Many people worry about the addiction risk of medications prescribed for mental health conditions, such as those used for depression, anxiety, bipolar disorder, ADHD, and schizophrenia. There are many misconceptions about the risk of addiction to these various medications that lead people to make choices that may not be in their best interest. Unfamiliarity about medications may persuade people to avoid medications that could be helpful (and relatively safe) for symptoms of their mental health disorder; it can also lead people who may not need medication to underappreciate the risk associated with its use.
The first step to appreciating the risk of addiction to various medications prescribed for mental health conditions is to review the various ways the body learns to adapt to a substance that is taken regularly. The body is designed to preserve homeostasis, which is an optimal set point that your body works hard to maintain. When you do something that disrupts homeostasis, your body engages in a compensatory behavior to try to remedy the disequilibrium. For example, we shiver when we’re cold to bring our body temperature back up and we sweat to try to reduce our body temperature when we’re overheated.
Medications have the potential to disrupt homeostasis in many ways. In general, medications used for mental health conditions create their effect by changing something about the body’s internal process. The body then adapts to the presence of this substance by making adjustments that compensate for its presence. If the medication is causing an increase in some process, such as activity of a neurotransmitter, the body reacts by making it harder for that effect to occur; if it causes a decrease in some function, the body does its best to create opportunities to maximize the impact of that function.
The term “tolerance” is used to describe a state where the person no longer responds to the substance in the same way they did initially. These changes may increase the risk of addiction for some substances (discussed later), but they also may underlie the therapeutic effect in many cases as well. There are also many pathways to tolerance within the body, but they all involve a common approach of compensating for the regular use of a substance that takes the body out of homeostasis. The two most common forms of tolerance are metabolic and cellular tolerance.
Metabolic tolerance involves physical adjustments that are aimed at a more rapid elimination of the substance from the body. By speeding up the metabolism of a substance it encounters often, the person ends up needing to use more of the substance in order to survive the enhanced metabolic process and create the intended effect. For example, if a certain enzyme is responsible for breaking down a substance in the liver, the body may create more of that enzyme, so it can eliminate the substance more quickly and therefore reduce the impact of that substance. At this point, the person will need a higher dose to get the same effect.
Cellular tolerance is another form of physical adaptation that occurs in response to frequent use of a medication. It involves adaptation within the cells that adjust for the activity of the medication in the brain and body. For example, when a benzodiazepine such as Xanax is used to manage anxiety, it works by enhancing the effects of a neurotransmitter called GABA that tends to have a relaxing effect. If Xanax is taken frequently, the body will attempt to counteract it and will make changes such as decreasing the number and sensitivity of the receptors where GABA must bind to create its effect. Xanax will continue to cause a spike in GABA activity, but because of limited binding potential, the person will not experience the same degree of impact (and hence, need a higher dose to get the effect they used to get).
A person can even develop tolerance to a substance they have never taken! This phenomenon, known as cross tolerance, may occur when two substances have similar impacts to the brain and body. The adaptations the body makes in response to one substance impacts the response to the similar substance as well. The body’s process of cellular tolerance to Xanax, for example, is associated with cross tolerance to alcohol because alcohol also activates GABA activity; because there are fewer GABA receptors, more Xanax and/or alcohol is needed to get the effect the person used to experience prior to tolerance.
Tolerance is not necessarily problematic or concerning. In fact, it’s necessary for the full beneficial effect of some medications, which helps to explain why options, such as many antidepressants, must be taken daily for a significant period of time (often 4 – 6 weeks) before they are maximally effective. However, tolerance does underlie addictive potential for habit-forming medications like Xanax that are associated with fast-acting, pleasurable effects and distressing, uncomfortable withdrawal symptoms.
Check in next week for Part 2 where we’ll discuss other factors that impact the risk of addiction to mental health medications.