I corrected this point later--see below. No one would have anticipated that
you would have dumped text the size of the Encyclopedia Britannica into a
newsgroup.
"Philip Peters" <philip@[EMAIL PROTECTED]
> wrote in message
news:4853c0f7$0$14345$e4fe514c@[EMAIL PROTECTED]
> anon schreef:
>> This is not a scientific study of a controlled population sample--it is
>> more anecdotal evidence from one physician who overprescribes benzos--
>
>
> Gotcha! You only read the first text which is an interview (I *knew*
this
> was going to happen, it's not the first time). You effectively fell into
> your own trap.
>
>
>
>
> of which
>> there are, alas, far too many. In fact, Big Pharma has so corrupted the
>> psychiatric profession in this country that SSRIs get handed out like
>> candy even though carefully vetted studies show that that most of them
>> are no more effective than--or only marginally more effective
>> than--placebos.
>
>
>
> The jury is still out on this, there are conflicting studies out there.
I
> totally agree that SRRI's are vastly overprescribed, as I said earlier,
> and often at the expense of those lovely benzo's (which actually were
> overprescribed in the seventies as well which gave them their bad
> reputation instead of the doctors who prescribed them at random without
> even a proper dagnosis). Nowadays Big Pharma has been hyping up SSRI's
> just like benzos were hyped up thirty years ago so what else is new?
When
> properly prescribed after a serious diagnosis has been established there
> is a place for both benzos and SSRI's etc. in the treatment of Panic
> Disorder. As im****tant, if not more, is to find a good CBT or
> REBT-therapist; the results of CBT etc. are at least as good if not
better
> than those of medication and often it makes sense to combine them, at
> least for a period of time.
>
>>
>> The do***entation of the powerfully addictive properties of benzos is
>> vast, along with an equally vast literature demonstrating the
potentially
>> life-damaging side effects that can come with long-term use, including
>> short-term memory loss, cognitive deficits, depression, and horrific
>> rebound anxiety and rebound insomnia during attempted withdrawal.
>
>
> See the literature I posted and you refused to read.
>>
>> For a survey of the vast scientific literature on the horrors of benzo
>> addiction withdrawal, see the references at the end of the following:
>>
>> http://en.wikipedia.org/wiki/Benzodiazepine_withdrawal
>
>
>> All of those listings constitute SCIENTIFIC LITERATURE, not the
>> comforting anecdotal bedtime stories proferred by this self-serving,
>> ethically irresponsible megalomaniac, who universalizes from his
>> microscopic corner of the universe.
>
>
> Do you really think Wikipedia is *scientific*? It's totally unreliable
> information brought together by whoever feels like it. In this case
> Wikipedia's stance on benzos reflects the UK *Anti Benzo Squad*'s. It's
> worth less than nothing.
> I universalized nothing from my own personal experience, on the contrary
I
> presented a lot of *scientific* literature and opinions by leading
> psychiatrists which you decided not to read. Maybe you could try again.
>
> Oh, I was out of this thread.
> Had to come back one more time to make it clear that I sent dozens of
peer
> reviewed studies accompaniet by a lot of anecdotal information and the
> only thing you did is read the first entry.
> Or you chose to ignore the rest because it doesn't help your agenda.
>
> Philip (don't know why I joined this thread after years of bickering
with
> the anti benzo boys, but hey, I'm out of it -again ;-)
>
>
>>
>> "Philip Peters" <philip@[EMAIL PROTECTED]
> wrote in message
>> news:4852fcbe$0$14344$e4fe514c@[EMAIL PROTECTED]
>>> anon schreef:
>>>> "Some" this, "some" that--all without any do***entation
>>>> but with a lot of
>>>> ad hominem sneering and name calling (the Anti-Benzo Squad), as
though
>>>> that compensates for do***entation and rational argument. This
poster's
>>>> message consists entirely of personal testimony and anecdotal
>>>> evidence--it's pure garbage. I've already posted the relevant
>>>> scientific do***entation from a variety of sources, none of which
this
>>>> snide smear artist has bothered to try to refute.
>>>
>>> See below.
>>>
>>>
>>> The point is--proceed
>>>> with caution, and try to use them only on a spot or short-term basis
>>>> unless a trusted doctor absolutely feels you must rely on them for a
>>>> longer period.
>>>
>>> Now here we agree. Never self-medicate, always have meds prescribed by
a
>>> trusted doctor.
>>> And with this little bouquet of quotations below I gracefully bow out
of
>>> this thread on to greener pastures and let everyone judge the matter
for
>>> themselves. Enjoy!
>>>
>>> Philip
>>>
>>> ---------------------------------------------------------
>>>
>>>
>>> A Conversation With a Colleague
>>>
>>> from Medscape General Medicine
>>> http://www.medscape.com/viewarticle/457797?src=search
>>>
>>> Thomas A. M. Kramer, MD
>>>
>>>
>>> The following is dialogue with a colleague who is a child psychiatrist
>>> and who has recently expanded her practice to treat more adults.
>>>
>>> Dr K: When do you actually use benzodiazepines to treat anxiety? I
>>> mean, how many other drugs will the patient actually have to fail
>>> before you would prescribe them?
>>>
>>> Dr. F: Well, sometimes none. A lot of the time, I would use them right
>>> away. First-line.
>>>
>>> Dr K: Really?
>>>
>>> Dr. F: Sure. It wasn't that long ago that benzos were used routinely
>>> as first-line treatment for generalized anxiety. It's only fairly
>>> recently that they've been supplanted by SSRIs and SNRIs.
>>>
>>> Dr K: And aren't those drugs better? Don't benzos tend to make
>>> patients sleepy, stupid, and addicted? I mean, not using benzos as
>>> first-line treatment is a step forward, right?
>>>
>>> Dr F: Certainly, SSRIs and SNRIs are im****tant treatment options. But
>>> benzos have their virtues, too. They work right away; antidepressants
>>> in general take a few weeks to work. When dosed appropriately, they
>>> don't make people sleepy or stupid. As far as addiction goes, that's
>>> pretty controversial, but my feeling is that the risk of addiction for
>>> benzos is grossly overstated. Certainly, in a vulnerable population,
>>> like people with substance abuse history or strong family histories of
>>> substance abuse, tolerance and dependence can be a problem. But that
>>> is a very small percentage of patients who present for treatment for
>>> anxiety. I've seen a lot of patients who have taken 10 mg a day of
>>> Valium for years with good result. They don't escalate the dose, and
>>> if they try to come off it or miss a few doses, all that happens is
>>> that they get anxious again. Benzos don't really have very many side
>>> effects besides the ones you mentioned, and since antidepressants have
>>> side effects of their own, there are some patients who can tolerate
>>> benzos who cannot tolerate antidepressants.
>>>
>>> Dr K: So why don't we use them any more?
>>>
>>> Dr F: I do. But the sense I get, in what little adult work I do, is
>>> that they have really fallen out of favor.
>>>
>>> Dr K: You're right, but I don't think that's for good reason. I think
>>> that's basically a function of marketing.
>>>
>>> Dr F: You mean, drug companies are trying to get us to write for their
>>> SSRIs and SNRIs for anxiety as opposed to benzos?
>>>
>>> Dr K: Exactly. The other side of that coin is that nobody is marketing
>>> benzos at the moment. That may change soon with the launch and
>>> subsequent marketing of rapidly dissolving Klonopin and Xanax XR, but
>>> for the time being, all of the marketing efforts of the pharmas for
>>> anxiety treatments are focused on antidepressants.
>>>
>>> Dr F: So you are saying that we all are really controlled by the
>>> pharmaceutical industry? That their marketing efforts really do
>>> control our behavior?
>>>
>>> Dr K: Well, no. I do think that at least some of us are capable of
>>> independent thought. The problem, I think, has more to do with sources
>>> of information. So much research and educational programming is funded
>>> by pharmas that they have an enormous amount of influence over what is
>>> defined as the state of the art. While they may not have direct
>>> control over the results of published research, or the content of
>>> educational programs at meetings, or the information that is sent to
>>> us in the mail, they have enough influence to determine a lot of what
>>> it is you are going to see when you go to "read the literature." You
>>> end up thinking that the treatments for which they choose to fund
>>> research and programs are indeed the state of the art. After all, you
>>> read all of these advantages of these new treatments. No one's putting
>>> material in front of you telling you about the advantages of the older
>>> treatments.
>>>
>>> Dr F: And no one is funding head-to-head studies between the new and
>>> the old treatments, either.
>>>
>>> Dr K: Exactly. Why should they? The only people who fund clinical
>>> trials these days are pharmas -- although that has changed a little
>>> bit with some new NIMH studies that are actually comparing different
>>> treatments without any pharma funding -- and pharmas are certainly not
>>> going to fund such a study because it may not look so good for them.
>>> Look, I have nothing against marketing. I think that the pharma
>>> industry, like any other industry, is entitled to promote its
>>> products. I am also sympathetic to the fact that is not easy for them
>>> to do this. It is hard to get the attention of busy physicians. My
>>> concern is that some things are marketing that aren't labeled as such.
>>> I am tired of hearing the words "unrestricted educational grant."
>>> There ain't no such animal. Simply deciding what it is you're going to
>>> fund with such an unrestricted educational grant gives you a fair
>>> amount of discretion as to what clinicians will hear about and know.
>>> And as far as research is concerned, it seems to me that the results
>>> of studies sponsored by pharmas seem to almost always be good news for
>>> the company actually doing the sponsoring. I'm not saying that they
>>> manipulate the data, but I am saying that they have a fair amount of
>>> control over what data you see and what data never sees the light of
>>> day.
>>>
>>> Dr F: I can see a little bit of this happening now with ADHD
>>> treatments. While stimulants can have bad side effects, particularly
>>> weight loss and insomnia, they do work for most kids, and as we start
>>> to get alternatives to stimulant medications for ADHD, some materials
>>> and programs I've seen are starting to imply that stimulants may
>>> become obsolete. Immediate-release stimulants are a very good example
>>> of what you're talking about. They're treated in current discussion as
>>> if they're obsolete, but they can have a great deal of clinical
>>> utility, particularly as augmenting medications.
>>>
>>> Dr K: I think the best example of this phenomenon is lithium. Lithium
>>> is a fabulous drug. Unfortunately, nobody is marketing it presently,
>>> and there's a lot of aggressive marketing of other medications for
>>> bipolar disorder. As a result, I think a lot of clinicians are
>>> becoming convinced that lithium is an inferior drug. There have even
>>> been a few papers written by old-timer psychopharmacologists defending
>>> lithium as a treatment of choice, particularly for classic, nonrapid
>>> cycling bipolar I disorder. I have even seen things written saying
>>> that lithium has become less effective over time. That's crazy.
>>> Lithium may have been used less than successfully for bipolar subtypes
>>> for which it is less effective, such as rapid cycling or mixed
>>> dysphoric states, but for classic mania it really works, and these
>>> days clinicians really need to be reminded of that fact. This kind of
>>> marketing has almost relegated a useful medication to the status of
>>> historical artifact.
>>>
>>> Dr F: Interesting.
>>>
>>> Dr K: Yeah, and you know what else? I think we just wrote my next
>>> column.
>>>
>>>
>>>
>>> Thomas A. M. Kramer, MD, Associate Professor of Psychiatry, University
>>> of Chicago, Chicago, Illinois
>>>
>>>
>>>
>>> Medscape General Medicine 5(3), 2003. © 2003 Medscape
>>>
>>>
>>>
>>> A study by Charles Medwar a member of the WHO's Advisory Panel on Drug
>>> Policies and management suggests that benzodiazepine withdrawal is
less
>>> severe than that from some SSRIs.
>>>
>>> In particular Dr Medwar review of UK safety data shows that from 1963
>>> to 1997, just over 230 million prescription for temazepam and diazepam
>>> generated only 25 notifications of withdrawal reactions. In the 10
>>> years to 1997, 5 million paroxetine (Paxil) prescription resulted in
>>> 802 notifications. In the 10 years that SSRIs have been available in
>>> Britain, 17,845 there have been official notifications of adverse
>>> effects from GPs.
>>>
>>> (Source: The International Journal of Risk and Safety in Medicine, vol
>>> 10, pge75.)
>>>
>>>
>>>
>>> >From Psychiatric Annals 25:3.March 1995 RE: Benzodiazepine Use:
>>> David G.Benzer, DO; David E. Smith, MD; Norman S. Miller, MD
>>>
>>> Pharmacological dependence is not the same as addiction and is not a
>>> reason for discontinuing therapy; it is an adaptation of the central
>>> nervous system to the persistent presence of the sedative drug. It is
>>> critical to slowly taper benzodiazepines in patients who are
>>> dependent;...
>>>
>>> Addiction refers to a preoccupation with acquiring a drug and the
>>> compulsive use of that drug despite the recurrence of adverse
>>> consequences. The loss of control over the use of the drug is the
>>> hallmark
>>> of addiction, an illness to which there seems to be a biologic
>>> predisposition. There is evidence that addiction-prone individuals
>>> subjectively perceive the effects of benzodiazepines differently. A
>>> study
>>> of alprazolam (1 mg "Xanax") in alcoholic and nonalcoholic men
produced
>>> positive mood changes in alcoholics *not* re****ted by the
nonalcoholics.
>>>
>>> Patients who are dependent on benzodiazepines merely need to be safely
>>> tapered off the drug when the course of therapy has ended. Addicts
>>> require
>>> the same careful discontinuation as well as treatment addressing their
>>> underlying addiction.
>>>
>>> ~~~~~~~~~~~~~~~~~
>>>
>>> >From Psychiatric Annals 25:3.March 1995 RE: Benzodiazepine Use:
>>> David G.Benzer, DO; David E. Smith, MD; Norman S. Miller, MD
>>>
>>> Dependence often accompanies the use of benzodiazepines for panic
>>> disorder. For example, alprazolam used at doses of 2mg or greater for
>>> more
>>> than 6 weeks must be assumed to create dependence. This is not
>>> necessarily
>>> a problem; it is neither a reason to not use benzodiazepines in these
>>> conditions nor is it a justification for discontinuing the medication
>>> prematurely. The patient and physician must mutually be aware to never
>>> abruptly discontinue the benzodiazepines. Gradual tapering is the
method
>>> that will safely and efficaciously allow the patient to discontinue
>>> benzodiazepine therapy when appropriate.
>>>
>>> ~~~~~~~~~~~~~~~~~
>>>
>>> Title: Addiction to benzodiazepines--how common?
>>> Title Abreviation: Arch Fam Med Date of Pub: 1995 Nov
>>> Author: Piper A Jr; Issue/Part/Supplement: 11 Volume Issue: 4
>>> Pagination: 964-70 Journal Title Code: BX6 Publication Type: JOURNAL
>>> ARTICLE
>>> Date of Entry: 951228N Entry Month: 9602 Country: UNITED STATES
>>> Index Priority: 1 Language: Eng Unique Identifier:96074207
>>> ISSN:1063-3987
>>>
>>> Abstract: Benzodiazepines have compiled an impressive record of safety
>>> and
>>> efficacy. Despite this record, however, physicians and laypersons
>>> frequently worry about the drugs' addictive potential. Overemphasizing
>>> these concerns may discourage prescription of benzodiazepines, thereby
>>> impeding treatment of anxiety disorders. This review first defines the
>>> term addiction. It then examines how frequently conditions meeting
that
>>> definition occur in patients without histories of substance abuse, who
>>> are
>>> prescribed benzodiazepines under medical supervision. In such
patients,
>>> benzodiazepines almost never induce
>>> behavior that satisfies any reasonable definition of addiction.
>>> Abstract By: Author
>>> Number of References: 111
>>>
>>>
>>>
>>> >From the APP Textbook of Psychopharmacology (Schatzberg & Nemeroff,
>>> eds.), p.
>>> 224 (chapter on benzodiazepines):
>>>
>>> "The controversy surrounding BZ administration and potential abuse or
>>> addiction
>>> in routine patient use is generally not sup****ted by the available
>>> scientific
>>> evidence. (See Shader and Greenblatt 1993 for an excellent review of
>>> this
>>> complex area.) In a large community study of long-term alprazolam
>>> users,
>>> Romach and colleagues (1992) found that dosage did not escalate over
>>> prolonged
>>> use and that most patients used the BZs as prescribed. In fact, if
>>> deviations
>>> occurred, it was generally that a patient took less than the
prescribed
>>> dosage."
>>>
>>> and p. 710 (in the chapter on substance abuse):
>>>
>>> "Most patients who are in fact physiologically dependent on
>>> benzodiazepines do
>>> not increase the dose of medication above the physician's prescription
>>> or in
>>> any other way abuse the prescribed medication. However, if the
>>> benzodiazepine
>>> were to be abruptly discontinued, the patient would, in all
probability,
>>> go
>>> through a withdrawal abstinence syndrome that could be extremely
severe.
>>> ...
>>> The fact that patients become physiologically dependent on therapeutic
>>> doses of
>>> benzodiazepines has led some in the field to equate any use of
>>> benzodiazepines,
>>> in any patient for long-term treatment, with abuse of the drug. This
is
>>> undoubtedly an overstatement of the abuse of these agents.
Significant
>>> abuse
>>> of benzodiazepines does in fact occur, but it is usually seen in
>>> patients also
>>> abusing other drugs, _not_ in the patient kept carefully monitored and
>>> kept
>>> stable on therapeutically indicated benzodiazepines."
>>>
>>>
>>> Written by a psychiatris who is also an associate Professor at
>>> University of Ky. The article was written on how to DC the Benzo
Xanax,
>>> but in the text of this paper it explains how this drug works and why
it
>>> is often the first choice for pure panic anxiety. Hope it helps you
>>> start to understand what is happening and how to deal with your
problems
>>> of this disorder. I have lived with all the symptoms of PNE without
>>> medication for years. Thus I have been through both methods of dealing
>>> with this problem. What I have learned in all the years of PNE is
>>> stopping the symptoms will start you into recovery sooner.
>>> lori
>>> For the layperson ---
>>> Dr. Steve's Guidelines for Discontinuing Xanax (alprazolam)
>>> Stephen Cox MD, Asst Clinical Professor of Psychiatry, UKMC
>>> This article is written in lay terminology and with analogies to make
>>> complicated medical science
>>> understandable.
>>> You've no doubt heard negative things about Xanax. We have all read
>>> stories of some negative aspect of the use of Xanax. These stories are
>>> surprising. I, personally, have seldom experienced difficulty in
>>> tapering Xanax in patients with panic disorder. This may be a surprise
>>> to those who are not experienced in prescribing psychoactive medicants
>>> for anxiety disorders.
>>> The fact is that Xanax works very well indeed in treating panic
>>> disorder. Tolerance develops to the initial dose. Dose increases are
>>> necessary in the first weeks of therapy. Why the tolerance? This is a
>>> very good question and should be answered before you start taking
Xanax.
>>> You can't possibly know how to go off Xanax unless you understand what
>>> happens to your body as you are going on it.
>>> There is a neurotransmitter in your brain called GABA. It stands for
>>> gamma amino butyric acid. GABA is your natural God-given tranquilizer.
>>> It is present at 80% of the nerve connections in your brain. When you
>>> are too nervous your brain cells release GABA which causes negatively
>>> charged chlorine atoms to stream into your nerve cells. That's good
>>> because it makes it harder for other stimulating neurotransmitters to
>>> trigger the firing of that nerve. If your brain were a car, anxiety
>>> might be like the car speeding down a hill toward a sharp curve. As it
>>> comes to a curve it must slow down. The car brakes are applied so that
>>> the car can negotiate the curve and not burst through the guard rail.
>>> The GABA molecules of your brain are like the brakes in your car. If
you
>>> don't have enough GABA, your brain is going to be like the car
speeding
>>> toward a curve with worn out brakes! Xanax acts by making what little
>>> GABA you do have work more strongly. This is sort of like applying
>>> stronger pressure on worn out brakes so that your car will negotiate a
>>> curve safely.
>>> When you take Xanax for a couple of weeks it usually works great for
>>> panic disorder but then it does not seem to work as well as time goes
>>> on. This is to be expected. Why? This could be for two reasons. One
>>> possibility is that your brain cuts back on the release of GABA. It is
>>> sort of like your brain says, "Gosh, things are a lot calmer in here.
I
>>> don't think I need to make as much GABA as I used to." Well, you
likely
>>> didn't have enough GABA to begin with. And now your brain makes even
>>> less than it did before you started taking Xanax. Naturally, the Xanax
>>> wouldn't work as well once GABA is reduced.
>>> A second reason for tolerance may be down in your liver. Your liver
gets
>>> rid of Xanax ultimately by making enzymes which destroy Xanax. After
you
>>> are on Xanax for awhile it is as if your liver says, "Hey we sure are
>>> getting a lot of Xanax these days. Let's make more Xanax-destoying
>>> enzymes." And so it does. Let's say your dose that you started out on
>>> was giving you a blood level of, say, 100 units. But after your liver
>>> makes more of this destroying enzyme you have a level of, say, 55
units
>>> of Xanax. No wonder you feel like the Xanax isn't working as well. It
>>> isn't! Even though you're taking the same dose, your blood level
>>> dropped. Remember, it does not really make any difference how many
>>> milligrams you swallow. What really matters is how much is
>>> running around in your bloodstream.
>>> So, tolerance normally develops to Xanax and it may be due to either
or
>>> both of the above reasons. If you didn't understand those two things,
go
>>> back and read it again because what follows won't make much sense
unless
>>> you understand those two ideas.
>>> Now, let's say we have a 26 year old woman, Monica, who has been on 6
mg
>>> of Xanax for panic disorder for 3 years. She's doing great. She can
>>> drive anywhere she wants and no panic attacks have occurred for 2
years.
>>> She even flew from Cincinnati to Cancun Mexico without a problem. She
>>> asked her psychiatrist if it would OK if she went off the Xanax now to
>>> see if she still needed it. The psychiatrist said yes, 'but you must
not
>>> do it faster than I order'. The patient was relieved to hear her
>>> psychiatrist was urging a gradual decline. You see, the patient's
>>> roommate, Suzy, had taken herself off Xanax from 6 mg per day to 3mg a
>>> day suddenly. And after only a week she stopped it completely. She
>>> thought she would die, she felt so bad; and, she blamed it on 'the
>>> addictive nature of Xanax'. Fortunately, Monica was told by her
>>> psychiatrist to cut her daily dose from 6.0 mg per day to 5.75 mg per
>>> day and to stay on that dose for two weeks. Then she was told to cut
to
>>> 5.5 mg a day for another 2 weeks, and so on by 0.25 mg off her daily
>>> dose every 2 weeks. Monica's psychaitrist explained that there was no
>>> way to tell if she still had panic disorder or not and by going down
>>> that slowly, if Monica should experience any anxiety symptoms, it
would
>>> be due to the reappearance of panic disorder symptoms that were
>>> inadequately treated by her lower dose of medicine. This would mean
that
>>> Monica still was afflicted with panic disorder and needed continued
>>> treatment, at least for the time being. If, on the other hand, she
>>> gradually
>>> tapered the Xanax down to zero and had no panic attacks, she would
>>> officially be either well or in remission.
>>> So, if you want to go off Xanax, ask your doctor how to do it. If
there
>>> is a rush, it can be done faster than the above method. But usually
>>> there is no rush. And it is usually best to go slowly.
>>> Now, let's review. Why didn't our patient Monica have any withdrawal
>>> when she tapered off Xanax, whereas her roommate, Suzy had severe
>>> withdrawal? The answer is that both women had a very, very low level
of
>>> GABA production and a very high level of liver Xanax-destroying
enzymes.
>>> When Suzy cut herself off over a week's time, she thought she was
>>> tapering off but it was actually much too fast. It takes a long time
for
>>> the brain to figure out that it needs to make more GABA and to do so.
It
>>> also takes a long time for the liver to quit making so much
>>> Xanax-destroying enzymes. Monica's psychiatrist wisely told her to
make
>>> these tiny cuts in the
>>> Xanax dose that were barely perceptible to her as far as the way she
>>> felt. And equally wisely she had her go 2 weeks on that dose to let
her
>>> brain GABA increase and liver enzymes decrease before cutting the dose
>>> further.
>>> Dr. David Sheehan of the University of South Florida suggested this
>>> method to me at a meeting in Tampa years ago. I cannot recall any of
my
>>> patients experiencing any bothersome withdrawal discomfort in going
off
>>> Xanax by the above method. Any difficulties I witnessed were relapses
of
>>> a clinically silent panic disorder that was previously adequately
>>> treated by the Xanax at the pre-taper dose.
>>> You should never, never, never decide to go off Xanax on your own
>>> without your physician's counsel and guidance. Xanax is a remarkably
>>> safe medicine except for two things: overdosing on it can be extremely
>>> hazardous to driving safety. Sudden or rapid stopping Xanax at daily
>>> doses of 4 mg or more can cause moderate to severe withdrawal and, in
>>> very rare instances, a convulsion could occur.
>>> You should carefully weigh the decision to go off Xanax with medical
>>> counsel. Is this a good time to go off it? Is this a stressful time?
If
>>> so, you should wait until a calmer time. Are you being pressured into
>>> going off Xanax prematurely by well-meaning, but uninformed family or
>>> friends who value more your 'being off medicine' than they do the
relief
>>> of your suffering with panic attacks and avoidance behavior. Panic
>>> disorder is not a trivial thing. It, untreated, is associated with the
>>> highest suicide attempt rate of all medical disorders. It, untreated,
>>> also has a higher mortality risk from cardiovascular cause than
>>> non-panic disorder persons. The general principles we have discussed
>>> with Xanax also holds true for other high potency benzodiazepines like
>>> lorazepam (Ativanô) and clonazepam (Klonopinô). The dosages however
are
>>> all different and the mg reductions do not apply to these other
>>> medicants.
>>> Despite popular beleif, it is my opinion that Xanax is under-utilized
by
>>> clinicians in their patients. Such medicines are remarkably safe.
Panic
>>> disorder patients seem rarely to abuse such medicine. Compliance
>>> problems (patients not following doctors orders) with panic disorder
>>> patients on Xanax are rare; and, when seen are most often a matter of
>>> the patient not taking as much medicine as is prescribed rather than
>>> taking too much.
>>> Dr. Stephen Cox
>>> http://lexington-on-line.com/naf_xanax.html
>>>
>>>
>>> To quote Dr Roy Baker, a board member of the American Society of
>>> Addiction Medicine [2]:
>>>
>>> :: All drugs with the potential to cause addictions share certain
common
>>> :: neurobiological characteristics: they activate the mesolimbic
system,
>>> :: principally the nucleus ac***bens, causing increased dopaminergic
>>> :: activity in that area of the brain. This results in an increase in
>>> hedonic
>>> :: tone.
>>> and
>>> :: "It is im****tant not to confuse physical dependence as evidenced by
>>> :: benzodiazepine withdrawal syndromes with addiction or drug
dependence
>>> :: (DSM-IV). "
>>>
>>> Benzodiazepine not only don't excite the N ac***bens but have been
>>> shown to inhibit cocaine's affect on dopamine receptors in the N
>>> ac***bens. [3] They should have the same positive effect on other
>>> recreational drugs, for the same physiological reason. Certainly,
>>> there is much evidence that benzos do reduce the withdrawal effects of
>>> most recreational drugs. Consequently, benzodiazepines are being
>>> increasingly used to mediate drug withdrawal in detox centers. [4]
>>>
>>> Another common test used to determine whether a drug is addictive is
>>> to apply the "3 C" test to its users. The term was coined by Dr David
>>> Smith of the Haight Ashbury Free Clinic and San Francisco Medical
>>> Center and is widely used by addiction specialists. To meet the
>>> addiction criterion, the patient must exhibit all three of the
>>> following:
>>>
>>> 1: Control: when the addicted person starts using their drug they
>>> episodically lose control over their ingestion.
>>> This is something that rarely happens to benzodiazepine users. To
>>> quote Prof Heather Ashton:
>>> :: "Given the number of people who are prescribed benzodiazepines,
>>> :: relatively few patients increase their dosage...."
>>> http://www.a1b2c3.com/drugs/benz02.htm
>>>
>>> The American Psychiatrists Association made the same point in their
>>> "Benzodiazepine Dependence, Toxicity, and Abuse: A Task Force
>>> Re****t" To quote:
>>> :: "There are no data to suggest that long-term therapeutic use of
>>> :: benzodiazepines by patients commonly leads to dose escalation or to
>>> :: recreational abuse"
>>>
>>> This is re-enforced by the recommendations in their current Panic
>>> Disorder III. Treatment Principles And Alternatives web page:
>>> :: "However, benzodiazepines may still be underused because of an
>>> :: inappropriate fear of addiction. The studies of long-term
alprazolam
>>> :: treatment for panic disorder show that the doses patients use at 32
>>> :: weeks of treatment are similar to those used at 8 weeks, indicating
>>> :: that, as a group, patients with panic disorder do not escalate
>>> :: alprazolam doses or display tolerance to alprazolam's therapeutic
>>> :: effects, at least in the first 8 months of treatment. However,
>>> :: studies of dose escalation following longer periods of
>>> :: benzodiazepine use are generally lacking."
>>> http://www.psych.org/clin_res/pg_panic_3.cfm
>>>
>>>
>>>
>>> Therefore, on all the criteria used to define addiction,
>>> benzodiazepines are not addictive drugs.
>>> However, they can and very often do cause dependency. Dependence is
>>> produced by the presence of a drug causing changes in body systems
>>> that then need to time to return to their pre drug state if the drug
>>> is withdrawn. A drug doesn't have to be active in the brain for
>>> dependency to develop - many cannot pass the blood-brain-barrier, but
>>> they must for true addiction to develop.
>>>
>>> Benzodiazepines do over time produce a small bio-feedback reduction in
>>> both benzodiazepine receptors and possibly expression of the
>>> neurotransmitter GABA.
>>>
>>> If the benzodiazepine is discontinued abruptly, this reduction in
>>> receptors and neurotransmitter can cause a rebound reaction with
>>> symptoms similar to anxiety and panic. In most cases with a slow
>>> taper, withdrawal symptoms can be minimized to a comfortable level.
>>>
>>> Moreover, not all withdrawal symptoms may be due to these
>>> physiological changes. Some, perhaps most, can be produced by
>>> psychology, that is the mind. It is well known that benzo withdrawal
>>> effects can often be induced simply by making patients believe their
>>> benzodiazepine dose has been reduced, even though no reduction
>>> actually occurs. This has been shown in a number of studies. [6]
>>>
>>> There is also evidence [7] that withdrawal is more intense in some
>>> patient groups, notably those who have neurotic personalities,
>>> females, former/current alcoholics, the less educated, and those with
>>> dependant personalities. It also appears that the worse the original
>>> anxiety disorder, the more severe the withdrawal.
>>>
>>> Probably the best indication that many of the withdrawal problems
>>> experienced by those who were taking benzodiazepines for anxiety
>>> disorders are mostly psychological rather than chemical is the fact
>>> that the other main benzo using patient cohort, epileptics, seem to
>>> have much fewer problems. Indeed, there are very few re****ts in the
>>> medical literature of epileptics having difficult withdrawals and I've
>>> been unable to find even one case of "Protracted Withdrawal Syndrome."
>>> Yet typical anti seizure benzo doses are much higher than those
>>> usually needed to control anxiety, 10mg Klonopin being about average,
>>> but 20mg/day or higher is not unusual.
>>>
>>> It should also be noted that many medications and supplements can
>>> produce dependency, even some over the counter ones like vitamin C.
>>> This may produce rebound scurvy if stopped suddenly after long term
>>> use at high doses (1,000mg+/day). Symptoms may include bleeding gums
>>> and nails. Extreme reactions may cause both tooth and hair loss.
>>>
>>> Other commonly used drugs that can induce dependence include:
>>> antibiotics, most heart medications (beta-blockers, ACE inhibitors
>>> etc), some cholesterol lowering drugs, antidepressants, most
>>> painkillers - including OTC, some cancer drugs, valerian, and St
>>> John's Wort.
>>>
>>>
>>>> Addiction vs. Dependency:
>>>> Benzodiazepines & Anxiety Disorders
>>>>
>>>>
>>>> RESEARCH
>>>> "In patients without histories of substance abuse, who are prescribed
>>>> benzodiazepines under medical supervision . . . benzodiazepines
almost
>>>> never induce behavior that satisfies any reasonable definition of
>>>> addiction" (Piper, Jr., A. "Addiction to Benzodiazepines -- How
>>>> Common?" Archives of Family Medicine 4.11 (1995): 964-970).
>>>>
>>>> "Long-term users of alprazolam/lorazepam . . . used a constant or
>>>> decreasing dose of medication . . . Persistant use of
>>>> alprazolam/lorazepam for therapeutic purposes did not represent abuse
>>>> or addiction as the terms are usually understood" (Romach, M., et.
>>>> al. "Clinical Aspects of Chronic Use of Alprazolam and Lorazepam."
>>>> American Journal of Psychiatry 152.8 (1995): 1161-1170).
>>>>
>>>> "The vast majority of the use of benzodiazepines is appropriate.
>>>> Problems of nonmedical use arise nearly exclusively among people who
>>>> abuse other drugs" (Woods, J.H. and G. Winger. "Current
Benzodiazepine
>>>> Issues." Psychopharmacology 118.2 (1995): 107-115).
>>>>
>>>> "With panic/agoraphobia patients there is no evidence of abuse.
Chronic
>>>> use is justified in these patients; risk must be weighed against
>>>> benefit, dependence against relief . . . Potential abusers are those
>>>> with personality disorders, dysphoria (mood disturbance) and current
or
>>>> previous substance abuse . . . there is no epidemic of misuse. Abuse
>>>> seems to be limited to substance abusers . . . chronic use is
justified
>>>> in chronic anxiety patients. Chronic use does not usually lead to
>>>> abuse" (American Psychiatric Association. Benzodiazepine Task Force
on
>>>> Use, Dependence, Toxicity and Abuse. May 1990).
>>>>
>>>>
>>>> The Definitions
>>>>
>>>> The term addiction is often equated with abuse. Addiction is
generally
>>>> marked by tolerance and/or psychological dependence. With tolerance,
a
>>>> person needs to increase the dosage of a medication over time in
order
>>>> to receive the same therapeutic benefits. Studies show that the
>>>> majority of people with anxiety disorders do not increase their
>>>> benzodiazepine dosages over time; in fact, most lower their dosages.
>>>>
>>>> When we think of addiction we are often thinking of psychological
>>>> dependence. With psychological dependence, a person continues to take
a
>>>> medication no matter what the consequences. The person will also seek
>>>> out the medication no matter what the consequences. Again, as with
>>>> tolerance, most studies show that people with anxiety disorders do
not
>>>> become psychologically dependent on benzodiazepines.
>>>>
>>>> The exceptions to the studies mentioned above are people who have a
>>>> history of addiction to other drugs. People with such a history are
>>>> possibly at risk for becoming addicted to benzodiazepines, too.
>>>>
>>>> A condition which does occur with long-term, regular use of
>>>> benzodiazepines is physical dependence. After using benzodiazepines
>>>> regularly for a few months (and the time varies for each individual),
a
>>>> person's body will usually adapt to the drug. If the medication is
>>>> stopped abruptly, the person will experience withdrawal symptoms.
These
>>>> symptoms may be lessened (or even eliminated) by slowly tapering off
>>>> the medication, if one chooses to stop taking it. Benzodiazepines
>>>> should be discontinued only with the supervision of a qualified
>>>> physician.
>>>>
>>>> People who are on medication for an illness for a long time are not
>>>> addicted to the medication; they are medically dependent on it. They
>>>> need to keep taking the medication in order to keep the symptoms of
the
>>>> illness away. The majority of anxiety disorders patients who take
>>>> benzodiazepines over the long term fall into the category of medical
>>>> dependence.
>>>>
>>>> The rest of the article is at
>>>>
>>>>
http://panicdisorder.about.com/health/panicdisorder/library/weekly/aa031
>>>> 997.htm
>>>>
>>>
>>>
>>> J Clin Psychiatry. 2005;66 Suppl 2:28-33.
>>>
>>> "Benzodiazepine use, abuse, and dependence"
>>>
>>> O'brien CP. Department of Psychiatry, University of Pennsylvania,
>>> Philadelphia, PA 19104, USA. obrien@[EMAIL PROTECTED]
>>>
>>>
>>> Although *benzodiazepines are invaluable in the treatment of anxiety
>>> disorders*, they have some potential for abuse and may cause
dependence
>>> or
>>> addiction.
>>>
>>> It is im****tant to distinguish between addiction to and normal
physical
>>> dependence on benzodiazepines.
>>>
>>> Intentional abusers of benzodiazepines usually have other substance
>>> abuse
>>> problems. Benzodiazepines are usually a secondary drug of abuse-used
>>> mainly
>>> to augment the high received from another drug or to offset the
adverse
>>> effects of other drugs.
>>>
>>> *Few cases of addiction arise from legitimate use of benzodiazepines*
>>>
>>> Pharmacologic dependence, a predictable and natural adaptation of a
body
>>> system long accustomed to the presence of a drug, may occur in
patients
>>> taking therapeutic doses of benzodiazepines. However, this dependence,
>>> which
>>> generally manifests itself in withdrawal symptoms upon the abrupt
>>> discontinuation of the medication, may be controlled and ended through
>>> dose
>>> tapering, medication switching, and/or medication augmentation.
>>>
>>> Due to the *chronic nature of anxiety, long-term low-dose
benzodiazepine
>>> treatment may be necessary* for some patients; this continuation of
>>> treatment should not be considered abuse or addiction.
>>>
>>>
>>> PMID: 15762817 [PubMed - indexed for MEDLINE]
>>>
>>>
>>>
>>>
>>> "The controversy surrounding benzodiazepine administration and
potential
>>> abuse or addiction in routine patient use is generally not sup****ted
by
>>> the
>>> available scientific evidence.
>>>
>>> In a large community study of long-term alprazolam users, Romach and
>>> colleagues (1992) found that dosage did not escalate over prolonged
use
>>> and
>>> that most patients used the benzodiazepines as prescribed. In fact, if
>>> deviations occured, it was generally that a patient took less than the
>>> prescribed dosage."
>>>
>>> from: "The American Psychiatric Press Textbook of Psychopharmacology"
by
>>> Schatzberg and Nemeroff, 2nd Edition (1998)
>>>
>>> ---------------------------------------------------------------------
>>>
>>> J Clin Psychopharmacol 1992 Oct;12(5):316-21
>>>
>>> Characteristics of long-term alprazolam users in the community.
>>>
>>> Romach MK, Somer GR, Sobell LC, Sobell MB, Kaplan HL, Sellers EM.
>>>
>>> Department of Psychiatry, University of Toronto, Ontario, Canada.
>>>
>>> The widespread use of benzodiazepines remains a source of concern to
the
>>> medical profession and the general public, especially as newer
compounds
>>> come on the market. Our goal was to characterize long-term alprazolam
>>> users
>>> in the community and to determine whether such use represented abuse
or
>>> behavioural dependence. We conducted three community surveys to learn
>>> about
>>> the natural history of long-term alprazolam use. Current long-term
>>> alprazolam users (those using the drug for 3 months or longer) were
>>> recruited on three separate occasions 1 year apart by identical
>>> newspaper
>>> advertisements in the metropolitan Toronto area. All respondents were
>>> mailed
>>> a questionnaire with a stamped, addressed return envelope.
>>>
>>> Our data from 312 respondents show that:
>>>
>>> (1) the majority of patients have a substantial history of prior
>>> medication
>>> use for symptom control (65%),
>>>
>>> (2) dose escalation is not a characteristic of long-term use,
>>>
>>> (3) patients change their initial pattern of regular use to one of
>>> symptom
>>> control only when required,
>>>
>>> (4) most physicians do not discuss discontinuation of the drug with
>>> their
>>> patients,
>>>
>>> (5) patients frequently try to stop their drug use (with a median of 2
>>> attempts) and often re****t symptoms upon discontinuation, and
>>>
>>> (6) patients perceive a need for medication use and indicate that
>>> alprazolam
>>> is effective (75%).
>>>
>>> We conclude that some patients persistently use alprazolam but that
this
>>> use
>>> does not represent abuse or behavioral dependence.
>>>
>>> PMID: 1479048 [PubMed - indexed for MEDLINE]
>>>
>>>
----------------------------------------------------------------------------
>>> ----
>>>
>>> Addiction.....Dependence........Withdrawal
>>>
>>> "Addiction and dependence are frequently confused. 'Addiction' is hard
>>> to
>>> define, with little consensus on what it means, and in fact is not
even
>>> defined as a condition in the DSM-IV.
>>>
>>> 'Addiction' usually refers to a behavioral pattern of drug abuse
>>> characterized by overwhelming involvement with use of a drug
(compulsive
>>> use) and with the securing of its supply and by a high tendency to
>>> relapse
>>> after discontinuation.
>>>
>>> The term 'addiction' is frequently employed by those who are not
experts
>>> in
>>> psychopharmacology when 'dependence' is what they mean.
>>>
>>> 'Dependence' is a physiological state of neuroadaptation produced by
>>> repeated administration of a drug, necessitating continued
>>> administration to
>>> prevent the appearance of a 'withdrawal syndrome'.
>>>
>>> 'Dependence' is a term that is not frequently used outside of
>>> psychopharmacology but in fact is a key feature of many
antihypertensive
>>> medications, hormones, and other treatments throughout medicine. Thus
>>> several antihypertensives can produce 'rebound' hyptertension, worse
>>> than
>>> the original blood pressure elevation, when suddenly discontinued.
These
>>> patients are not 'addicted' to the blood pressure medications although
>>> they
>>> are 'dependent' on them.
>>>
>>> 'Withdrawal' is the term for the adverse psychological and
physiological
>>> reactions to abrupt cessation of a dependence-producing drug."
>>>
>>>
>>> from: Essential Psychopharmacology, 2nd Edition (2000), Stephen M.
>>> Stahl,
>>> published by Cambridge University Press
>>>
>>> (Dr. Stahl is a PhD and MD, and is a Professor of Psychiatry at the
>>> University of California, San Diego. He has conducted numerous
research
>>> projects awarded by the National Institute of Mental Health, the
>>> Veterans
>>> Administration, and the pharmaceutical industry. Dr. Stahl is an
>>> internationally recognized clinician, researcher, and teacher in
>>> psychiatry
>>> with subspecialty expertise in psychopharmacology.)
>>>
>>>
--------------------------------------------------------------------------
>>>
>>> "Although it is wise to avoid prolonged hypnotic use, prolonged use of
a
>>> benzodiazepine hypnotic may be less harmful than is often said and
may,
>>> in
>>> fact, provide some benefit. The available evidence from sleep
>>> laboratories
>>> suggests that hypnotics improve sleep measurably for only a few weeks,
>>> though placebo-controlled studies have shown no diminution in the
>>> efficacy
>>> of hypnotics for up to 24 weeks, and single-blind studies show
efficacy
>>> up
>>> to a year. So far, no studies have clearly established a treatment
>>> duration
>>> after which benzodiazepine hypnotics fail to work. Many confirmed
users
>>> of
>>> hypnotics swear that the hypnotics are always helpful and even vitally
>>> necessarry for years."
>>>
>>> from "Manual of Clinical Psychopharmacology", Edition 2003,
Schatzberg,
>>> Cole, and DeBattista
>>>
>>>
----------------------------------------------------------------------------
>>> --------------
>>>
>>> Quoted from "Panic Disorder: The Medical Point of View", by William
>>> Kernodle, M.D.
>>>
>>> "Our society appears to have a phobia concerning benzodiazepines. I
>>> believe this fear started many years ago when Valium was prescribed
for
>>> minor anxiety and patients were not made aware of the potential for
>>> developing physical dependence. It is physical addiction that most
>>> patients worry about with a benzodiazepine. I believe *addiction*
>>> refers to a severe form of drug abuse in which the individual craves a
>>> substance despite negative consequences and needs more and more for
the
>>> same effect. I do not think that patients with panic disorder crave
the
>>> benzodiazepines for their effect or frequently develop physical
>>> tolerance (with the possible exception of substance abusers). It is
>>> possible for patients to develop *physical dependence* on the
>>> benzodiazepines when used at moderate to high doses over months or
>>> years. However, this simply means that the benzodiazepine has to be
>>> tapered slowly rather than stopped abruptly to avoid having a
withdrawal
>>> symptom" (p 115).
>>>
>>>
>>>
>>> Title: Maintenance drug therapy of panic disorder.
>>> Title Abreviation: J Psychiatr Res Date of Pub: 1993
>>> Author: Curtis GC; Massana J; Udina C; Ayuso JL; Cassano GB; Perugi G;
>>> Issue/Part/Supplement: Volume Issue: 27 Suppl 1 Pagination: 127-42
>>> Journal Title Code: JTJ Publication Type: CLINICAL TRIAL
>>> Date of Entry: 940505N Entry Month: 9407 Country: ENGLAND Index
>>> Priority: 2
>>> Language: Eng Unique Identifier: 94194428 ISSN: 0022-3956
>>>
>>> Abstract: The efficacy of tricyclics and benzodiazepines in the short
>>> term
>>> (approximately 2-4 months) treatment of panic disorder is well
>>> demonstrated, but
>>> efficacy over the longer term is not considered established. The
present
>>> study
>>> provided systematic data from a double blind comparison of maintenance
>>> therapy
>>> (up to 8 months) of panic disorder with or without agoraphobia with
>>> alprazolam,
>>> imipramine, or placebo in 181 patients who had responded to the same
>>> regimen in
>>> a randomized 8-week treatment trial. All three groups had improved
>>> during the
>>> first 2 months (active treatments more than placebo and about equal to
>>> each
>>> other), and all maintained or extended their improvement over the next
6
>>> months
>>> without any significant change in dose. More than twice as many
>>> alprazolam and
>>> imipramine than placebo patients (15%) remained in treatment for the
>>> full 8
>>> months and did slightly better on symptom measures than the remaining
>>> placebo
>>> patients. Both medications were well tolerated during the maintenance
>>> period.
>>> The data suggest sustained efficacy and safety of imipramine and
>>> alprazolam over
>>> an extended period. More specifically, they suggest that tolerance
does
>>> not
>>> develop to the therapeutic effects of either drug.
>>> Abstract By: Author
>>> Address: University of Michigan, Ann Arbor.
>>>
>>>
>>>
>>>
>>> Some links:
>>>
>>>
>>>
>>> http://www.biopsychiatry.com/clonazepam.html
>>>
>>>
>>> http://www.ncbi.nlm.nih.gov/pubmed/7298586?dopt=Abstract
>>>
>>>
http://www.ncbi.nlm.nih.gov/pubmed/17881433?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
>>>
>>>
>>>
http://www.ncbi.nlm.nih.gov/pubmed/16103667?ordinalpos=17&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
>>>
>>>
>>>
http://www.ncbi.nlm.nih.gov/pubmed/15907150?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
>>>
>>>
>>>
>>> Tolerance to the anxiolytic effects has been shown in
>>> various animal studies [94,95], although not by all authors
>>> [9,96], and when detected it appears to occur at a slower rate
>>> than that of sedative tolerance [88]. Further, it has been
>>> difficult to demonstrate tolerance to the anxiolytic [8] or antipanic
>>> effects of benzodiazepines [97,98] in man. In fact, when
>>> treated for generalised anxiety disorder patients develop
>>> tolerance to the sedative effects without there being a re****ted
>>> decrease in anxiolytic efficacy [8].
>>>
http://www.ingentaconnect.com/content/ben/cpd/2002/00000008/00000001/art00002
>>>
>>>
>>>
>>> Benzodiazepine derivatives--side effects and dangers.Lader MH,
Petursson
>>> H.
>>> The benzodiazepines are generally safe and effective drugs with
usually
>>> only
>>> minor side effects, dose-related sedation being the most common. A
range
>>> of
>>> paradoxical effects can occur of which release of aggressive and
hostile
>>> feelings has excited most attention. These responses are idiosyncratic
>>> however, as most patients re****t decrease of such feelings while
taking
>>> benzodiazepines. Dependence on benzodiazepines with escalation of
dosage
>>> and/or social abuse is uncommon set against their widespread use.
>>> Recently
>>> though, evidence has ac***ulated that patients on normal doses for
>>> prolonged
>>> periods can commonly experience withdrawal symptoms, often unpleasant
>>> and even
>>> severe. These drugs should be reserved for patients suffering from
>>> defined
>>> clinical anxiety syndromes and not used indiscriminately in patients
>>> with
>>> normal stress responses.
>>>
>>> PMID: 6130800 [PubMed - indexed for MEDLINE]
>>>
http://www.ncbi.nlm.nih.gov/pubmed/6130800?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
>>>
>>>
>>>
>>> They may also be regarded as necessary for more severe psychiatric
>>> disorders,
>>> usually as an adjunct to other therapy. In such instances the
dependence
>>> risk
>>> is acknowledged but the benefits of treatment are considered to
outweigh
>>> them.
>>> There may also be patients who are dependent on benzodiazepines but
the
>>> alternative of withdrawing the drug may lead to dependence on a more
>>> dangerous
>>> drug such as alcohol. In such cases it is reasonable to regard
continued
>>> prescription of the benzodiazepine as the least dangerous course of
>>> action. It
>>> is im****tant to maintain a perspective of dependence on minor
>>> tranquillizers,
>>> particularly as attitudes are in danger of being distorted by
excessive
>>> media
>>> attention. To date there is no evidence that dependence on
>>> benzodiazepines
>>> leads to any dangerous long term sequelae although there is concern
over
>>> their
>>> effects on higher cognitive function. Nevertheless, the dangers of
>>> barbiturates, alcohol and nicotine are so much greater that it would
be
>>> unfortunate if public concern led to excessive restrictions on the use
>>> of
>>> benzodiazepines.(ABSTRACT TRUNCATED AT 400 WORDS)
>>>
>>> PMID: 2894676 [PubMed - indexed for MEDLINE]
>>>
http://www.ncbi.nlm.nih.gov/pubmed/2894676?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
>>>
>>> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
>>>
>>>
>>>
>>> J Psychiatr Res. 1990;24 Suppl 2:81-90.Links
>>> A practical approach to benzodiazepine discontinuation.DuPont RL.
>>> Department of Psychiatry, Georgetown University School of Medicine,
>>> Wa****ngton, D.C.
>>>
>>> Non-medical use of benzodiazepines is rare among patients with anxiety
>>> disorders. Numerous studies have found that non-medical use, or abuse,
>>> of
>>> benzodiazepines occurs usually among patients with histories of
alcohol
>>> and
>>> drug abuse--those who use those drugs to get "high". This article
>>> distinguishes between medical and non-medical use of benzodiazepines
in
>>> clinical practice, and offers practical approaches to discontinuation
of
>>> benzodiazepine treatment for both medical and non-medical users of
those
>>> medicines. The major barrier to clear thinking about the abuse of
>>> benzodiazepines is the confusion of "addiction" and "withdrawal".
>>> Addiction
>>> means high, unstable dosing outside medical and social boundaries for
>>> "recreational" purposes, loss of control over use, and continued use
>>> despite
>>> clear evidence of harm. Alcoholism and heroin addiction are typical
>>> examples
>>> of addiction (Kalant, 1989). In contrast, withdrawal is a
>>> pharmacological
>>> consequence of discontinuation of a substance on which a person has
>>> become
>>> dependent. Many drug-addicted people have only minor withdrawal
symptoms
>>> when
>>> they stop drug use. Many medical patients, with no evidence of
>>> addiction, have
>>> withdrawal symptoms when they stop treatment, especially when they
stop
>>> abruptly (e.g. surgical patients using narcotic analgesics and
>>> epileptics
>>> using benzodiazepines or barbiturates in their treatment). Addiction
to
>>> benzodiazepines, in the sense of loss of control over use and
continued
>>> despite harm, is virtually limited to people with pre-existing drug or
>>> alcohol
>>> abuse, while withdrawal symptoms after prolonged daily use are common
>>> among
>>> medical users of benzodiazepines. The serious nature of both drug
abuse
>>> and
>>> anxiety disorders is not emphasized sufficiently during medical school
>>> or in
>>> the professional literature. The distress and disability from which
both
>>> groups of patients and their families suffer is profound. Fortunately,
>>> both
>>> drug abuse and anxiety patients receive tremendous benefit from
>>> successful
>>> treatments, both pharmacological and nonpharmacological (DuPont,
1986a;
>>> DuPont, 1984). This article discusses the use of benzodiazepines in
two
>>> distinct populations--drug abusers and patients with anxiety
>>> disorders--and
>>> helps clinicians distinguish between the use of benzodiazepines in the
>>> two
>>> groups. The central distinction made in this article is reflected in
the
>>> common use of the words "drugs" and "medicines". The former term often
>>> denotes
>>> non-medical substance use, while the latter term refers to traditional
>>> pharmacotherapy.
>>>
>>> PMID: 1980703 [PubMed - indexed for MEDLINE]
>>>
>>>
>>> August 01, 2007 Vol. 24 No. 7
>>> Risk Versus Benefit of Benzodiazepines
>>> Jay M. Pomerantz, MD
>>>
>>>
>>> As Salzman31 pointed out, "dependence" is not necessarily "addiction."
>>> Developing dependence is a predictable phenomenon, influenced by
dosage,
>>> duration of treatment, and other patient factors. Most often,
dependence
>>> is a
>>> normal consequence of long-term pharmacological receptor-site
activity.
>>> Addiction implies not only dependence, but also nonmedical use,
>>> pleasure-seeking use, and often polysubstance abuse. Most
benzodiazepine
>>> use
>>> is not addictive, but appropriate use can sometimes result in
>>> dependence.
>>>
http://www.psychiatrictimes.com/topic/Anxiety/showArticle.jhtml?articleID=201201859&pgno=3&topic=Anxiety
>>>
>>>
>>>
>>> Issues in the Long-Term Treatment of Anxiety Disorders
>>>
>>> Edward Schweizer, Karl Rickels, and Eberhard H. Uhlenhuth
>>>
>>>
>>>
>>>
>>>
>>>
>>>
>>> INTRODUCTION
>>>
>>>
>>> The goal of this chapter is to review issues relating to the long-term
>>> treatment of anxiety disorders. The review does not pretend to be
>>> exhaustive, but it has been written with the intention of critically
>>> addressing clinically im****tant aspects of long-term anxiolytic
>>> therapy. The scope of the review is limited to panic disorder with or
>>> without agoraphobia, generalized anxiety disorder (GAD), and social
>>> phobia. Most of the emphasis is placed on drug therapy. Space
>>> limitations, and the limitations of the authors themselves, have
>>> dictated that results from psychotherapy studies could only be
>>> highlighted. It was felt, though, that the rapidly expanding
>>> literature of controlled psychotherapy research simply could not be
>>> ignored, because their preliminary results stake a claim to the
>>> achievement of sustained efficacy post treatment.
>>>
>>> The review will first undertake to establish whether there is any need
>>> for long-term or maintenance anxiolytic therapy. Long-term therapy can
>>> only be justified if there is evidence that the course of illness of
>>> panic/agoraphobia, GAD, and social phobia are frequently chronic. The
>>> longitudinal nature of these disorders will be evaluated in terms of
>>> retrospective re****ts, prospective studies of community samples (ideal
>>> but not generally available), and follow-up studies of treated
>>> samples. Acute (short-term) treatment studies will also be reviewed:
>>> High rates of relapse or recurrence in the months and years following
>>> acute treatment suggest that such treatment is inadequate, and that
>>> continuation or maintenance treatment may be beneficial. Establi****ng
>>> how beneficial leads us to a brief review of recent research on the
>>> degree of disability and impairment in quality of life caused by the
>>> anxiety disorders. The justification section will conclude with a
>>> brief review of the extent to which the natural history of the three
>>> anxiety disorders is complicated by Axis I and Axis II comorbidity.
>>> Long-term treatment planning cannot be undertaken without considering
>>> these high rates of comorbidity.
>>>
>>> Next will come a brief review of published evidence for the efficacy
>>> of long-term treatment of each of the three anxiety disorders.
>>> Evidence for long-term efficacy will be reviewed for the various
>>> cl***** of antidepressants, as well as for the benzodiazepines and
>>> buspirone. Long-term treatment will be conceptualized, in keeping with
>>> the terminology employed in the affective disorders literature, as
>>> either "continuation" treatment or "maintenance" treatment.
>>> Continuation treatment consists of the extension of drug therapy for 6
>>> months beyond the acute phase in an attempt to prevent relapse,
>>> defined as a return of the current episode of anxiety. Maintenance
>>> treatment consists of the long-term use of drugs whose goal is to
>>> prevent a recurrence of a subsequent episode of anxiety in a patient
>>> who has demonstrated high chronicity, a high rate of recurrence,
>>> and/or significant levels of severity or disability associated with
>>> previous episodes.
>>>
>>> The putative benefits of long-term (continuation or maintenance)
>>> therapy, insofar as they have been established, will be contrasted
>>> with the potential risks attendant upon such therapy. The abuse
>>> liability, dependence, and withdrawal risks associated with the
>>> benzodiazepines will be especially emphasized. Miscellaneous issues
>>> relating to long-term therapy, such as predictors of chronicity,
>>> safety and benefits of combination therapy (drug–drug or
>>> drug–psychotherapy), compliance, and intermittent medication
>>> strategies, will be reviewed next. The chapter will conclude with a
>>> review of methodologic issues in studying long-term treatment, suggest
>>> some promising research designs, and identify areas for future
>>> research.
>>>
>>> THE EVIDENCE FOR CHRONICITY
>>>
>>>
>>> Only belatedly has it been recognized that the anxiety disorders tend
>>> to be chronic and/or recurrent conditions. This recognition has not
>>> yet reshaped our basic treatment approach, which still focuses almost
>>> exclusively on the acute control of symptoms and only secondarily
>>> acknowledges that treatment may need to be either continued or
>>> reinitiated. Treatment planning for bipolar disorder, for
>>> schizophrenia, and, recently, for unipolar depression is premised on
>>> the chronicity of each illness, whether a maintenance or an
>>> intermittent drug treatment strategy is ultimately utilized.
>>>
>>> But what is the evidence for chronicity for panic disorder (with or
>>> without agoraphobia), GAD, and social phobia? The evidence comes
>>> mostly from cross-sectional and retrospective *****sments of duration
>>> of illness and, much less frequently, from prospective studies. These
>>> latter prospective studies are not long-term, but generally consist of
>>> patient samples followed naturalistically post treatment, in which
>>> case they provide evidence not only for the chronicity of the
>>> disorder, but also for the insufficiency of acute therapy alone.
>>>
>>> Panic Disorder
>>>
>>> In the ECA community survey (51), the median age of onset was 23, and
>>> the mean duration of panic disorder was 7.1 years for the subset of
>>> patients whose panic was in remission. The duration of panic in the
>>> majority (81%) who continued to re****t panic was apparently not
>>> computed, because the illness was still ongoing. Treatment studies
>>> find a similar mean duration of illness (ongoing at the time of
>>> evaluation) in the range of 5–12 years (4, 56, 59). The
>>> retrospectively *****sed age of panic onset in these treatment studies
>>> was in the mid-twenties, comparable to the results obtained in the ECA
>>> community survey, suggesting that the re****ted duration of illness was
>>> long not simply due to a sampling bias with respect to the type of
>>> patient applying for treatment in a drug study. Overall, the course of
>>> illness of panic disorder appears to be chronic in the majority of
>>> patients, but with many re****ting periods of remission lasting 6
>>> months or longer.
>>>
>>> Generalized Anxiety Disorder
>>>
>>> For GAD, the ECA community survey re****ted a median age of onset in
>>> the early twenties (51). For the good outcome cases that had remitted,
>>> mean duration was 4.5 years, with 40% re****ting durations of illness
>>> of longer than 5 years. For currently active cases of GAD, the mean
>>> duration of illness to date was re****ted as 8.5 years. Duration of
>>> illness for still-active cases of GAD entering both drug and
>>> psychotherapy treatment studies (45, 47) ranges from 5 to 15 years,
>>> confirming that GAD has high chronicity. Several researchers (5, 29)
>>> have noted that the clinical course of GAD is both more chronic and
>>> more unremitting than panic disorder. Noyes et al. (35!popup(ch127),
>>> in one of the few prospective studies (of anxiety neurosis), re****ted
>>> that 48% of patients continued to have moderate-to-marked symptoms at
>>> the 4- to 9-year follow-up.
>>>
>>> Social Phobia
>>>
>>> Much less information is available about the course of illness of
>>> social phobia, but available data from both community (23, 54) and
>>> patient samples (19, 24) suggest an age of onset in the mid to late
>>> teens, with a chronicity that is equal to or greater than that of
>>> panic disorder, with mean duration of illness exceeding 5 years.
>>>
>>> AGE OF ONSET: EVIDENCE FROM ADOLESCENT POPULATIONS
>>>
>>>
>>> As has been mentioned, panic/agoraphobia appears to have a mean age of
>>> onset, estimated retrospectively, to be in the early to mid twenties,
>>> GAD in the early twenties, and social phobia in the mid teens. Because
>>> retrospective recollection is prone to bias, in the direction of
>>> either over- or underestimation, it would be a useful corrective to
>>> study anxiety directly in its early incarnations. This is especially
>>> true in light of the lack of reliable course of illness data from
>>> prospective community samples followed over time. Fortunately, recent
>>> research provides data on the onset of panic, social phobia, and GAD
>>> in contem****aneous child and adolescent populations. Structured,
>>> prospectively conducted DSM-III-R *****sments of a random community
>>> sample of 1710 adolescents found a lifetime prevalence rate, to date,
>>> of 1.2% for panic disorder, 0.6% for agoraphobia, 1.5% for social
>>> phobia, 4.3% for separation anxiety disorder, and 1.2% for overanxious
>>> disorder (23). A similar community survey of adolescents (70) found
>>> prevalence rates of 0.6% for panic disorder and 3.7% for GAD. Other
>>> community prevalence estimates place the rate of panic attacks post
>>> puberty as high as 12–13%. The panic/agoraphobia, GAD, and social
>>> phobia prevalence rates for adolescents are in the range of rates
>>> re****ted for adults, suggesting that the age of onset and duration of
>>> illness estimates gleaned from retrospective re****ts in adults are, if
>>> anything, an underestimate.
>>>
>>> THE ADEQUACY OF SHORT-TERM (ACUTE) TREATMENT
>>>
>>>
>>> Panic Disorder
>>>
>>> Ac***ulated evidence across multiple controlled trials suggests that
>>> the high-potency benzodiazepines (the most studied is alprazolam) are
>>> effective drugs for the short-term treatment of panic disorder, either
>>> with or without agoraphobia (e.g., see refs. 4, 12, and 58). Similar
>>> short-term treatment efficacy has been re****ted for the tricyclic
>>> antidepressants (12, 58), the MAOI antidepressants (59), and, in pilot
>>> studies, the SSRI antidepressants (8).
>>>
>>> Only a few studies, though, have examined clinical and drug treatment
>>> status after naturalistic follow-up 1–3 years post acute study
>>> treatment. Studies re****ting outcome after short-term benzodiazepine
>>> therapy find that many patients experience transient rebound anxiety
>>> symptoms to a level above their pretreatment baseline (38, 56). By 1–3
>>> years, approximately 50% or more of acutely treated patients have had
>>> a recurrence (34), and at least 50% have resumed treatment, either
>>> with a benzodiazepine or with an antidepressant.
>>>
>>> Acute treatment with antidepressants appears to have a similar
>>> clinical and drug treatment outcome at follow-up, with re****ts of
>>> relapse ranging from 25% to 70% (30, 36). Less data are available at
>>> follow-up for the MAOI antidepressants, but here again clinical
>>> experience suggests that relapse rates are comparable. The similar
>>> relapse rates after both antidepressant and benzodiazepine therapy
>>> suggest the need for continuation therapy. They also suggest that
>>> relapse is not simply an iatrogenic byproduct of benzodiazepine
>>> therapy.
>>>
>>> Generalized Anxiety Disorder
>>>
>>> We are not aware of any published research that re****ts reliable
>>> relapse/recurrence rates for GAD patients treated with
>>> antidepressants. With azapirones, however, Rickels and Schweizer (48)
>>> found GAD patients treated with buspirone for 6 months to have a lower
>>> relapse at 3 years post treatment than did patients treated with
>>> clorazepate.
>>>
>>> A few studies have examined relapse/recurrence rates after acute
>>> benzodiazepine therapy. Rickels et al. (42) re****ted an 81% anxiety
>>> recurrence rate at 1 year for patients who had received 4 weeks of
>>> benzodiazepine therapy. In another study, Rickels et al. (44) treated
>>> 138 GAD patients for a minimum of 6 weeks with diazepam. A recurrence
>>> rate of 63% was re****ted at 1 year, with 50% of the patients
>>> sustaining improvement for at least 3 months. Overall, it appears that
>>> 60–80% of GAD patients (at least the ones applying for drug therapy)
>>> require additional treatment by 1 year.
>>>
>>> Another index of the inadequacy of acute benzodiazepine treatment is
>>> the percent of patients who relapse in the week or two immediately
>>> after discontinuation of acute treatment. In a 4-week treatment study
>>> utilizing both a long-and a short-half-life benzodiazepine, 30% of
>>> patients had relapsed by 2 weeks (46). In fact, approximately 20%
>>> achieved HAM-A scores that were equal to or higher than their
>>> pretreatment baseline, indicating a rebound anxiety that, it has been
>>> speculated, might be an early precursor of the benzodiazepine
>>> withdrawal syndrome. Other studies have re****ted similar rates of
>>> rebound anxiety after short-term benzodiazepine therapy, ranging from
>>> 25% to 44% (17). It is unclear what percent of patients experience
>>> rebound anxiety as a transient and self-limited phenomenon, and in
>>> what percent it serves to trigger a recrudescence of the underlying
>>> generalized anxiety.
>>>
>>> Relapse/Recurrence Rates After Psychotherapy
>>>
>>> The published outcome research for the psychotherapy of GAD is
>>> hampered by small sample sizes and low-power, frequently inadequate
>>> inclusion/exclusion criteria and characterization of the study
>>> populations, as well as a variety of other methodological problems.
>>> Therapies that appear to have the most well-established efficacy are
>>> cognitive therapy (with various degrees of behavior therapy added in)
>>> and anxiety management therapies. Despite poor power, the tentative
>>> evidence to date consistently suggests some degree of acute efficacy
>>> for the psychotherapies (6, 9, 16, 40). Of special interest is that 3-
>>> to 12-month follow-up suggests that GAD treated by cognitive or
>>> anxiety management therapy may be unusually effective in sustaining
>>> improvement, with less than one-third of patients relapsing in the
>>> immediate 6- to 12-month follow-up period. If these results are
>>> confirmed, especially in drug versus psychotherapy trials, it would be
>>> a significant advance in the long-term management of GAD.
>>>
>>> Social Phobia
>>>
>>> Much less treatment research has been conducted on social phobia.
>>> Treatment experience with MAOI antidepressants consists of at least
>>> two open-label studies (63, 64) and three controlled studies (19, 24),
>>> all of which suggest efficacy over 8–16 weeks of acute treatment. Only
>>> one of these studies (69) examined efficacy during continuation
>>> therapy for up to 1 year. This latter study found efficacy to be
>>> sustained. None of the studies examined rates of relapse or recurrence
>>> after MAOI discontinuation.
>>>
>>> Clonazepam has also shown pilot evidence of efficacy, but only in
>>> open-label studies (13). Fluoxetine and buspirone have both also been
>>> used successfully in short-term pilot studies (55). Again, no data
>>> were re****ted for post-drug relapse or recurrence rates, so no
>>> conclusions can be drawn concerning whether there is a role for
>>> continuation therapy. Anecdotal experience, though, with all its
>>> shortcomings, does suggest, at least for the MAOIs and clonazepam,
>>> that relapse frequently occurs within 3–6 months of discontinuing
>>> short-term treatment.
>>>
>>> LEVEL OF DISTRESS, DISABILITY, AND QUALITY OF LIFE IMPAIRMENT
>>> ASSOCIATED WITH ANXIETY DISORDERS
>>>
>>>
>>> It can be concluded with some degree of confidence (albeit with
>>> methodological caveats) that the evidence is fairly strong and very
>>> consistent and that the three anxiety disorders all have substantial
>>> chronicity. But to what extent is this chronicity associated with
>>> significant distress, disability, and impairment in functioning and
>>> quality of life? In the end, judgments about the benefits and risks of
>>> long-term anxiolytic therapy must be placed in this broader context.
>>>
>>> The evidence regarding disability and quality of life is not
>>> substantial, but appears to be fairly consistent as far as it goes.
>>> For panic disorder, significant psychosocial impairment appears to be
>>> a common feature of the disorder. In the 1979 National Survey of
>>> Psychotherapeutic Drug Use, significant pro****tions of respondents
>>> with anxiety syndromes re****ted impaired role performance due to
>>> psychological and other factors: for panic/agoraphobia, 41% and 25%;
>>> for other phobias, 33% and 23%; for general anxiety, 22% and 45% (66).
>>> The rates for panic/agoraphobia were comparable to those for major
>>> depression in the same study: 47% and 31%. Substantial pro****tions of
>>> respondents with anxiety syndromes utilized treatment during the year
>>> prior to the survey: panic/agoraphobia, 62%; other phobias, 32%;
>>> general anxiety, 50%; compared to 26% of the general population (67).
>>>
>>> The ECA survey re****ted that approximately 58% of their community
>>> sample of persons with panic disorder had some degree of financial
>>> disability, whether welfare, disability, or social security payments
>>> (28, 51). Massion et al. (29), re****ting on 234 panic patients in an
>>> outpatient setting, found approximately 50% to be employed full time
>>> and found 27% to be receiving some form of public assistance. In the
>>> ECA community survey, 86% had sought medical outpatient evaluation and
>>> treatment in the previous 6 months (compared to 8% of persons without
>>> panic), and 51% had sought mental health evaluation and treatment. In
>>> keeping with these figures, 35% of the community ECA sample rated
>>> their physical health as fair to poor, and 38% rated their emotional
>>> health as fair to poor (28). In the ECA survey, 7% of panic patients
>>> without comorbid depression re****ted a history of suicide attempts,
>>> while Massion and colleagues (29) found a rate of 3%. In a large group
>>> of high utilizers of medical outpatient care, Katon et al. (20) found
>>> a 12% rate of current panic disorder and a 30% rate of lifetime panic.
>>> This overrepresentation of panic disorder is especially high in
>>> medical subspecialty clinics, where rates of panic range from 20% to
>>> 50% for medically unexplained episodes of chest pain, tinnitus,
>>> dizziness, irritable bowel, and chronic fatigue (7, 27).
>>>
>>> For GAD, the best information currently available probably comes from
>>> the ECA community survey (51) and from a multisite survey of
>>> psychiatric outpatients (29). The overall picture for GAD is one of
>>> significant psychosocial impairment (albeit somewhat less severe than
>>> is observed with panic disorder), with 38% of ECA subjects and 71% of
>>> outpatients characterizing their emotional health as fair to poor; 27%
>>> and 25%, respectively, were receiving disability payments, and only
>>> about one-half worked full time. Of those who were working, 38% of the
>>> patient population had missed at least 1 week of work in the past year
>>> due to their anxiety. The ECA survey found a strong correlation
>>> between occupational status/income and GAD, with presence of GAD being
>>> associated with (a) a threefold greater likelihood of working at a low
>>> occupational level and (b) a more than twofold greater likelihood of
>>> earning less than $10,000 per year. Medically, 35% of the ECA sample
>>> with GAD, and 23% of the patient population of Massion et al. (29),
>>> re****ted that their physical health was fair to poor. This latter
>>> finding is corroborated in an outpatient medical setting by Katon et
>>> al. (20), who found that 24% of all high utilizers of medical
>>> outpatient care had a diagnosis of GAD.
>>>
>>> The early onset and the high degree of chronicity, disability, and
>>> medical and psychiatric morbidity associated with GAD have led some
>>> researchers to speculate that GAD might not be an independent
>>> diagnosis, but instead a trait or vulnerability factor that
>>> predisposes to later problems. Whatever its status, the chronicity and
>>> disability associated with GAD make it an unlikely candidate for a
>>> cure or sustained remission after short-term drug therapy.
>>>
>>> Quality-of-life issues and the degree of disability associated with
>>> social phobia have been much less well studied. Unfortunately, social
>>> phobia was not analyzed as a separate part of the ECA survey, so good
>>> community-based information is not available.
>>>
>>> As can be seen, the anxiety disorders are not only chronic in nature,
>>> but are often accompanied by a wide range of moderate impairments in
>>> both psychosocial functioning and quality of life. The impairment and
>>> early onset of these disorders raise questions about what
>>> developmental distortions they may produce and what benefits early
>>> treatment may provide.
>>>
>>> THE DEVELOPMENT OF COMORBIDITY DURING THE LONGITUDINAL COURSE OF
>>> ANXIETY DISORDERS
>>>
>>>
>>> One of the most im****tant issues in the long-term treatment of the
>>> anxiety disorders is the presence of comorbidity. Any long-term
>>> anxiolytic treatment strategy must take account of the high rates of
>>> comorbidity that appear to develop during the longitudinal course of
>>> panic, GAD, and social phobia—and that complicate these disorders, in
>>> fact, from their very inception. Comorbidity rates for adolescent
>>> anxiety disorders have been re****ted to range from approximately 20%
>>> to 60%, with higher rates recorded for patient samples that are under
>>> treatment (21).
>>>
>>> It is well-established that comorbidity is significantly higher for
>>> patients seeking treatment than for persons not in treatment in the
>>> community. Nonetheless, even community surveys suggest a high rate of
>>> comorbidity, especially for GAD. In the ECA survey (51), 1-year
>>> prevalence estimates, reflecting current comorbidity, showed that
>>> approximately 25% of patients with a diagnosis of GAD also suffered
>>> from either panic or major depression, while an additional 30%
>>> (approximately) suffered from another Axis I diagnosis, leaving only
>>> about 40–45% of patients with "pure" GAD (at least from an Axis I
>>> standpoint, though the extent to which social phobia might have been
>>> an undetected source of comorbidity is unclear). This figure re****ts
>>> only 1-year prevalence rates for comorbidity, and as such is a likely
>>> underestimate because anxiety has been shown frequently to evolve into
>>> either depression or panic (10) over time.
>>>
>>> Patient surveys show even higher rates of comorbidity, though the
>>> samples studied are obviously much smaller. Massion et al. (29) found
>>> that of 123 psychiatric outpatients diagnosed with GAD, 51% had a
>>> history of comorbid panic disorder. When these patients were edited
>>> out, 46% of the remaining patients had a history of comorbid major
>>> depression and 27% had social phobia. Overall, only 1.6% (2 of 123
>>> patients in a psychiatric treatment setting) were felt to have "pure"
>>> GAD, with no history of comorbid depressive or anxiety disorders.
>>> Similarly, Brown and Barlow (10) have re****ted high comorbidity rates
>>> for outpatients with a principal diagnosis of GAD. Thirty-six percent
>>> suffered from concurrent panic disorder with or without agoraphobia,
>>> 29% suffered from concurrent social phobia, and 29% suffered from
>>> concurrent major depression or dysthymic disorder. In another study
>>> (37) of outpatients who had been recruited through the media, 34% had
>>> a history of major depression and 17% had a history of social phobia
>>> (a panic disorder diagnosis was a reason for exclusion).
>>>
>>> The ECA community survey (51), as well as the Zurich cohort of Angst
>>> (2), found that 73% of patients with panic disorder had other comorbid
>>> conditions. Massion et al. (29), in their outpatient sample of 294,
>>> re****ted the following rates of comorbidity, depending on whether the
>>> patient was diagnosed with panic alone versus panic with agoraphobia:
>>> social phobia, 6% versus 15%; major depression, 27% versus 22%; OCD,
>>> 10% versus 7%. Twenty percent of panic patients suffered from comorbid
>>> GAD, but these patients were excluded from the previously re****ted
>>> comorbidity rates. Brown and Barlow (10), in a sample of 232
>>> outpatients with a panic disorder diagnosis (both with and without
>>> agoraphobia), re****ted comorbid social phobia ranging from 6% to 36%,
>>> comorbid GAD ranging from 20% to 36%, and comorbid major depression
>>> ranging from 7% to 36%, largely depending on the presence and severity
>>> of the associated agoraphobia. In a sample of patients with panic
>>> disorder alone versus panic with agoraphobia who were recruited for a
>>> trial of psychotherapeutic medication, substantially higher rates of
>>> comorbidity were found; for example, social phobia, 26% versus 64%;
>>> GAD, 32% versus 68%; major depression, 26% versus 68% (61).
>>>
>>> Comorbidity patterns for social phobia are less well-studied. The ECA
>>> community survey offers no data on social phobia. Brown and Barlow
>>> (10) re****ted the following comorbidity rates among 76 outpatients
>>> with a principal diagnosis of social phobia: panic disorder, 9%; GAD,
>>> 17%; major depression, 11%; and dysthymic disorder, 13%.
>>>
>>> Substance abuse and Axis II personality disorders constitute two other
>>> im****tant, but often neglected, categories of comorbidity which may
>>> complicate the natural history of the anxiety disorders and which must
>>> be taken into account when planning treatment interventions over time
>>> (39, 62). Studies of alcoholic patients suggest a range of 25–45% for
>>> comorbid anxiety disorders, with social phobia and panic/agoraphobia
>>> being the most prevalent (60). Conversely, prevalence rates of
>>> alcoholism in anxiety disorder populations range from 15% to 40% (29,
>>> 37, 61, 63). The ECA community survey found, not surprisingly, much
>>> lower rates of alcohol dependence/abuse. Van Ameringen et al. (68)
>>> have re****ted a 28% rate of alcoholism in a group of outpatient social
>>> phobics.
>>>
>>> Comorbidity rates for substance abuse are lower for all three anxiety
>>> disorders, ranging from about 10% to 36% in patient samples (29, 37,
>>> 61). Again, these rates are much lower in the ECA community survey
>>> (51).
>>>
>>> Multiple studies have re****ted rates of comorbidity for the anxiety
>>> disorders and Axis II disorders, most commonly the anxious "Cluster C"
>>> type. Axis II comorbidity rates for panic/agoraphobia generally range
>>> from about 30% to 60% (18, 37), with more severe agoraphobia being
>>> associated with increased rates (18). Axis II comorbidity rates for
>>> GAD have been re****ted in the same 30–60% range (37, 53).
>>>
>>> As can be seen from the above review, comorbidity is the rule and not
>>> the exception in the clinical picture of the anxiety disorders.
>>> Long-term treatment planning cannot be undertaken except on the
>>> assumption that the majority of patients suffering from a principal
>>> anxiety disorder diagnosis also suffer from another disorder, or will
>>> suffer from one in the near future. This clinical reality makes it
>>> im****tant to maintain an index of suspicion concerning the development
>>> of other disorders, and to carefully reevaluate the patient at
>>> intervals. This is especially true if patients fail to respond fully
>>> to a course of drug therapy or if an initial good response is lost. In
>>> both instances, unsuspected comorbidity is frequently the culprit.
>>>
>>> The high rates of comorbidity among anxiety and depressive disorders
>>> also raise serious questions about the true independence of these
>>> disorders. An alternative way of conceptualizing comorbidity, with
>>> depression for example, is to view the two disorders as varying
>>> manifestations of one underlying diathesis—that is, two phenotypic
>>> expressions of a common underlying "genotype." Such a view has been
>>> proposed by Tyrer et al. (65), who speak of a "general neurotic
>>> syndrome." Recent genetic analyses of women suffering from major
>>> depression and GAD (22) provide some confirmation for this
>>> perspective, with results suggesting that the genetic vulnerability
>>> for both disorders is largely shared.
>>>
>>> EVIDENCE FOR SUSTAINED EFFICACY (PREVENTION OF RELAPSE AND RECURRENCE)
>>> DURING CONTINUATION AND MAINTENANCE THERAPY
>>>
>>>
>>> Previous sections of this chapter have established that the anxiety
>>> disorders are frequently chronic conditions associated with (a) a high
>>> degree of comorbidity and (b) impairment in both psychosocial
>>> functioning and quality of life. Furthermore, evidence has been
>>> presented that acute (4–12 weeks) drug therapy frequently results in
>>> early return of symptoms (relapse) or subsequent episodes (recurrence)
>>> when treatment is discontinued. What is the evidence, though, that
>>> continuation therapy is effective in preventing relapse, or that
>>> maintenance therapy is effective in preventing recurrences?
>>>
>>> Unfortunately, there is little controlled research addressing these
>>> issues for panic/agoraphobia or GAD, and none for social phobia. The
>>> evidence for the efficacy of continuation and/or maintenance therapy
>>> of panic disorder is currently being studied in an NIMH-funded
>>> multicenter trial that compares imipramine to a form of
>>> cognitive-behavioral therapy.
>>>
>>> Schweizer et al. (58) have conducted an 8-month, placebo-controlled
>>> study of continuation therapy for panic disorder with alprazolam and
>>> imipramine that found sustained efficacy for both compounds with no
>>> dose escalation, suggesting an absence of tolerance to the therapeutic
>>> effect. When drug was discontinued after 8 months of maintenance
>>> therapy, at 3 weeks post discontinuation, approximately 25% of
>>> patients had experienced a return of their panic attacks. At 1 year
>>> follow-up, 30% of patients had a recurrence of their panic, and 49%
>>> had restarted or never stopped their medication (50). Of course, the
>>> selection bias that was likely operating in the choice of patients for
>>> the initial study, as well as the naturalistic nature of the
>>> follow-up, makes this only a suggestive pilot study.
>>>
>>> Preliminary evidence for the efficacy of continuation therapy of GAD
>>> comes from two studies (43, 47). In both studies the benzodiazepine
>>> therapy achieved sustained remission of anxious symptomatology with no
>>> tolerance and no dose escalation over a 6-month period. In the second
>>> study, buspirone also achieved a comparable sustained remission of
>>> anxious symptoms, though the significantly higher attrition rate by
>>> patients treated with buspirone complicates the interpretation of
>>> results. In both studies, about 25% of the patients experienced a
>>> return of their initial anxiety within 4 weeks of drug
>>> discontinuation.
>>>
>>> There is no good published evidence for the sustained efficacy of
>>> either antidepressants or the benzodiazepines in the continuation or
>>> maintenance treatment of social phobia. The only published re****ts
>>> found both tranylcypromine (69) and clonazepam (13) to sustain
>>> efficacy over an 11- to 12-month period of treatment.
>>>
>>> The 1979 National Survey of Psychotherapeutic Drug Use (67) indicates
>>> that a small fraction of patients with anxiety syndromes take
>>> psychotherapeutic medications for a year or more (panic/agoraphobia,
>>> 25%; other phobias, 6%; general anxiety, 6%). On the other hand,
>>> experts in the pharmacotherapy of these disorders, aware that they are
>>> chronic, severe, and disabling, generally recommend vigorous,
>>> long-term treatment. Here, as is so often the case, clinicians have
>>> had to use their best judgment in addressing clinical problems that
>>> lie beyond the scope of existing empirical evidence. Whether long-term
>>> drug treatment represents effective continuation or maintenance
>>> therapy, or patients continue to take medication because it elicits
>>> only a partial response, is uncertain. Two of the present authors have
>>> re****ted HAM-A scores of 16 in anxious patients with a mean of 6 years
>>> of benzodiazepine therapy, suggesting that long-term drug therapy, at
>>> least in this population, may have been continued even though (and
>>> perhaps because!) it was less than effective. The public health
>>> interest urgently requires clinical research to address these
>>> long-term issues of efficacy.
>>>
>>>
>>> RISKS OF LONG-TERM MEDICATION TREATMENT
>>>
>>>
>>> The efficacy obtained from drug therapy must always be weighed
>>> carefully against the potential adverse effects of the drug. This is
>>> especially true when it comes to long-term or maintenance drug
>>> therapy. What is considered tolerable, and even safe, during acute
>>> treatment may be neither of the above during chronic administration.
>>> This section will focus most intensively on the safety of long-term
>>> administration of the benzodiazepines. Not only have they been the
>>> object of intense scrutiny and concern, both publicly and
>>> scientifically, over the past 10–15 years (see ref. 71 for an
>>> excellent review), but they continue to be widely prescribed,
>>> sometimes for long-term therapy. The most recent survey data indicate
>>> that 1.6% of the adult population in 1980 took benzodiazepine for 12
>>> months or longer in the previous re****ting year (32). Some decline in
>>> long-term usage appears to have occurred since then, but it is still
>>> estimated that approximately 1% of the adult population has currently
>>> or recently received long-term benzodiazepine therapy.
>>>
>>> Benzodiazepines
>>>
>>> Discussion of the safety of the benzodiazepines during chronic use can
>>> be usefully reviewed under two headings: (i) the psychological and
>>> behavioral effects and (ii) the medical or physiological effects.
>>>
>>> A variety of psychological and behavioral effects have been attributed
>>> to the benzodiazepines when chronically administered. These include:
>>> persistent attentional, psychomotor, cognitive, and memory-impairing
>>> effects; abuse liability; physical dependence and withdrawal;
>>> post-withdrawal craving; and effects on coping and stress response
>>> capabilities. A brief review of each of these potential safety
>>> concerns is necessary in order to obtain a more complete picture of
>>> the benefit–risk equation regarding long-term therapy.
>>>
>>> Attentional, Psychomotor, Cognitive, and Memory Effects
>>>
>>> Substantial tolerance appears to develop to the attentional and
>>> psychomotor effects of benzodiazepines, beginning after the first few
>>> weeks of acute administration. The actual clinical significance (e.g.,
>>> effects on driving ability) of subtle residual impairments, or the
>>> potentiation of these impairments by low levels of alcohol consumption
>>> that otherwise would pose no problem, is uncertain. Results of
>>> laboratory *****sments, including driving simulation, have had very
>>> variable and contradictory results (see refs. 1 and 71 for reviews).
>>> But there appears to be some persistent attentional and psychomotor
>>> impairment that may be relevant to the execution of complex real-world
>>> tasks.
>>>
>>> Preliminary research suggests that cognitive tasks and (especially)
>>> short-term memory tasks continue to be impaired even after long-term
>>> (5–10 years) daily administration of benzodiazepines (25), apparently
>>> exhibiting less tolerance than psychomotor function. The existence of
>>> differential rates of tolerance development is an intriguing
>>> phenomenon, and may depend on subtle regional differences in the
>>> monomeric constituents of the benzodiazepine receptor. The amnestic
>>> effect of benzodiazepines, which appears to be relatively resistant to
>>> tolerance in humans, probably has a hippocampal substrate. It should
>>> be cautioned that statistically "significant" amnestic findings
>>> ascertained, for example, using meaningless word lists may have little
>>> generalizability to life situations. Furthermore, since
>>> moderate-to-severe anxiety frequently has been noted to impair
>>> performance, the net effect of benzodiazepine treatment may be an
>>> enhancement of performance. Nonetheless, the subtle effects on
>>> learning and motivation of chronic, mild benzodiazepine-induced
>>> amnesia have not been well-studied.
>>>
>>> A final behavioral effect for which there is no good evidence that
>>> tolerance does, or does not, develop with long-term benzodiazepine
>>> administration is irritability and hostility.
>>>
>>> Abuse Liability
>>>
>>> Benzodiazepines have a potential for recreational abuse (1, 71). But
>>> actual recreational abuse appears to occur principally in persons who
>>> abuse other drugs (see ref. 71 for review).
>>>
>>> The abuse liability of the benzodiazepines in drug and alcohol abusers
>>> appears to stem in large part from marked individual differences in
>>> the euphoriant effects of benzodiazepines. Drug addicts, alcoholics,
>>> and even the nonalcoholic sons of alcoholics appear to be much more
>>> susceptible to the euphorigenic properties of the benzodiazepines
>>> (11). In most other populations, even among anxious persons (14),
>>> benzodiazepines do not appear to have much of a euphoric effect. In
>>> fact, the reinforcing properties of the benzodiazepines appear to be
>>> relatively low compared to every other drug of abuse (71). The
>>> reinforcing property of a drug appears to be an im****tant behavioral
>>> correlate of abuse liability that tends to be fairly consistent across
>>> primate species. Even when one corrects for availability, diazepam and
>>> alprazolam are more widely abused in at-risk populations. It is
>>> unknown whether this re****ted effect is due to methodological problems
>>> with the adjustment for availability or to the rapidity of onset of
>>> action (lipophilicity, etc), or to differences in the intrinsic
>>> efficacy of the benzodiazepine at the receptor.
>>>
>>> Another indicator of abuse liability that has been identified is drug
>>> liking or preference in normal human subjects. Here, again, the
>>> benzodiazepines appear to elicit much less drug liking than do
>>> traditional drugs of abuse (14, 31).
>>>
>>> Physical Dependence and Withdrawal
>>>
>>> An ineluctable consequence of chronic benzodiazepine therapy is
>>> physical dependence, along with the likelihood of developing a
>>> withdrawal syndrome upon drug discontinuation. The clinical picture of
>>> benzodiazepine withdrawal is not always easy to distinguish from
>>> anxiety, though the tem****al pattern of onset is of some help. Further
>>> confounding the clinical picture is that the experience of
>>> benzodiazepine withdrawal may serve, in turn, to trigger a
>>> recrudescence of the patient's underlying anxiety. Common symptoms of
>>> the benzodiazepine withdrawal syndrome consist of increased anxious
>>> mood and nervousness, insomnia, restlessness, tension, irritability,
>>> lethargy, nausea, depression, hyperacusis, and tinnitus. There appear
>>> to be no pathognomonic symptoms that are unique to the withdrawal
>>> syndrome and that do not commonly occur in anxiety disorders. After
>>> abrupt discontinuation of a short half-life benzodiazepine (e.g.,
>>> alprazolam or lorazepam), withdrawal symptoms begin to appear within
>>> 6–12 hr, with a peak severity generally at 2–4 days. Symptoms usually
>>> subside within 1–3 weeks. After abrupt discontinuation of a long
>>> half-life benzodiazepine (e.g., diazepam or clorazepate), withdrawal
>>> symptoms begin to appear within 24–36 hr, peak at 4–7 days, and
>>> subside within 2–4 weeks. The benzodiazepine withdrawal syndrome,
>>> unless complicated by other medical or psychiatric illness or by other
>>> drug or alcohol problems, can be managed in an outpatient setting.
>>>
>>> Several factors have been identified that appear to contribute to the
>>> development of benzodiazepine withdrawal and that add to its severity.
>>> The first of these is duration of therapy. Rebound anxiety (to a level
>>> above pretreatment baseline) has been observed after as little as 4
>>> weeks of benzodiazepine treatment (46). Such transient rebound
>>> reactions are thought to be the prodromal signs of a developing
>>> pattern of dependence and withdrawal. By 3–4 months, physical
>>> dependence is likely to have been established, and a withdrawal
>>> syndrome upon benzodiazepine discontinuation can clearly be observed
>>> in a significant number of patients. There is no good evidence that
>>> longer durations of maintenance therapy beyond 12 months contributes
>>> to greater dependence and withdrawal liability (49, 57).
>>>
>>> A second factor that contributes to dependence and withdrawal is the
>>> daily dose of the drug. It is im****tant to note, though, that
>>> dependence and withdrawal do not require aggressive dosing. Patients
>>> treated with as low as 5–10 mg of diazepam or its equivalent have been
>>> noted to experience withdrawal reactions upon drug discontinuation.
>>> The clinical implications of the dose and duration of treatment
>>> factors is that only the most short-term treatment is without risk of
>>> physical dependence and withdrawal. The medical–legal implication of
>>> this situation is that information on dependence and withdrawal
>>> effects should probably be a routine part of the educational
>>> introduction of all patients to the benefits and risks of
>>> benzodiazepine therapy.
>>>
>>> Several other factors contribute to the severity of benzodiazepine
>>> withdrawal. These include the rate of taper (obviously abrupt
>>> discontinuation poses a greater problem than a gradual taper over 4–8
>>> weeks) and the presence of Axis I and II disorders. Residual anxiety,
>>> panic, and depressive symptoms also predict greater difficulty with
>>> withdrawal.
>>>
>>> One unresolved issue is whether the benzodiazepine withdrawal syndrome
>>> may persist, in some form and in some patients, for many months, or
>>> even years. A subset of patients subjectively re****ted ongoing
>>> symptoms and complaints (3), and a "post-withdrawal syndrome" has even
>>> been proposed (64). The pharmacologic mechanism of this proposed state
>>> of persistent withdrawal is unclear, though a putative "receptor
>>> ****ft" has been suggested. It is, of course, difficult to disentangle
>>> persistent symptoms of withdrawal from a recrudescence of anxiety. The
>>> fact that the symptoms differ from a patient's previous experience of
>>> anxiety is no guarantee that an iatrogenic state has been triggered,
>>> because symptoms of anxiety can change over time. It is also of
>>> interest that two of the authors (Rickels and Schweizer) have noted an
>>> absence of any re****ts of persistent withdrawal states in abstinent
>>> patients with a history of benzodiazepine dependence, but in whom
>>> benzodiazepines were not prescribed for anxiety. In most cases, such
>>> post-benzodiazepine discontinuation symptoms are most likely related
>>> to the patient's Axis I and Axis II disorders. Still, it is a topic of
>>> concern, and deserves further research, whether chronic administration
>>> of benzodiazepines may in some way permanently alter the
>>> benzodiazepine-GABAergic system.
>>>
>>> Post-withdrawal Craving of Drug and Restarting Benzodiazepine
>>>
>>> It is an almost universal feature of drugs of abuse that they
>>> intermittently evoke craving in the user long after the withdrawal
>>> syndrome has subsided. Alcohol, tobacco, cocaine, amphetamines,
>>> opiates, and even coffee engender cravings in the months and years
>>> after drug discontinuation. Preliminary research (26) suggests that
>>> there is little or no craving associated with long-term dependence on
>>> benzodiazepines. Certainly former benzodiazepine-dependent patients do
>>> restart their benzodiazepine, but resumption of benzodiazepine use is
>>> almost exclusively caused by a recurrence of symptoms of anxiety.
>>> Naturalistic follow-up studies of chronic benzodiazepine users find a
>>> clear trend over time toward lower daily doses, and eventual
>>> discontinuation. The pharmacoepidemiological data (32) also indicate
>>> that the vast majority of regular daily benzodiazepine use continues
>>> less than a year (85%) and usually less than a month (67%).
>>>
>>> Long-Term Medical/Physiological Effects
>>>
>>> The risk of adverse medical or physiological effects from chronic
>>> benzodiazepine therapy has not been systematically studied. Medical
>>> evaluations of over 400 benzodiazepine-dependent patients (mean
>>> duration of use: >5 years), which included blood chemistries, complete
>>> blood count with differential, urinalysis, and electrocardiogram, have
>>> yielded no obvious abnormalities (Rickels et al., personal
>>> communication). A question has been raised concerning whether chronic
>>> benzodiazepine treatment might be associated with increased
>>> ventricular–brain ratios on computerized tomography scans. Several
>>> studies have yielded conflicting results on this subject, but because
>>> a variety of other comorbid medical factors, particularly alcohol use,
>>> were not excluded, the issue remains unresolved (1).
>>>
>>> Several other physiological effects appear to result from chronic
>>> benzodiazepine treatment. Preliminary data suggest that chronic
>>> treatment alters the functional status of one or more components of
>>> the benzodiazepine– GABAergic receptor complex (33). One of the
>>> hypothesized mechanisms for benzodiazepine withdrawal suggests that
>>> the symptoms can be explained by the "overdrive" of downstream
>>> noradrenergic, s** |
