"Anti-anxiety" Benzodiazepines

Anti-anxiety Tower

This mini-booklet reviews the relative effectiveness, safety and harms of benzodiazepine drugs that are commonly prescribed to people diagnosed with anxiety problems.

How is the information about psychiatric drugs on this page different from what’s provided by other online resources, and why should I read it?

Inner Compass Initiative has developed these informational pages because many descriptions of the safety and effectiveness of psychiatric drugs that are provided by popular online medical, psychiatric and mental health websites are often brief, vague, and more promotional than factual. (For an examination of some of the reasons why this is the case, please read ICI’s “How Psychiatric Drugs are Researched and Marketed”.) We believe that, when trying to make serious, potentially life-changing decisions about whether to take or discontinue psychiatric drugs, people deserve a fairer opportunity to properly understand and evaluate the potential risks and benefits, and thereby be empowered to make informed choices. Our articles will take you more time to read because they provide more detailed information than most of the overviews you’ll read elsewhere – but isn’t your health worth the investment?

If you notice an error, broken link or needed update, please contact us. Click here to learn more about Inner Compass Initiative.

Why do Inner Compass Initiative’s reviews of safety and effectiveness focus mainly on the FDA-approved drug labels?

Inner Compass Initiative’s mini-booklets about the six main classes of psychiatric drugs do not review all of the scientific research about these drugs. That would be an extremely ambitious effort that could easily fill an entire book for each drug class, after which even the most neutral team of researchers could still be accused of “cherry picking” evidence from tens of thousands of available studies. We have taken a different approach. We’ve focused mainly on reporting and clarifying what is arguably the single most important body of evidence: The evidence that drug companies themselves provided to government health regulators in order to try to establish evidence that their drugs are safe and effective.

If a pharmaceutical company wishes to market a prescription drug for a specific use in the United States, the company is legally required to provide scientific evidence in support of its application to the Food and Drug Administration (FDA). If the drug is approved by the FDA, this evidence is then summarized in the official “drug label”. The information pamphlets for consumers that come with prescription drugs are often unregulated, general information about the drug or just a brief collection of highlights from the drug label. In its complete form, the official drug label can be ten to fifty pages or longer in length, and includes the “Full Prescribing Information” and “Medication Guide” that are intended to inform physicians, psychiatrists, pharmacists and others about the most important scientific evidence relating to the safety and effectiveness of that drug. Since the drug labels are generally based on evidence provided to the FDA by the drug companies themselves, and are developed in collaboration between the drug companies and FDA, they tend to be strongly biased in favor of the drugs. Yet even with this bias, we at Inner Compass Initiative believe that most readers, like us, will find much of the information in them to be enlightening, surprising, concerning and even at times shocking – and nothing if not helpful for making more informed decisions weighing the potential risks and benefits of psychiatric drugs. So in creating our mini-booklets, we distilled the contents of a representative sampling of drug labels from each major class of psychiatric drugs -- supplemented at times with information from related scientific studies and the FDA's own medical reviews. (Also included are some general Q&As about key ideas in psychiatric science such as safety, effectiveness, and drug dependence, which apply to essentially all psychiatric drugs and are duplicated across the mini-booklets.)

Still, we urge anyone who is considering or already taking any psychiatric drug to read the official drug label in full. These are freely available online at a variety of commercial websites, but the most reliably up-to-date sources are those run by the federal government such as DailyMed. (Instructions and links for obtaining and understanding drug labels and related information such as FDA medical reviews can be found in “The Withdrawal Project's Guide to the FDA-approved Drug Labels”.) We also strongly recommend doing additional self-directed research, such as examining the FDA’s internal medical reviews, using online tools for searching scientific journal articles, perusing Inner Compass Initiative’s “Resources” section, conferring with people who’ve taken the drug, and consulting with well-informed, supportive prescribers or pharmacists. Choice is only truly meaningful – and truly possible – when it is informed.

What are anti-anxiety benzodiazepine drugs and what are they prescribed for?

Benzodiazepines are a class of chemically similar drugs that tend to have strong sedating properties and are often prescribed to people diagnosed with anxiety. They are also called anxiolytic or hypnotic drugs. Generic names for the active ingredients in some benzodiazepine drugs include alprazolam, clonazepam, diazepam, lorazepam, oxazepam and many more. U.S. brand names for benzodiazepine drugs include Xanax, Klonopin, Valium and Ativan.

Benzodiazepines are sometimes prescribed as sleep aids, muscle relaxants, anti-epileptics or anticonvulsants, to promote relaxation and memory loss before surgery, for behavior control, and more. Most of these uses are not actually approved by the U.S. Food and Drug Administration (FDA), but some psychiatrists and physicians prescribe them “off-label”. (When a physician prescribes a drug for a use that has not been approved by the FDA and is not listed on the official drug label, the physician is prescribing “off-label”.) This class of drugs also includes the so-called “date rape” drugs such as Flunitrazepam (e.g. Rohypnol).

Antidepressant and antipsychotic drugs are also sometimes prescribed to treat people diagnosed with anxiety disorders. For more about those drugs, please read ICI’s mini-booklets about antidepressants and antipsychotics. The rest of this page focuses on benzodiazepines.

How do benzodiazepines work?

Notably, the answer to the above question is, in some important ways, similar for all of the major classes of psychiatric drugs: We don't truly know. It can be misleading to talk about how benzodiazepines work, because the word “work” implies that the drugs have a well-understood effect on a discrete area or pathway in the brain that’s involved in anxiety, or cure an abnormal biological condition, disease or disorder. For many it can be surprising to hear because we’re so often led to believe otherwise, but there is still today no known, biologically detectable mental disorder or discrete aspect of the brain that benzodiazepines treat or cure. (For more information, read ICI’s “How Mental Disorders are Diagnosed” and “How Psychiatric Drugs are Researched and Marketed”.)

Benzodiazepines are psychoactive chemicals that act on the brain in a variety of ways, and the research is unclear about exactly how it is that these drugs affect people’s moods or experiences. Indeed, the FDA and pharmaceutical manufacturers have developed the most up-to-date, definitive medical descriptions for the mechanisms of action of all of the benzodiazepines that are approved for use in the United States. These can normally be found in the “Clinical Pharmacology” section of the official drug label. (Instructions and links for obtaining and understanding drug labels can be found in “The Withdrawal Project's Guide to the FDA-approved Drug Labels”.) According to these explanations, the biological mechanisms by which any benzodiazepine drugs might affect some people diagnosed with mental disorders in therapeutic ways are “unknown”.

It is known that benzodiazepines, in part, mimic or enhance the activities of the natural brain chemical GABA (gamma-aminobutyric acid). GABA is a neurotransmitter or chemical messenger that is essential in the basic internal communications and functional systems of the central nervous system, brain and body. GABA’s main role seems to be “inhibitory”; it causes biochemical reactions that tell neurons to slow down or stop sending certain impulses. By enhancing the activity of GABA, benzodiazepines strongly inhibit or reduce some of the activities of neurons, and also reduce the activities of other important neurotransmitters, including norepinephrine, serotonin, acetylcholine and dopamine.

Because electrical and chemical activities are being altered or reduced in many cells throughout the body and brain, benzodiazepines can cause a wide range of effects. Benzodiazepines often cause sedation and can affect or impair alertness, memory, muscle co-ordination, emotional responses, endocrine gland secretions, heart function, and a host of other brain and body functions. This is why we still today do not fully understand all of the complexities of what benzodiazepines do or how they work – or how their impacts change over time as the body adapts to their presence.

Most users report that in the short term benzodiazepines create a feeling of mild-to-strong sedation or somnolence, and for some people this helps reduce anxiety. In other words, it’s possible that some of the most commonly recognized side effects of benzodiazepines are for some people the primary means by which these drugs “work”. Meanwhile, some people have very different reactions to the drugs, such as becoming highly agitated or physically aggressive. In addition, during regular use over periods of a week or longer, benzodiazepines start to produce other effects in most people, and cause drug tolerance and physical dependence to form (see below for more information).

Benzodiazepines are also known to often provide a temporary sensation of relaxation that can feel euphoric, which is part of what makes them a popular recreational drug and potentially very addictive.

Are benzodiazepines effective? – But first, what does “effective” mean?

We often hear that certain psychiatric drugs are effective. But it’s rarely explained what exactly “effective” means. Does effective mean that the drug makes everyone feel completely better? Or if some people feel better when taking the drug, in what ways do they typically feel better, by how much, and for how long a time? And do some people feel worse in certain ways because of the drug?

Unless you ask probing questions, or carefully and critically analyze scientific studies yourself, it’s difficult to know exactly what certain people mean when they state that a particular psychiatric drug is effective. Often, different people can even look at the same scientific evidence and reach opposite conclusions about whether a psychiatric drug demonstrated true effectiveness or not. (For more information, please read ICI’s “How Outcomes are Measured in Psychiatric Research” and “How Psychiatric Drugs are Researched and Marketed”.) Yet when deciding if a drug is right for you or for someone you care about, it is very important to have a strong understanding of in what ways the drug is apparently effective and to what degree it is apparently effective, so that you can reasonably weigh the potential benefits of the drug against its potential adverse effects.

As we described in our introductory section, one helpful way to resolve these challenges and learn about a psychiatric drug’s effectiveness is to examine the actual medical evidence that resulted in the FDA approving the drug to legally be described by the pharmaceutical manufacturer as “effective” for the drug’s intended use. This evidence comes from the clinical trials that a pharmaceutical company presented to the FDA in order to try to establish their drug’s effectiveness. Though these trials were sponsored and selected by the drug companies and so tended to be biased in favor of the drugs, they are still extremely instructive. So in this article, we provide some representative examples of how drug companies tried to prove to the FDA that their drugs were effective – and we examine what “effective” actually meant in that context.

How effective are benzodiazepines and in what ways are they effective?

It is commonly said that benzodiazepines are effective at relieving anxiety. Certainly, most users report almost immediate, significant, physically relaxing and mentally sedating effects from these drugs. However, when we review the original scientific evidence that led to the FDA legally allowing drug companies to state that some of the benzodiazepines were effective for helping people diagnosed with anxiety disorders, it becomes clear that benzodiazepine effectiveness rapidly declines over time. After just a few days or weeks of regular use benzodiazepine effectiveness tends to be at best extremely modest – and can even cause worsening anxiety.

For example, the common benzodiazepine drug clonazepam (Klonopin) was approved by the FDA for treating people diagnosed with Panic Disorder on the basis of just two clinical trials that lasted only about six weeks. In one of these trials, people were grouped into those receiving placebo pills (pills that have no medical effects) and those receiving daily clonazepam. Over the six weeks of the trial, the people taking placebo had about 2 panic attacks per week, while the people on various dosage levels of clonazepam had on average about 1.5 panic attacks per week. In addition, the participants and clinicians scored various types of anxious feelings that the participants were having on numbered scales of 1 to 7 or 1 to 10 – ranking the feelings from not present to extremely strong. (For more information, see ICI’s “How Outcomes are Measured in Psychiatric Research”.) On average, the people taking relatively higher doses of clonazepam typically scored as being only about 1-2 points or 20% less anxious overall than the people receiving placebo pills.

And significantly, other aspects of the researchers’ findings suggested that these results were even weaker than they appeared:

  • There were no significant differences between the drug and placebo groups in people’s levels of  anxiety specifically about work or social situations.
  • The people taking clonazepam reported experiencing many times higher rates of side effects, including sleepiness and somnolence, loss of muscle and motor control, depression, dizziness, fatigue and irritability. The increases in these experiences, though, were not relevant to the measuring of the effectiveness of clonazepam at reducing panic attacks and other specific experiences associated with anxiety.
  • After the six-week period of taking clonazepam regularly, the participants had to then be tapered off the dependence-forming drug. During an ensuing seven-week taper phase, the people taking clonazepam started reporting much higher frequencies of headaches, insomnia and other withdrawal effects. On average, they also began scoring worse than the placebo group on all of the measures of anxiety. And the people tapering off clonazepam started having more panic attacks per week than they’d had before ever taking the drug.

Nevertheless, this clinical trial and another with similar findings were enough for the FDA to allow the pharmaceutical company to state that Klonopin is effective in treating people diagnosed with Panic Disorder.

These findings are fairly representative of the relative effectiveness of benzodiazepines for people diagnosed with anxiety disorders. As another example, in a multi-center trial of alprazolam (e.g. brand names Xanax, Niravam), participants scored only about 5.5 points lower on an anxiety scale of 56 total points after 4 weeks, while after 8 weeks their scores were not significantly different than the scores of people taking placebo.

These short-term, very modest levels of effectiveness are important to understand when trying to appropriately weigh the potential benefits of benzodiazepines against their potential harms.


Related reading:

Rosenbaum, J F, G Moroz, and C L Bowden. “Clonazepam in the Treatment of Panic Disorder with or without Agoraphobia: A Dose-Response Study of Efficacy, Safety, and Discontinuance. Clonazepam Panic Disorder Dose-Response Study Group.” Journal of Clinical Psychopharmacology 17, no. 5 (October 1, 1997): 390.

Laakmann, G., C. Schüle, G. Lorkowski, T. Baghai, K. Kuhn, and S. Ehrentraut. “Buspirone and Lorazepam in the Treatment of Generalized Anxiety Disorder in Outpatients.” Psychopharmacology 136, no. 4 (April 1, 1998): 357–66. doi:10.1007/s002130050578.

Ballenger, James C., Graham D. Burrows, Robert L. DuPont, Ira M. Lesser, Russell Noyes, John C. Pecknold, Arthur Rifkin, and Richard P. Swinson. “Alprazolam in Panic Disorder and Agoraphobia: Results From a Multicenter Trial: I. Efficacy in Short-Term Treatment.” Archives of General Psychiatry 45, no. 5 (May 1, 1988): 413–22. doi:10.1001/archpsyc.1988.01800290027004.

Are benzodiazepines effective for long-term use?

None of the benzodiazepine drugs have been approved by the FDA for long-term use. In fact, some of the drug labels for benzodiazepines include explicit warnings against using benzodiazepines regularly beyond even just 2 to 4 weeks. This is because, even at normal, prescribed doses, these drugs cause physical dependence and tolerance to develop. As distinct from dependence, benzodiazepines can also be extremely addictive (see below for more information).

If benzodiazepines aren’t very effective, why do I/do some people seem to become so much better when taking them?

If you read all of ICI’s mini-booklets on the major psychiatric drug classes you will notice that, based on the clinical trial information that was provided to the FDA, most psychiatric drugs seem to have at best very modest, short-term effectiveness in helping people diagnosed with mental disorders. These findings generally match the findings in the broader scientific literature as well. Yet some people report that they benefit immensely from taking certain psychiatric drugs. What is going on?

Many psychiatric drug trials do show that a percentage of people respond much more positively than most other people to certain psychiatric drugs. However, the studies generally cannot shed light on why that’s happening. Are these random, “lucky” occurrences? Is there a particular subgroup of people who respond better to certain psychiatric drugs due to unknown genetic, biochemical or lifestyle differences? Do a person’s responses tend to be greater or smaller depending on what is actually causing the person’s problems?

One important factor has been extensively studied: Psychiatric drug trials tend to have the highest placebo response rates in all of medicine. Most psychiatric drug trials show the majority of participants scoring substantially better on improvement tests whether they are taking a drug or placebo – apparently, simply hoping or believing that they are taking a potentially helpful psychiatric drug seems to be very helpful for many people. Indeed, in most trials this placebo effect accounts for a much larger portion of people’s apparent improvements than the drugs themselves. So while we can determine scientifically that the overall positive effects of a particular psychiatric drug are relatively modest, some people will experience the effect of the drug plus a very substantial placebo effect, which can make the drug seem to be much more effective than it otherwise might to those people personally.

There can also be, for example, “social placebo” effects, where having the encouragement and support of mental health professionals, family, and other people around you when you take a psychiatric drug can change both their and your feelings and behaviors in ways that can contribute significantly to the positive overall impacts of a drug. In addition, after experiencing some initial benefits from a drug, over time some people can have a tendency to attribute further positive developments in their moods and experiences to the drug while attributing negative developments to re-emergence of their own underlying problems.

Alternatively – and some experts argue most importantly – some people might simply more strongly like or have positive therapeutic responses to the sedating, numbing or stimulating effects of certain prescribed psychiatric drugs on their feelings, experiences or behaviors, in similar ways to how some people respond positively to the effects of coffee, cigarettes, painkilling medication, alcohol, marijuana or other drugs.

If benzodiazepines aren’t very effective, why do I/do some people seem to become much worse when stopping them?

Many people find that, when they stop taking psychiatric drugs after long periods of regular use, they rapidly start to feel worse. They may then believe (or they may have been told by their prescriber or others) that this is because the underlying problem that the drug was treating has re-emerged. This could be the case; however, there is actually a more likely explanation.

All psychiatric drugs are, to greater or lesser degrees, dependence-forming – today, the majority of drug labels for all classes of psychiatric medications include indications of this fact. Benzodiazepines, stimulants, and Z-drugs are specifically classified as Controlled Substances in the United States due to their potential for causing dependence and addiction. And the drug labels for most antidepressants and anticonvulsant “mood stabilizer” drugs, along with many antipsychotics, include specific cautions about “drug discontinuation syndromes” (withdrawal symptoms) that have been observed.

Essentially, “dependence-forming” means that, over time, the human body adjusts to the presence of these drugs in biochemical and structural ways. When stopping the drugs suddenly, many people will experience very uncomfortable or even dangerous physical and mental withdrawal symptoms, as the body is forced to rapidly re-adjust to the absence of the drugs.

Among many other possible withdrawal symptoms, abrupt discontinuation of psychiatric drugs commonly produces unusually extreme and intense manifestations of some of the feelings, experiences or behaviors that the drugs were helping to suppress. For example, stopping a sedating drug is likely to cause withdrawal symptoms such as abnormally intense anxiety and agitation. Stopping a numbing drug is likely to cause withdrawal symptoms such as hypersensitivity and moodiness. Stopping a stimulant drug is likely to lead to feelings of unusually intense depression. Moreover, some withdrawal symptoms can continue for weeks, months, or even years until the body and brain have had enough time to fully re-adjust to the absence of the drug. (For more information, see The Withdrawal Project’s overview essay, “Psychiatric Drug Tolerance, Dependence and Withdrawal”.)

How safe or dangerous are benzodiazepines? Do I really need to read about and concern myself with all of those apparently minor or rare adverse effects?

It’s often claimed that psychiatric drugs are safe. But what does “safe” actually mean? Different people can mean different things when they say that a drug is generally safe.

The FDA requires pharmaceutical companies to conduct some basic studies into the safety of their drugs. The findings from these studies are then included in the official FDA-approved drug labels under the assumption that patients and prescribers will then together review and weigh a drug’s potential risks and benefits. All prescribing physicians, psychiatrists and pharmacists are ethically and legally required to ensure that patients are informed about the potential harms of any drug that is being prescribed to them. In practice, though, this rarely occurs with respect to any drugs let alone psychiatric drugs, and patients often receive information which is incomplete or inaccurate. 

Prescribers themselves are not always fully informed. The lists of potential adverse effects for most psychiatric drugs are lengthy, and many prescribers are too busy to either learn about them all or, if they do learn them, convey them all to patients. Some prescribers don’t want to dissuade or frighten people from taking psychiatric drugs that they are recommending. Even the more responsible prescribers often just direct patients to read unregulated information or brief highlights of the drug labels that may accompany packages of prescription drugs. Relatively few of us ever read even these inserts, though, and instead we simply trust general reassurances from prescribers. This attitude is usually founded on a basic, deep trust of the medical profession, drug regulators, and scientific research. To learn more about why this trust should be balanced with healthy skepticism, please read ICI’s “How Psychiatric Drugs are Researched and Marketed”.

As we discussed in our introduction, even though the risk and safety information included in the drug labels tends to be biased in favor of the drugs, these labels can still be very informative. That said, it’s easy to feel like it’s not worth the effort to read about all of the adverse effects identified in these lengthy drug labels, because many of them can seem relatively trivial, while many of the more serious side effects are identified as being rare. However, there are other important factors to take into consideration:

  • The real adverse effect rates are unknown and often higher. Most of the adverse effects that are listed in the FDA-approved drug labels are the ones that appeared in relatively short clinical trials involving small numbers of people – so the actual adverse effects in typical users are unknown, and reasonably likely to be (and are often later found to be) much larger in number and varied in type. Indeed, sometimes the drug labels include reports of many more adverse effects in a section called “Post-marketing Experience” – these are lists of adverse effects that started being identified and voluntarily reported to the FDA after many more people in the general population began regularly using the drugs. Because these reports are voluntary, though, the absence of such reports cannot be taken as evidence of a drug’s safety.
  • "Infrequent" doesn’t always mean unlikely. It’s true that any particular, individual user is relatively unlikely to experience any one particular, infrequent adverse effect. However, taken all together, in most cases it’s very likely that most users will experience at least some of the listed adverse effects.
  • "Rare" can add up to a lot of people. In the drug labels, some potentially very serious adverse effects may be described as “rare”. This refers to the fact that small numbers of people will experience a particular adverse effect relative to the overall number of people taking the drug. However, it’s important to remember that, with millions of Americans taking certain psychiatric drugs, “rare” can easily mean that thousands or ten of thousands of Americans will be experiencing that very serious adverse effect.
  • Minor adverse effects may be warning signs. Apparently minor adverse effects can sometimes be early warning signs for more serious, rarer adverse effects; therefore, knowing the minor adverse effects could help prevent more serious harms or even, sometimes, save your life. 
  • Adverse effects reveal a lot about how a drug works. Understanding the full range of possible adverse effects helps you better understand the ways in which a drug is acting on your body and brain.
  • Your choice is better informed. Understanding the adverse effects helps you make a more informed choice about whether, for you, the relative effectiveness of a drug truly outweighs the potential harms.

Deciding to take a psychiatric drug or encouraging a friend or loved one to take a psychiatric drug, especially when it could potentially be for a long time, is a significant choice that could change the course of your or someone else’s life. The only way to make a truly, meaningfully informed choice is to try to ensure that you get the best information and advice that you can to help you think through the decision. If you or someone close to you is taking or considering taking any psychiatric drug, we encourage you to make the time to read the entire drug label. In this article, we have reviewed only a small sampling of the adverse effects identified in these labels, so below we also include links to several places where the U.S. FDA-approved drug labels can be viewed freely in full. However, in light of the limitations of this information, it’s even better to supplement it by examining the FDA’s “drug approval packages” (which include internal medical reviews of a drug), doing wider research, and consulting with well-informed, supportive practitioners.

At the same time, for anyone taking any psychiatric drug, the complexity of all of this information is an important reminder of the vital importance of always trying to listen closely to the wisdom in what your own body is telling you.


Related reading:

Instructions and links for obtaining and understanding drug labels can be found in “The Withdrawal Project's Guide to the FDA-approved Drug Labels”.

U.S. Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products.

U.S. Food and Drug Administration. Drugs@FDA Instructions: Health Information. (A quick guide to searching the FDA’s drug information system.)

U.S. National Library of Medicine. DailyMed

What are the immediate and most common adverse effects of benzodiazepines?

In one-time use, benzodiazepines most often cause sedation, short-term drowsiness, dizziness, muscle weakness, impaired coordination, impaired concentration and cognition, memory impairment, and motor speech disorders. Children and the elderly are substantially more likely to experience adverse effects.

Can benzodiazepines cause memory loss?

Benzodiazepines have long been known to cause particular types of memory impairment and memory loss. Partly due to the way in which the drugs impair concentration and attention, the acquisition of new memories about immediate events in particular seems to become deficient – this is called loss of “episodic” memory. Because of these effects and their relaxant effects on the body and brain, many doctors prescribe benzodiazepines to patients as “prep” drugs before surgical procedures.

Are benzodiazepines safe for the elderly? Is it true that benzodiazepines increase the likelihood of dementia?

Older people metabolize benzodiazepine drugs much less efficiently than younger people do, and are more likely to experience stronger effects for longer periods of time even at much lower doses. Over-sedation, loss of balance and muscle control, and depressant effects in the elderly are very common, and likely contribute to increased numbers of falls and fractures, and diagnoses of depression.

Also more common in the elderly are more pronounced psychological effects from benzodiazepines such as confusion, night wandering, and combinations of short-term memory loss and cognitive impairment. Paradoxical reactions such as hyper-agitation and mania are also more common in the elderly.

Some recent studies have suggested that long-term benzodiazepine use could increase Alzheimer’s and dementia in the elderly. However, there is some lack of certainty about cause and effect, since prescribers often give benzodiazepines to people diagnosed with dementia.


Related reading:

Pariente, Antoine, Sophie Billioti de Gage, Nicholas Moore, and Bernard Bégaud. “The Benzodiazepine-Dementia Disorders Link: Current State of Knowledge.” CNS Drugs 30, no. 1 (January 2016): 1–7. doi:10.1007/s40263-015-0305-4.

Are there circumstances under which benzodiazepines can potentially be lethal?

When used on their own at normal prescription levels, benzodiazepines are generally considered to be much less toxic than some other common psychiatric drugs. According to their drug labels, though, benzodiazepines tend to suppress normal breathing and respiration. And while the long-term risks of mild but chronic respiratory depression from benzodiazepines have not been studied, it is known that in rare cases benzodiazepines can cause extreme, fatal respiratory depression. These mortality risks are much higher if benzodiazepines are combined with alcohol or other medications.

Are benzodiazepines safe to take during pregnancy?

The drug labels for benzodiazepines warn against women taking the drugs when they are pregnant, especially during the first trimester, because some human studies have suggested an increased risk of birth defects. There have been few reliable large-scale human studies. Some animal studies with large doses have identified incidences of more severe birth defects.

Much more commonly, human studies have shown that benzodiazepines cross the placenta, and babies can be born drug-dependent and with "floppy infant syndrome" – a condition in which babies have lax muscles, are heavily sedated, and fail to suckle. It can take weeks for infants to fully metabolize the drug, after which they have been reported to have drug withdrawal symptoms such as hyperexcitability, high-pitched crying, feeding problems, hypothermia, metabolic inability to respond normally to cold temperatures, and impaired breathing. Benzodiazepines have also been detected in human breast milk in significant concentrations, and the drug labels warn against taking these drugs while breastfeeding.

Can benzodiazepines cause people to become depressed or suicidal?

Emotional blunting and depression are common effects of benzodiazepines, especially during long-term use. The drug labels for benzodiazepines warn that the drugs can cause depression to emerge, re-emerge or worsen. The labels also state that all of the anti-epileptic drugs including benzodiazepines have been shown in placebo-controlled clinical trials to double the likelihood of people having suicidal feelings, thoughts or behaviors.

Can benzodiazepine drugs cause people to become irritable, agitated, manic or violent?

Benzodiazepine sedatives can cause what are called “paradoxical” reactions, such as insomnia, hyperstimulation, mania, agitation, rage, irritability, aggressiveness, hallucinations, and physically hostile and violent behavior. According to their drug labels, violent assaults and even murders have been linked to paradoxical reactions to normal prescription doses of benzodiazepines. Though these appear to be relatively uncommon reactions, irritability and argumentativeness are much more common reactions, especially in children and the elderly.

Some of the side effects from psychiatric drugs seem to diminish over time – isn’t that a good thing?

When you complain about adverse effects after starting a psychiatric drug, it is common for physicians and psychiatrists to advise you to continue to take the drug anyway because some adverse effects will likely stop. Even popular medical websites like WebMD do this, advising that some of the adverse effects “may go away after you take the medicine for a while” because “your body can adjust” to the presence of the drugs.

This is certainly possible. What is not often explained, though, is that this body “adjustment” indicates growing drug tolerance. Your body is compensating for the presence of a foreign chemical and is developing ways to diminish some of the chemical’s impacts. So while you may begin experiencing fewer adverse effects or less intense adverse effects as your body compensates and adapts to the presence of the drug, it’s possible that you’ll begin experiencing decreased beneficial effects as well. And other adverse effects will often be continuing, if unnoticed.

Further, this increasing tolerance also indicates that your body is starting to develop physical dependence on the drug, which could bring the risk of uncomfortable, painful or even dangerous withdrawal symptoms if you try to stop the drug suddenly. Prescribers should warn patients more often about the risks of developing dependency on and tolerance to psychiatric drugs, but they often do not.

Are benzodiazepines addictive or dependence-forming even at normal dosages prescribed by my doctor or psychiatrist?

Benzodiazepine drugs are both addictive and dependence-forming even at normal dosages. This means that the drugs can induce addictive “cravings” for more of the drugs. Yet even without that happening, the drugs can still cause physical dependence to develop. Their drug labels warn that, even at normal, prescribed doses, physical dependence that produces difficult withdrawal symptoms can develop after as little as one week of benzodiazepine use. When taking short-acting benzodiazepines on a normal, prescribed schedule, withdrawal symptoms such as increased anxiety can even start happening between doses.

It is not fully understood how benzodiazepines affect the body and brain, and so it is also not understood exactly how sudden discontinuation of these drugs can produce such a wide variety of difficult or dangerous withdrawal symptoms even after relatively brief periods of regular use. However, it is known that benzodiazepines at least in part enhance some of the activities of the neurotransmitter GABA. (Neurotransmitters are the key chemical messengers in the brain and body’s internal communications and functional systems.) GABA’s main role seems to be to “inhibit” or decrease the activities of other neurotransmitters in the body and brain. Over time, the body compensates for or adapts to the ongoing presence of the benzodiazepine in part by reducing its sensitivity to GABA. Consequently, if you suddenly stop taking the drug after a period of regular use and the drug’s “quietening” influence is released, you’ll likely experience an equally sudden, dramatic “hyperexcitability” or increase in biochemical and electrical activities throughout your central nervous system until your sensitivity to GABA is naturally restored.

According to the drug labels, withdrawal symptoms such as anxiety, moodiness and insomnia can occur after even just one week of taking regular, prescribed doses of benzodiazepines. And the anxiety that is experienced is often more intense and frequent than one had before taking a benzodiazepine – this is referred to as “Rebound Anxiety”. After longer-term use, withdrawal symptoms can be much more varied and serious. The drug labels state that these withdrawal symptoms can include extreme anxiety and panic attacks, severe muscle cramping and twitching, depression, confusion, sweating, numbed extremities, hypersensitivity to sensations, bizarre mental effects such as derealization and depersonalization, and much more. Some of these withdrawal symptoms can even be life-threatening, such as severe seizures. A trial with the benzodiazepine Xanax found that about 1 in 250 people began to have seizures when undergoing abrupt drug discontinuation after just three months of use.

If I want to stop taking benzodiazepines, what should I know?

Though it’s widely known that benzodiazepine drugs cause physical dependence and withdrawal symptoms, there have been very few formal scientific studies of methods and time frames for tapering.

Stopping any psychiatric drug can be risky or even dangerous. In particular, many official drug labels, formal scientific studies, and a growing evidence base of anecdotal reports from physicians and patients alike suggest that coming off psychiatric drugs abruptly or too rapidly for the central nervous system to manage tends to be especially risky and in some circumstances can even produce severe seizures or other life-threatening withdrawal reactions. Therefore, aside from situations where a medical emergency may deem rapid withdrawal to be necessary, tapering off a psychiatric drug is a major decision that is very personal and should involve forethought and careful planning. All of the possible benefits, risks and consequences of tapering should be carefully weighed in light of each individual’s life circumstances, physical health, resources, supports, and other factors.

If you or someone close to you is considering tapering, you may find it helpful to visit The Withdrawal Project, where ICI has been gathering the anecdotal reports and accumulated insights from laypeople who have experienced psychiatric drug withdrawal. There you can find discussions about common methods of tapering, what “slow” and “responsible” tapering looks like, how to prepare for tapering, and how to develop a plan of action for withdrawal that ideally involves the collaborative support of a well-informed prescriber, pharmacist, family and friends. At TWP Connect, people considering coming off psychiatric drugs can also connect with others who have experienced psychiatric drug withdrawal, are in withdrawal, or are considering withdrawal. (If you’re simply generally interested in connecting with others who are learning more and thinking critically about all things “mental health”, please consider joining ICI Connect.)