Thinking about other hypnotics, e.g. melatonin, diphenhydramine, trazodone, amitriptyline) how might these compare to benzos and Z-drugs when it comes to accidental or intentional fatal self-consumption?
This was a great discussion article! I am looking forward to hearing everyone's thoughts and discussing it in person.
I found this article to be very interesting. As a practice, I always try to encourage alternatives to medication when counseling clients about anxiety and sleep disturbances, but of course, benzos and sleep aids tend to come into the conversation at some point. Some of the people I work with also have a really hard time implementing interventions, as they are too preoccupied or tired to concentrate. I was under the assumption that they were all pretty risky to prescribe, due to the risk of overdose, dependence, tolerance, but I was not aware that there was such a drastic hierarchy of risk attached to them. This study is valuable as a preliminary look at the medications.
The authors also brought up important details to look into in the future. I really appreciated their mentioning that the studies examined did not assess how the person who had self-poisoned obtained the medication. A study that addresses this could provide insight also into our prescriptive practices - were these their own prescription, how many were they getting at one time, what was the dose, how closely were they followed, etc., were all questions that popped into my head while reading this.
Really in all clients I am reluctant to start or continue prescription benzos/sleep aids, but I do think that it is a tool we need to be willing to use, as they are effective! I have also found that often when a client has tried benzos, they don't perceive as much efficacy from other medications, as their is less immediate action. Has this happened with anyone else? I usually discuss sleep hygiene first, adjust medication doses if there is one that causes sedation that could be adjusted, then melatonin, then diphenhydramine or trazodone depending on presentation, saving the strongest options for later. This is in cases were close follow up is possible, but of course would vary depending on how much contact I have with the client.
After reading this article my opinion about benzos and hypnotics remain the same. I believe I will use caution in prescribing these medications for people who are at high risk such as those suffering from anxiety, depression, and insomnia. Although benzos are commonly used anxiolytics I would much rather prefer prescribing SSRI’s as first line of treatment for anxiety.
Using hypnotics for insomnia should be the last resort in my opinion. I would much rather treat the underlying issue that is causing insomnia than to prescribe a pill to help someone sleep.
During my last clinical rotation one of the psychiatrists gave an informative lecture about sleep hygiene that are similar to UpToDate suggestions. Some of the suggestions were using the bedroom for only sleep and sex, avoiding the bed and bedroom when unable to sleep, rather sit on floor until tired and then return to bed. Exit bedroom when unable to sleep because this can create a mental association with insomnia. Keep bedroom a cooler temperature, stay away from bright lights or electronic devices 30 minutes before going to bed. Also, avoid naps during the day (Bonnet & Arand, 2018). I would educate my patients on trying these sleep hygiene tips first before initiating a hypnotic.
Reflecting back to clinical experience, most patients would complain that hypnotics lose their ability to help with insomnia over time. This can easily create a risky situation and allow a person to accidentally overdose on hypnotic medication using the rationale that more pills will solve the problem. Medications such as the Z drugs appear to have a very short half-life indicating that they are meant for short term use. Zaleplon (Sonata) and Zolpidem (Ambien) have a half-life of about an hour and is effective for patients having difficulty falling asleep and is not indicated for long-term use (Bonnet & Arand, 2018).
Other medications commonly used to treat insomnia are diphenhydramine, Remeron, Seroquel, and Trazadone, however these medications are not recommended for long term use to treat insomnia. It appears that medication is not the answer in treating chronic insomnia, rather these cases should be treated with combination therapy of CBT, sleep hygiene, and short term use of medication for best results (Bonnet & Arand, 2018).
Bonnet, M.H., Arand, D.L. (2018). Behavioral and pharmacologic therapies for chronic insomnia. UpToDate. https://www-uptodate-com.ucsf.idm.oclc.org/contents/behavioral-and-pharmacologic-therapies-for-chronic-insomnia-in-adults?search=insomnia%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H4
Hi Evelyn,
Thank you for your post. I agree that alternative interventions are great for patient’s suffering from chronic insomnia. I personally don’t think medication is the answer to insomnia, but for short term use is acceptable. I think that education around sleep hygiene and therapy is much more effective in the long run. Also, therapy helps get to the underlying issue that may be causing insomnia.
Something I found very interesting is that patients who suffer from insomnia stay in bed longer trying to make up for lost sleep, which causes a shift in their circadian rhythm and reduces their homeostatic drive and makes sleep onset even more difficult the following night (Bonnet & Arand, 2018). One of the therapies commonly used to help with insomnia is sleep restriction therapy. This therapy requires lots of education, but ultimately informs the patient that the body and brain create associations with the bed or bedroom when not used for sleep. Here is the article if you are interested in using in practice.
Bonnet, M.H., Arand, D.L. (2018). Behavioral and pharmacologic therapies for chronic insomnia. UpToDate. https://www-uptodate-com.ucsf.idm.oclc.org/contents/behavioral-and-pharmacologic-therapies-for-chronic-insomnia-in-adults?search=insomnia%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H4
Thank you for choosing this interesting and relevant article. This article has somewhat changed my views for prescribing benzodiazepines and hypnotics in new patients, but not by a lot. The article describes that patterns of fatal and non-fatal self-poisoning (both accidental and non-accidental). The article reveals that Temazepam (Restoril) is 10x more toxic than Diazepam (Valium). It also describes that Diazepam is frequently implicated in self-poisonings. Z-drugs (including Ambien) are also frequently used in self-poisonings. Generally, I would not prescribe or recommend any of these medications to my patients. They all have worrisome risks without providing compelling benefits. If I strongly believed that a client would benefit from a benzo, I would prescribe Lorazepam (a med that the authors identified as significantly less toxic in cases of self-poisoning). For clients seeking sleep aid, I always recommend melatonin (start 3 mg, increase to 5mg, then 10mg if absolutely necessary). If that didn't work, I would consider other agents (including trazadone and mirtazapine). Finally, if these agents did not work, I would move on to Lorazepam. For individuals already prescribed the problematic drugs, I would try to cross-titrate them on to less risky meds (including Lorazepam) ASAP.
One other aspect of this article that I found especially compelling was its uncovering of the fact that people with sleep issues (bad enough to necessitate meds) are at a higher risk for suicide by self-poisoning. Indeed, sleep deprivation is a huge, huge health concern. I always think "it's no wonder this is a tried-and-true form of torture." Sleep issues appear to constitute a risk factor for suicide in and of itself. Going forward, I may try to slip in some covert safety planning with clients that disclose significant, chronic sleep difficulties. I can also understand how individuals desperate for sleep might over-dose themselves with sleep aid medications and die from accidental self-poisoning. Quite tragic indeed. This is an area ripe for sensitive, compassionate care.
Marlene - I completely agree with what your plan is for patients. I’m glad that you highlighted the fact that people with sleep issues are at a higher risk for suicide by self-poisoning, as I think this finding is very important for us to keep in mind when going into practice. We need to be prepared to act when clients come in complaining of sleep issues, and relay that we are hearing their concerns. There have been a few times in clinicals when I have seen preceptors fail to validate client’s sleep difficulties, and I think it was at the disservice to the relationship. Clients also tend to be much more reactive with poor sleep (in general, of course, not as a rule), and validating feelings can really do wonders. I also think this information could be useful when we discuss our treatment plan - being transparent in our reluctance to prescribe benzos due to the risks associated, and also letting them know that their judgment might be impaired as a result of their insomnia (impulsivity). Just wanted to add my two cents. I am wondering how other people have approached this.
Evelyn - I’ve run in to that sticky situation as well – I’ve found in my own experience that once someone has been prescribed benzos, it’s a tough sell to switch to pretty much anything else, in part because as you mentioned the onset of action isn’t as immediate, so many other options do not provide that quick relief that one can anticipate with a benzo. I’ve found that with clients who schedule an office visit with the specific intent with leaving with a benzo, anything else simply isn’t adequate. Perhaps you’ve also heard clients say, “But nothing else works!”. With clients who are medication-naïve I’ve found that sleep hygiene changes are a good first start, in particular with transitional age youth limiting screen time close to bedtime. That said, with clients who have requested benzos, I have deferred this request, mostly because I am starting them on other sedating medication for other symptoms (e.g. psychosis) that may be a two-for-one and address their sleep issues at the same time.
Marlene – you make a really important point about the importance of sleep, and how debilitating sleep deprivation can be. Indeed, disrupted and/or limited sleep cycles can be not only debilitating but outright dangerous, and can be a major risk factor for our clients. As someone who has stayed awake for up to 30 hours at a time, I can certainly speak to the cognitive fogging, mood dysregulation, and poor impulse control associated with sleep deprivation.
Evelyn,
Very well said. I believe that sleep issues definitely affects quality of life. It reduces our ability to function to the highest quality and can put strains on our relationships, careers, and physical and mental health. I've been lucky enough to have preceptors who made sleep a priority with their clients. Sleep is a very important factor in mental health, which is why it is always assessed during a psychiatric interview. Someone's sleep pattern can give an insight into their mental health, therefore guiding the path to treatment. As a provider, I will be conscientious about my patient's sleep concerns and also the type of interventions that will be provided having this article in mind. Great discussion, everyone!
Hi all,
this article is very intriguing. The number of lives lost due to intentional or accidental drug overdose via benzodiazepines or the use of hypnotics is staggering. The portion of the article that caught my eye, and I have some limited experience with is the involvement of alcohol in these scenarios. While precepting at the VA as well as in Campbell, CA., I have had some encounters with patients that on occasion mix their prescription hypnotics with alcohol. They say that it enhances the medication and/or gives them a peaceful uninterrupted night sleep. I can remember almost from day one of this program, the instructors teaching on the negative outcomes that can occur from these practices. My preceptor and I warn them about this, telling them of the effects on the respiratory system. Reading this article made all of these facts surreal. To see the numbers in black and white (though not large, thankfully) however very significant, allowed me to revisit those conversations of the past. Moving forward it is my goal to educate with emphasis on the hazards of mixing these substances. This article in particular provides proof of how dangerous this practice can be. I looked forward to tonight’s discussion and hearing from my peers on this subject.
This article does not necessarily change the way I think about how to use benzos and hypnotics in my new patients, instead, it has given me some new insights and perspectives to keep in the back of my mind whenever the subject of benzos arise with my patients. It is good to know these information about the fatality of some of these medications, however, it should not prevent a provider from prescribing it if is obviously needed. It comes down to us as providers to educate our clients on these medications, and conducting a thorough risk assessment to avoid any accidental or non-accidental poisoning. If my patients are already prescribed these agents, I will re-evaluate their need for them, and provide other interventions that can provide the same benefit.
This is where I think about the power of therapy. It can be very efficacious in combination with these medications, and then down the road, after the medications can be tapered off or switched to a less risk of fatal accident medication.
I also found it very compelling that people with sleep issues had a higher risk for suicide by self-poisoning. As a nurse myself, I have had some time in the past where I would go multiple days without sleep due to balancing schoolwork, motherhood, and work. I found myself to be lacking proper insight and judgement in those times of no sleep. I would say, put a teabag in a cup of coffee, or put sugar in the scrambled eggs instead of salt, and this was only a temporary thing for me. So imagine those that have chronic insomnia or difficulty sleeping and have to deal with this. They can easily accidentally poison themselves with hypnotics by over-dosing. This again, comes down to us as providers to provide support, education, and multiple resources to help these patients avoid an unnecessary death.
Thank you Nana for your insightful and reflective post.
After the journal club meeting, I too began to focus on the educational aspect and informing my patients on the possible potential dangers of hynotics and benzos. I have had preceptors in the past that would stir clear of prescribing benzos,or if they inherited a client on them, they would immediately began trying to convince the client to switch to another medication or taper them off of the benzo.However these drugs are necessary for some clients. I remember one preceptor, that prescribed them PRN and would monitor how much of the medication the client would consume over a certain period of time. If the client went over a certain amount of the drug, the describer would call them into the office for medication education concerning this medication. I have witnessed this practice to be effective on several occasions.
I also found it interesting that people with insomnia or sleep hygiene issues were at a higher risk for self-poisoning.This could be because of a knowledge deficit on the client's part. I have heard many client's say in the course of an interview in the office, that if one pill worked well, then two or three would work twice or three times as well. It is my belief that education, monitoring, and periodic education while the client remains on the medication will help with self-poisoning and/or self-harming activities in the stable client. Thanks again for your delightful post.
Does this article change the way you think about how to use benzos and hypnotics in your NEW patients? How about patients already prescribed these agents?
It was great to get some additional data on benzo and hypnotic use from the article and discussion. In general I've been very reluctant to prescribe benzodiazepines and at least some of that is due to the fact that most of my patients have had comorbid substance abuse. Additionally, the data on the cognitive impairment associated with long-term use was surprising to me and inspires further caution and reluctance on my part to prescribe them. That said, I am aware that they are some of the most potent anxiolytics available for acute anxiety. So, interestingly, I've actually come from a place of more reluctance to prescribe them to a more balanced approach I think. For all medications I think we do a risk benefit analysis and it was helpful to have the information about overdose incidence to help assess that risk. Our risk benefit analyses are obviously on a case by case basis and the more information I've learned about the specific risks associated with benzo use the better able I am to determine whether the risks of them outweigh the potential benefits. Overall I think my approach has increasingly become using them in patients with low abuse potential for short-term anxiety relief. Most of the patients I've had have come to me already on benzodiazepines and I've not initiated anyone on them. Seeing how long it's taken patients to discontinue their use, in some cases years, has made me weary of starting anyone on them, but for someone without a history of substance misuse, who isn't taking other medications/substances that interact with benzos--CNS depressants, with a low risk of developing dependence and acute anxiety I would consider it. That said I think as someone mentioned in our journal club, starting a benzo with a plan for discontinuation set at the beginning of treatment is an option I really like. It sets the expectation from the beginning that the medication is only for short-term use.
As far as inheriting patients already on benzos, how I would manage their meds depends on the patient but for the majority I'd want to taper them off. If it's someone who uses them infrequently for acute anxiety and their use hasn't increased over time I might continue them provided they're clear on the potential for dependence and long-term negative effects on cognition but I'd want to have a thorough discussion about alternatives, risks and precautions. I'm also pretty open to slow tapers if a patient finds it the dose decreases particularly distressing. I've seen tapers as slow as 5-10% (generally the first dose reduction is higher, but ongoing ones are 5-10%) which obviously isn't ideal but if that's what an individual can tolerate and it maintains a therapeutic alliance between patient and provider then I think it's a reasonable strategy.
Thinking about other hypnotics, e.g. melatonin, diphenhydramine, trazodone, amitriptyline) how might these compare to benzos and Z-drugs when it comes to accidental or intentional fatal self-consumption?
It really depends on what hypnotic you're talking about. Melatonin is generally the first medication I think of because of it's low abuse and overdose potential. If I'm treating someone for depression or someone with memory or cognitive impairments, which would put them at potentially higher risk of self-harm or intentional or accidental OD, I might start with trazadone or mirtazapine. If those don't work what I'd go to next depends on the person's psych and medical illnesses. Potentially diphenhydramine or for someone with psychotic symptoms potentially a sedating antipsychotic. In terms of accidental or intentional overdose I would, of course, choose something other than a TCA, would avoid benzos or at least prescribe them in limited quantities and be sure I knew about any other medications they were taking.Lastly, another excellent point is that sleep disturbance itself isn't benign. Lack of sleep, poor or interrupted sleep and unrestful sleep all affect someone's cognition, judgement and risk profile so it's not as if we're treating something benign with something potentially dangerous. Considering all these factors/points is obviously important, as is having a plan for the medication course and providing anticipatory guidance to patients with anxiety and sleep disturbances.
The last point that's worth making I think is that there are many alternatives to medication to improve sleep (and anxiety)--psychotherapy, especially CBT-i, good sleep hygiene, progressive relaxation, guided meditation, regular exercise at least a few hours before bedtime, limiting screen time especially before bedtime, light boxes to help regulate sleep, chamomile tea, self-hypnosis and identifying and treating any underlying medical/psych conditions.
http://www.cpsa.ca/wp-content/uploads/2017/06/Benzodiazepine-Clinical-Toolkit-Use-and-Taper.pdf
https://www.va.gov/PAINMANAGEMENT/docs/OSI_6_Toolkit_Taper_Benzodiazepines_Clinicians.pdf
References:
Molen, Yara Fleury, Carvalho, Luciane Bizari Coin, Prado, Lucila Bizari Fernandes do, & Prado, Gilmar Fernandes do. (2014). Insomnia: psychological and neurobiological aspects and non-pharmacological treatments. Arquivos de Neuro-Psiquiatria, 72(1), 63-71. https://ucsf.idm.oclc.org/login?url=https://dx.doi.org/10.1590/0004-282X20130184
Clinician Toolkit: Benzodiazepine Use and Taper. (2017). National Pain Center, College of Physicians and Surgeons of Alberta. Retrieved from http://www.cpsa.ca/wp-content/uploads/2017/06/Benzodiazepine-Clinical-Toolkit-Use-and-Taper.pdf
U.S. Department of Veterans Affairs, National Center for PTSD. (2013). Effective Treatments for PTSD: Helping Patients Taper from Benzodiazepines. Retrieved from https://www.va.gov/PAINMANAGEMENT/docs/OSI_6_Toolkit_Taper_Benzodiazepines_Clinicians.pdf
Hi Jamie,
Your post resonated quite strongly with me and I agree with many of your points. Similar to you, I am reluctant to prescribe benzos, due to the cognitive sequelae as well as the physiological and psychological dependence that can be challenging to address later down the road. Something I learned from my preceptor this year (which you spoke about), is to start off prescribing benzos with a plan to taper and to treat it like a short-term solution. He likened this strategy to how one might prescribe prednisone-- there is always a taper to be expected. Using benzos can act as a bridge (while anti-depressants are kicking in) or to get through a difficult, short-term transition period. This sets an initial precedent for patients’ expectations, so that a schedule is already in place and conversations around getting patients off benzos will (hopefully) not be as challenging when trying to wean patients off.
It is also important to refer out for therapy (or do it yourself, if the setting permits), so that behavioral strategies (i.e., CBT, DBT) around regulating anxiety can be learned. Emphasizing the power of therapy will be imperative to helping minimize dependence on medications for reduction in anxiety.
This article definitely speaks volumes in terms of safety concerns and elucidates the potential adverse outcomes from misuse of these medications. This was one of the areas that I felt nervous navigating in practice. I have this fear that I’ll have patients that will be demanding and expect a prescription for benzos, but now I feel well prepared in my response and how I will manage these requests in the future. This article also exposed the ways in which people have used these medications for suicide. Moving forward, I know that I have to be sure to do thorough risk assessments in all patients but particularly for the ones I prescribe any of these medications to.
After having many discussions around this topic in case conference and during clinical with preceptors, I am more confident with my response to new patients. I think it’s important to acknowledge their needs and have a conversation about the medication. In my experience, I found it helpful do provide a lot of psychoeducation around the medications to patients and to also explore other symptoms they me having that other medication might be able to target. I have had patients that were simply blown away about sleep hygiene and architecture. They stated, “I had no idea, “and I was able to have a better alternative for sleep than prescribing benzodiazepines.
Other hypnotics like melatonin diphenhydramine etc. also have high potentials for intentional fatal self-consumption. I think when people are depressed and hopeless they will take anything they can get their hands on to commit suicide. I also think they might be easier to obtain because benzo can potentially carry a certain stigma around them when patient ask their providers for them. I think providers might be more willing to prescribe things like trazadone or a Z-drug compared to benzos. I also think that medications like TCA’s definitely carry a higher mortality than benzos. With benzo overdose you can administer flumazenil to quickly reverse its effects, however with Benadryl and TCA’s I am not of a medication to counter act its effects.
Thanks for bringing up the issue of sleep architecture! We're often told that because benzos and similar drugs change sleep architecture (benzos in particular suppress REM sleep), it's not "good" sleep.
Last year, I had the chance to hear a lecture from John Winkelman, MD, PhD, the Chief of the Sleep Disorders Clinical Research Program in the Department of Psychiatry at Massachusetts General Hospital and Professor at Harvard Medical School, at the 2017 Harvard Psychiatry conference. Among the mountain of great advice and updates for clinical practice, this really stuck out: "There is no indication that preserving normal sleep architecture should be a goal." Basically, even when we can map sleep architecture, we don't actually know what the clinical meaning of it is or whether any parts are good, bad, or necessary - if the client feels rested, that's success.
He also stressed that every single person with insomnia should be screened for trauma and PTSD, and that we should always consider sleep apnea in any client on psychiatric medications who complains of insomnia. Sleep apnea is often comorbid with PTSD (and both disorders predispose the individual for the other disorder), and actually has an atypical presentation in many of those clients (may not be overweight, may present as insomnia more than daytime sleepiness).
Last year, I had the chance to hear a lecture from John Winkelman, MD, PhD, the Chief of the Sleep Disorders Clinical Research Program in the Department of Psychiatry at Massachusetts General Hospital and Professor at Harvard Medical School, at the 2017 Harvard Psychiatry conference. Among the mountain of great advice and updates for clinical practice, this really stuck out: "There is no indication that preserving normal sleep architecture should be a goal." Basically, even when we can map sleep architecture, we don't actually know what the clinical meaning of it is or whether any parts are good, bad, or necessary - if the client feels rested, that's success.
He also stressed that every single person with insomnia should be screened for trauma and PTSD, and that we should always consider sleep apnea in any client on psychiatric medications who complains of insomnia. Sleep apnea is often comorbid with PTSD (and both disorders predispose the individual for the other disorder), and actually has an atypical presentation in many of those clients (may not be overweight, may present as insomnia more than daytime sleepiness).
Thanks Ladies for bring up the sleep hygiene and architecture peace to this.
My clinical instructor at Sunnyvale leads his interviews with how his clients sleeps. From there he asks questions about medications , side effects and so forth. As Laura mentioned in her commentary, he also believes that insomnia and nightmares are due in large part to some repressed or depressed PTSD, and sleep apnea is another manifestation of it. I came across an article that suggests that as many as 70% of patients with nightmares and/or insomnia has PTSD(Peters,2018).If this continues , it can lead to chronic anxiety which is associated with isolated sleep paralysis(Peters,2018).
Many people with insomnia often try to self medicate with alcohol which further disrupts normal breathing patterns during sleep and fragments REM sleep. Looking at this from another perspective gives different symptoms to consider.Peters,2018 advocates treating other symptoms associated with sleep apnea such as depression, anxiety, panic disorders and/or substance abuse will help lessen the symptoms of insomnia GREAT POST !!
References:
Peters, B.(2018) How does PTSD affect sleep: PTSD may lead to nightmares and insomnia. Retrieved from https://verywell health.com/how-does-ptsd-affect-sleep3014682?print.
Robert,
I too am glad you brought up sleep architecture. Sleep architecture is something my preceptor brings up frequently with PAMF, and we've had that similar "blown away" response from patients. Not only are they typically very receptive to learning about it, but it also allows them to make a more informed decision on their treatment. For patients who want to learn more about it, I have this pamphlet printed out that I sometimes handout to patients: https://www.tuck.com/stages/
In addition to benzos and Z-drugs disrupting sleep architecture, another thought I had is that ambien also has a short half-life. For patients we have that have trouble STAYING asleep, ambien will typically get them to sleep quickly, but it doesn't always keep them asleep due to its short half-life. I usually recommend trazodone for sleep maintenance, and then go over that there is evidence that it improves our sleep architecture, particularly by prolonging the deep phase of sleep (the delta phase). I cited a review for this in my other post.
Some great points being made in this discussion. I found that I really enjoyed this article, as benzodiazepines and their place in outpatient use is a topic that seems to be rearing its head relatively frequently in my clinical placement. As it seems that many people here feel, I too am hard-pressed to think of a time that I would prescribe benzodiazepines or the hypnotics discussed in this article in an outpatient setting. Restoril and the z-drugs have been presented to us in the program as medications to be very wary of, and this data seems to back that up. Although sleep can be a major factor that contributes to mental health symptoms, there are other effective pharmacological agents that have been mentioned here, including the melatonin agonist ramelteon, exogenous melatonin capsules, mirtazapine, trazadone etc. And lets not forget good old fashioned sleep hygiene, as our culture is more and more polluted with LED streetlights, glowing phone screens, and social media distractions.
As mentioned in the paper, there are concerns about risks of these drugs beyond just the capacity for overdose which have led to legislative changes in some areas. Despite this, these medications are being prescribed, and it is therefore important to know which are more likely to be fatal in the case of overdose. I did find the following line from the paper to be interesting:
“Furthermore, given the potential impairment in functioning and distress associated with insomnia and in the absence of safer drug alternatives, there is a need for greater focus on psychological management of sleeping problems, especially when dealing with vulnerable patients.”
I would take issue with the statement that there is an absence of safer drug alternatives, as a number of these have been mentioned in this tread. However, this misleading sentence does nothing to weaken the importance of the data derived from the study.
Thanks for an interesting topic and a lively discussion!
Does
this article change the way you think about how to use benzos and
hypnotics in your NEW patients? How about patients already prescribed
these agents?
I was surprised that the fatal-toxicity of Z-drugs (or at least zolpidem/zoplicone) was so much higher than diazepam, at least as assessed by the authors. If anything though, this study made me feel a little better about the fatal overdose potential of benzos and Z-drugs. Anecdotally, based on 11 years of working in psych and emergency rooms, it's relatively hard to kill yourself by overdose. Many over-the-counter drugs have a much higher risk of non-fatal catastrophic injury (as with acetaminophen) or a similar rate of fatality (acetaminophen, valproate, troglitazone [which had 148 reported fatalities in 2000 alone], trimethoprim/sulfamethoxazole, and more) (Bjornsson & Olsson, 2006), so I don't find benzos or z-drugs particularly frightening in regards to overdose.
The acute and long-term risks of benzodiazepine use are increasingly well-documented, and I think it's harder these days to justify keeping patients on benzos long-term, especially without attempting other treatments like CBT-I and sleep hygiene. I am unlikely to prescribe most Z-drugs - they aren't as effective as benzos, have a similar or greater side effect profile (contrary to early hopes), and now are apparently more toxic in overdose.
Personally, if a client has been well-maintained on a benzo for a prolonged period, I am comfortable with educating them about longterm risks and encourage them to taper off, but I am also generally comfortable with continuing their current therapy if it's effective and within reasonable parameters. Exceptions include misuse or evidence of doctor-shopping (frequent ER visits, multiple providers in CURES database) or certain physical or psychiatric risk factors (falls, amnesia, cognitive decline, MVA, need for opiate medication or other medications that suppress respiratory drive). I don't generally start anyone on a benzo other than for a short-term, time- and situation-limited use, and I'm very clear about this with the client up front. However, there will always be some cases where daily benzos are necessary to maintain any semblance of functioning or quality of life, so I never say never.
Thinking about other hypnotics, e.g. melatonin, diphenhydramine, trazodone, amitriptyline) how might these compare to benzos and Z-drugs when it comes to accidental or intentional fatal self-consumption?
We can't really make judgments about hypnotics as a group, as each of these meds has a different side effect and risk profile. Amitriptyline is highly lethal in overdose, and should never be given to clients who are at risk for intentional overdose. Diphenhydramine overdose can cause seizures, coma, and psychosis at high doses (especially above 3 g), and EKG changes even at moderate overdose (1 g) (Radovanic et al., 2000). Some of the psychic burden is removed from us as providers though when we know the client can just buy the medication OTC if they're determined to overdose.
I think when prescribing, we have to weigh the worst outcomes (intentional overdose) with the drug's efficacy and general tolerability. Melatonin isn't very effective and isn't free of side effects (hyperprolactinemia, may impact fertility), and trazodone and diphenydramine have a lot of side effects that are poorly tolerated (daytime grogginess, anticholinergic side effects like dry mouth, blurred vision). In addition, like benzos, long-term use of anticholinergics (including diphenhydramine, benzos, antispasmodics like oxybutynin) is linked to dementia, cognitive and functional decline, and increased fall risk (Koyama et al., 2014).
Bjornsson, E. & Olsson, R. (2006). Suspected drug-induced liver fatalities reported to the WHO database. Digestive and Liver Disease, 38(1), 33-38. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16054882
Koyama, A., Steinmann, M., Ensrud, K., Hillier, T. A., & Yaffe, K. (2014). Long-term cognitive and functional effects of potentially inappropriate medications in older women. Journal of Gerontology, 69(4), 423-429. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24293516
Radovanic, D., Meier, P. J., Guirguis, M., Lorent, J. P., & Kupferschmidt, H. (2000). Dose-dependent toxicity of diphenhydramine overdose. Human and experimental toxicology, 19(9), 489-495. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11204550
Hi Laura, thank you for your informative post. I completely agree with a lot of what you had to say. This year, I inherited several clients who were already taking benzos on a regular basis (mostly low doses). Just like you mentioned, I worked with them on recognising the long-term effects of benzo use, especially as the clients were getting older. I think I was successful at reducing doses because I spent the time speaking to my clients about their use and allowing them to feel supported in the timing of tapering down. I had one client who agreed it was time to start tapering down after I had seen her and discussed a taper with her for three months. By allowing her the time to ask questions and think about how she wanted to go about preparing for discontinuing the medication, she felt better prepared and was more knowledgeable about exactly why it was a good idea to decrease the dose.
For new clients, I am already hesitant to prescribe benzos. However, I know that sometimes they are quite necessary. In class, we spoke about having a plan for tapering and discontinuing prior to even initiating the medication so that the client knows exactly what to expect ahead of time. I thought this sounded very practical and informative for clients and that it is a strategy I may practice.
Laura,
Thanks for your thoughtful post. I am struck by your clinical pearls, client-centeredness and commitment to commonsense care. It's always refreshing to read your posts.
Similar to Michelle, I've also inherited patients that have been on benzos long-term and have big fears about tapering down. I've heard long-timer providers talk about how benzodiazepines are the opioids of the future. While benzos do have a proven substantial risk for dependence, their risks must be weighed with their benefits. As you mentioned, some individuals have truly crippling anxiety and truly benefit from daily benzodiazepines. This is a really hard decision to make--especially in middle or older aged individuals (due to risks for cognitive decline). As many of our professors have noted in the past, these types of scenarios point to the reality of psychiatric practice (as opposed to clear-cut textbook examples).
When it comes to thinking about my future prescribing practices, I believe I'll still stick to trazadone and melatonin as first-line agents. If these do not prove effective (and something like mirtazapine is not indicated), I will consider Lorazepam.
Hi All,
I really like this conversation, including one part in particular that piqued my interest: i.e., melatonin in context of Seth’s question, “Thinking about other hypnotics, e.g. melatonin, diphenhydramine, trazodone, amitriptyline) how might these compare to benzos and Z-drugs when it comes to accidental or intentional fatal self-consumption?” I have tended to consider melatonin to be a relatively safe alternative, though the posts here, such as Laura's, are an always helpful reminder that likely no medication is without potential risks.
For instance, Lexicomp includes the following in its list of more common adverse effects: “1% to 10%: Central nervous system: Dizziness (2%), Gastrointestinal: Diarrhea (3%), vomiting (2%), abdominal pain (1%), constipation (1%), Neuromuscular & skeletal: Arthralgia (4%), back pain (4%), asthenia (2%), peripheral pain (2%), Infection: Influenza (2%), Respiratory: Nasopharyngitis (4%), upper respiratory tract infection (3%), cough (2%), lower respiratory tract infection (2%), pharyngitis (2%), pharyngolaryngeal pain (2%), muscle cramps (1%), rhinitis (1%), Genitourinary: Urinary tract infection (2%)” (Lexi-Comp Online, n.d.).
Furthermore in Lexicomp, there are notable and potentially quite relevant drug interactions noted with melatonin that include ethyl alcohol (“Risk X: Avoid Combination”), benzodiazepines (“Risk C: Monitor Therapy”), cannabis (“Risk C: Monitor Therapy”), and fluvoxamine (Risk D: consider therapy modification”) (Lexi-Comp Online, n.d.).
Still, it was interesting that even when I was focusing a literature search on melatonin’s risks, the literature available tended to point more towards its benefits. For instance, some of the literature points toward some promising (albeit developing) results relating to melatonin and a more favorable metabolic profile (such as in as decreasing metabolic syndrome) (Navarro-Alarcón et al., 2014).
Fortunately, the research continues, and as time goes on, we are likely to have a clearer and clearer picture of such medication choices' potential risks versus benefits.
References:
Lexi-Comp Online. (n.d.) Retrieved from http://online.lexi.com/ Hudson, OH: Lexi-Comp, Inc.
Navarro-Alarcón, M., Ruiz-Ojeda, F. J., Blanca-Herrera, R. M., A-Serrano, M. M., Acuña-Castroviejo, D., Fernández-Vázquez, G., & Agil, A. (2014). Melatonin and metabolic regulation: A review. Food & Function, 5(11), 2806-2832. doi:10.1039/c4fo00317a
Thank you for your comments Christopher and for the article on melatonin and metabolic regulation. One of things I try to always remind myself when I'm talking with patients about medication is that all medications have a "cost" associated with them. At the very least they must be absorbed, distributed, metabolized and excreted and they always have the potential to cause unwanted actions in the body. "Natural" substances routinely have negative impacts on our bodies and things like ingesting excess sugar can cause symptoms as severe as those similar to a panic attack. It was interesting you looked at melatonin and metabolic regulation. I hadn't thought of the two being related but, of course hormones are key mediators of metabolism.
One thing I think that reassures providers when prescribing/recommending melatonin is that it is does not appear to have ever been fatal in single medication overdose (Duke et al., 2002). Because so many of the other sleep medications are lethal in overdose it may have lead to overstating melatonin's safety.
Interestingly, I've had a couple patients report worsening depressive symptoms when starting melatonin, but haven't found a lot of support for that in the literature. Conversely, actually, there seems to be evidence that is may help with depressive symptoms, although it's unclear whether it's the melatonin or the sleep that improves symptoms. Obayaski et al. (2015) found higher levels of melatonin in elderly individuals were associated with better cognitive function and lower prevalence of depressed mood. They found that the relationship endured after accounting for age, gender, SES, physical activity and sleep/wake cycles suggesting that physiological melatonin levels reflect something about how the brain is functioning that may confer benefit. It's a good example of the importance of making the distinction between benefits of an endogenous chemical level versus supplementation.
The article you cite was fascinating and I appreciated that it brought neurochemistry and genetics into the discussion! I couldn't help but think about dietary sources of melatonin and how maybe at the end of the day eating more fruits, vegetables and unprocessed, complex carbs really is the answer.
Duke, J.A. (2002). Melatonin. In Handbook of Medicinal Herbs (2nd ed).p. 498. CRC Press, Boca Raton, FL.
Meng, X., Li, Y., Li, S., Zhou, Y., Gan, R.-Y., Xu, D.-P., & Li, H.-B. (2017). Dietary Sources and Bioactivities of Melatonin. Nutrients, 9(4), 367. https://ucsf.idm.oclc.org/login?url=http://doi.org/10.3390/nu9040367
Navarro-Alarcón, M., Ruiz-Ojeda, F. J., Blanca-Herrera, R. M., A-Serrano, M. M., Acuña-Castroviejo, D., Fernández-Vázquez, G., & Agil, A. (2014). Melatonin and metabolic regulation: A review. Food & Function, 5(11), 2806-2832. doi:10.1039/c4fo00317a
Hi Christopher,
I appreciated your discussion on melatonin. It was interesting to see the list of adverse side effects, given the fact that many consider it to be mild and without risks. In a similar vein, i wanted to discuss the use of trazodone for sleep. I’ve often seen this used in clinical practice as an alternative to the use of benzos or Z drugs. In my personal experience, it seems to be considered on the "milder side" (perhaps, a step above melatonin, but below benzos/Z drugs). In an effort to decrease the frequency of prescribing benzos and Z drugs, which are associated with a multitude of risks, trazodone seems to be the next best medication option. However, trazodone is also not without it’s own set of risks.
Bossini et al. (2015) reported multiple side effects associated with trazodone. These include residual daytime sedation, dizziness, orthostatic hypotension, and psychomotor impairment. Due to these adverse effects, trazodone remains off-label for the treatment of insomnia in many countries.
Thus, this speaks to your point that there is no medication that does not have it’s own set of consequences. Using pharmacological agents (Z drugs, benzos, melatonin, trazodone, and so on) when addressing sleep should be contextualized per patient (i.e., based on their age, potential for abuse, cognitive status, risk for falls) and ideally, be used only as a short-term strategy or “bridge” while other interventions are being implemented (i.e., CBT or other alternative strategies).
References
Bossini, L., Coluccia, A., Casolaro, I., Benbow, J., Amodeo, G., De Giorgi, R., & Fagiolini, A. (2015). Off-label trazodone prescription: evidence, benefits and risks. Current pharmaceutical design, 21(23), 3343-3351.
Does this article change the way you think about how to use benzos and hypnotics in your NEW patients? How about patients already prescribed these agents?
This article somewhat changes the way I think about using benzos and hypnotics, but mostly, it reinforces my dislike for Z-drugs in patients with insomnia. For patients presenting with sleep problems, I prefer to start by going over their current bed time routines (screen time before bed, late night snacks/beverages before bed, anxiety levels before bed, current exercise regiment, evening alcohol use, etc). Depending on the patient presentation and circumstance, I then go over specific sleep hygiene tips (we have a sleep hygiene form we give to the patients at PAMF so they can read along and take it home with them), and if times permits, I take my patients through a quick 3-5 minute progressive muscle relaxation exercise that they can practice before bed.
With respect to prescribing practices, for new patients, it really depends on the patient's presentation. Generally speaking, melatonin is better for sleep initiation, whereas trazodone is better for sleep maintenance. If the patient merely has trouble falling asleep, I try melatonin first. If the person has trouble staying asleep, I usually would try trazodone first (25mg, take 1-2 tabs before bed PRN). I go over side effects (day time grogginess in particular); in my experience, 50-75 mg tends to be the sweet spot for most of my patients. I In providing psychoeducation, I like to also review the stages of sleep. My preceptor told me that trazodone actually increases the deep phase of sleep (the delta phase), which is our most restorative phase of sleep. I found a review in the literature that goes more into this, and also states that the "hangover" effect of trazodone commonly resolves within 2-3 days of consistent use (Gursky & Krahn, 2000). If melatonin or trazodone are ineffective, I would consider mirtazapine at 15 mg, especially if the patient could benefit from of its antidepressant properties. In this case, I go over mirtazapine's tendency to increase appetite, espcially if my patient is already overweight.
With patients who already have well established benzo regimens and are doing well, I usually have a discussion on the risks vs. benefits of their regimen and go over repercussions of long term use (short term memory loss, tolerance, cravings, addiction, risk for falls, seizures upon withdrawal, tendency to induce delirium with infections, interaction with alcohol, etc). After hearing that spiel, most patients are at least willing to try a slow and steady taper. However, similarly to what Laura said, I have no problem keeping a patient on their current regimen if they are doing well on it and have exhausted other options.
Reference:
Gursky, J. T., & Krahn, L. E. (2000). The effects of antidepressants on sleep: a review. Harvard review of psychiatry, 8(6), 298-306.
This article validated my concerns about prescribing benzos and “Z” drugs. It was helpful to learn which specific medications were most toxic in overdose and it was surprising to learn that tempazepam was the most toxic drug, accounting for the highest number of benzo-associated deaths, despite the fact that diazepam was the most frequently prescribed benzo. I will be especially careful to avoid temazepam as a first-line sleep aid and appreciate that the study mentions the tendency for providers to choose it due to its relatively short duration that is protective against daytime drowsiness. This underscores the importance of careful consideration of side effects, patient preference, safety, thorough assessment, and consultation with interprofessional colleagues when prescribing sleep aids.
Like others have said, sleep habits/hygiene must be carefully assessed for all patients experiencing insomnia. Overall health, nutrition, and daytime activity level are also important considerations. Medications should be a bridge to better sleep, not a lifetime crutch. Without making proper adjustments to sleep hygiene, lifestyle, and diet, a prescription sedative/hypnotic will be unlikely to lead to sustainable sleep improvement.
I don’t intend to prescribe Z drugs for my patients and will be extremely cautious with prescribing benzos for sleep. None of my UCSF preceptors prescribed benzos with any frequency, but I know this is a sensitive topic for many patients and providers that will arise in my clinical practice. My go-to sleep aid in my 2nd year internship was Trazadone and I anticipate continuing to use it before considering benzos for most patients with insomnia.
I will approach each patient as an individual and don’t think there is a one-size-fits-all approach for new patients who have been on benzos or Z drugs long term with their PCP or another psychiatric provider. In general, though, I intend to carefully assess each patient’s sleep disturbances and approach medication management in a holistic manner with a focus on patient’s goals, safety, lifestyle, comorbidities, and readiness for change.