Sunday, February 04, 2007

Research frenzy

Thank you everyone for your encouragement & support, I am getting there slowly & dreaming of the sun!

I have wandered off into a frenzy of research and am now the country's leading authority on SSRI discontinuation sydrome (hardly!). Rambling research notes to follow....everyone should know this stuff....

Selective serotonin reuptake inhibitors (SSRIs)

The first anti depressants were introduced in the 1950’s. It was not until 1987 that the first SSRI, Prozac, hit the market. By 1991 Prozac was the biggest selling AD in the world with a market worth $1 billion.

A group has now been developed: fluoxetine (Prozac), fluvoxamine
(Faverin), paroxetine (Seroxat), sertraline (Lustral) and citalopram (Cipramil).

On their introduction they were hailed as a miracle cure. They were thought to be safer and have less side affects than the older models and were said to be non addictive. They are also used to treat illnesses other than depression, such as OCD, Bulimia and PTSD. No-one really understands why work but they are still prescribed.
Dr Timothy Petersen (Clinical psychologist at Harvard) says ‘despite there being a lack of evidence in efficacy between old and new (AD’s) clinicians perceive the newer agents to be more efficacious than the older drugs’. He believes that the general perception is that the side effects of the newer drugs are less and that this perception is fuelled by marketing.

SSRI’s work on the chemical systems in the brain (neurotransmitters) which carry messages between nerves, muscles, glands and other organs. They boost activity in these systems and increase the levels of serotonin in the brain by preventing its reuptake. This in turn improves the patient’s mood.

It has since been found that they are associated with a withdrawal reaction on discontinuation after regular use. This usually occurs when treatment is stopped abruptly. But can also happen when it is reduced slowly over time and even if a dose is missed for just one day.

The exact mechanism is unknown, but one explanation is that it is a result of the brain attempting to reach neurochemical stability after an abrupt change. The drug increases levels of neurotransmitters which can reduce the number of receptors present in the brain. Once the drug is withdrawn there may not be enough receptors left which can reduce the amount of seratonin in the brain.
The clearance of the drug can occur faster than the brain can readjust to the absence of medication. The down-regulated receptors will remain in a relatively hypo active state for days to weeks.

Symptoms usually occur 1-10 days after discontinuation. The time of emergence depends on the half-life of the drug. The half-life is defined as the amount of time it takes for the quantity of the drug in the bloodstream to reduce by half. These times vary from 10-21 hours for paroxetine (the shortest) to 2-6 days for fluoxetine (the longest).

Symptoms are usually mild and last an average of 10 days. They can also be severe and last for much longer. They respond rapidly (usually within 72 hours) to the readministration of the same SSRI. They are sometimes confused for a recurrence of the disorder being treated. The symptoms are often mistaken for illnesses such as ME of Glandular Fever. Patients can go through months of tests before SSRI’s are found to be the cause.

In 2006 Dr Black (from Dept of Psychiatry at Dalhousie University in Halifax Nova Scotia) developed a system of diagnosis. SSRI discontinuation disorder was defined by 2 or more of the following symptoms occurring within 7 days of stopping: dizziness, lightheadedness, vertigo, feelings of fainting, nausea, headache, visual disturbances, anxiety, shock like sensations, tremor, fatigue, insomnia, irritability, gait instability and diarrhea.

These symptoms are reported to range between 35% - 86% of patients in controlled studies. This is much lower in databases based on reported cases as the majority of patients do not report them to their GPs.

72% of psychiatrists & 30% of GPs were aware that patients might suffer. Only 20% of psychiatrists & 17% of doctors in a survey of 100 said that they always warned patients of the possibility withdrawal effects.

Out of a study of 42 patients in 2000: 82% suffered after 1-2 days, 94% after a week and 100% after 2 weeks.

60% of people who talked to MIND said that they had difficulty coming off their medication, of all the psychiatric drugs SSRIs caused the most difficulty.

Most people (50%) recover within a week, however some can take longer and a small percentage still report symptoms after 18 months.

If symptoms persist patients will usually be put back onto their original SSRI. They can, however, be put on one with a longer half-life which may reduce the chance of symptoms when they stop.

There is much debate and disagreement over the terminology of this syndrome. The pharmaceutical companies argue that ‘dependence’ is a syndrome involving various features and certain of these don’t apply here. Patients don’t, for instance, develop tolerance to the drugs or cravings and they don’t use them for non-medical (recreational) purposes. Therefore (the pharmaceutical companies say) they are not ‘addictive’.

Critics argue that the pharmaceutical industry has a vested interest in creating a distinction between ‘addiction’ and ‘dependence’. They say that the arguments against the term ‘withdrawal’ are used primarily so as not to frighten patients or alienate potential customers. ‘Withdrawal’ is a symptom of ‘physical dependence’, they say, not ‘addiction’.

Hugh James Solicitors are investigating compensation claims on behalf of 550 patients in the UK who have experienced adverse reactions to Seroxat. It can be very difficult to come off after as little as 2 days. They are bringing litigation under the Consumer Protection Act. This can, at the moment, only be based on it being the ‘worst in class’. Prozac actually rates as the worst for incidents of suicide and aggression so they can only bring action against Seroxat for withdrawal. They are currently trying to overturn this ruling so that they can take action for other SSRI’s. They told me that they constantly had people contacting them about other drugs such as Citalopram. Their medical experts agree that it is very difficult to get patients off Citalopram.


Dr Breggin was the first to warn about SSRI withdrawl in his book ‘Talking to Prozac’ published in 1994.

In 1999 David Taylor (head pharmacist at the Maudlsey Hospital) published a paper called ‘Truth Withdrawal’. He had not only studied withdrawal symptoms of SSRIs but also had first hand experience of them. He dismissed the claims of the pharmaceutical industry and wrote ‘the real truth is that, for many people, antidepressant withdrawal syndrome is neither mild or short lived’. He raises the question that clinicians might be blinded to the negative aspects of new drugs by the wish to find harmless new cures. The selling point of SSRIs had been that people were not supposed to become physically dependent on them, unlike older drugs.

In 2001a US jury ordered GlaxoSmithKline (the manufacturers of Seroxat) to pay £4.6million to the family of a man who killed his wife, children and himself after taking Seroxat for 2 days. David Healy was an expert witness in this case. He showed that studies indicated rates of problems on discontinuation of paroxetine in over 30% of patients. Hence he argued that for GSK to ‘characterise paroxetine withdrawal reactions as very rare, transient, mild and/or virtually impossible to detect and distinguish from underlying psychiatric illness is simply an untenable position’

In 2001 GSK updated their label for Praxil (Seroxat) to include a specific mention of withdrawal reactions.

In January 2002 Br Peter Breggin published clinical evidence that all of the SSRI’s can cause serious withdrawal problems.

Some effective headway was made in 2003 by Dr David Healy and Charles Medawar of Social Audit, assisted by reporters at the Guardian, BBC Panorama and Richard Brook of MIND. The struggle is still ongoing.

In June 2003 the first Panorama programme was aired, this led to the Government stating that under 18’s shouldn’t take Seroxat and to the MRHA saying that adults shouldn’t suddenly stop.

In the programme Dr David Healy, an expert on Seroxat, said ‘If they aren’t the right drug for you they can cause a range of problems, they can make you suicidal, they can throw you into a state of mental turmoil and even if they are the right drugs for you, in some cases they can leave you hooked’.

The MHRA have issued warnings to prescribers about withdrawal reactions for SSRIs in 1993 and 2000 and warnings were added to patient information leaflets regarding suicidal thoughts in the early stages of treatment.

In 2003 the warnings were sent to all doctors and pharmacists in the UK however they added ‘the benefits of paroxetine in adults are well established in the treatment of depressive illnesses and anxiety disorders and are considered to outweigh the risks’. The MHRA are paid by the pharmaceutical industry who are in effect their employers.

In 2003 Seroxat was banned by the MHRA for under 18’s. They were the first regulator in the world to do so. Shortly after the US FDSA issued similar warnings.

In 2004 the MHRA issued a warning about sudden withdrawal of Seroxat.

2 months ago David Taylor (of the Maudsley) contributed to a paper published in the Journal of Affective Disorders which stated that it is not only Seroxat which causes withdrawal. The pharmacists information line for people with concerns about psychiatric medication told me my symptoms were ‘quite normal’. They said it doesn’t matter how slowly you taper off them you will still have effects. The symptoms will start any time within the first 2 weeks of stopping and last, they say, up to 7 days (although there are countless individual stories of them lasting substantially longer). If I had called 2 months ago (before the publication of Taylor’s paper) they would have told me that I had probably caught a bug.

MIND are still calling for other SSRIs to be looked into.

Yet the manufacturers still refuse to admit that they are ‘addictive’. User groups are not looking for a ban, as they agree that the drugs help millions of people, they are just looking for better information to accompany the drugs.

The information notes accompanying my particular brand of Citalopram contain no mention of withdrawal affects, only possible side affects during administration. In fact there is no mention of how to come off the drugs at all, not even a warning to do it slowly.

Labels: , , , ,