Nature Neuroscience | Action Potential

Anti antidepressants

By now, you’ve likely read a shocking headline questioning the effectiveness of the latest generation of antidepressants. Kirsch et al. report that selective serotonin reuptake inhibitors (SSRIs) are only slightly more effective than placebos at reducing depression in a meta-analysis of US Food and Drug Administration (FDA) data. Are these data really worth all the fuss?


As Nicola Jones points out in the Great Beyond, drug companies are not required to publish negative data. Suspicious that published data on SSRI effectiveness were biased, the authors obtained FDA data via the US Freedom of Information Act. Researchers use the Hamilton Rating Scale of Depression (HRSD) to rate depression severity. Antidepressant treatment should reduce depression scores. Placebos often also reduce HRSD scores. A meta-analysis of FDA data showed that most SSRIs significantly (in the scientific sense) reduced HRSD scores relative to placebo, but the relative reduction was less than the effective criterion established by the UK National Institute for Health and Clinical Excellence (NICE). Thus, by NICE criteria, SSRIs would not benefit most people (Note: I am unaware whether the FDA has a similar effectiveness criterion).

By NICE standards, does anyone benefit from SSRIs? The authors found that people with high HRSD scores (people with severe depression) showed SSRI-induced HRSD reductions that passed by NICE criteria, suggesting that SSRIs effectively combat severe depression. However, placebos were less effective at reducing HRSD scores in people with severe relative to mild depression, which may explain the relative increase in SSRI effectiveness, according to the authors.

I’m not a physician, nor am I a policy maker, so I can’t comment on NICE’s effectiveness criteria. However, based on this study, it is inaccurate scientifically to describe SSRIs as ‘ineffective’. That does not suggest that I have feelings about whether they should or should not be prescribed. Are antidepressants overprescribed? Probably. Should people stop taking their SSRIs. NO! It is never safe to reduce, change or stop antidepressant treatment without the supervision of a physician. Perhaps, in the end, effectiveness is in the eye of the patient and his or her prescribing physician.

Comments

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    Michael said:

    Peter Kramer wrote a good piece about this topic. Basically he says that not all of the trials are constructed well enough to distinguish the drug from the placebo. So you can’t necessarily lump every single trial together.

    http://www.slate.com/id/2182585

    “In the rush to bring patented compounds to market, pharmaceutical houses sometimes enroll research subjects who barely meet criteria for the condition under study (in this case, depression). In some early trials, researchers may purposely use low doses; the idea is to squeak by the FDA’s minimum efficacy requirements without raising concerns about side effects.”

    “Instead, the study shows an elevated placebo response rate. And then the research tends not to get published, because it’s simply not credible. Or the consequence is worse yet. Every researcher in the field can name a promising substance that was lost for patient use as a result of poor study design or overeager recruitment of subjects, resulting in astronomical placebo response rates.”

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    Kerry D. Friesen, M.D. said:

    As a practicing physician for more than 17 years, I can say with confidence that SSRI’s ARE clinically effective. While RCT’s represent the scientific standard, a drug’s ultimate efficacy is decided by clinical observation and post-marketing surveillance. If you want to KNOW what a drug is truly capable of, release it, N= ten’s of thousands, stir liberally and then observe. That’s when the fun begins. Remember Vioxx? Baycol? Ketek. Now watch out for Chantix.

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    Katharine Dickson said:

    SSRIs work. There’s no doubt about that.

    Perhaps the placebos are effective. If one tricks the individual into thinking they’re dealing with their depression, placebo pills might be an ideal way to wean an individual off a drug, whether to put them on another or to stop antidepressants.

    Comments from the psychiatrists on this?

  4. Report this comment

    Flug Denpasar said:

    The placebo effect is the healing force of nature.

    For me there are two points to be aware of when you use placebos. First: it could be critical when the patient gets to know that he has been tricked. Second: Is it morally ok when you trick your patient in lie him into the face?

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    anti depression said:

    I believe there are so many depressed people in our society because they aren’t happy with themselves. There are sooooooo many outside pressures——including the ones we let in through the media etc., that we are bombarded with how we should act, feel , work, play and so on. Come on people—-forget the status quo!!!

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    Greg said:

    I believe antidepressant side effects are all too often ignored by the general public because most people feel so low that they figure its worth the risk, when in fact it’s really not. See these true stories for all the proof you need to avoid using antidepressants as a depression treatment.

    The other issue is also that most people don’t look past their doctor for help. There are some great non-medication depression self help treatments out there but if your only going to rely on your doctor (who we all know are getting pharmaceutical kick-backs) to prescribe what’s in your best interest then you may be putting your health in the hands of a wolf dressed in sheep’s clothing.

    Do a google search on self help depression treatments and you’ll find a whole host of options, some good, some not so good but you will certainly find some much better options than just accepting the seriously detrimental side effects of antidepressants.

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    Dr Rav said:

    I have recently been doing a lot of research at alternative depression solutions. Been looking at various dialog across the internet, which offer depression treatment without the aid of drugs. Found a rather new concept which appears to be an interesting read. Please feel free to take a look.