No Support for Antidepressants Over Benzodiazepines for Anxiety

Kermit Cole

A review of all the relevant research comparing benzodiazepines (BDZ) to antidepressants (AD) for the treatment of anxiety was published Psychotherapy and Psychosomatics this Friday. The study, by researchers in Italy and the United States, concludes “The change in the prescribing pattern favoring newer AD over BDZ in the treatment of anxiety disorders has occurred without supporting evidence. Indeed, the role and usefulness of BDZ need to be reappraised.”

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Offidania, E., Guidia, J., Tombaa, E., Fava, G.; Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis. Psychotherapy and Psychosomatics. Online September 20, 2013

Of further interest:

An editorial by Karl Rickers, a significant researcher in the pharmacotherapy of anxiety, in the same issue of Psychotherapy and Psychosomatics (“Should Benzodiazepines Be Replaced by Antidepressants in the Treatment of Anxiety Disorders? Fact or Fiction?“) notes:

“In fact, no evidence for the superiority of the newer ADs over BZs, both in terms of efficacy or safety, exists for either short-term or long-term treatment. BZ toxicity, adverse events, and withdrawal symptoms, not better efficacy, are usually cited in support of the use of ADs over BZs in anxiety disorders. Yet ADs are not better tolerated than BZs and they also cause withdrawal symptoms. Therefore, gradual, not abrupt, taper is indicated after treatment with BZs and ADs, and a distinction between withdrawal symptoms and a return of anxiety, often a most difficult task, is critical for clinical management.

“A well-conducted comparison trial of a BZ and a newer AD simply does not exist, neither for acute nor chronic treatment. In fact, when in the late 1970s the National Institute of Mental Health (NIMH) made the decision to withdraw largely from supporting clinical trials of new drugs, turning new drug development over to industry, many clinically important trials, such as a comparison of BZs versus selective serotonin reuptake inhibitor ADs in anxiety disorders for example, were simply not done. It is therefore time that such comparison trials are conducted if possible under other sponsorship than that of the industy.”


  1. It’s odd that benzos have become more and more out of favour the further out of patent they have gotten, what could possibly be the reason? Sure there may be issues with dependency but AD also have issues with dependency as shown by the amount of people that are on them for years and years.

    I have seen loads of people given AD for anxiety and I don’t recall anyone saying they felt much less anxious, at times the opposite in fact. Only the clinicians prescribing seem happy with the change from benzos to AD.

    Indeed AD can cause anxiety, clinical trials at times have used benzos to help people through the trial period with AD.

    • Robb, Actually that’s a good point but it’s not just “at times.”
      It is routine( see Glenmullen, Healy) in tests of SSRIs for FDA approval to include administration of a benzodiazapine–its use is not even mentioned in the articles on tests. This is another one of the under-handed tricks the drug industry gets away with. Presumably the anxiety caused by SSRIs would be much greater and undermine its “therapeutic efficacy” (already low) if it were not given with a “minor tranquilizer.” One could infer that violent and suicidal acts would also be more frequent. Of course SSRIs are not routinely given with benzo’s in the “real world.”
      Seth Farber, Ph.D.

        • Many people DO take SSRIs alone. When you read about violent act by someone on drugs, it is usually just SSRIs, which seem to have the distinctive ability to make a small group (but large enough to do great damage) non-violent subjects violent.
          I also have met many people who would have liked to get a benzo for anxiety(obviously they are least harmful when used for emergencies–so that tolerance does not develop) and were only given the choice of SSRIs and/or neuroleptics. (That is not to say the benzo.s are harmless but used with caution and moderately they are benign compared to SSRIs and neuroleptics.)
          Another disadvantage of the benzo.s is that they are not compatible with the serious “mental illness” diagnoses shrinks prefer. They are for everyday “anxiety” as indicated by their class, “minor tranquilizers.”

      • Hi Seth. My knowledge of this subject comes primarily from Irving Kirsch’s book “The Emperor’s New Drugs” which, as I’m sure you know, is an exhaustive analysis of SSRI’s FDA trials. Also, I’ve read the mainstream media articles on the topic in the Atlantic and NY Times. Kirsch doesn’t mention simultaneous administration of benzos. Do you have more exact references, or should I just do a search under the two (?) authors you mention?

        When I asked one MD psych about the “new truth” of SSRIs, she kind of shuffled and squirmed, then said “well, they’re still useful for anxiety, and all depressed people are anxious.”

        Daniel Heller N.D.

        • Daniel,
          I read it so often I don’t remember where.(I did not read Kirsh but I’ve read enough references to his book–I am surprised he omits that.) But it would certainly be in Healy.But I’m not sure if it’s in both of Healy’s relevant books–see below. (I tried reading some other books by Healy but they were not worth the effort.) Only Healy, Breggin and Ann Blake Tracy focus on the bizarre Jekyl and HYde type quality SSRIs have on a small group of people. (Healy is or was an establishment psychiatrist so his claims might be more believable to skeptics–that is to believers in Psychiatry.)I say small meaning relative to all the people on SSRIs but it is a large group when compared to those who commit violent crimes-it turns out 67% of violent acts were committed by persons on psych drugs (SSRIs mostly).The book by Healy on this issue is Let Them Eat Prozac. I don’t recall if he talks here about how benzos are given with SSRIs in the tests.

          It would certainly be mentioned in Pharmageddeon –the best book written on the reduction of “scientific” testing to PR operation by the drug companies– which does not focus on SSRIs . Also America Fooled by Timothy Scott definitely covers this,not as original and sophisticated as Healy but easier to read. Healy talks about all the tricks performed to disguise dangers of drugs in Pharmageddeon. Breggin’s Medication Madness is an easy and entertaining book to read, but it’s just on the dangers of SSRI, almost all narratives. (I give it to people who are not readers whom I want to encourage to get off psych drugs on any kind although it focuses on SSRIs–but it would not be in THAT book.) Another book that DOES mention the concurrent prescription of benzos is Joseph Glenmullen book on Prozac–an establishment shrink who hates the SSRIs.

          Breggin probably wrote an article on it–so Google might be the quickest way.Here’s a quote from a Breggin article: “The FDA allowed the drug company to include in its efficacy data those patients who had been illegally treated with concomitant benzodiazepine tranquilizers in order to calm their over-stimulation. With these patients included, statistical manipulations enabled the FDA to find the drug marginally approvable. Basically, Prozac was approved in combination with addictive benzodiazepines such as Ativan, Xanax, and Valium; but neither the FDA nor the drug company revealed this information.”(–just accessed) But if you read other sources you will find this is ROUTINE–Kirsh’s failure to include it means the efficacy of SSRIs are even less that Kirsch stated, i.e., less than the placebo!

    • That a very big statement (I have seen loads of people given AD for anxiety and I don’t recall anyone saying they felt much less anxious). I took zoloft for over 15 years and it totally stopped my panic attacks and anxiety. I am in no way syaing it helps every one or doesnt have its problems but they do help alot of people with anixety.

      • Evidently, according to the above, BZDs were phased out and replaced by SSRIs. There have been no studies comparing the two.
        Lisa you don’t know that you were not experiencing a placebo effect.We know that SSRIs do not outperform active placebos in the alleviation of depression–for which it was designed.They are only slightly better than sugar pills. It would be surprising if SSRIs were better for anxiety than for depression!! BTW the placebo effect is greater if the patient has a positive relationship with the prescriber.I think you did. We have no way of knowing that you were not benefitting from placebo effect rather than SSRIs, as do almost all those taking SSRIs for depression.
        One issue would be the cost/benefit ratio.A BZD is more likely to be abused since people use it to get high.So this is going to be relevant for specific populations–those with a tendency toward alcohol or drug abuse. Another problem is one quickly develops a tolerance for BZPs–which is all the more reason NOT to use it every day.
        But SSRIs I think have far more adverse side effects. First there is a risk of suicidal thoughts or actions increasing with use of SSRI.Healy found the risk of suicidality is 7 times greater with Zoloft than with placebo.People with no history of suicide became suicidal. For men the incidence of sexual dysfunction is 50% according to Glenmullen. Women report a reduction in sexual interest. There is tardive dsykinesia and akathisia.Glenmullen’s book on Prozac discusses the risk.
        SSRIs are more harmful drugs than BZDs–of course this would not be true if the person were given massive dosages of the latter.
        There is copious evidence that meditation is effective for the alleviation of anxiety. If meditation were supplemented by giving clients access to BZDs to take in an emergency or until they become adept at meditating, one could avoid the harmful effects of SSRIs. Unlike SSRIs a benzo has an immediate effect.It occasional and moderate use is far less harmful than regular usage of SSRIs.
        Seth Farber, Ph.D.

        • I can see both sides of this question. There is no doubt that people with depression and anxiety respond to SSRIs. There is also no doubt that SSRIs cause harm in some cases, and haven’t been PROVEN to be superior to placebo for anxiety.

          Unfortunately, science and medicine have not answered some fundamental questions, such as “why do SSRIs work in some people and not in others, and is it more than placebo? Since depression and anxiety are no longer though to be neurotransmitter issues, is there another mechanism whereby these medications could work? Is there some way, perhaps through genomic testing, to predict who will have adverse reactions, and who will benefit, from these medications.”

          It’s hard for everyone to have so many unanswered questions, and confusing. Unfortunately, Big Pharma and Medical Associations and M.D.s tend to be allergic to saying “We don’t know”, and it is an emotional and passionate issue.

          But we don’t know if what is happening is placebo or something else. We DO know that SSRIs are overprescribed, and they don’t work – if they work at all – in the way that people think they do.

  2. You know the reason Benzos went out of favor is because the pharma companies and doctors could make more money on the SSRIs. Besides which, SSRIs favored the “chemical imbalance” theory much better, being “targeted” at a specific neurotransmitter, even though nobody had or has a clue as to why they even have an impact on depression or anxiety.

    Personally, I find a glass of beer to be an excellent antianxiety agent. It’s cheap and readily available without prescription, and fast-acting like the benzos. Sure, there’s the problem of dosage control, but people get addicted to benzos as well. I’d love to see controlled dosages of alcohol go up against benzos and SSRIs. I bet alcohol would win out, both for effectiveness and lower side effects. Marijuana in low doses is probably also better than either benzos or SSRIs, and probably even better than alcohol on the side effect profile. But as long as no one can control the supply and make big enough bucks for their corporation off of them, alcohol and marijuana will remain “drugs” rather than “medications.” In the end, there isn’t much difference, except for who profits.

    Do I sound cynical?

    —- Steve

    • I am currently reading “Anatomy of an Epidemic” by Robert Whitaker, and I happen to be on the chapter on benzos. He makes two points: a) they started going out of fashion in the late 70s, when people began to realize how addictive and destructive they are and b) they haven’t ever really gone THAT far out of fashion. You’d think that the researcher whose book contributed the name of this blog/site/forum would be among the first to point out a collusion that favored SSRI and big pharma profits by shelving benzos. But he makes a very different point.

  3. You can read testimonials from 100s of people who failed to get any relief from anxiety whatsoever or made worse from using anti depressants and many others who are hopelessly addicted to benzodiazepines here:

    Its very sad to read forums like this , these people suffer much more from the drugs than the condition itself. I know this cause I was one of these people for a long time “looking for the right meds” (ssris) or trying to keep my benzo supply from running out.

  4. The authors compare benzos to TCA’s not really a fair comparison as TCA’s are not routinely used for depression or anxiety much today.

    As a pharmacist working specifically in mental health who does not like to take medications in my own personal life (and advocate for stopping useless medications for patients I serve) I often am straddling the fence between rhetoric of Pharma and blogs such as this. As best I can my goal is to provide education on risk and benefit and let individuals make their own mind.

    My issue with many of the posts on this blog and others is the continued argument that the public is being fooled by this or that study to use a group of medication (over a cheaper alternative) for financial gain of pharmaceutical company. However not a single SSRI is still under patent of big Pharma. Venalafaxine, mirtazapine and bupropion (other 2nd gen antidepressants) are also all generically available for mere cents per tablet. Out of the 4 branded antidepressants available, only Cymbalta is one that I see being used with any frequency.

    Benzodiazepines are not all bad but come on the withdrawal between a benzo and antidepressant are not even close in safety, less we forget of fatalities from benzo withdrawal. Also withdrawal does not equate to abuse or drug seeking behavior, the later of which SSRIs does not cause. Nor the same level of toxicity when combined with alcohol, opioids or even alone.

    • . However not a single SSRI is still under patent of big Pharma.
      That is irrelevant. They need to fulfill certain criteria.
      For years they have done that through various subterfuges. A recent study found 90% of psych drugs approved by FDA had no advantage over drugs on the market. If you read the critics –say Pharmageddeon by David Healy– you’d see FDA does not protect the consumer and ever since FDA collects fee from drug companies it is in their service. You would see in the Healy book that the science today is just a PR operation of the drug industry.
      It’s hard to come up with new patent after 25 years
      but they will.Or they will increase consumption by conquering new markets when they should not even be used, particularly on children. Bob Whitaker shows that SSRIS cause manic states. This is one reason there are 6 million bipolars today–they are a product of SSRIs. Once labeled bipolar they will be put on neuroleptics as well as a cocktail.
      THE SSRIs have no value as their efficacy is no better than placebo and these drugs greatly increase the risk of suicidal and violent behavior. The common side effects range from akathisia to sexual impotence. AT least half the males experience some sexual dysfunction. Yet SSRIs are along with neuroleptics the most commonly prescribed psychiatric drugs.
      The benzo.s are more often abused because threy have a pleasing effect unlike the SSRIs. Yes if on regulat dose of benzos getting off can be dangerous but the advantage of a benzo is their effect is immediate and they can be taken when “patient” NEEDS them,e.g., once or twice a week, for a week if one is under stress and then stopped before tolerance. SSRIs are always taken daily for years and patients find it extremely painful to go off–the withdrawal effects are extremely disturbing.
      I doubt that you have read Ann Blake Tracy(Prozac:Panaceo or Pandora) or any of the books by Healy or Breggin I mentioned above. For example, almost all of the school shooters were on SSRIs. Not any of the other commonly prescribed drugs. IN other words it isnot just a correlation– thus, I argue, the effect of SSRIs is causal, it makes some people violent. Even people with no history of violence.
      Seth Farber, PhD

    • “The authors compare benzos to TCA’s not really a fair comparison as TCA’s are not routinely used for depression or anxiety much today.”

      >> Your concern is addressed at the beginning of the discussion on page 359: “Our systematic review found a paucity of studies providing a controlled direct comparison of AD and BDZ in anxiety disorders. Most of the studies were concerned with TCA and only 3 with newer antidepressants. The superiority of AD over BDZ in terms of efficacy and tolerability was not supported by the available evidence.
      This joins a long list of findings that SSRIs don’t have much evidence to support their use, in any condition.

  5. Just ran into this article. I was given BOTH ADs (switched up many many times to find the ‘right combination’ and Klonopin )lowest dose possible (it’s such a small dose, don’t worry-you don’t have an addictive personality…) and I’m here to tell you that K withdrawal is hell on earth, and I DO wonder how many who try to quit kill themselves…because that is how I have been feeling when the wave hits and I must ride out wanting to die for days/weeks on end…and hell no, I can’t afford ‘therapy’. Help lines? Hah what a joke they are.

    These drugs have ruined my life. I have absolutly nothing to look forward to. But benzos, by far, are the worst, and they are still being handed out like candy.

  6. Over the last 20 + years I have watched the rise of anti-depressants and the fall of benzos. Happy to stumble upon this article, it gives me acknowledgement that I am not crazy.

    Psychiatric drug information is almost entirely controlled by Big Pharma. Their greed and blatant disregard for the safety of patients are the only reasons for the paradigm that exists among the populace.

    Google lawsuits lost by big pharmaceutical companies. They know what they are doing is wrong and they commit fraud and cover up wrong-doings. They have been fined billions of dollars for it…… but their profit margins are much higher than their fines.

    I have been on one mg xanax taken once a day for over 8 years. For me this drug has improved my quality of life immensely. I don’t like to take any drug but I have chosen the lesser of 2 evils. I have never needed to increase my dose. I don’t think it is as bad as the “establishment” would have you believe. I am treated like a drug addict by my doctor and at the pharmacy.

    Yet SSRI’s are thrown at us like candy…… no thank you! I have had many bad reactions and one life threatening reaction from SSRI’s. Then when I refuse SSRI’s I am labeled non-compliant.

    SSRI’s make money, Benzos don’t. Period.