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The Benzo Bias

"Benzos"  (benzodiazepines) like Xanax, Klonopin, and  Ativan may be the most effective and safest psychoactive drugs on the market.  They are also the most maligned. As in previous articles, I'll refer to the drugs by their brand names, since that may make reading easier-no looking up on your favorite search engine what "alprazolam" is-why not just write "Xanax"?

If you could design the perfect drug, certainly three characteristics you'd be interested in would be efficacy, side-effect profile, and safety.  Ideally, all drugs would score high on these and other measures of drug therapeutic quality.  But as we found out with Zyprexa, drug development and drug choice just aren't that simple-we're back in Shades of Greyland.  Antihypertensive drugs (blood pressure lowering drugs) are a case in point: "compliance"-the willingness to actually take the medication each day is less than stellar for this set of drugs, as is well known.  Many people find that when they take  antihypertensives, they experience being tired, impotent, depressed, rounded off with a chronic cough (with first-generation ACE-inhibitors in particular) and insomnia [1].  If they stop taking the medication, they feel much better.  Surprise!  The patient stops taking the medication and becomes "non-compliant".  Maybe they should have tee shirts that have a large red "N" printed on them for those folks.  The point is that if lowering blood pressure  in the long term is a good thing, the physician has to convince the patient to take their medication, a task made much more difficult if there are significant side effects.   Oh, yes, and the antihypertensive drug has to actually lower the blood pressure enough, too, which isn't always the case-that was number one on our list of Ideal Drug Characteristics: efficacy.  The last characteristic mentioned is "safety", related to the "therapeutic index"-the ratio of the dosage that can be taken which is  effective to the dosage that causes toxicity.  Put simply, the ideal drug could be taken in large amounts and nothing worse than discomfort would occur.

What does all that background have to do with Xanax and friends?  Let's say you have an anxiety mental disorder which could be treated by Xanax (or one of the other compounds in the same category-Klonopin, Ativan, maybe Valium) most anxiety disorders, you probably will plagued with the disorder for the rest of your life-so I'm not talking about minor situational anxiety problems, like your pet goldfish Marvin hasn't been eating well.  Let's evaluate the three main pharmacological ways a chronic anxiety disorder can be treated in terms of efficacy, side-effect profile, and  safety.

SSRI Antidepressants (e.g., Prozac, Paxil, Lexapro)

Efficacy: data varies, but probably will be helpful to 30-50% of people within 4-8 weeks. Very new research [2] suggests that Paxil (and therefore, probably most SSRI's) are only  better than placebo for severe mental illness; this study was not the usual all-medication-for mental-illness-is trash rantings that one reads about regularly, usually emanating from the UK.

Side-effect profile: typically insomnia, sleepiness, nausea, loss of both sexual desire and ability.

Safety: Recently linked to an increase in risk of stroke and all-cause death in some populations [3]

but traditionally rated as "safe".


Atypical antipsychotic ( e.g., Seroquel, Zyprexa)

Efficacy: Varies significantly as to effectiveness and  time until onset of relief.

Side-effect profile: typically a few of the following: headache, nausea, dry mouth,  sleepiness, insomnia, diarrhea or constipation, lethargy, loss of sexual desire and ability, massive weight gain, possibility of diabetes. And some really nasty side effects [4].

Safety:  Eli Lilly is willing to part with at least 1.2 billion dollars to people who claim they were "injured" by a member of this class of drug, Zyprexa.  Remember?  Then there are those "really nasty" effects [4].


Benzodiazepines (e.g., Xanax, Ativan, Klonopin)

Efficacy: Excellent, often within hours.

Side-effect profile: Excellent-some initial sedation initially which can be resolved by lowering the dose.

Safety: Excellent, exceptionally non-toxic.  Causes dependence (often incorrectly referred to as "addiction") if used continuously over an extended period, requiring a tapering down of the dosage to avoid withdrawal discomfort.  Dependence is often stated as occurring with about 50% of those taking benzodiazepines for an extended period; my guess is that is a very conservative figure.  If you are going to take Xanax, etc.-expect that you will have to very slowly taper off the drug in the future.


O.K.!  The benzo family reduces anxiety and has few, maybe no, negatives. Sounds like just what you need right now, since you are scared silly of just about anything in life.  Well, sorry, you’re going to have to pry a prescription for Xanax (alprazolam) out of your doc’s hand because the medical community is very afraid of alprazolam and the benzo family in general.  It’s the dependence thing-it takes on a paternalistic tone: your doc just knows that avoiding the  chance that you will have some withdrawal symptoms someday is worth you suffering severely now.  Your doc might see things very differently if she were suffering right now instead of you.  An informed doc will tell you of the possibility of dependence; tell you of the benefits of the medication, and then the two of you  make a join decision.  If your doc does handle the situation in the latter manner, you have an informed and compassionate doc-hold on to him or her.

Well, if the benzos are non grata, what drugs can be used?  The favorites in terms of medication are currently the SSRI’s (selective serotonin reuptake inhibitors), such as Prozac, Paxil, and Lexapro.  Prozac, Lexapro, and Paxil are available generically as fluoxetine, escitalopram, and paroxetine.   The SSRI’s won’t give you immediate relief from your anxiety symptoms, it will probably be more like 4-6 weeks, in the 30% chance that the drug works at all.  During the waiting period, you’ll be busy fighting off the extra anxiety the drugs produce, trying to stay awake during the day because of insomnia, but on the positive side, you’ll have more time because you probably will neither be interested nor able to participate in sexual activities. Oh, sorry, you’ve been taking Prozac for 6 weeks and no relief of symptoms?-time to switch to Lexapro and wait another anxious, sleep-deprived, sexless 4-6 weeks. For balance, not everyone has such a difficult time with SSRI's, but realistically, many, if not most,  people do.  Imagine going to the doctor and being in pain and having the doctor prescribe something that causes you to be in more pain-that just wouldn’t happen, right? 

This is the paragraph where one would expect I'd make sense out of this apparent pharmaceutical confusion.  I could offer the idea that the withdrawal side-effect of benzos trumps their excellent efficacy and safety compared to  the alternatives-but SSRI's have been found to cause dependence, too.  Google an antidepressant name (especially Paxil and Effexor) and put the word "withdrawal" after it.  Look on drug-withdrawal sites and see if benzos are well-represented in terms of withdrawal problems.  They are not. While you are looking things up, look up "benzo withdrawal", too. Let's be clear: benzos do cause dependence for most people, if used regularly, and a tapered, perhaps uncomfortable withdrawal may occur.  But isn't that just part of the risk versus benefit gamble of taking any drug?  Why are benzos singled out as such a problematic drug to prescribe when they clearly work very well and are very non-toxic?  

Why is there such a bias against using benzos?  I think the answer is simple: the stigma of mental illness.  There are "real" illnesses, like cancer, and "pretend" illnesses, like anxiety and depression. The "pretend" illnesses, depression and anxiety, are almost certainly the reason suicide is the leading cause of death in adults under the age of 35.












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