CATR: Dr. Stalcup, please tell us a little bit how you started in addiction medicine.

Dr. Stalcup: I started out and got certified in addiction medicine at the Haight Ashbury Free Clinic, which was run by David Smith and Darryl Inaba, who I think of as basically the founding fathers of modern addiction medicine. They had a major interest in outpatient management of sedative hypnotic dependence, and I was trained to look at these drugs very critically.

CATR: When you talk about sedative hypnotics, do you mean benzodiazepines?

Dr. Stalcup: Yes, sedative hypnotics include benzodiazepines, but they encompass other agents as well—sleeping pills like Ambien and muscle relaxants such as Soma are all essentially the same medicine. And of course, barbiturates and alcohol are also in that category as well. One good way to think of benzodiazepines is that they are literally, physiologically anyway, alcohol in a pill. Especially the fast-onset/fast-offset benzodiazepines like alprazolam (Xanax) have a very similar pharmacologic profile to alcohol.

CATR: Interesting. I certainly have heard the alcohol-in-a-pill analogy, but I think the experience of most of us is that something like a typical 0.25 mg to 1 mg dose of Xanax doesn’t really feel the same as having a drink. Is that effect something that occurs with a high enough dose?

Dr. Stalcup: I definitely think you can get an alcohol-like buzz with a high enough dose. On the street, Xanax is sold as 2 mg “Xannie bars,” and one bar will usually generate alcohol-like intoxication. Right now Xanax is fast emerging in California as a major drug of abuse. We’re seeing teens taking somewhere between 8 mg and 15 mg a day—huge, huge amounts—to get that alcohol buzz feeling. 

CATR: That’s pretty scary. I assume the kids are not getting Xanax from their doctors?

Dr. Stalcup: No, it’s a street drug now. Anyone who sells heroin or meth will deal you alprazolam.

CATR: Are most legal prescriptions for benzodiazepines originating from psychiatrists?

Dr. Stalcup: Actually, psychiatrists probably prescribe a minority of the benzodiazepines out there compared to everybody else. They’re very commonly used in family practice, in general internal medicine, and most frequently prescribed by primary care doctors. 

CATR: Benzodiazepines continue to be our first-line drug of choice for immediate relief of anxiety in the short term. Do you agree with this practice?

Dr. Stalcup: Benzodiazepines are the best drugs for relieving short-term anxiety and panic. The problems arise with long-term use; although sold for “short-term use,” many patients receive benzos for years (including sedative-hypnotic sleeping pills, such as Ambien/zolpidem). This leads to the development of tolerance, defined by previously effective doses becoming less effective and the appearance of withdrawal symptoms if the medication is withheld. The management of tolerance/withdrawal emerges as a major therapeutic issue in long-term use. Most important is the severe complication in tolerant folks of kindling.

CATR: What is kindling? 

Dr. Stalcup: Kindling is a process in which repeated episodes of withdrawal have the property of sensitizing target chemistry in the brain. The effect of that kindling sensitization is that withdrawals get worse and worse over time, cravings increase, and time to relapse is shortened. In the end stage of kindling, seizures, delirium, and dementia will develop (Post RM, Epilepsy Res 2002;50(1–2):203–219). Many patients are worked up in neurology offices for seizures, tremors, and myoclonus, when in fact what they have is benzo tolerance (Rogawski R, Epilepsy Curr 2005;5(6):225–230). They don’t necessarily tell their doctor that they are drinkers or take sleeping pills and/or muscle relaxants either from shame and embarrassment, or because they don’t think that what they are taking or using could be related to seizures. And sometimes the neurologists themselves aren’t familiar with the kindling/seizure issue, and don’t consider sedative-hypnotics to be a contributing factor (Breese GR et al, Psychopharmacology (Berl) 2005;178(4):367–380).

CATR: So if you’re using a benzodiazepine or a sedative hypnotic several days a week, you’re typically going to become tolerant to some degree.

Dr. Stalcup: Short-acting, fast-onset/fast-offset benzos produce tolerance more quickly than long-acting benzos like Librium (chlordiazepoxide) or Klonopin (clonazepam). Tolerance is almost certainly going to happen with long-term use. However, tolerance and withdrawal are not the same thing as addiction: Some individuals are dependent, but not addicted. The risk for addiction per se is not homogeneously distributed. We know that about 15% to 20% of people are at exceptionally high risk for addiction. But most patients given benzos for long-term uses are at very high risk of becoming dependent and tolerant; those people are often not recognized (Uhl GR, NeuroRx 2006;3(3):295–301, Bevilacqua L and Goldman D, Clin Pharmacol Ther 2009;85(4):359–361).

CATR: How can you tell if a patient is developing increased tolerance?

Dr. Stalcup: The main sign that someone’s becoming sensitized to the drugs is worsening symptoms with each episode of withdrawal. We see many people who are pathologically attached to benzos because every time they try to reduce or discontinue them they get terribly anxious and panicky.

CATR: Can you speak to the differences between dependence and addiction?

Dr. Stalcup: Addiction is loss of control over use of a substance in the face of adverse consequences. I’d say that of the patients that I’m currently treating who have been viewed as addicts, about 50% are dependent on sedatives but are actually not addicted. They certainly are med seeking because they are frightened if they can’t get their medication, but they’re not drug addicts; they’re physically dependent on the drug and they experience remarkable distress if they stop. These patients got dependent on medicines that were prescribed by a doctor who didn’t recognize the tolerance potential, the dependence potential, and the kindling potential.

CATR: Are the terms dependent and tolerant interchangeable?

Dr. Stalcup: The appearance of tolerance and withdrawal define dependence. Tolerance means it takes more of the drug to get an effect than it used to. So once tolerance sets in, from that point forward, the kindling process comes to increasingly dominate the clinical picture. You see this in a lot in pain management—people who aren’t addicted to a drug, but they are chemically dependent and they will go through withdrawal. A lot of these folks get put in a hospital and treated using traditional 12-step approaches as if they were addicts, but they’re not drug addicts, they are dependent.

CATR: You mentioned that 20% or so of the population are more vulnerable to addiction, possibly genetically. Clinically, are there things that we can find out or ask that can help us discern this vulnerability in patients?

Dr. Stalcup: That’s an important question. The main red flag is family history. People most likely to become addicted to benzos have family histories of addiction. It’s a high number: About 65%–70% of addicted people have a family history. Other risk factors are previous alcohol abuse histories, and people who’ve been exposed over time to short-acting benzos, in particular alprazolam.

CATR: It’s interesting to try to understand because certainly there are people out there that seem to be able to take or leave these agents very easily.

Dr. Stalcup: Probably most people, but the ones that trouble us are ones that this doesn’t apply to.

CATR: Right. So, as a general psychiatrist, say I have a patient that was initially treated for depression or anxiety with an antidepressant and some Klonopin. Over the months, the patient continued on that low dose of Klonopin, which stretched on to a few years, and now I have someone who is clearly dependent in my office saying, “Doc, I want to get off of this.” Rather than recommended a 12-step program or a rehabilitation clinic, how do we help get these types of patients off benzodiazepines?

Dr. Stalcup: The process is not a casual one, but it is very doable. The key to getting a patient off benzos is switching from an as-needed, “prn” dosing schedule, to a fixed daytime schedule that will lead to steady state brain levels of the drug. It has to be done meticulously with symptom scoring and vital signs monitoring to prevent the development of withdrawal symptoms.

CATR: Can you give me an example? 

Dr. Stalcup: If the patient is taking a short-acting benzo, like alprazolam, we usually switch them to Librium or phenobarbital because they are longer acting and allow for a smoother taper; steady-state is achieved within three to five days. We adjust the dose until we eliminate all withdrawal symptoms without causing sedation. So if they’re hypertensive or shaky or anxious or can’t sleep, we will add doses to reduce symptoms and maintain diastolic blood pressure and pulse below 90 (we call it the “90 and 90 rule”). We familiarize the patients with the sedative hypnotic withdrawal assessment key. We’ll often equip them with an automated blood pressure cuff if they don’t have one so they’ll be able to track this at home. Once you’ve done the 10 days to two weeks or so of getting them onto steady state at a comfortable level, you begin the process of a symptom-guided taper. 

CATR: How do you do that taper?

Dr. Stalcup: It is basically in the range of about a 10% taper per week. Much above a 10% decrease, and patients begin to develop increased pulse, blood pressure, tremor, sweats, shakes, very similar to an alcohol withdrawal syndrome. We establish a rate and amount of taper to prevent recurrence of withdrawal symptoms. 

CATR: So they can do this at home; how often do you have these patients come back into the office?

Dr. Stalcup: We will usually see them on average each week or every two weeks. They bring us the information on their vitals or they send it to us by email. And there’s always someone on call to help them with rough patches. 

CATR: So you’ve had good results with your patients feeling okay during the process as long as they stay steady at the 10% taper?

Dr. Stalcup: Correct, they feel fine. They don’t feel medicated during that time; they just feel normal. That’s true even for folks who’ve been on benzos for years and years, even elderly patients who’ve been on Xanax for 40 years. Using the symptom-guided approach, they’re comfortable throughout the taper. 

CATR: How long does it take until they are safely off?

Dr. Stalcup: That depends on the initial steady-state dose. The higher it is, the longer it will take to taper. We’ve had people who necessitated 12 months of taper.

CATR: Are there cases in which you just can’t get a patient to taper for whatever reasons? 

Dr. Stalcup: Yes, we have patients we can’t get to taper any further, without precipitating withdrawal symptoms. With enough experience, we know we can actually maintain them comfortably on a fixed dosing schedule usually with a morning and evening dose, and sometimes just a bedtime dose of 25 mg or 50 mg of Librium. 

CATR: That’s good to know. Thank you very much for your time, Dr. Stalcup.