant, but of marginal clinical significance (National Institute for Health and Clinical Excellence - NICE)

(3) Doctors are biased about the effectiveness of medication Expectation that medication will produce improvement may itself produce apparent benefit

(3) Doctors are biased about the effectiveness of medication Expectation that medication will produce improvement may itself produce apparent benefit To prevent expectations influencing outcome the trial is conducted “double-blind”

(3) Doctors are biased about the effectiveness of medication Randomised clinical trials are not as "double-blind" as is commonly assumed

(3) Doctors are biased about the effectiveness of medication Randomised clinical trials are not as "double-blind" as is commonly assumed Subjects and doctors may be cued in to whether subjects are taking active or placebo medication

(3) Doctors are biased about the effectiveness of medication Both doctors and subjects can guess treatment more accurately than would be predicted by chance

(3) Doctors are biased about the effectiveness of medication Both doctors and subjects can guess treatment more accurately than would be predicted by chance Degree of unblinding correlates with treatment effect

(3) Doctors are biased about the effectiveness of medication Effect size also correlates with proportion of patients having side effects

(3) Doctors are biased about the effectiveness of medication Effect size also correlates with proportion of patients having side effects Raters' expectations and patients' suggestibility could entirely explain the small effect size

(3) Doctors are biased about the effectiveness of medication Doctors do not generally tell patients about small effect size and substantial non ‑ response rate of antidepressants for fear of undermining effectiveness

(3) Doctors are biased about the effectiveness of medication Doctors do not generally tell patients about small effect size and substantial non ‑ response rate of antidepressants for fear of undermining effectiveness Questioning the effectiveness of antidepressants is legitimate

Conclusion Perhaps not that surprising that doctors were slow to recognise antidepressant discontinuation reactions, as focus too much on short- term fix, not psychologically minded and too quick to peddle medication

Conclusion Perhaps not that surprising that doctors were slow to recognise antidepressant discontinuation reactions, as focus too much on short- term fix, not psychologically minded and too quick to peddle medication Not all doctors fit this stereotype

Conclusion Psychiatry can be practised without the justification of postulating brain pathology as the basis for mental illness

Conclusion Psychiatry can be practised without the justification of postulating brain pathology as the basis for mental illness Mental disorders must show through the brain but not always in the brain

Conclusion "Psychiatry is naked," the child said. Psychiatry could not admit to that. It thought it better to continue the procession under the illusion that anyone who couldn't see its clothes was either stupid or incompetent