A Primer on Psychiatric Drug Dependence, Tolerance and Withdrawal

Psychiatric drug-induced dependence is a physical condition that develops when the body (especially the brain and central nervous system) changes its structure and functioning in response to the ongoing presence of a psychiatric medication. These changes develop naturally as the body acclimates to and tries to adjust to or compensate for the continuing influence(s) that the drug is having. This is also sometimes called “neuroadaptation”, or described as an “adaptive neurological state”.

Dependence is not addiction. Addiction involves a person experiencing conscious “cravings” for a drug. Certain classes of psychiatric drugs can at times lead to addictive behaviors, but generally, a person is not even aware that they are becoming or have become physically dependent on a prescribed psychiatric medication. People usually only become aware that they have developed physical dependence if they start to experience a need for higher doses of a psychiatric medication to achieve the same effects (tolerance) or they suddenly stop taking the drug and experience uncomfortable, disruptive or even dangerous mental, emotional and physical reactions (withdrawal symptoms).

There is no scientific consensus on exactly how to detect the presence of drug dependence itself; however, the emergence of drug tolerance (reduced effects of a drug) or the emergence of withdrawal symptoms upon stopping a psychiatric medication are considered to be reliable indicators that dependence has developed. In that respect, all of the major classes of psychiatric medications are known to cause dependence.

Today, the Food and Drug Administration-approved drug labels and medication guides for most psychiatric drugs include indications of this fact. All of the benzodiazepine sedatives, Z-drugs (“sleep aids”), and central nervous system stimulants such as Ritalin and Adderall are classified in the United States as Controlled Substances due to their potential for causing physical dependence, tolerance and also addiction. The drug labels for most antidepressants, anticonvulsants like Lamictal and Depakote, and many antipsychotics/neuroleptics include sections about some of the most common “drug discontinuation syndromes” (withdrawal symptoms) that are known to be associated with these classes of drugs. (For more information about obtaining and understanding the official drug labels, see TWP’s “Guide to the FDA-approved Drug Label”.) In addition, the rapidly accumulating anecdotal reports that have been emerging from the layperson withdrawal community overwhelmingly show that all psychiatric medications have the potential to cause a wide range of withdrawal symptoms upon reducing or stopping a dose.

The vast majority of people who find themselves in a state of psychiatric drug-induced dependence have taken their medications exactly as their doctors have told them to—they have never “abused” them or “misused” them. They are not “addicts”. In fact, as discussed earlier, many people taking these medications don’t even know that they’ve become physically dependent.

One possible by-product of drug dependence is drug tolerance. When a person has developed tolerance to a drug, it means that the person’s body is having a progressively reduced level of reaction to the drug after repeated exposure to it. The medical term for tolerance is tachyphylaxis, and it is sometimes also referred to as drug “poop out” in the research literature, as well as by doctors and patients.

The most common types of psychiatric drugs that are associated with tolerance are benzodiazepines (“anti-anxiety” sedatives) and Z-drugs (“sleep aids”). When in a state of tolerance to a prescribed psychiatric drug, some people simply notice that the effects of the drug that may once have felt helpful are no longer as strong. Some people find aspects of tolerance to be a positive experience, because various noticeable adverse effects of a drug may also diminish – for example, they may experience less somnolence when taking benzodiazepines, or less of the insomnia commonly caused by stimulants.

Another by-product of psychiatric drug-induced dependence is the emergence of mental, emotional, physical, cognitive, and sleep-related problems upon the reduction or cessation of a medication. Psychiatric drug withdrawal is a very unique, individual experience that can involve few or many of a vast spectrum of symptoms. It is becoming clear based on anecdotal reports from the withdrawal community that two people can take the same amount of the same drug, or take a drug for the same length of time, and have completely different withdrawal experiences.

However, we are also seeing some strong commonalities and tendencies emerging. Some of the most commonly reported psychiatric drug withdrawal symptoms – particularly during rapid withdrawal – include impairment of concentration, memory, and cognition, increased anxiety, panic attacks, paranoia, mild to intense depressed feelings, rage, uncontrollable physiological “fight or flight” responses, restlessness, irritability, agitation, and insomnia and other sleep-related problems. It is not uncommon for people to report physical symptoms such as inexplicable numbness or tingling, electrical “zaps” in the brain, muscle pain and tension, muscle spasms, and gastrointestinal disorders. Some of the more severe withdrawal symptoms that have been seen in the layperson withdrawal community, and that are listed in some drug labels, include epileptic-like convulsions and seizures, and experiences sometimes labeled by clinicians as “extreme depression”, “mania” and “psychosis”. (To find a more detailed list of psychiatric drug withdrawal symptoms, visit our Withdrawal Symptoms A to Z section.) It is therefore not uncommon that many ordinary people and clinicians alike can mistake psychiatric drug withdrawal for a “relapse” or a “re-emergence of a pre-existing mental illness” or a "worsening psychiatric disorder", or even diagnose it as a “new psychiatric disorder” that requires “treatment” with more or different drugs.

Overall, it is becoming evident that rapid or abrupt reductions or cessations of a psychiatric drug greatly increase the odds of setting off more severe withdrawal symptoms. When symptoms are set off by a too-fast taper, they are typically described in the layperson withdrawal community in terms of three stages: Acute, Post-acute and Protracted. During Acute Withdrawal people often report experiencing a cluster of very intense physical and mental symptoms. During Post-acute Withdrawal symptoms seem to generally become less intense and more manageable, though they can remain problematic and feel disabling for some. (It’s often reported that people recover during this period of time and return to their lives.) Others, however, can experience Protracted Withdrawal. During this phase, symptoms can disappear completely for a time and then suddenly re-surface for no apparent reason or in response to triggers such as stress, poor health, diet, physical illness, or the use of other medications, supplements, herbs, or psychoactive substances. And while some symptoms dissipate, entirely new withdrawal symptoms may inexplicably emerge. This phase of withdrawal can be complicated, discouraging, unpredictable and confusing for people to go through, and many even find it hard to believe that it’s “still” withdrawal because of the lengthy period of time that may have gone by—sometimes years—since the drugs were completely stopped.

Unless they’ve experienced it themselves, some people find it difficult to believe that Protracted Withdrawal can sometimes last for years after the last dose of a drug was taken (see above for more details). Many of us are accustomed to images from popular culture of people withdrawing from opiates in a matter of days – albeit an excruciatingly painful few days—and then feeling completely free of withdrawal symptoms soon after. Why would withdrawing from psychiatric drugs often be so different? The answer to this question is generally not well understood. However, the structural and functional changes that take place in the body after regular use of psychiatric drugs typically happen not just in the central nervous system (the brain and spinal cord), but in various other systems as well, such as the endocrine, digestive, immune, and circulatory systems. Therefore, removing a psychiatric drug that has been taken daily for a few weeks or longer does not instantly return the entire body and brain to the state that they were in before the drugs were ever taken. Instead, after the drug is taken away, the body and brain begin to re-acclimate themselves to the new biochemical conditions – and depending on a variety of factors including how many changes and what types of changes the drug caused in the body and brain, this transition or healing process can in some cases take a lot of time.

It’s not surprising, then, that anecdotal reports from the lay withdrawal community suggest that the more time a person has spent on a psychiatric drug, the more significant the drug-induced changes to their brain and body tend to be, and the more time ends up being needed for the brain and body to successfully re-acclimate to the drug’s absence – though this is by no means a universal rule. Ultimately, the nature, intensity and duration of withdrawal symptoms seem to depend on a variety of factors such as a person’s physical health, genetics, metabolism and life circumstances, their usual ways of reacting and adapting to pain and discomfort, along with the particular drug, the dosage, the period of time spent taking the drug and, most importantly, the rapidity with which the drug is withdrawn after regular use.

Researchers have far from a complete understanding of the multi-leveled and cascading impacts of psychiatric drugs on the brain and body. Generally, all psychiatric drugs are known to act on the central nervous system primarily by altering the basic functionality of various neurotransmitter systems. (For more detailed explanations of how each class of psychiatric drugs is known to act on the brain and body, along with what’s known about their safety and effectiveness, visit Inner Compass Initiative’s Learn/Unlearn  section.)

Neurotransmitters are the brain’s primary chemical messengers. They seem to be responsible for much of basic human functioning, activity and experience. Some psychiatric drugs primarily block neurotransmitter processes, while other drugs primarily increase, mimic or otherwise alter the activities of neurotransmitters. Most psychiatric drugs begin to affect a variety of neurotransmitters in different ways immediately and simultaneously, and then these effects and the body’s responses to them change over time. It is these compensatory responses of the body in response to the ongoing presence of the drug – as the drug itself and the body’s reactions to it gradually become part of the body’s new "normal state" – that lead to physical dependence and sometimes tolerance.

One good way to understand psychiatric drug-induced dependence and withdrawal is with a simple analogy. Picture your brain as a car cruising along at a steady, stable rate of 20 miles per hour. You begin to take a psychiatric drug that, among other things, blocks the function of a particular neurotransmitter in your central nervous system—in other words, this drug acts on your brain function by pushing down on a metaphorical brake, slowing things down to a speed of 10 miles per hour. Your central nervous system has now been forced out of its previous natural state. In order to compensate for this change, your central nervous system begins to push down on its metaphorical accelerator, counteracting the braking force of the drug. Eventually, it returns itself back, close to its previous cruising speed of 20 miles per hour—only now it’s pushing twice as hard on its accelerator as it needed to before, just to stay at that speed.

So what happens if you now decide that you want to suddenly stop taking the medication? Continuing with this analogy, you are essentially deciding to abruptly remove your foot from the metaphorical brake. However, the problem is, your brain is still pressing down hard on the accelerator. When you release your foot from the drug-induced brake, your brain will suddenly take off at 30 miles per hour.

And since the neurotransmitters that psychiatric drugs affect are often involved in practically every function and activity in the body and brain, what happens when many of the neurotransmitters inside you are suddenly released from a drug-induced braking action and “take off” in this way? The brain needs time to re-acclimate to the sudden absence of the drug, and until such time has elapsed, this state of disequilibrium and disruption in your central nervous system can lead to a variety of physical, emotional, cognitive, and mental problems. These are called symptoms of psychiatric drug withdrawal.

If some level of physical dependence has developed, people can begin to experience drug withdrawal symptoms in between doses, even while taking their medications regularly and as prescribed – this is called interdose withdrawal. Interdose withdrawal can also occur from irregularly spacing out or taking lopsided doses of a drug, rather than taking evenly and equally-spaced doses. Some people have also reported that interdose withdrawal developed as they were tapering and their total daily dose decreased.

Interdose withdrawal most often occurs with drugs that are short-acting (i.e. have short half-lives), which means that they are metabolized and removed from the body more quickly than other drugs. A “short-acting” drug is generally understood as being one that has a half-life of less than 20 hours, which means that it will take under 20 hours for the concentration of that drug in the average healthy person's blood to be reduced by half (though different people’s bodies metabolize the same drugs at different speeds depending on a variety of factors such as age and physical condition.) The drugs most commonly reported to cause interdose withdrawal are short-acting benzodiazepines such as alprazolam (Xanax) and lorazepam (Ativan), stimulants such as amphetamine (Adderall) and methylphenidate (Ritalin), and antidepressants such as paroxetine (Paxil), venlafaxine (Effexor), and duloxetine (Cymbalta).

Interdose withdrawal symptoms are essentially the same as the symptoms caused by coming off a psychiatric drug too quickly—except that they are reported to typically resolve upon taking the next scheduled dose. Commonly reported interdose withdrawal symptoms include increased anxiety, shakiness, lack of concentration, gastrointestinal disruptions, muscle tension, panic attacks, or nerve problems like tingling, pain, or numbness, among many other possible symptoms. Like tolerance, interdose withdrawal can often go unrecognized, leading people to believe instead that their "psychiatric condition" is so severe that they shouldn't be on a lower dose of medication for any length of time, or that they are experiencing some sort of newly emerging "psychiatric condition”.

It’s difficult to know exactly what percentage of people who stop or reduce a psychiatric drug will go through symptoms of withdrawal, in light of the relative lack of formal research into this issue. Anecdotally, however, there are countless thousands of online self-reports of withdrawal problems caused by every class of psychiatric drug, sometimes even after just a few weeks of use or at very low doses. Many more anecdotal experiences likely go unreported because of misinterpretations of psychiatric drug withdrawal symptoms as “relapses of mental illness”.

A July 2017 report by the Institute for Safe Medication Practices (ISMP) found that, “Clinical discontinuation studies of antidepressants with shorter half-lives showed 46%-78% of patients experienced two or more symptoms [of withdrawal].” ISMP’s related investigation of reports to the FDA’s voluntary Adverse Event Reporting System (FAERS) found that withdrawal symptoms were also reported in people taking longer-acting antidepressants, “anti-anxiety” benzodiazepines, Z-drugs, anticonvulsants/mood stabilizers, stimulants (“ADHD” drugs), and antipsychotics. ISMP noted that, while “stark warnings” about dependence and withdrawal were included in the drug labels for most benzodiazepines and Z-drugs, the same was not true for other psychiatric drugs. For example, ISMP reported that, “Both the FDA-approved warnings for physicians and information for patients give no hint of the extent of withdrawal symptoms that a majority of patients taking antidepressants will experience.” In light of how many people in the United States and elsewhere take psychiatric drugs, ISMP stated that, “It is hard to identify a risk of therapeutic drugs that potentially affects a larger fraction of the adult population.”

Generally, though not always, the likelihood of experiencing withdrawal effects seems to increase with higher doses and longer periods of time taking a drug. In addition, as discussed above, tapering slowly is thought to give the body the time it needs to re-acclimate itself to diminishing levels of the drug after it had to compensate for higher levels of the drug, and this is commonly reported in the layperson withdrawal community to significantly reduce the likelihood that people will experience problematic withdrawal symptoms.

The Withdrawal Project’s entire website and our Companion Guide to Psychiatric Drug Withdrawal are here to share the wealth of emerging anecdotal wisdom from the layperson withdrawal community about what can be done to help minimize the odds of experiencing withdrawal symptoms, or cope effectively with withdrawal symptoms should they emerge. But the single most important factor seems to be finding a taper rate that is slow enough that the particular person’s central nervous system is able to effectively manage dose changes without getting overly disrupted – in other words, tapering slowly seems to help facilitate fewer, shorter, and much less intense withdrawal symptoms. (See below for a more detailed discussion of what “slow” means with respect to psychiatric drug withdrawal.)

There is a great deal of research in the scientific literature documenting what the mainstream medical establishment typically refers to as “discontinuation syndromes” caused by stopping psychiatric drugs. As discussed above, “discontinuation syndromes” and sometimes explicitly “withdrawal symptoms” are also acknowledged in many of the official drug labels and prescribing information for all of the major psychiatric drug classes.

It is unclear why the mainstream medical establishment has chosen to adopt the phrase “discontinuation syndromes” when referring to psychiatric drugs – but many in the layperson withdrawal community believe it is because most psychiatric researchers, academics and practitioners alike tend to want to avoid use of more widely recognizable and obviously concerning terms like dependence and withdrawal.

No matter which terms are being used, though, there is in any case often a complete dearth of knowledge about psychiatric drug withdrawal or “discontinuation syndromes” in clinical, hospital, and therapy settings. Average clinicians are often surprisingly (and worrisomely) under-informed about the psychiatric drugs that they are prescribing, are not aware of the possibility of withdrawal effects from these drugs, and in some cases won’t even acknowledge that withdrawal effects are real.

Instead, recognition and validation of the very real and sometimes very debilitating, prolonged symptoms of psychiatric drug withdrawal are usually found mostly in the grassroots, layperson withdrawal community, which is increasingly spreading awareness about withdrawal to the broader public. Why is this the case? Unfortunately, it may be that many clinicians who prescribe psychiatric drugs or who work with people on psychiatric drugs do not want to know about or admit to the harms that these drugs can cause.

When it comes to psychiatric drugs, what many people consider to be a slow taper is not actually slow. Even if they are aware of the dependence-forming nature of psychiatric drugs, many prescribers taper people in a matter of a few days, weeks or months, or even not at all, meaning that drugs are stopped all at once. In the layperson withdrawal community, this is considered extremely dangerous. Instead, it’s been found that roughly about a 5-10% reduction of a person’s current dosage per month (so that the “cuts” get progressively smaller over time) is a taper rate that, for most people most of the time, seems to yield the smoothest and best outcomes.

There are, however, other very important factors that also come into play. For more detailed discussions of taper rates considered to be the least harmful and most risk-minimizing by the layperson withdrawal community, see “How Slow is "Slow" When it Comes to Psychiatric Drug Tapering?” 

There are innumerable factors that can significantly influence a person’s ability to taper successfully besides the taper rate, including personal commitment, physical health, age, employment and social circumstances, family support and more. There are also a number of other extremely important physical factors that can strongly influence the level of safety or risk for a person during psychiatric drug withdrawal that should be highlighted. All of these issues are explored in depth in TWP’s Companion Guide to Psychiatric Drug Withdrawal. Below we include brief descriptions and links for more information on some of these physical factors:
 

1. Genetics of drug metabolizing: Due to their genetic make-up, an estimated 10-30% of people (in part depending on racial heritage) are known to be “poor metabolizers” of certain psychiatric drugs. This means that these people cannot process drugs out of their bodies as quickly as others. In some cases, an average dose for most people could be as much as ten times stronger and longer lasting for a person who is a poor metabolizer. Read more...
    
2. Prescription drug interactions: There are many types of risky drug-drug interactions that can have serious consequences for a person’s health and safety; however, some raise specific concerns during tapering. Some prescription drugs and other substances such as alcohol, nicotine, caffeine, and even certain foods can actually accelerate the metabolizing of other drugs, while other drugs and substances significantly interfere with and reduce the metabolizing of other drugs. If a person is taking one or more drugs or substances of any kinds – especially if the person is also a “poor metabolizer” – this can create many unknowns and extreme risks when trying to taper from a psychiatric drug. It’s vital to know the inducers from the inhibitors. Read more...
    
3. Use of psychoactive substances: Aside from their potential for causing drug interactions, supplements, herbs, alcohol, marijuana, caffeine, and other psychoactive substances can have significant impacts on the central nervous system, and many people find that their central nervous systems become highly sensitized to the presence of these and other types of substances during psychiatric drug withdrawal. Adding new psychoactive chemicals and other substances to the body during a taper is considered to be very risky, and can lead to complicated, intensified, and prolonged withdrawal problems. Read more...
    
4. Diet: It’s very common for people tapering off psychiatric drugs to notice new sensitivities, allergies, and reactions to a wide variety of foods that they may never have had problems with before. Becoming aware of the impact that psychiatric drugs can have on the gut, some of the most commonly reported triggering foods, and possible ways to help the drug-injured brain heal through nutrition, are important parts of the self-education process. Read more...

If you are considering tapering off psychiatric medications and haven’t yet spent time with our complete Companion Guide to Psychiatric Drug Withdrawal, we encourage you to do so. You’ll have the chance to more closely explore all of these important issues.

Also, TWP’s Help Hub is currently under development and in future will offer layperson-sourced information regarding some of the most commonly asked questions regarding psychiatric drug withdrawal.