Ask Your Doctor
Imagine you go to your doctor because following a marriage break up / redundancy / bereavement you find yourself unable to function as usual. You cry a lot, can’t eat or sleep, have lost interest in things you usually enjoy, feel worthless or guilty and have thoughts of ending it all.
Your doctor diagnoses you with depression and prescribes antidepressants. He or she extols the benefits of the drugs while warning they may cause anxiety, dizziness, headache, insomnia, nervousness, somnolence, tremor; diarrhoea, nausea; fatigue, dry mouth, sleep disorder and changes in sexual functioning.While the side effects sound unpleasant, they’re a minor irritant compared to the symptoms the doctor promises will be alleviated by the drug… and besides, your doctor tells you they will be ‘mild and transient.’
The side effects the doctor warns you of are those listed as very common or common by the company that manufactures the drug, occurring in between 1% and 10% of patients. They were identified in clinical trials conducted by the drug company in order to secure the approval for their drug necessary to releasing it on the market. They are not independent trials conducted by objective parties but trials whose goal was to produce data showing the drugs were safe and effective and allow those conducting the trials to create huge revenues. They were conducted decades ago. They are phase III clinical trials, not the more recent phase IV trials.
Clinical trials comprise five phases. The studies from which your doctor, and the regulator are gathering and promulgating adverse reaction information, are phase III trials. These trials test the drug on small, carefully selected populations who take the drug over a short period of time. Given the small number of participants, the exclusion of large groups of people from the trials and their short duration, they provide limited information on the adverse reactions caused by the drug being tested. The real test of how a drug will impact the people to whom it is prescribed comes in phase IV trials – the data collected from doctors and their patients after the drug has been released onto the market and studies conducted after the drug or treatment has been marketed.
Phase IV trials often test the drug’s interactions with other drugs and its effectiveness in certain populations that were not represented in previous clinical trials. In this phase, drugs are monitored for long-term side effects that clinical trials were unable to detect. This is important given the relatively short duration of phase III trials doesn’t allow for the collection of evidence of a drug’s long-term impact on subjects. A number of drugs approved as safe and effective following phase III trials have subsequently been withdrawn from market as a result of serious harms detected after the drug was released on the market.
While your doctor is unlikely to quote a study conducted by McDonalds in the 1980s to inform you of the risks and benefits of eating cheeseburgers three times a day, he or she is prepared to use drug company trial data to inform you of the risks of antidepressants, because the regulator promotes their doing so and because the drug company hands it to them on a plate and they are not required to make any effort to keep themselves properly informed.
What might your doctor tell you about the risks and benefits of antidepressants if he or she believed they were responsible for doing a bit of independent research to ensure you had all the information required for fully informed consent? What information might the regulator provide to you and your doctor if they were serious about their mission to “To enhance the health of New Zealanders by regulating medicines and medical devices to maximise safety and benefit.”
Perhaps they would tell you about the phase IV trial data on adverse reactions experienced by those prescribed the drug in New Zealand which the regulator has gathered over the past 12 years. Data which tells a very different story than that told by the phase III clinical trials – a story your doctor should know about and should be telling you.
Below is a chart showing the most frequently reported psychiatric adverse reactions and the percentage of patients they affected, as recorded by the Centre for Adverse Reaction Monitoring (CARM) in New Zealand. Those in red are reported in the drug company data as commonly occurring adverse reactions. Those in black are not – and are consequently not risks patients are informed about by their doctors
Now imagine you go to your doctor with your original symptoms and he or she explains that aggression and death are as common as dizziness in reports from doctors about adverse reactions to the drug you have been prescribed. That suicidal ideation and suicide attempt are as common as insomnia.
Imagine you were told that while being exposed to these risks, the post-marketing data showed that the most likely adverse reaction you would experience would be that the drug didn’t work or stopped working. How might your decision on this particular treatment option be affected? Might you ask why your doctor was prescribing you a drug that caused depression, lethargy, somnolence, weight loss or gain, suicidal thinking and behaviour to treat a disorder whose symptoms are depression, lethargy, somnoloence, weight and appetite changes and suicidality? Might you ask what alternatives were available? Might you refuse the prescription?
Might you then avoid the situation where after your child kills himself on antidepressants, you have to listen to the following exchange during your child’s inquest, as I did. An exchange that illustrates the impact of regulators allowing pharmaceutical companies to provide the offical advice on adverse reactions to lazy doctors who do not take their duty to patient care seriously?
Lawyer: It is correct, is it not, that one of the side effects of Fluoxetine is that it can deepen one’s depression?
Prescribing Psychiatrist: The indication for Fluoxetine is the treatment of depression.
Lawyer: Is it correct that it can also worsen somebody’s depression?
Prescribing Psychiatrist: It is not something I am that familiar with. Clearly it is indicated in the treatment of depression, not in the causation of depression.
Emergent or worsening depression has been the subject of adverse reaction reports in 2% of patients on whom CARM has been provided data. According to drug company protocols this makes it a ‘common reaction.’ Shame they forgot to mention it in the information they provide to doctors to inform their prescribing practice.
Drug companies, and probably doctors and regulators would argue that phase IV data is incomplete in that it represents a small fraction of patients taking the drug and only those adverse reactions doctors choose to report. I would argue that this is no different to phase III trials which include small numbers of subjects and have been proven to failed to report adverse reactions the drug companies didn’t want the regulator to know about.
In the end, our regulator advises doctors that informed consent requires patients be provided with information that a reasonable consumer, in that consumer’s circumstances, would expect to receive. Given phase III clinical trials of antidepressants did not include New Zealanders, particularly those from ethnic minorities and that recent data showing the actual impacts of these drugs on the health and functioning of New Zealanders is available for the past 12 years, it is my view that a reasonable consumer would want both the phase III and phase IV data when considering whether to take antidepressants.
I know how betrayed a parent feels when they are provided with this data only after their child dies from antidepressant-induced suicide.
My advice is that next time a drug company, regulator or TV advertisement urges you to ‘ask your doctor’ you ask not whether an antidepressant is right for you but how familiar they are with the New Zealand phase IV trial data and to what extent they use this data in making prescribing decisions.