Benzo vs other options for anxiety

This forum made possible through the generous support of SDN members, donors, and sponsors. Thank you.
Not a MD/DO psychiatrist or resident but I've seen other psychologists chiming in...

I wish that people prescribing benzos would consider that these medications make exposure-based therapies less effective. Especially before they refer these patients for therapy to address anxiety.

Our clinic's psychiatrists don't really prescribe benzos, which I greatly appreciate. But we're in the VA and I think that might be a VA policy thing as well.

Members don't see this ad.
 
  • Like
Reactions: 10 users
I know this is considered acceptable, but I've found that doing this creates far more problems than benefits. I've never had a patient who tolerated the "short-term" benzo who didn't then request that it be continued. The argument is always "it works so much better than the antidepressant, why can't I just continue it?" If the antidepressant-related anxiety should only be transient anyway and if it doesn't resolve in a few weeks it shouldn't be continued anyway. I don't see a reason to throw on another med to alleviate what should be a relatively mild and transient side effect, especially something like a benzo.
I've had a couple of patients who get really intolerable SSRI-induced activation even on very low starting doses. They successfully used a 3-4 week course of clonazepam to get on to an SSRI and are now doing great without the benzo. I think patient selection is critical when deciding who to offer this approach to, though.
Not a MD/DO psychiatrist or resident but I've seen other psychologists chiming in...

I wish that people prescribing benzos would consider that these medications make exposure-based therapies less effective. Especially before they refer these patients for therapy to address anxiety.

Our clinic's psychiatrists don't really prescribe benzos, which I greatly appreciate. But we're in the VA and I think that might be a VA policy thing as well.
100%, I try to avoid PRN benzos as much as possible for this reason. Generally if I'm doing a benzo Rx it's intended to be taken scheduled for a short period of time then discontinued. Otherwise we're reinforcing taking pills rather than using coping strategies/experiencing extinction.
 
  • Like
Reactions: 6 users
Attending psychiatrist.

1. I use benzos in extreme agitation associated with ID, where I have no choice because if I didnt there wouldnt be any quality of life. I have one severe ID patient on a peg tube, and hes on chronic benzo therapy as its the only thing that calms him down enough. I have a peds patient, teenager, with agenesis of part of his brain, i believe agenesis of the corpus callosum, don't quote me on that, and he has ID as a result and this gives him some quality of life.

2. I see about 15-20 pts a day, higher acuity. I have on average 3-4 that ive OKed and kept on chronic benzo therapy for anxiety, because its klonopin .5mg PRN and they aren't using it more than once or twice a week.

3. I never use chronic/continuous benzos in a regular person, I am pretty adamant against that, unless special circumstances.

4. Benzos teach avoidance of anxiety, long term there's no real benefit when the fundamental aspect behind benzos is that they don't teach the patient to start to cope with their anxiety, they just reinforce it. Not to mention the other countless issues with it.

I inherited two clinics at my current job. One clinic, the physician had placed over 1/3 of her pts on benzos. I went in, and I cleaned house. it was extremely hard and painful. Providers often don't understand (particulary those not in the MH field) once someone is on moderate-high dose benzos, it is such a chore getting them off. Obviously, can't just stop the medication, so have taper them off and that is not a fun process when you're doing it to several people at once. In my mind, once someone has tasted a benzo for 10 years, anything you give for anxiety will never feel like its enough to the patient. It's almost like tainting treatment, to a degree.

I detest using benzos, to be quite honest. I never prescribe ativan or xanax, besides in catatonia would I use ativan. Even giving klonopin gives me the ick at times.
 
  • Like
Reactions: 7 users
Members don't see this ad :)
I have sympathy for but am unable to have empathy for what it's like to be in the other position of taking someone off of a benzodiazepine versus being in the position of tapering.

My only slight difference in take is that it's not so much that after benzodiazepines there's nothing else that treats anxiety, but rather there's nothing else that treats the benzodiazepine damage. The symptoms of withdrawal are not anxiety. They overlap with the symptoms of anxiety disorders. But they are different and all over the place (although some from the forums are surprisingly consistent: de novo OCD and intrusive thoughts, hypersexuality are some of the ones I see very frequently that I don't see mentioned much in the official literature). I think that's kind of evidenced by the fact, that as you said you can't just stop it. It's not as if if you just stopped it the person would be extremely anxious. The outcome would be variable, but it could include psychosis, for example, which is obviously not a return of anxiety, not to mention all the autonomic and seizure activity that could take place. But just because it's done slower, I don't think means you can assume what you are seeing is a re-emergence of anxiety and inability to handle it with other methods. Not everyone put on benzodiazepine was put on them for anxiety.

As far as whether anything works the same after you've "tasted" benzos, there are studies looking at Buspar which shows no efficacy for withdrawal. Which to me makes total sense at the biological level. I saw on the forums one poor woman, elderly, put on benzos for restless legs for a decade. Her doctor took her off quite quickly. And she's now on every neuroleptic and antidepressant under the sun to try to quell the symptoms since stopping the benzos. And she's a mess. And I mean it makes sense. The brain is damaged. Those other drugs aren't known to heal that type of damage. When I say damage, I am speaking to the presumed glutamate hyperexcitability and downregulation of GABA-A receptors. There might be a better term. I used to say benzodiazepine disease.

So I guess I don't see it entirely as nothing else working for the anxiety post benzos (though that may be part of it) but nothing else working for the benzodiazepine damage (or whatever you want to call it). There are people who do feel their anxiety lessen post withdrawal, as well, but might still have other lingering withdrawal symptoms they wouldn't categorize as anxiety. It seems quite variable.
 
  • Like
Reactions: 2 users
Not a MD/DO psychiatrist or resident but I've seen other psychologists chiming in...

I wish that people prescribing benzos would consider that these medications make exposure-based therapies less effective. Especially before they refer these patients for therapy to address anxiety.

Our clinic's psychiatrists don't really prescribe benzos, which I greatly appreciate. But we're in the VA and I think that might be a VA policy thing as well.
Definitely a VA policy thing, one which I appreciated when I rotated there. Pretty much anyone I'm treating for more than mild anxiety I'm strongly recommending therapy or giving them resources for workbooks. I only start benzos for anxiety in patients who have either previously tapered off successfully without significant problems or patients who have either done significant therapy or have ongoing therapy who already have solid coping skills.


I've had a couple of patients who get really intolerable SSRI-induced activation even on very low starting doses. They successfully used a 3-4 week course of clonazepam to get on to an SSRI and are now doing great without the benzo. I think patient selection is critical when deciding who to offer this approach to, though.

100%, I try to avoid PRN benzos as much as possible for this reason. Generally if I'm doing a benzo Rx it's intended to be taken scheduled for a short period of time then discontinued. Otherwise we're reinforcing taking pills rather than using coping strategies/experiencing extinction.
Why use a benzo though? Hydroxyzine, propranolol, Trazodone, etc are all typically far more benign options that are far easier to discontinue. I agree patient selection is important, but the intense activation should still only be temporary and if it's not I doubt you continue with that particular med anyway.
 
  • Like
Reactions: 4 users
Second that benzo decreasing is a VA policy. It's an amazing part of working in the largest healthcare organization in the world. Communication is good and we work as a team, particularly around DEA controlled substances. Benzos can definitely hurt the efficacy of more supported therapeutic modalities for anxiety.
 
  • Like
Reactions: 2 users
I think in terms of benzos for anxiety, the biggest question is regarding safety and tolerability rather than efficacy. One of the risks that people are concerned about is developing an addiction to benzos. However, what is that risk? The APA task force concluded that the number of patients actually abusing benzos is "relatively small" (about 1%). Even former substance abusers do not appear to be at greatest risk for abusing benzos (hot take, I know).

There's also some concern that it would cause substance use disorder relapse, but some research suggests the opposite is true and that benzo use may actually lead to lower rates of substance relapse despite being contradictory to clinical experience.

In relevance to OP's post, one exception to this rule is that opioid users often report utilizing benzos specifically to enhance the opioid "high" despite having negative consequences on health outcomes and overdose lethality. Benzos are therefore contraindicated in current opioid users.

However, with regards to efficacy, it's important to distinguish between the 5-6 different anxiety disorders as the role of benzos in each specific anxiety disorder is distinct. It's not sufficient to diagnose patients with "anxiety" because there's mental anxiety vs physical anxiety, what they are anxious about, panic attacks (fast onset, quick off) vs anxiety exacerbations (slow onset, builds up over time, and then comes down slowly).
  • Panic Disorder/agoraphobia - sudden onset, overwhelming, crippling. Patients want immediate relief, so the best choice is usually Xanax or Klonopin Wafers (even faster than Xanax). For most patients, just knowing they have an antidote in their pocket or purse goes a long way toward staving off future panic attacks. I think it's pretty good for panic attacks that are infrequent. If they're happening daily, then an SSRI is a better long-term solution. However, SSRIs don't always work since they might not be effective, they might not be well tolerated, or the patient wants to avoid taking something daily for something that happens once every few weeks. CBT should be offered as an alternative and I've seen it cure panic disorder. But if they don't feel their anxiety (such as on benzos) then this actually prevents long term benefits that CBT can offer so in these situations, I work with the therapist to plan to taper benzos as an exposure exercise itself and is actually a desired aspect of the therapy rather than a negative side effect of withdrawal.
  • Generalized anxiety disorder - chronic worriers who have excessive and persistent anxiety, cannot relax easily, extremely taxing on energy, concentration, tolerance for bull**** from others. I would not use benzos in this case because their anxiety is chronic and often daily (although the DSM only requires anxiety >50% of the time). However, it is part of a treatment algorithm after trying the traditional options but I would even try kava and Silexan before this.
  • Social Anxiety Disorder - SSRI/CBT is best bets. If they get very anxious in circumscribed, low frequency situations, then they might benefit from a benzo immediately before that situation instead of taking a daily medication or doing weekly therapy for months (which also have their own risks), but I'd rather try a beta blocker first.
  • Specific phobia - I probably use benzos most often for this one, particularly flight phobias since flights tend to be infrequent as long as they aren't driving when they land. I tend not to use it for driving anxiety although some people might with the argument that crippling anxiety can have a higher risk of motor vehicle accidents than benzos, but always in conjunction with CBT.
I sometimes use benzos for SSRI initiation to help with the initial anxiety/activation that can come with it, but in adolescents/young adults, using this doesn't make a difference on how long a person stays on an SSRI for (although they didn't measure earlier improvement or faster return to baseline).

I'll throw some additional fire into the flame. Xanax has 21 clinical trials showing in a Cochrane meta-analysis to be better than placebo and as effective as TCAs (yes, low quality studies, heterogeneity, short term, but still made the Cochrane inclusion criteria which is tough). Where does this fall into your treatment algorithm for depression?
 
Last edited:
  • Like
Reactions: 6 users
Thank you to all those who answered my question. Extremely helpful and enlightening to learn from the experts!
By all means please continue the discussion as I'm learning from you all, but I want to ensure I thank you.

As a side note for those of you who may be interested in the opioid side of things because of interactions, many pain physicians are no longer prescribing 24 hr a day chronic opioids for the same reasons you no longer provide 24hr/day benzos. Tolerance, dependence, abuse, etc.

Outside of palliative care, there is terrible literature to support taking opioids all day for any condition. The vast majority of patients become tolerant to the pain relief of opioids but not to the side effects, and opioid induced hyperalgesia is common, and I have seen many patients report less pain completely off opioids, than taking oxy 24hrs a day because of tolerance and opioid-induced hyperalgesia.

Patients with significant pathology and stable enough to trust with opioids in my practice are not allow to take more than 30 morphine equivalents a day, and/or more than 2 doses. Again, if their body is exposed to opioids all day long, it will become dependent and tolerant.

If I have a non terminal patient who either truly needs 24hr coverage, then they are switched to buprenorphine, generally butrans, but there are different options with bup including belbuca or bup tablets. I go straight from BID vicodin to bup, quite frequently. I will allow a rescue dose or QHS dose of vicodin, but patients are not allowed to take standard opioids more than once a day with their bup, because after a few months the standard opioids will stop working if their mu receptors are exposed to standard opioids all the time.
There is dramatically less tolerance to buprenorphine because it is a partial agonist-antagonist.

Finally, with pain patients it is extremely important to treat patients with anything but opioids. Only a small percentage of my patients take chronic opioids daily.
Most are treated with steroid injections, PRP injections, sensory nerve ablations, spinal cord stimulators, physical therapy, chiropractic, acupuncture, pain psychology, neuropathic meds, tramadol, celebrex, etc.
 
Last edited:
  • Like
Reactions: 2 users
Why use a benzo though? Hydroxyzine, propranolol, Trazodone, etc are all typically far more benign options that are far easier to discontinue. I agree patient selection is important, but the intense activation should still only be temporary and if it's not I doubt you continue with that particular med anyway.
Hydroxyzine is not going to work in that situation. It's a good point that maybe I should try propranolol or trazodone in someone but the main reason for the benzos is I want something I think has a high chance of working. It's very significant agitation/activation/anxiety increase. If it were tolerable for two-three weeks then we wouldn't be doing the benzo thing. We also wouldn't be doing the benzo thing if we hadn't already tried multiple other serotonergic options at that point. We're usually coming back to whichever one was least severe to do the benzo-aided 2-3 weeks initiation because they experience the intolerable activation as a class effect.
 
  • Like
Reactions: 1 user
I'll throw some additional fire into the flame. Xanax has 21 clinical trials showing in a Cochrane meta-analysis to be better than placebo and as effective as TCAs (yes, low quality studies, heterogeneity, short term, but still made the Cochrane inclusion criteria which is tough). Where does this fall into your treatment algorithm for depression?
Essentially non-existent given the risks and the following statement from the study: "We cannot conclude whether this is due to its specific antidepressant effect or to a non-specific effect on sleep and anxiety." If I'm trying to treat anxiety or severe difficulties with sleep-onset, I'll throw benzodiazepines as a low-line option on the list, but not for independent depression. That said, I have anecdotally had a couple of patients who felt like nothing helped their depression as much as Xanax, so not all that shocked that there may actually be a physiologic component behind this.


Hydroxyzine is not going to work in that situation. It's a good point that maybe I should try propranolol or trazodone in someone but the main reason for the benzos is I want something I think has a high chance of working. It's very significant agitation/activation/anxiety increase. If it were tolerable for two-three weeks then we wouldn't be doing the benzo thing. We also wouldn't be doing the benzo thing if we hadn't already tried multiple other serotonergic options at that point. We're usually coming back to whichever one was least severe to do the benzo-aided 2-3 weeks initiation because they experience the intolerable activation as a class effect.
Why not? Works for many the patients who have requested something short-term during SSRI/SNRI initiation that I've had. It won't work for everyone, but I don't write it off. It also depends on what we're prescribing the SSRI for (I'm assuming anxiety) and the form of the anxiety. Like Clozareal mentioned, we likely aren't treating pure GAD the same as a true panic disorder or a specific phobia. I'm also curious how often you actually see people who have such severe anxiety/activation when starting SSRIs that they require benzos to prevent discontinuation, but don't have ongoing anxiety 2/2 the SSRI. If a patient has been on multiple SSRI/SNRI meds and had severe enough anxiety that could warrant the use of benzos for over 2 weeks for any of those, why not change to other med classes?
 
  • Like
Reactions: 1 users
Why not? Works for many the patients who have requested something short-term during SSRI/SNRI initiation that I've had. It won't work for everyone, but I don't write it off. It also depends on what we're prescribing the SSRI for (I'm assuming anxiety) and the form of the anxiety. Like Clozareal mentioned, we likely aren't treating pure GAD the same as a true panic disorder or a specific phobia. I'm also curious how often you actually see people who have such severe anxiety/activation when starting SSRIs that they require benzos to prevent discontinuation, but don't have ongoing anxiety 2/2 the SSRI. If a patient has been on multiple SSRI/SNRI meds and had severe enough anxiety that could warrant the use of benzos for over 2 weeks for any of those, why not change to other med classes?

with the activation syndrome hes talking about, in my experience that improves within 2 weeks of when it starts for most people. I tend to see it more in younger, female patients, but that's just personal experience.

I know what you mean- I had the internal debate for a bit as to providing low dose benzos for that activation syndrome, stopping the medication, or adding in PRN vistaril. Typically someone that has that issue though does not want to stay on that medication anyways and ends up quitting it, so the use of prn benzos in that scenario become redundant. Then I usually switch to another SSRI, and if that fails, another class. And i may give a little vistaril too or gabapentin on the second attempt for an SSRI.

Even if the patient doesnt become addicted to the benzo, when they use it they will inevitably develop the mindset "wow this stuff works great". Usually they dont want to lose access to it.

I think its time I relearn my organic chemistry and develop "Dramazing's amazoril pill". PRN for anxiety, non benzo class, minimal potential for addiction. I would be a billionaire.
 
  • Like
Reactions: 6 users
Thank you to all those who answered my question. Extremely helpful and enlightening to learn from the experts!
By all means please continue the discussion as I'm learning from you all, but I want to ensure I thank you.

As a side note for those of you who may be interested in the opioid side of things because of interactions, many pain physicians are no longer prescribing 24 hr a day chronic opioids for the same reasons you no longer provide 24hr/day benzos. Tolerance, dependence, abuse, etc.

Outside of palliative care, there is terrible literature to support taking opioids all day for any condition. The vast majority of patients become tolerant to the pain relief of opioids but not to the side effects, and opioid induced hyperalgesia is common, and I have seen many patients report less pain completely off opioids, than taking oxy 24hrs a day because of tolerance and opioid-induced hyperalgesia.

Patients with significant pathology and stable enough to trust with opioids in my practice are not allow to take more than 30 morphine equivalents a day, and/or more than 2 doses. Again, if their body is exposed to opioids all day long, it will become dependent and tolerant.

If I have a non terminal patient who either truly needs 24hr coverage, then they are switched to buprenorphine, generally butrans, but there are different options with bup including belbuca or bup tablets. I go straight from BID vicodin to bup, quite frequently. I will allow a rescue dose or QHS dose of vicodin, but patients are not allowed to take standard opioids more than once a day with their bup, because after a few months the standard opioids will stop working if their mu receptors are exposed to standard opioids all the time.
There is dramatically less tolerance to buprenorphine because it is a partial agonist-antagonist.

Finally, with pain patients it is extremely important to treat patients with anything but opioids. Only a small percentage of my patients take chronic opioids daily.
Most are treated with steroid injections, PRP injections, sensory nerve ablations, spinal cord stimulators, physical therapy, chiropractic, acupuncture, pain psychology, neuropathic meds, tramadol, celebrex, etc.

I just wanted to say that I actually lurk on the pain medicine forum quite often (working in the VA, pain and patients upset about losing their opioids are something I encounter quite a bit) and I find all of your discussions so interesting to read! I would say chronic anxiety is similar to chronic pain where we have some really great behavioral treatments for it, but of course they require tolerating discomfort and doing more work than taking a pill. And, like opioids, 1) there can be really strong rebound effects and 2) it can be really hard to get someone off of a benzo because, as mentioned above, other interventions will not have as immediate an effect.

Also, I specialize in PTSD and we (both therapists and psychiatrists) actually tell our patients that it's contraindicated for that diagnosis specifically. The National Center for PTSD has some great patient educational resources about it.
 
  • Like
Reactions: 3 users
Members don't see this ad :)
Why not? Works for many the patients who have requested something short-term during SSRI/SNRI initiation that I've had. It won't work for everyone, but I don't write it off. It also depends on what we're prescribing the SSRI for (I'm assuming anxiety) and the form of the anxiety. Like Clozareal mentioned, we likely aren't treating pure GAD the same as a true panic disorder or a specific phobia. I'm also curious how often you actually see people who have such severe anxiety/activation when starting SSRIs that they require benzos to prevent discontinuation, but don't have ongoing anxiety 2/2 the SSRI. If a patient has been on multiple SSRI/SNRI meds and had severe enough anxiety that could warrant the use of benzos for over 2 weeks for any of those, why not change to other med classes?
TBH it feels like you aren't listening to what I'm saying. You're seem to be arguing about a few totally different and much more mundane situations--SSRI treatment failure, persistent SSRI adverse effects, and short-term anxiety treatment while waiting for an SSRI to kick in. Meanwhile, I'm talking about the rare but totally well described situation of patients who haven't had a chance to have a proper duration SSRI trial because of significant SSRI-induced activation (they have new/significantly worsened sleep difficulty, dramatically worsened anxiety, feel agitated.) I never mentioned treating with long term benzos which is your implication with "for over 2 weeks." It's not some vague "more than 2 weeks" it's for the 2-3 weeks that the activation syndrome typically lasts for and discontinuation at that time is planned and discussed with the patient prior to starting the SSRI and benzo in the first place.

I've had ~four patients (out of ~1000 outpatients including residency) where they had convincingly really bad activation from multiple SSRI's/SNRI's. We'd probably already tried buspirone without success and most pts are against mirtazapine the second I mention weight gain. It's been an extremely helpful approach for those four patients who are now on SSRI's with much better controlled anxiety and no lasting issues with benzo use or SSRI induced activation.

Several other people ITT mentioned also taking a similar approach to SSRI-induced activation. It's not like I just made this up.
 
Last edited:
  • Like
Reactions: 5 users
I've had ~four patients (out of ~1000 outpatients including residency) where they had convincingly really bad activation from multiple SSRI's/SNRI's. We'd probably already tried buspirone without success and most pts are against mirtazapine the second I mention weight gain. It's been an extremely helpful approach for those four patients who are now on SSRI's with much better controlled anxiety and no lasting issues with benzo use or SSRI induced activation.

Several other people ITT mentioned also taking a similar approach to SSRI-induced activation. It's not like I just made this up.
I definitely see early SSRI activation not infrequently but it has never occurred to me to manage it with a benzo. Usually I either switch to a different drug or just reduce the dose to whatever is tolerable (can be like 12.5 Zoloft or 2.5 Lexapro, I've even gone to liquid Lexapro 1mg for very sensitive patients), educate the patient, and edge up slowly as tolerated. Usually within 3-4 weeks the activation is gone and the patient feels better.
 
  • Like
Reactions: 4 users
I definitely see early SSRI activation not infrequently but it has never occurred to me to manage it with a benzo. Usually I either switch to a different drug or just reduce the dose to whatever is tolerable (can be like 12.5 Zoloft or 2.5 Lexapro, I've even gone to liquid Lexapro 1mg for very sensitive patients), educate the patient, and edge up slowly as tolerated. Usually within 3-4 weeks the activation is gone and the patient feels better.
That is my initial approach. These are patients for whom we didn't find a more acceptable agent even at very low doses. Hence only a handful of patients where it's actually been necessary. I guess I haven't technically tried liquid form of some meds yet, I'll have to see if liquid SSRI's are on formulary in our system.
 
  • Like
Reactions: 1 user
I'll throw some additional fire into the flame. Xanax has 21 clinical trials showing in a Cochrane meta-analysis to be better than placebo and as effective as TCAs (yes, low quality studies, heterogeneity, short term, but still made the Cochrane inclusion criteria which is tough). Where does this fall into your treatment algorithm for depression?
The duration of those studies was 4-6 weeks. I'm not surprised you would see an early euphoria with bzd use, but as GABA receptor downregulation sets in, things will look very different over time.
 
  • Like
Reactions: 3 users
2. I see about 15-20 pts a day, higher acuity. I have on average 3-4 that ive OKed and kept on chronic benzo therapy for anxiety, because its klonopin .5mg PRN and they aren't using it more than once or twice a week.
Interesting, I wouldn't consider this 'chronic' use as it seems unlikely that use 1x/week would result in significant receptor downregulation. I'm fine with people who need an Ativan for plane flights a few times a year. I don't consider that chronic use. My rule of thumb is if they're needing it 1x/week or more often then we need to find a better solution.

Although I do observe that the development of tolerance is highly patient-dependent. Some people find it stops working after a couple of weeks of daily use. Others take it daily for years and never escalate (although again by that point it is only 'working' in the sense of preventing bzd withdrawal).
 
  • Like
Reactions: 1 user
Interesting, I wouldn't consider this 'chronic' use as it seems unlikely that use 1x/week would result in significant receptor downregulation. I'm fine with people who need an Ativan for plane flights a few times a year. I don't consider that chronic use. My rule of thumb is if they're needing it 1x/week or more often then we need to find a better solution.

Although I do observe that the development of tolerance is highly patient-dependent. Some people find it stops working after a couple of weeks of daily use. Others take it daily for years and never escalate (although again by that point it is only 'working' in the sense of preventing bzd withdrawal).

didn't mean chronic in the specific sense of the word, just rather "prolonged" PRN therapy. But these are the same people who dont have to fill it every month.
 
TBH it feels like you aren't listening to what I'm saying. You're seem to be arguing about a few totally different and much more mundane situations--SSRI treatment failure, persistent SSRI adverse effects, and short-term anxiety treatment while waiting for an SSRI to kick in. Meanwhile, I'm talking about the rare but totally well described situation of patients who haven't had a chance to have a proper duration SSRI trial because of significant SSRI-induced activation (they have new/significantly worsened sleep difficulty, dramatically worsened anxiety, feel agitated.) I never mentioned treating with long term benzos which is your implication with "for over 2 weeks." It's not some vague "more than 2 weeks" it's for the 2-3 weeks that the activation syndrome typically lasts for and discontinuation at that time is planned and discussed with the patient prior to starting the SSRI and benzo in the first place.

I've had ~four patients (out of ~1000 outpatients including residency) where they had convincingly really bad activation from multiple SSRI's/SNRI's. We'd probably already tried buspirone without success and most pts are against mirtazapine the second I mention weight gain. It's been an extremely helpful approach for those four patients who are now on SSRI's with much better controlled anxiety and no lasting issues with benzo use or SSRI induced activation.

Several other people ITT mentioned also taking a similar approach to SSRI-induced activation. It's not like I just made this up.
Not trying to be difficult, but I am aware of what you're specifically referring to and the use of benzos for SSRI-induced activation. I've done that a couple of times at the recommendation of my attendings early in residency and in every situation it turned into a battle of "the benzo works so much better than the SSRI, why can't I just continue that?!?" It's just not a battle I'm willing to fight and will lay out multiple other options for the patient to try. In the few cases I've had where the patients were hypersensitive to low-dose initiation of SSRI/SNRI meds, we've either found that therapy + another med was adequate or underlying personality pathology became apparent.

However, the etiology of why we're using the SSRI is also worth considering. Someone who has typical depression is very different from someone with minimal depression but anxiety is constantly 7/10 and they always feel like their sympathetic system is activated and the SSRI kicks that to 11/10. I'm a lot more worried about one of those patients getting off of short-term benzos than the other.

As I said, I realize that it's a well-documented option and that you're not making this up. I've just found that in my somewhat limited experience it is far more problematic in practice to actually implement than the benefits are worth.
 
  • Like
Reactions: 4 users
That is my initial approach. These are patients for whom we didn't find a more acceptable agent even at very low doses. Hence only a handful of patients where it's actually been necessary. I guess I haven't technically tried liquid form of some meds yet, I'll have to see if liquid SSRI's are on formulary in our system.

ive found that once patients experience it, they are extremely hesitant at the idea of staying on the medication, even at a lower dose. They usually want to try a diff medication which I generally do. Ive found that although they may have this effect with zoloft, they may be fine with prozac or vice versa.

I would say this syndrome isnt uncommon for me, i see it quite a few times.

ive had some luck with gabapentin for it, and often just giving them PRN gabapentin makes them a little more confident trying the second medication.
 
  • Like
Reactions: 1 users
Not trying to be difficult, but I am aware of what you're specifically referring to and the use of benzos for SSRI-induced activation. I've done that a couple of times at the recommendation of my attendings early in residency and in every situation it turned into a battle of "the benzo works so much better than the SSRI, why can't I just continue that?!?" It's just not a battle I'm willing to fight and will lay out multiple other options for the patient to try. In the few cases I've had where the patients were hypersensitive to low-dose initiation of SSRI/SNRI meds, we've either found that therapy + another med was adequate or underlying personality pathology became apparent.

However, the etiology of why we're using the SSRI is also worth considering. Someone who has typical depression is very different from someone with minimal depression but anxiety is constantly 7/10 and they always feel like their sympathetic system is activated and the SSRI kicks that to 11/10. I'm a lot more worried about one of those patients getting off of short-term benzos than the other.



As I said, I realize that it's a well-documented option and that you're not making this up. I've just found that in my somewhat limited experience it is far more problematic in practice to actually implement than the benefits are worth.

I got burned in a similar fashion in this sort of circumstance a few times and at this point I am genuinely more inclined to give someone a temporary course of Seroquel 25-50 mg than reach for anything BZD related. Hardly going to give them diabetes in three weeks and no one ever robbed a gas station to pay for their quetiapine.

Risperidone and olanzapine in very low doses are also serious considerations, possibly thorazine if it weren't so damnably expensive.
 
  • Like
Reactions: 4 users
Not trying to be difficult, but I am aware of what you're specifically referring to and the use of benzos for SSRI-induced activation. I've done that a couple of times at the recommendation of my attendings early in residency and in every situation it turned into a battle of "the benzo works so much better than the SSRI, why can't I just continue that?!?" It's just not a battle I'm willing to fight and will lay out multiple other options for the patient to try. In the few cases I've had where the patients were hypersensitive to low-dose initiation of SSRI/SNRI meds, we've either found that therapy + another med was adequate or underlying personality pathology became apparent.

However, the etiology of why we're using the SSRI is also worth considering. Someone who has typical depression is very different from someone with minimal depression but anxiety is constantly 7/10 and they always feel like their sympathetic system is activated and the SSRI kicks that to 11/10. I'm a lot more worried about one of those patients getting off of short-term benzos than the other.

As I said, I realize that it's a well-documented option and that you're not making this up. I've just found that in my somewhat limited experience it is far more problematic in practice to actually implement than the benefits are worth.
This is exactly why I almost never write for chronic standard opioids. After a patient had those for a while they don’t want/accept gabapentin and tramadol.

I go to butrans very early if I think a patient might truly need daily mu receptor activation for pain.

Buprenorphine helps many many people with pain. just as I expect SSRIs helps many people with anxiety.

This way I don’t “ruin” the pain patient with daily opioids for a month just like you don’t “ruin” an anxious psych patient with daily chronic benzos.
 
Last edited:
As far as whether anything works the same after you've "tasted" benzos, there are studies looking at Buspar which shows no efficacy for withdrawal. Which to me makes total sense at the biological level. I saw on the forums one poor woman, elderly, put on benzos for restless legs for a decade. Her doctor took her off quite quickly. And she's now on every neuroleptic and antidepressant under the sun to try to quell the symptoms since stopping the benzos. And she's a mess. And I mean it makes sense. The brain is damaged. Those other drugs aren't known to heal that type of damage. When I say damage, I am speaking to the presumed glutamate hyperexcitability and downregulation of GABA-A receptors. There might be a better term. I used to say benzodiazepine disease.
I find this interesting, and I'm wondering if any of the psychiatrists here can comment about this.

And does this sort of thing have any connection to the phenomenon my attending told me about on my psych rotation, we had a patient that had purely strictly only auditory hallucinations for years after quitting drinking, he was a heavy, heavy user of alcohol for decades, and he told me that it was not that uncommon to see that kind of thing in alcoholics, that usually it would start when they were still drinking, but could persist for months years decades forever in some individuals even after stopping.

Also saw some young folks that had been former alcoholics, dealing with chronic anxiety. I was told this was frequently a side effect of cessation of long term alcohol abuse and that it would often be present for a year or much more.

In both cases I was told this was a side effect of essentially saturating the GABA receptors, and then they are upregulated, downregulated, and then when you stop the alcohol, the whole thing goes haywire.
 
Last edited:
  • Like
Reactions: 1 user
I find this interesting, and I'm wondering if any of the psychiatrists here can comment about this.

And does this sort of thing have any connection to the phenomenon my attending told me about on my psych rotation, we had a patient that had purely strictly only auditory hallucinations for years after quitting drinking, he was a heavy, heavy user of alcohol for decades, and he told me that it was not that uncommon to see that kind of thing in alcoholics, that usually it would start when they were still drinking, but could persist for months years decades forever in some individuals even after stopping.

Also saw some young folks that had been former alcoholics, dealing with chronic anxiety. I was told this was frequently a side effect of cessation of long term alcohol abuse and that it would often be present for a year or much more.

In both cases I was told this was a side effect of essentially saturating the GABA receptors, and then they are upregulated, and then when you stop the alcohol, the whole thing goes haywire.
Gaba receptor downregulation in response to excessive tonic stimulation is well documented. It is very much reversible however, so I wouldn't call it anything like 'brain damage.' However the time course of reversibility is slow, hence the need for slow stepwise benzo tapers to allow for receptor expression to recover in stages.

Alterations in receptor expression in response to tonic stimulation or blockade are a common homeostatic mechanism and are not confined to Gaba receptors. Tardive dyskinesia, for example, results from dopamine receptor upregulation in response to tonic blockade by antipsychotics. This is an example of the converse mechanism: receptor upregulation in response to blockade, vs downregulation in response to hyperstimulation.
 
  • Like
Reactions: 2 users
Gaba receptor downregulation in response to excessive tonic stimulation is well documented. It is very much reversible however, so I wouldn't call it anything like 'brain damage.' However the time course of reversibility is slow, hence the need for slow stepwise benzo tapers to allow for receptor expression to recover in stages.

Alterations in receptor expression in response to tonic stimulation or blockade are a common homeostatic mechanism and are not confined to Gaba receptors. Tardive dyskinesia, for example, results from dopamine receptor upregulation in response to tonic blockade by antipsychotics. This is an example of the converse mechanism: receptor upregulation in response to blockade, vs downregulation in response to hyperstimulation.
But I thought tardive dyskinesia usually doesn't fully resolve? or that it doesn't always. So I am following you that the chronic benzos don't necessarily damage the brain, my understanding was that in some individuals neuroleptics do seem to cause some permanent damage to the dopamine areas, which sort of makes sense given that you do see that in Parkinson's, that perhaps those areas of the brain or those circuits are in fact susceptible to toxicity or death and don't always recover in some individuals. But I could see that this may not be the case with GABA. Although as I'm sitting here thinking about it, I did think there was such as thing as GABA toxicity to neurons and that leading to permanent damage? But I could see that perhaps that is more in line with say uncontrolled szs vs what you get with benzos.

thank you for this explanation, makes sense, and makes sense that you might see symptoms for a while

I was told that, for example, the anxious patient who stopped drinking would likely eventually recover and become less anxious if they could manage not to drink or use benzos for it, for long enough, like on the order of a year or more, and this fits with what you all are saying about benzo taper.

Can anyone speak to the "alchoholic who develops persistent auditory hallucinations" thing? Was my attending onto something or was this just his n=1 observation? And yes, I'm aware this is a bit off the original thread topic.

I'm just trying to digest whatever I can about these more experiential ideas of how benzos and alcohol and GABA all play together.
 
  • Like
Reactions: 1 users
But I thought tardive dyskinesia usually doesn't fully resolve? or that it doesn't always. So I am following you that the chronic benzos don't necessarily damage the brain, my understanding was that in some individuals neuroleptics do seem to cause some permanent damage to the dopamine areas, which sort of makes sense given that you do see that in Parkinson's, that perhaps those areas of the brain or those circuits are in fact susceptible to toxicity or death and don't always recover in some individuals. But I could see that this may not be the case with GABA. Although as I'm sitting here thinking about it, I did think there was such as thing as GABA toxicity to neurons and that leading to permanent damage? But I could see that perhaps that is more in line with say uncontrolled szs vs what you get with benzos.

thank you for this explanation, makes sense, and makes sense that you might see symptoms for a while

I was told that, for example, the anxious patient who stopped drinking would likely eventually recover and become less anxious if they could manage not to drink or use benzos for it, for long enough, like on the order of a year or more, and this fits with what you all are saying about benzo taper.

Can anyone speak to the "alchoholic who develops persistent auditory hallucinations" thing? Was my attending onto something or was this just his n=1 observation? And yes, I'm aware this is a bit off the original thread topic.

I'm just trying to digest whatever I can about these more experiential ideas of how benzos and alcohol and GABA all play together.
Well if you consider that GABA and Glutamate are inextricably linked, via multiple means, in pursuit of excitatory-inhibitory balance in the brain- then an induced GABA receptor hypofunction seems like it could fit in with glutamatergic theory of schizophrenia, right? Insofar as a relative excess of cortical glutamate is the endpoint.

I’ve recently seen new psychosis w/ catatonia that seems to be triggered rather purely from BZD withdrawal (though too early to tell how long lasting), and in another case pretty purely from intoxication vs withdrawal of prolonged massive doses of DXM
 
  • Like
Reactions: 1 user
Well if you consider that GABA and Glutamate are inextricably linked, via multiple means, in pursuit of excitatory-inhibitory balance in the brain- then an induced GABA receptor hypofunction seems like it could fit in with glutamatergic theory of schizophrenia, right? Insofar as a relative excess of cortical glutamate is the endpoint.

I’ve recently seen new psychosis w/ catatonia that seems to be triggered rather purely from BZD withdrawal (though too early to tell how long lasting), and in another case pretty purely from intoxication vs withdrawal of prolonged massive doses of DXM
We see catatonia purely from benzo withdrawal frequently (at least one case every month or two). It's something I make sure all my juniors know about because there have been some scary near misses and bad outcomes from those patients being sent to psychiatry instead of to a medical floor for high dose IV benzos. These patients often cannot be managed solely with oral medications. It can progress extremely quickly and then the patients return to normal baseline very very quickly if the withdrawal is adequately treated (unlike with either purely psychiatric or catatonia from other medical causes).

I'm in a city where... Let's just say in substance use we could be considered a trendsetter. Get ready, folks, street 'xanax' is some wild ****.
 
  • Like
Reactions: 3 users
Nah, it doesn't. Alkermes tried it with buprenorphine/samidorphan (latter to block mu-opiod receptor to isolate kappa antagonism) but it didn't differentiate from placebo in two trials; in a third in that the bup/samid patients did *worse* than placebo.

That's not to say buprenorphine doesn't help with depression. It just does it through mu-opioid agonism.
 
  • Like
Reactions: 6 users
There’s a lot of legacy benzo patients around and they are even harder to taper than legacy opioid patients since if they run out early, they could seize and not just have w/d.

EDIT: In fact, in patients on both opioids and benzos it is usually recommended to address opioids first, it goes much quicker and thus risk is reduced more quickly.
 
Last edited:
  • Like
Reactions: 4 users
But I thought tardive dyskinesia usually doesn't fully resolve? or that it doesn't always. So I am following you that the chronic benzos don't necessarily damage the brain, my understanding was that in some individuals neuroleptics do seem to cause some permanent damage to the dopamine areas, which sort of makes sense given that you do see that in Parkinson's, that perhaps those areas of the brain or those circuits are in fact susceptible to toxicity or death and don't always recover in some individuals. But I could see that this may not be the case with GABA. Although as I'm sitting here thinking about it, I did think there was such as thing as GABA toxicity to neurons and that leading to permanent damage? But I could see that perhaps that is more in line with say uncontrolled szs vs what you get with benzos.

thank you for this explanation, makes sense, and makes sense that you might see symptoms for a while

I was told that, for example, the anxious patient who stopped drinking would likely eventually recover and become less anxious if they could manage not to drink or use benzos for it, for long enough, like on the order of a year or more, and this fits with what you all are saying about benzo taper.

Can anyone speak to the "alchoholic who develops persistent auditory hallucinations" thing? Was my attending onto something or was this just his n=1 observation? And yes, I'm aware this is a bit off the original thread topic.

I'm just trying to digest whatever I can about these more experiential ideas of how benzos and alcohol and GABA all play together.
I can speak to the chronic etoh thing. Almost 30 years of experience with many recovering alcoholics in various stages of recovery and have not heard of or seen this dynamic. Plenty who have reported DTs of all different types but none persisted. I have seen quite a few people who have a comorbid psychotic disorder and their symptoms will often persist and it is pretty clear from my experience that alcohol use can trigger psychotic episodes in a vulnerable patient although much less reliably than does marijuana. Last few years I worked with many dual diagnosis type patients and it appeared that a patient who was Bipolar with psychotic features was more likely to have an episode triggered by etoh use than a patient with schizophrenia. However, the patient with schizophrenia hits a dab pen and it might take six months or even never to get them back to their baseline.
 
Last edited:
  • Like
Reactions: 2 users
But I thought tardive dyskinesia usually doesn't fully resolve? or that it doesn't always. So I am following you that the chronic benzos don't necessarily damage the brain, my understanding was that in some individuals neuroleptics do seem to cause some permanent damage to the dopamine areas, which sort of makes sense given that you do see that in Parkinson's, that perhaps those areas of the brain or those circuits are in fact susceptible to toxicity or death and don't always recover in some individuals.

You are right that TD isn't only about receptor upregulation. There seem to be a number of parallel mechanisms that increase sensitivity to dopamine after long-term blockade, including increased release of endogenous dopamine and the growth of new synaptic terminals, and these don't seem to be entirely reversible.

Parkinson's involves degeneration of a specific population of dopaminergic neurons in the substantia nigra. They actually die, they don't just reduce their receptor complement. There is overlap in the clinical appearance but PD is not caused by dopamine blockade. It is the result of the death of a specific population of dopaminergic neurons in the substantia nigra. You can treat symptomatically by providing exogenous dopamine for a period of time to get the most out of the surviving neurons, but this strategy ultimately has an expiration date.

(Also the provision of exogenous L-dopa is of course not specific to nigrostriatal neurons, so while you are pounding the nigra with extra dopamine to wrest some motor function out of that circuit, you are also saturating the dopamine receptors in the mesolimbic and mesocortical pathways, resulting in the visual hallucinations seen in older PD patients on high doses of L-Dopa. 'Little people in the corner' are classic for this.)

But I could see that this may not be the case with GABA. Although as I'm sitting here thinking about it, I did think there was such as thing as GABA toxicity to neurons and that leading to permanent damage? But I could see that perhaps that is more in line with say uncontrolled szs vs what you get with benzos.
Are you thinking about glutamate excitotoxicity? Glutamate is the brain's major excitatory neurotransmitter and excessive neuronal activation (including uncontrolled seizure activity) is well documented to lead to neurotoxicity and cell death. GABA is the brain's major inhibitory neurotransmitter (at least postnatally) and I am not personally aware of inhibition-related cellular toxicity (not to say that it couldn't be a thing, just that I haven't heard of it). A quiet neuron does end up with fewer/weaker connections in the long run however.

thank you for this explanation, makes sense, and makes sense that you might see symptoms for a while

I was told that, for example, the anxious patient who stopped drinking would likely eventually recover and become less anxious if they could manage not to drink or use benzos for it, for long enough, like on the order of a year or more, and this fits with what you all are saying about benzo taper.

Can anyone speak to the "alchoholic who develops persistent auditory hallucinations" thing? Was my attending onto something or was this just his n=1 observation? And yes, I'm aware this is a bit off the original thread topic.

I'm just trying to digest whatever I can about these more experiential ideas of how benzos and alcohol and GABA all play together.
Alcoholic hallucinosis is a thing but I'm not an expert on the pathophysiology. However I just did some quick reading and it sounds like the thought is that alcohol has NMDAR blocking properties which are normally psychotomimetic, but the psychotomimetic effect can be prevented by coadministration with a GABA agonist. Since alcohol has intrinsic GABAergic function it's not common to see psychosis with acute intoxication, but it sounds like somebody who has been a chronic user and therefore has reduced GABA receptor expression might see 'uncovered' psychotomimetic effects from the NMDAR blocking property of the ethanol. Or something like that.

 
Last edited:
  • Like
Reactions: 5 users
You are right that TD isn't only about receptor upregulation. There seem to be a number of parallel mechanisms that increase sensitivity to dopamine after long-term blockade, including increased release of endogenous dopamine and the growth of new synaptic terminals, and these don't seem to be entirely reversible.

Parkinson's involves degeneration of a specific population of dopaminergic neurons in the substantia nigra. They actually die, they don't just reduce their receptor complement. There is overlap in the clinical appearance but PD is not caused by dopamine blockade. It is the result of the death of a specific population of dopaminergic neurons in the substantia nigra. You can treat symptomatically by providing exogenous dopamine for a period of time to get the most out of the surviving neurons, but this strategy ultimately has an expiration date.

(Also the provision of exogenous L-dopa is of course not specific to nigrostriatal neurons, so while you are pounding the nigra with extra dopamine to wrest some motor function out of that circuit, you are also saturating the dopamine receptors in the mesolimbic and mesocortical pathways, resulting in the visual hallucinations seen in older PD patients on high doses of L-Dopa. 'Little people in the corner' are classic for this.)


Are you thinking about glutamate excitotoxicity? Glutamate is the brain's major excitatory neurotransmitter and excessive neuronal activation (including uncontrolled seizure activity) is well documented to lead to neurotoxicity and cell death. GABA is the brain's major inhibitory neurotransmitter (at least postnatally) and I am not personally aware of inhibition-related cellular toxicity (not to say that it couldn't be a thing, just that I haven't heard of it). A quiet neuron does end up with fewer/weaker connections in the long run however.


Alcoholic hallucinosis is a thing but I'm not an expert on the pathophysiology. However I just did some quick reading and it sounds like the thought is that alcohol has NMDAR blocking properties which are normally psychotomimetic, but the psychotomimetic effect can be prevented by coadministration with a GABA agonist. Since alcohol has intrinsic GABAergic function it's not common to see psychosis with acute intoxication, but it sounds like somebody who has been a chronic user and therefore has reduced GABA receptor expression might see 'uncovered' psychotomimetic effects from the NMDAR blocking property of the ethanol. Or something like that.

Thank you for clarifying all these points for me!
 
  • Like
Reactions: 1 user
There’s a lot of legacy benzo patients around and they are even harder to taper than legacy opioid patients since if they run out early, they could seize and not just have w/d.
Legacy benzo patients usually come from old psychiatrists or NPs.

There's almost always some red flag that will eventually surface when the first thing a new inherited patient says is, "I just need my benzos refilled. It's the only thing that works!" Whereas patients who say, "Oh gosh golly, I didn't know benzos are addictive or had cognitive effects!" are the exact opposite.
 
Legacy benzo patients usually come from old psychiatrists or NPs.

There's almost always some red flag that will eventually surface when the first thing a new inherited patient says is, "I just need my benzos refilled. It's the only thing that works!" Whereas patients who say, "Oh gosh golly, I didn't know benzos are addictive or had cognitive effects!" are the exact opposite.

Yes, surprise Pikachu face when told benzos have significant drawbacks = positive prognostic sign.
 
  • Like
Reactions: 2 users
I would say there is utility for benzo use in anxiety disorders with concomitant panic attacks. Those patients may find relief if starting SRIs and benzos at the same time, and SRIs alone may not stop all the attacks (even after 6+ months), or reduce the symptom burden enough for the patient to be fully functional. That may take time to taper clonazepam down to figure out the right level, or see if it can be stopped completely.
I think clonazepam would be the most rational benzo to use in this setting. I think xanax for panic attacks or anxiety disorders is harmful (possibly not true for extended release versions).

Also, not everyone is a candidate for psychotherapy.
 
  • Like
Reactions: 2 users
I would say there is utility for benzo use in anxiety disorders with concomitant panic attacks. Those patients may find relief if starting SRIs and benzos at the same time, and SRIs alone may not stop all the attacks (even after 6+ months), or reduce the symptom burden enough for the patient to be fully functional. That may take time to taper clonazepam down to figure out the right level, or see if it can be stopped completely.
I think clonazepam would be the most rational benzo to use in this setting. I think xanax for panic attacks or anxiety disorders is harmful (possibly not true for extended release versions).

Also, not everyone is a candidate for psychotherapy.

This is a pretty small group. Our therapies for panic disorder are some of the most efficacious that we have. This is a disorder that lends itself very well to time-limited, easily understood behavioral interventions. This and PTSD are my therapy specialties.
 
  • Like
Reactions: 6 users
I would say there is utility for benzo use in anxiety disorders with concomitant panic attacks. Those patients may find relief if starting SRIs and benzos at the same time, and SRIs alone may not stop all the attacks (even after 6+ months), or reduce the symptom burden enough for the patient to be fully functional. That may take time to taper clonazepam down to figure out the right level, or see if it can be stopped completely.
I think clonazepam would be the most rational benzo to use in this setting. I think xanax for panic attacks or anxiety disorders is harmful (possibly not true for extended release versions).

Also, not everyone is a candidate for psychotherapy.

I think this idea that Xanax is somehow more addictive than other benzos is mostly mythology. Comparative studies of abuse potential largely find minimal differences for the agents commonly used in outpatient psychiatry in the US. The second study below finds that the relative abuse potential is pretty similar among diazepam, lorazepam, clonazepam, and alprazolam and mainly tracks with the dose equivalent, not with the specific agent.



Additionally, if your purpose is to minimize the development of tolerance and dependence, you may be better off with a drug that has a shorter half-life and thus isn't exerting GABAergic tone chronically. Particularly for panic attacks which are short-lived anyway, it seems like you might as well use something that will work quickly and then not hang around impairing your driving and building tolerance for the next 12 hours.

I wouldn't usually start a benzo while titrating an SSRI. Just opens up a can of worms I'd rather not have to deal with. I usually just emphasize calm breathing/distress tolerance skills to tide them over until SSRI is therapeutic.

I wouldn't try to take the benzos away from people already on them before SSRI is therapeutic though.
 
  • Like
Reactions: 4 users
I think this idea that Xanax is somehow more addictive than other benzos is mostly mythology. Comparative studies of abuse potential largely find minimal differences for the agents commonly used in outpatient psychiatry in the US. The second study below finds that the relative abuse potential is pretty similar among diazepam, lorazepam, clonazepam, and alprazolam and mainly tracks with the dose equivalent, not with the specific agent.
I'm very interested to hear you say this. Whenever I see autopsy and OD data the percent that die with Xanax dwarfs all other benzodiazapines combined. Unless this equals the prescribing data, I would think this very hard sign of addiction/abuse (causing literally death) would speak strongly against it being equal.

With my robust N=1 in a career just over a decade, I can't even come close to counting the number of patients who have abused Xanax, it's well into the hundreds. I have seen maybe a dozen or so w/ Ativan or Klonapin in that same time frame. I recognize my personal sample size is meaningless but it's such a factor of magnitude difference I have a hard time wrapping my head around that just being chance.
 
  • Like
Reactions: 1 user
I think this idea that Xanax is somehow more addictive than other benzos is mostly mythology. Comparative studies of abuse potential largely find minimal differences for the agents commonly used in outpatient psychiatry in the US. The second study below finds that the relative abuse potential is pretty similar among diazepam, lorazepam, clonazepam, and alprazolam and mainly tracks with the dose equivalent, not with the specific agent.



Additionally, if your purpose is to minimize the development of tolerance and dependence, you may be better off with a drug that has a shorter half-life and thus isn't exerting GABAergic tone chronically. Particularly for panic attacks which are short-lived anyway, it seems like you might as well use something that will work quickly and then not hang around impairing your driving and building tolerance for the next 12 hours.

I wouldn't usually start a benzo while titrating an SSRI. Just opens up a can of worms I'd rather not have to deal with. I usually just emphasize calm breathing/distress tolerance skills to tide them over until SSRI is therapeutic.

I wouldn't try to take the benzos away from people already on them before SSRI is therapeutic though.

While the “potential” for addiction with other benzos certainly exists, clinically it is rare to see addiction to most other benzos in my area. Having worked in a detox facility for years, I may have seen 0-2 total cases of Diazepam, Lorazepam, etc. Clonazepam maybe 3-10. Alprazolam was in the hundreds. I’m a N-1, but the numbers are striking.

I sporadically see Lorazepam dosing at 25+mg/day for anxiety. The patients don’t meet DSM criteria for a use disorder. They take them exactly as prescribed. I confirm with records. I have yet to see that with Alprazolam.

You could argue that PCP’s and NP’s are the ones Rxing Alprazolam more at inappropriate starting doses which could contribute to the higher likelihood of needing treatment. Maybe it’s easier for patients to self-taper other benzos without medical intervention. There are lots of confounders that are difficult to analyze.

As far as impairment and decreased productivity related to benzos, I’d say Alprazolam far exceeds the others.
 
  • Like
Reactions: 3 users
I'm very interested to hear you say this. Whenever I see autopsy and OD data the percent that die with Xanax dwarfs all other benzodiazapines combined. Unless this equals the prescribing data, I would think this very hard sign of addiction/abuse (causing literally death) would speak strongly against it being equal.

With my robust N=1 in a career just over a decade, I can't even come close to counting the number of patients who have abused Xanax, it's well into the hundreds. I have seen maybe a dozen or so w/ Ativan or Klonapin in that same time frame. I recognize my personal sample size is meaningless but it's such a factor of magnitude difference I have a hard time wrapping my head around that just being chance.
That's very interesting. It may be that I just don't see this because it doesn't come into my practice area much. So I defer to those of you who are routinely working with severe substance use disorders.

I will say that I'm not super surprised that someone who already has a substance use disorder would go for something fast-acting given they have a plan for recreational use. That may be different from the likelihood that the choice to prescribe a particular agent will generate tolerance, dependence or addiction in a given individual.

There may also be prescribing culture/preferences that come into play. One of the earlier papers I saw on comparative addictive potential fingered diazepam as the biggest culprit; but it seems like that might have been related to the fact that it was commonly used to treat alcohol withdrawal, increasing the likelihood that people who had existing substance use disorders would be exposed to it and find out they liked it.
 
  • Like
Reactions: 1 user
I think this idea that Xanax is somehow more addictive than other benzos is mostly mythology. Comparative studies of abuse potential largely find minimal differences for the agents commonly used in outpatient psychiatry in the US. The second study below finds that the relative abuse potential is pretty similar among diazepam, lorazepam, clonazepam, and alprazolam and mainly tracks with the dose equivalent, not with the specific agent.



Additionally, if your purpose is to minimize the development of tolerance and dependence, you may be better off with a drug that has a shorter half-life and thus isn't exerting GABAergic tone chronically. Particularly for panic attacks which are short-lived anyway, it seems like you might as well use something that will work quickly and then not hang around impairing your driving and building tolerance for the next 12 hours.

I wouldn't usually start a benzo while titrating an SSRI. Just opens up a can of worms I'd rather not have to deal with. I usually just emphasize calm breathing/distress tolerance skills to tide them over until SSRI is therapeutic.

I wouldn't try to take the benzos away from people already on them before SSRI is therapeutic though.

Just to clarify. I think clonazepam is a better drug for panic attacks than xanax. Not due to addictive potential, but rather for the reinforcement they provide to the panic. For this reason, I dont like using PRN for panic disorder, of which, xanax is the typical agent chosen. Clonazepam is preventative treatment, xanax is catch up. I prefer a scheduled benzo approach in conjunction to SRIs for this reason. Head to head trials show clonazepam is a better drug for panic disorders anyway (compared to SRIs). Using both is a no brainer. When the benzo is reduced they are more likely to be ready for the uncomfortable therapy (8-12 wks later).

Again, not everyone is a candidate for therapy. PTSD and Panic therapy is very effective, but very uncomfortable. Some people fail it. Cant blame them.

Also, I dont think the GAD + panic disorder patients are really that rare. Just like other medical illnesses, Anxiety disorders tend to run together. Someone with GAD is more likely to have other anxiety related disorders.
 
  • Like
Reactions: 1 users
Just to clarify. I think clonazepam is a better drug for panic attacks than xanax. Not due to addictive potential, but rather for the reinforcement they provide to the panic. For this reason, I dont like using PRN for panic disorder, of which, xanax is the typical agent chosen. Clonazepam is preventative treatment, xanax is catch up. I prefer a scheduled benzo approach in conjunction to SRIs for this reason. Head to head trials show clonazepam is a better drug for panic disorders anyway (compared to SRIs). Using both is a no brainer. When the benzo is reduced they are more likely to be ready for the uncomfortable therapy (8-12 wks later).

Again, not everyone is a candidate for therapy. PTSD and Panic therapy is very effective, but very uncomfortable. Some people fail it. Cant blame them.

Also, I dont think the GAD + panic disorder patients are really that rare. Just like other medical illnesses, Anxiety disorders tend to run together. Someone with GAD is more likely to have other anxiety related disorders.

 
Just to clarify. I think clonazepam is a better drug for panic attacks than xanax. Not due to addictive potential, but rather for the reinforcement they provide to the panic. For this reason, I dont like using PRN for panic disorder, of which, xanax is the typical agent chosen. Clonazepam is preventative treatment, xanax is catch up. I prefer a scheduled benzo approach in conjunction to SRIs for this reason. Head to head trials show clonazepam is a better drug for panic disorders anyway (compared to SRIs). Using both is a no brainer. When the benzo is reduced they are more likely to be ready for the uncomfortable therapy (8-12 wks later).

Scheduled benzo --> chronic GABA receptor activation --> receptor downregulation --> tolerance --> distress upon withdrawal --> vicious cycle of continued administration to avoid withdrawal. It's just a bad idea.

Benzodiazepines have been reported to impair the efficacy of exposure therapy as pointed out by the psychologists (carasusanna and WisNeuro) above on this thread. Reduction in existing GABA receptor complement does not make people 'more ready for the uncomfortable therapy.'
 
  • Like
Reactions: 5 users
When you say the psychotherapy is too uncomfortable to be effective for some, I don’t know if that is the right message. A skilled psychotherapist can titrate the exposure to the feared stimuli. Maybe the patient had a bad experience with it or was unable to for a connection with the therapist. The technique is only one part of the treatment, the therapeutic relationship is another. Solid therapeutic rapport can reduce anxiety, hell, my cat helps reduce anxiety. The message should be that we will use every tool we have and go as slowly and “you will be in charge of that”, but we will work on this together. Benzos are part of the toolkit and I have worked with several patients for whom it has taken years to get to a point where they have resumed functioning normally and the benzo taper was still goin. I am completely of with going slow as long as we are making progress. Time-limited therapy interventions are not the only tool we have as psychologist, they are just the easiest to research.
 
  • Like
Reactions: 5 users
When you say the psychotherapy is too uncomfortable to be effective for some, I don’t know if that is the right message. A skilled psychotherapist can titrate the exposure to the feared stimuli. Maybe the patient had a bad experience with it or was unable to for a connection with the therapist. The technique is only one part of the treatment, the therapeutic relationship is another. Solid therapeutic rapport can reduce anxiety, hell, my cat helps reduce anxiety. The message should be that we will use every tool we have and go as slowly and “you will be in charge of that”, but we will work on this together. Benzos are part of the toolkit and I have worked with several patients for whom it has taken years to get to a point where they have resumed functioning normally and the benzo taper was still goin. I am completely of with going slow as long as we are making progress. Time-limited therapy interventions are not the only tool we have as psychologist, they are just the easiest to research.

How the therapy is presented and the milieu matters. In a university clinic setting (that saw students and non-students) I never had anyone that did not complete a round of therapy for PTSD or panic. Zero. However, in the VA, with SC, distrust, and common myths being floated around about things like PE/CPT, the amount of people ho won't engage or drop out very early is quite high.

But, outside of VA type settings, my experience of people not being appropriate for anxiety treatments has been extremely low. A skilled therapist can work within this framework in most presentations.
 
  • Like
Reactions: 2 users
How the therapy is presented and the milieu matters. In a university clinic setting (that saw students and non-students) I never had anyone that did not complete a round of therapy for PTSD or panic. Zero. However, in the VA, with SC, distrust, and common myths being floated around about things like PE/CPT, the amount of people ho won't engage or drop out very early is quite high.

But, outside of VA type settings, my experience of people not being appropriate for anxiety treatments has been extremely low. A skilled therapist can work within this framework in most presentations.
I also think that the message with those time limited interventions should be that for some people follow-up therapy could be useful or necessary to assist with the other areas of your life that may or may not be problematic or contributory. For example, PTSD symptoms could be significantly reduced after course of therapy, but the patient still has difficulty with interpersonal skills and come from an unhealthy/unsupportive family system. The stress of not being able to develop tools and strategies to improve that area could very easy bring about a recurrence of PTSD symptoms. A lot of the work I do is with people who have had courses of therapy, these days it’s mostly EMDR that they reference and I try not to react when they reference how great it was. Keep in mind that I tend to work with the patients with more of the Borderline traits so obviously just a course of trauma focused therapy probably won’t be sufficient.
 
  • Like
Reactions: 1 user
When you say the psychotherapy is too uncomfortable to be effective for some, I don’t know if that is the right message. A skilled psychotherapist can titrate the exposure to the feared stimuli. Maybe the patient had a bad experience with it or was unable to for a connection with the therapist. The technique is only one part of the treatment, the therapeutic relationship is another. Solid therapeutic rapport can reduce anxiety, hell, my cat helps reduce anxiety. The message should be that we will use every tool we have and go as slowly and “you will be in charge of that”, but we will work on this together. Benzos are part of the toolkit and I have worked with several patients for whom it has taken years to get to a point where they have resumed functioning normally and the benzo taper was still goin. I am completely of with going slow as long as we are making progress. Time-limited therapy interventions are not the only tool we have as psychologist, they are just the easiest to research.
I've yet to meet a patient with intact cognition who wasn't a candidate for therapy. I've met many people where the chances of finding a genuinely skilled therapist they could actually see for the amount of time required was essentially the same as being struck by lightening. This includes both people in therapy, people who have never been in therapy, and people who have been in therapy for years and think therapy doesn't work because the therapist does nothing make sympathetic noises.

Doesn't mean Im free with the benzos, but I find therapists of all sorts have a really hard time actually wrapping their heads around how bad the supply issue is--after all, they only see patients who've made it to them! It's us psychiatrists stuck desperately trying to help people for whom effective therapy is at best a pipe dream.
 
  • Like
Reactions: 7 users
Top