Shining a Light on Numbers Needed to Treat (NNT)

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I see my cardiologist once a year about my high blood pressure and we also have conversations about the current state of healthcare, both the quality and cost. These conversations started when he asked me (knowing I am a psychologist) why antidepressants are always among one of the top four selling drugs.

We had discussions about this and they continued after I gave him a copy of my book What’s Wrong With Much of U.S. Healthcare and How to Fix It. He obviously read it because he had pertinent comments and questions about much of the material, particularly the great number of psychiatric and non-psychiatric FDA approved drugs that have only marginal clinical effectiveness.

For example, researchers were able to analyze the data for all randomized placebo-controlled depression drug clinical trials submitted to the FDA. They found that almost half (49%) of the submitted trials found no significant difference in improvement between those on the drug and those on inert placebo! As a psychologist trained in graduate school to conduct sound experiments and research, and with the expertise needed to critically examine the research of others, this one statistic is enough evidence that antidepressant drugs are not effective or justified in treating clinical depression.

In addition to allowing the elimination of mildly depressed patients from these trials, the FDA incorrectly allows introduction of a placebo washout period to remove additional subjects whose depression might improve on placebo alone! This policy is another violation of sound science, since in the real world the drug will be dispensed to a larger group of depressed patients than those in the biased clinical trial!

Despite this attempt to remove those depressed patients who would improve on inert placebo alone (about one-third of all depressed patients), Irving Kirsch found that 75% of the improvement was due to the placebo effect and only 25% was the drug effect! Again, another finding that seriously questions the advisability of using drugs to treat depression.

At one time, I believed that only FDA-approved psychiatric drugs had only marginal effectiveness and not the vast majority of non-psychiatric drugs for the treatment of “medical” problems. However, when I expanded my review to all health research, I found I had been wrong. I discovered in the literature that many popular drugs for “medical” problems also have only marginal clinical effectiveness.

My cardiologist and I discussed this, and he offered the opinion that physicians prescribe these drugs for fear of being charged with malpractice if they do not prescribe them since some patients do get better on many of these drugs! Let’s look at my cardiologist’s justification of this defense of prescribing FDA-approved drugs with very limited effectiveness. However, before doing so the reader needs some background information to understand a statistic among others that describes a treatment’s effectiveness.

The Number Needed to Treat (NNT)

There is an important statistic in healthcare called the Number Needed to Treat (NNT). This number is the number of patients with the health problem that must be treated in order to have an impact on one person/patient. NNT can vary from an NNT of 1 (one person treated, one person helped) to an NNT of 100 and more.

According to a Cochrane review of antidepressants as a treatment for depression, the NNT for SSRIs is 7, and 9 for tricyclics. That is, one would have to give seven depressed patients an SSRI to ensure that one of the seven would improve more than if all seven had been treated with inert placebos. In other words, one of the seven would benefit from the treatment and the other six would be needlessly exposed to the adverse side effects of the antidepressant.

With an NNT of seven, depressed patients need to make this decision: Is the one-in-seven chance of a benefit beyond placebo worth the risk associated with taking the drug?

Common side effects of antidepressants are nausea, weight gain, lack of sexual desire/impaired orgasm, fatigue, insomnia, dry mouth, blurred vision, and constipation. More serious and rarer side effects include suicidal thoughts, allergic reactions, mania, seizures, and tardive dyskinesia (TD). In figuring the cost of drug treatment of depression, one must also include the cost of drugs (and physician charges) to treat some of the adverse side effects of antidepressants.

Based on my review of the “medical” literature, it is not uncommon to find that for treatments of “medical” problems, the NNT is often 10 to 15 and even considerably higher. The higher the NNT, the worse the efficacy. What about statins to prevent heart attacks and strokes? Statins have an NNT of 60 for preventing a heart attack and an NNT of 268 for stroke! Those are the numbers of healthy people needed to take statins for five years for those projected outcomes to be achieved!

With NNTs like these, how does the medical profession continue to recommend statins? Or other drugs with similar NNTs?

I have never heard a physician recommending a statin say anything about side effects. For statins, the Mayo Clinic reports that serious side effects include muscle pain, liver damage, and some cases of memory loss or confusion. With such outcomes and possible side effects, I am glad I looked at the research on statins and stopped taking statins 10 years ago against my physician’s advice (with life style improvements, my cholesterol is now in the normal range).

Psychiatrists might say, shouldn’t antidepressants be prescribed even though only one in seven patients—about 14% of all patients—experience a reduction in symptoms beyond what would be achieved with placebo?

So let’s do the math. Imagine you prescribe antidepressants to 10,000 depressed patients. That would mean 1,400 patients would benefit. Prescribers must be concluding that this provides a good risk-benefit ratio for all 10,000 patients.

But isn’t it malpractice to expose 8,600 patients to the side effects of antidepressants without their experiencing any benefit in reduction of symptoms beyond placebo? And then, of course, many of these patients will be exposed to other drugs to treat the antidepressant’s side effects. I believe that is the greater malpractice!

Moreover, in the above case, the 14% are those who achieved a reduction in symptoms at the end of a six- to eight-week trial. In assessing the effectiveness of any health treatment, one must factor in that many health conditions such as the flu, upper respiratory infections, depression, and others are also self-limiting: They often get better with or without treatment, particularly over longer periods of time.

In many health problems, the NNT will vary considerably for individual patients depending on the severity of their illness, and whether they are at high or low risk for having the bad outcome. The provider should discuss all of these factors so that patients are informed about the benefit/risk ratio when offered a prescription by their provider.

What are some other measures of effectiveness for cardiovascular therapies?

Warfarin and aspirin are both blood thinners to present strokes. In atrial fibrillation, warfarin has an NNT of 80.  Fewer than two patients in this group will perform better than those on aspirin.

In studies of aspirin to prevent a first-time heart attack or stroke, no deaths were prevented.

In studies of coronary bypass surgery to prevent heart attacks, one death was prevented in every 25 treated patients; one in every 10 to 14 treated were helped (ie, the drug prevented a non-fatal heart attack).

In studies of coronary stenting for non-acute coronary disease, compared to drug treatment, there were no significant differences in outcome: 145 deaths in surgically-treated patients vs. 144 deaths in medication-treated patients.

I will leave it to the reader to decide if any of the above therapies are justified and which treatments should or should not be authorized for payment in any health plan. I heartily concur with the need for respecting patients’ rights in receiving health services. But unless they are informed of NNT risks and benefits, their right to make an informed choice is being denied.

One plan to reshape the current healthcare system

I don’t think we can rely on physicians to provide patients with NNT data so they can make informed decisions. This information will have to come from other sources.

One tool for improving healthcare in this way is to have the payer for the proposed treatment do this NNT assessment, and then decide whether the potential harms outweigh the potential benefits to the patient population as a whole. If the harms outweigh the benefit, then the payer can present other treatment options with a better NNT.

For instance, a payer could determine that an NNT of 7 for treating depressed patients with drugs does more harm than good, and thus promote alternative treatments. During my days managing behavioral health care for a management company, 65% the callers complained of depression and or anxiety symptoms. Yet, my firm never authorized drug treatment for these symptom disorders. The callers were instead referred to Ph.D. psychologists and clinical social workers and the average treatment took just under six sessions.

And what was the result for patients? Ninety percent or more expressed satisfaction with this care, versus a 76% satisfaction rate for the behavioral health industry as a whole.

My reading of the health literature leads me to believe that improving the quality of healthcare, and lowering its costs, will require major changes to the present system. Nothing short of revolutionary change is required to improve the current healthcare system.

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Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.

13 COMMENTS

  1. “… why antidepressants are always among one of the top four selling drugs.” Because they’re being handed over under the guise of “safe … meds.” And because a middle aged woman cannot walk into a hospital in America, with an exercise related pain, not a depression related symptom. Without being asked, by an aptly named but idiotic Dr. Paine, “Are you depressed?”

    Thankfully, saying no, and mentioning you’re allergic to the anticholinergic drugs, does encourage those who are pill pushing pains to quickly walk away.

    “With an NNT of seven, depressed patients need to make this decision: Is the one-in-seven chance of a benefit beyond placebo worth the risk associated with taking the drug?” I agree with you, “I don’t think we can rely on physicians to provide patients with NNT data so they can make informed decisions.” Despite the fact that giving informed consent to patients is probably the most important aspect of their job.

    “But isn’t it malpractice to expose 8,600 patients to the side effects of antidepressants without their experiencing any benefit in reduction of symptoms beyond placebo?” Absolutely it is. “And then, of course, many of these patients will be exposed to other drugs to treat the antidepressant’s side effects. I believe that is the greater malpractice!” I couldn’t agree more, where’s my malpractice money?

    “My reading of the health literature leads me to believe that improving the quality of healthcare, and lowering its costs, will require major changes to the present system. Nothing short of revolutionary change is required to improve the current healthcare system.”

    Again, I agree. And that’s all those of us speaking out on this website are saying. We’re not the enemies, merely because we speak the truth, we’re the canaries in the coal mine.

  2. Of course you’re right. Many common treatments offer no benefits to most patients for whom they’re prescribed. But there’s another factor here. People have an insatiable desire for physicians to do something to help them. What physician would dare say, yes you have a greater risk of a heart attack because of your family history, blood pressure, age, and cholesterol level, but I have no drugs that can help you, or at best there’s only a slight chance the drugs will be beneficial? For many people the medical field and the physician have taken the place of religion and the medicine man. A doctor who refuses to fill this role will lose patients. It’s hard to believe revolutionary change is coming any time soon.

    • A benefit in a study over placebo can occur due to any number of flaws in the study.

      All psych drugs cause a wide range of physical effects such as dry mouth, stomach issues, headaches, sedation, stimulation and so on. Because of this they cause an active placebo effect. Irving Kirsch in his review reported on research finding that 78% of patients and 88% of psychiatrists knew who was taking the drugs. Psych studies use subjective measurements done by the psychiatrist (who has a conflict of interest) to determine benefits.

      Almost every single Psych study utilizes a withdrawal design where they take people currently on the drugs and withdrawal half to create the mislabeled “placebo” group. Psych studies pretend harm caused by the drugs are benefits. Looking at the Ham D depression scale this becomes obvious because someone gaining weight, or believing they are “mentally ill”, or having the same health symptoms but reporting them less to medical professionals have a larger “benefit” than the entire reported drug benefit in flawed short term corporate studies.

      According to Psychiatry AD’s help the person by making them fatter, lowering their self esteem, and getting them to shut up about their complaints.

  3. Let’s be honest. Ant-depressants are very popular prescriptions for general practitioners, internists, ob-gyns, etc. A woman going to the doctor for any number of complaints could probably receive anti-depressant as the prescription to help her deal with her issue. We already know that the psychiatric doctors and their prescribers do not tell all about these drugs. The non-psychiatric doctor tells even less. And, when some people experience stress or sadness, many times they do feel more comfortable speaking to their regular doctor. To avoid these dangerous prescriptions, I would say they would be better off to speak with their minister, but so many mainstream denominations now train their ministers to be “alert” for signs of “mental illness” the person still will end up in the anti-depressant prescription zone. The very worst part of all these ant-depressant prescriptions and usage is that anti-depressants are basically gateway drugs to the atypical anti-psychotics and others, probably leading to “poly-pharmacy”, a very dangerous cauldron of chemicals.. But, we also withdrawal from anti-depressants can be excruciating and they also affect the brain in extremely adverse ways. Actually, my uniquely personal gateway drug was “lithium.” However, they first started me on “tegretol” but my body rejected it due to a very low white blood count. At first, they also subjected me to “klonapin”, claiming due to a garden-variety pen and pencil paper test, I had “ocd.” That particular diagnosis haunted me for years and it was patently untrue, however, as they increased my drugs, including stronger and stronger anti-psychotics, amongst other horrific side effects was “ocd.” And, as my drugs increased, so the plethora of diagnoses they gave me. Let’s see, they see “clothes make the man.” I say “psych drugs make the patient—ill of a million and one things, including that which they say the person has been diagnosed.” Thank you.

  4. In related news:

    From “Corke et al., Meta-analysis of the strength of exploratory suicide prediction models; from clinicians to computers'” data the number needed to harm for replacing psychiatrists in suicide prediction by monkeys throwing darts at an appropriately colored dartboard is around 300. (I couldn’t bother to calculate the exact number, so I simulated it.) On average one truly suicidal patient will be missed per 300 evaluated patients. So as monkeys work literally for peanuts this could save lots of money.

    This also assumes the monkeys have no emotional intelligence whatsoever, which is obviously wrong and unfair, so in practice the monkeys would do better than calculated.

  5. Dr. Ruthven,

    It is interesting that your cardiologist speculated that physicians prescribe so many drugs because they are worried about malpractice.

    What if it was the other way around. What if doctors were more worried about malpractice from dangerous drugs they prescribe?

    The current opioid class action lawsuit has a large list of defendants — including every link in the supply chain of manufacturing, distributing and dispensing — who are accused of aggressively marketing painkillers while downplaying the risks of addiction and overdose. The marketing tactics cited are shameless.

    I cannot help but see some of the same tactics perpetrated with psychiatric drugs, which are aggressively advertised and pushed by nearly all medical professionals who sell them as safe interventions, downplaying the immense risk of dangerous side effects and physical dependence.

    The Numbers Needed to Treat (NNT) should not be a mystery or surprise to patients but part of informed consent and full disclosure from the pharmaceutical and medical communities.

    Thank you for sharing this important information.

    • What you are say is right. The damage drugs do, and especially, psychiatric drugs is hidden from the public, maybe even some of the prescribers. Perhaps, many of the prescribers are trained to believe that is not the drugs causing the problem, but something they just made up to hide the problem. I, seriously, think that it is not only psychiatric drugs that do damage to the body and brain; however of all the prescribed drugs, it is the psychiatric drugs that at more likely to do the damage to the most important organ, the brain. Non-psychiatric drugs, depending on the drug, could damage the brain also, but the psychiatric drugs definitely do it. It has been proven, but like the old saying goes, “My mind is made up, don’t confuse me with the facts.” The psychiatrists and those who prescribe these drugs most obvious “mantra.” Thank you.

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