Hello and welcome to today's training. The topic is the management of other substance use disorders including benzodiazepines, cocaine, other stimulants, and cannabis. I am Edward Nunez. I'm an addiction psychiatrist at Columbia University Medical Center. In terms of disclosures, I have no relevant financial relationships with ACGME defined commercial interests to disclose that are relevant to this talk. The target audience. So the overarching goal of PCSSMAT is to make available the most effective medication-assisted treatments to serve patients, primarily patients with opioid use disorders in a variety of settings, including primary care, psychiatric care, pain management settings. So today, we're going to be talking about other substance use disorders outside of opiate use disorder, which often co-occur with opioid use disorder. The educational objectives for today's presentation at the conclusion of this slide show and talk, it's hoped that you'll be able to diagnose and formulate a treatment plan for misuse and use disorders of other substances including benzodiazepines, cocaine, and other stimulants like methamphetamine, and also cannabis. We'll touch briefly on alcohol as well although there is another whole webinar available on alcohol. So we're not going to focus primarily on alcohol, there is another full talk that covers co-occurring alcohol, which also occurs commonly in conjunction with opioid use disorder. So the outline of today's talk, again, we're going to provide an overview of the evaluation and treatment of benzodiazepine use disorder, cocaine, methamphetamine, and prescription stimulants use disorders, and cannabis use disorder. Again, noting that there is an entire separate talk about alcohol and alcohol use disorders, although I'll touch on it a little bit here just to highlight some common themes in the evaluation and treatment across all of these different substance use disorders. So why is it important to look at co-morbidity of these other substance use disorder? Well, other substance use disorders co-occur are co-morbid, very commonly with opioid use disorder. The presence of one substance use disorder increases the likelihood that a patient will have other substance use disorders. Substance use disorders have common risk factors they often go together. So among individuals with opioid use disorder, you'll often see other substance use and sometimes use disorders. Benzodiazepine use is very common, cannabis use is very common, cocaine use is very common. So when one substance is present, ask about other substance, look for other substances. Ask the patient what else are they using. Now, we're going to do a general overview of diagnosis and treatment. DSM-5 provides criteria for substance use disorders and these are the standards in the field, and then there's some general principles of intervention that we'll go over. Screening, brief intervention, and then treatment planning including pharmacological interventions, behavioral interventions, and levels of care. We'll talk about these in general and also with regard to each of the specific substances. So how does DSM-5 define substance use disorders? DSM-5 lists 11 criteria or symptoms and I find it useful to think of these as falling into three broad categories. Symptoms that reflect loss of control of substitutes, symptoms that reflect impairment due to substance use, and symptoms that relate to physiological tolerance and withdrawal. So the loss of control symptoms include using more of the substance than the patient intended. I was just going to have one drink and then I ended up having five or six. I was just going to take a half a Xanax and then I ended up taking two or three. Second one, tries and fails to cut down or control use. I keep telling myself I'm going to smoke less pot and I keep smoking three times a day. Every time I try to cut down, I can't seem to do. Number 3, spends a lot of time using and recovering. Substantial amount of time spent using, spent being intoxicated, to some extent spent seeking sources of drug, and then craving. Craving is a new symptom in the criteria, but it was felt important to add because many patients with substance problems described this. They described, I just have a hunger for the drug, I need to get some. They struggle with the craving. They describe it, they struggle with it. So those are the loss of control of substance. Impairment. Fairly self-explanatory. Fails to meet obligations, late to work, doesn't show up to work, that sort of thing or could be household obligations, family obligations, social or interpersonal problems. Relationships are damaged, gives up important activities, stops working, stops socializing, stops engaging in hobbies that they used to engage in. The drug is taking over the person's life. Uses when physically hazardous, drunk driving, driving while intoxicated or on other drugs. Physical or psychological problems. This patient is getting depressed or is developing stomach problems, or headaches, or chest pains as a result of clearly in response to using substances. So those are the impairment criteria. Then there's tolerance and withdrawal. Tolerance means the patient describes using more and more of the substance and yet the effect, particularly the work effect that the person is seeking diminishes over time, although tolerance develops to the other effects of a substance as well, and then withdrawal. Withdrawal are characteristic withdrawal symptoms that occur if a person has been using a drug regularly and then stops using, and each of the drug classes has distinct withdrawal syndrome and they are each defined in separate sections of the DSM. DSM-5 also encourages clinicians to rate the severity of the substance use disorder based on how many of the symptom criteria are met. So two or three of those 11 criteria shown in the previous slide, two or three is defined as mild substance use disorder, four or five symptoms or criteria is defined as moderate, and six or more is defined as severe. This is a nice general rule or forms and it's fairly face valid and also clinically valid. So and just to make the point, if a patient has only one criterion. They meet only one criterion and technically they don't meet criteria for substance use disorder, it's often. But certainly even if a patient had one of these criteria clinically, you would pay attention to it or keep an eye on and wonder whether it represents a substance use disorder that's very mild, end of the spectrum currently, [inaudible]. Now, what about the approach to the management? First is screening. How do you ask about substance use? The basic principle is to ask and to not feel uncomfortable about asking. So ask about use of other substances, ask about pills if you tried to take, try to use, colloquial language? Do you take tranquilizers or downers? Do you take sleeping pills? Do you smoke pot, or do you sometimes like to take cocaine, and so forth. Just that. Then if the patient says, "Yeah, I do," then you try to ascertain quantity, how much, how often. Try to ask about the DSM-5 criteria, the loss of control, the impairment, the tolerance and withdrawal. Generally when screening for substance use disorders, it's helpful to use the principles of motivational interviewing, and I reference Miller and Rollnick's classic textbook about the whole separate topic. But just for the purposes here, motivational interviewing adheres to what's called the spirit of motivational interviewing which is collaborative, it means that you're collaborating with the patient, you're not telling the patient what to do or kind of acting too much like the authority figure. Evocative; which means you're trying to listen as much as possible and hear the patient's point of view about things. Then support the autonomy of the patient which means really keep the ball in the patient's court, and ask open-ended questions and use reflections and try to get the patient talking. You'll have more information asking the patient an open question like, "Tell me about your cannabis use?" Let him talk about it and then you'll hear things that tell you about impairment and loss of control, rather than rattling off a list of specific closed questions, you sometimes feel like you've tried to cut down and you can't, yes, no. The open-ended questions sometimes gets you a lot further, try and encourage the patient to open up about substance use. If the patient talks about the substance use disorder and acknowledges that they see it as a problem, then you try to set goals, ask the patient to set goals. But honing to the spirit of respecting the autonomy of the patient, put the ball in the patient's court, ask the patient, "What are your goals with regard to your pot smoking? What would you like to do about it?" Let the patient formulate a goal and work with them with their goals. The spirit of motivational interviewing, again collaborative, evocative, respecting the autonomy of the patient. In screening, use the tactics of motivational interviewing which the main things are open questions, "Tell me about your pot smoking, what's it like?" Get the patient talking, and trying to get the patient to set goals. There are a number screening instruments that are useful, the AUDIT for example for alcohol, urine toxicology, there are dipsticks available, office based that are quite handy, they can be administered in advance. If the patient screens positive for benzodiazepines or cannabis or whatever you can say, "Hey, it looks like you've got some of this in your urine. Do you sometimes smoke?" You're trying to phrase your questioning in a way that you're accepting of their use, you're not judgmental, so that it will encourage people to open up and tell you what's going on. Let's move on to treatment planning. We want to be thinking about levels of care, outpatient, intensive outpatient, inpatient, or maybe just a little bit of advice in a primary care setting and a follow-up. Behavioral treatments, pharmacological treatments, and the principle of looking for co-occurring disorders and particularly co-occurring psychiatric disorders, which are very common in conjunction with opioid use disorder and in conjunction with cannabis, benzodiazepines, stimulant, alcohol, all of these disorders, the psychiatric disorders commonly co-occur. The evidence really suggest they should be identified and treated, and that will help in the overall treatment of the patient and their substance use disorder. What do we mean by levels of care? We want to recommend to a patient a level of care that corresponds to the superiority of their substance use disorder. The levels could include managing a patient within a primary care or in other office based setting like a psychiatric outpatient office or clinic. Outpatient and intensive outpatient substance use treatment, where it's a clinic that really specializes in the treatment of substance use disorders, and then there are residential treatment programs or medically supervised inpatient programs. What I have often gone in the past by the name of detoxification programs, although that's a term that I think is perhaps becoming somewhat outmoded, also dual diagnosis programs where you have patients that have combinations of severe psychiatric and substance use disorders. Now in terms of levels of care, there's some criteria called the ASAM criteria, the American Society of Addiction Medicine criteria. These criteria have been developed and refined over many years to help clinicians match patients with the appropriate level of care. The ASAM criteria ask you to evaluate the patient based on six different dimensions of severity, so acute intoxication or withdrawal potential, that's the first dimension. Biomedical conditions and complications, that's the second dimension, high blood pressure, heart problems, liver problems, that sort of thing. Emotional, behavioral, cognitive conditions, depression, anxiety, and so forth. Readiness to change; to what extent is the patient motivated to stop using? That really can vary widely. Dimension five; potential for relapse and continued use. Dimension six is closely related to dimension five, recovery living environment. Often the potential for relapse has a lot to do with where the patient's living, or what kind of environment they're in. Are they living in a home or an apartment building or in a neighborhood where there's a lot of drug use, and the dealers live there and so forth? That's really going to raise the risk for relapse. The recovering living environment are very important, does patient have a stable living situation? Is it a healthy living situation? Is it a living situation that would help the patient to avoid substance use? Those are the levels of care in an ASAM criteria. What about behavioral treatments? We're talking about behavioral treatments are useful generally for substance use disorders, and they include medication management which involves clinician, physician often meeting with a patient in a simple office visit to review how they're doing, and it includes practical advice about how how things are going with a substance use disorder and how to cut down or quit. There's motivational interviewing, we talked about that a little bit already, a 12-Step facilitation which encourages and guide patients in beginning to participate in Alcohol Anonymous or Narcotics Anonymous. Those are self-help programs that could be very useful to patients, patients often need a lot of help to get started, and that's what 12-step facilitates such a facilitation, equips clinicians with strategies to help their patients get involved in AA or NA. There's cognitive behavioral relapse prevention, which are a set of cognitive behavioral treatments. Contingency management; which basically rewards patients for a target behavior such as abstinence from drugs, drug negative urines, or it can also be rewarding patients for coming to treatment sessions. There's something called network therapy which involves getting significant others to come into the office with the patient to strategize about how the significant others can help and support the treatment plan. Then there's couples and family therapy, these are all different strategies. There's pharmacological treatments, medications for detoxification, anticonvulsants or benzodiazepine tapers for alcohol or benzo or sedative use disorder for example, obviously there are detoxification strategies for opioid use disorder. Alcohol use disorder, there's medication treatments including Naltrexone pills or injection Naltrexone, Vivitrol, there's Disulfiram and Acamprosate, again there are entire separate webinars in this series that cover alcohol. Then opioid use disorder, Methadone, Buprenorphine, and extended-release injection Naltrexone, are the three medications with clear evidence for effectiveness. [inaudible] in terms of other substance-use disorders, cannabis, cocaine, stimulants, benzodiazepine, there aren't such clearly indicated medications, although there are some that may be useful and we'll mention them later in the talk when we talk about the specific substances. Screening for co-occurring psychiatric disorders. This is a principle that cuts across substitutes problems that co-occurring psychiatric disorders are common and you should look for them. Mood disorders like major depression, post traumatic stress disorder is also very common. Stress and trauma are risk factors for the development of substance use disorder, so you'll often see these disorders go together. Other anxiety disorder, social anxiety, agoraphobia, also Attention Deficit Hyperactivity Disorder, very common. It's very useful when you're getting to know a patient with substance-use disorders, you have to ask them about their childhood school history, and look for whether they appear to have had a characteristic history of attention deficit disorder, or were they ever diagnosed with attention deficit disorder. Are they still having the symptoms now as an adult. So the general principle when there's a patient using substances too much, this may be a signal that other disorders are present. So where there's smoke, there's fire. Look, you see smoke, that's the substance use disorder, look for the other disorders as well. Here's a case vignette just to give us a clinical scenario to think about with benzodiazepine and alcohol use. A 35-year-old man with an opioids use disorder. Prescription opioids progress to heroin has initiated office-based treatment with buprenorphine. Now, buprenorphine has advanced to 16 milligrams a day and you report ceasing opioids use, and his urine toxicologies are negative for opioids, but they're positive for buprenorphine. So far so good. However, his urines are intermittently positive for benzodiazepine. He also describes drinking alcohol twice a week, sometimes to intoxification. Question. What is the most important next step in his treatment? What do you think? A, increase buprenorphine dose to 24 milligrams, B, refer him to a methadone maintenance treatment programs, it's better for buprenorphine. C, admit to inpatient detoxification. D, start an outpatient long acting benzodiazepine taper or E, obtain more history. I would say the answer is E, obtain more history because we don't really know that much yet about the patient. So there's no evidence that increasing buprenorphine dose or switching the methadone maintenance would be effective in addressing the sedative or the alcohol use. You need more history to really find out what's going on, and what would be the appropriate level of care that the patient needed. In-patient detox from the alcohol or will the patient be fine with some counseling for starters, and goal setting and other things like, is there psychiatric co-morbidity present? So you need some more history before taking any next step. Now we're going to spend some time going through the specific disorders, because it's kind of mentioned alcohol very quickly. Alcohol use disorders, is the most common substance use disorder along with nicotine. Prevalence in the population according to the NESARC survey is 30 percent lifetime, 8.5 percent within the last 12 months of the general population have an alcohol use disorder, very common, and it's very common among patients with opioids use disorders. Currently, approximately 30 percent of the patients with an opioids use disorder will have at least a lifetime history of alcohol use disorder. So it's very common and you should look for it. Main point about alcohol. Alcohol is a sedative. It's on a broad continuum with benzodiazepines and other tranquilizers. It's been extensively studied. The risk factors include genetics and stress. There's behavioral treatments like motivational interviewing, 12-Step facilitation, cognitive behavioral approaches. Alcohol was synergized with other sedative, so the combination of alcohol and benzodiazepines is particularly dangerous and a combination of alcohol, benzodiazepines, and opioids is especially dangerous, particularly with respect to respiratory depression. Overdose, and death with opioids, which is a big public health problem now, often involves co-administration of opioids with alcohol and benzodiazepine or other tranquilizers. There are three FDA approved medications, Disulfiram, Acamprosate, and Naltrexone. So they should be thought about and then there are a number of other meds. Spank, again, a lot of research on alcohol that have shown some promise for treatment of alcohol use disorders. Anti-convulsants like Gabapentin, Carbamazepine, Topiramate, Varenicline, the nicotine partial agonist and anti depressants. If there's co-occurring depression and then Buspirone if there is co-occurring anxiety disorders. So let's talk about benzodiazepines and other sedative. Benzodiazepines are therapeutically useful medications. They're highly effective for treatment of acute anxiety and insomnia, they act as GABA-A receptors, and they have an inhibitory effect on neurons. They have abuse potential in vulnerable individual. I say in vulnerable individuals because most individuals in the general population are probably not vulnerable to developing a benzodiazepine disorder. The don't find benzodiazepine all that reinforcing, but some individuals do and they're the ones that are vulnerable to becoming addicted. Benzodiazepine used disorder prevalence is low in the general population, but it is common among patients with opioids use disorders. Again, potentially dangerous because of the risk of overdose and again opioids overdose deaths often involve combination of opioids with benzodiazepine. So let's talk about benzodiazepine among patients who are being treated on methadone maintenance. Here you've got a prevalence of 20 to in some series as high as 60 percent of methadone patients have got benzodiazepine use. Studies have shown that benzodiazepine use among methadone maintenance patients is associated with other drug use, is associated with high risk behaviors, high-risk sex and so forth. It's associated with depression and anxiety disorders. Not uncommon for patients to seek out benzos on the street because they're struggling a lot of anxiety and benzos help them feel a little better. If benzo use is associated with increased mortality among methadone patients. So it's a signal of poor prognosis and the danger should be dealt with. Why are benzos frequently co-morbid with opioids use disorder? Well, they're used to self treat anxiety and insomnia. Many patients with opioids use disorder complaint of insomnia. Benzodiazepines are helpful to people to help them try to sleep. Many patients will seek out benzos to help them sleep. Co-occurring mood and anxiety disorders, post-traumatic stress disorder. So it starts with self treatment and then the benzodiazepine use can evolve into a use disorder where the patient starts to lose control and develop impairment from the benzodiazepine. So it's important to look for this and institute effective treatments. You know, truthfully, most of what we know about the treatment of benzodiazepine use disorder is by extrapolation from alcohol use disorder, but CBT anti-depression medicines if the patient's depressed or anxious, again, one can extrapolate for the behavioral treatments anyway, as a treatment for alcohol use disorder. There's a spectrum of benzodiazepine use from legitimate medical use to misuse to use disorders. So legitimate prescribe use is generally low dose. There is no escalation of the dose over time, patient takes the medicine as prescribed and have a good therapeutic response. So you see a methanol patient who's seeing a psychiatrist, been diagnoses with anxiety disorder is taking half a milligram of Klonopin twice a day for the past two years. No sign of abuse as a convincing anxiety disorder that the Klonopin helps for and probably a legitimate medical use. But, even if the use appears legitimate, it's important to keep an eye on it because there are non addictive alternatives for anxiety and depressive disorders, antidepressants for depression or anxiety disorders to dating antidepressants like trazodone or [inaudible] The next category is misuse, risky use. Misuse is defined as using the Benzodiazepines not as prescribed or illicitly procured, bought on the street, taking higher doses than prescribed. Now of course there's use disorder define as, according to the DSM-5 criteria we previously went over. So what are some of the red flags for misuse or diversion? Certainly, symptoms of intoxication or withdrawal. They come to the office and they look flogged, they look sedated, demands for a particular usually fast acting medication like alprazolam or Xanax. The patients will say things like, "Klonopin doesn't work for me, it's Xanax that works for me. Only Xanax works for me." Repeated loss prescriptions, "I spilled it down the toilet or down the drain." Discordant pill counts, the patient runs out of their prescriptions early, they're excessively preoccupied with getting refills, and certainly multiple prescribers. Now that we have statewide prescription monitoring programs, it's much easier to find out if your patient is getting controlled substance prescriptions from multiple providers. So these are the red flags for misuse or diversion or use disorders. So benzodiazepine abuse potential depends in part on the pharmacokinetics. So benzodiazepines vary in how rapidly they are absorbed and also in how rapidly they are metabolized. So rapid absorption generally is associated with a rapid onset of effects, more of a euphoria or high, which is more addictive. So Alprazolam and diazepam are both relatively rapidly absorbed orally, and for that reason, may have more abuse or addictive potential. On the other hand; clonazepam, Klonopin and lorazepam, Ativan; chlordiazepoxide, Librium; oxazepam, Serax were slowly absorbed. So if you need to treat a patient with benzodiazepine that has other substance use disorders, these slowly absorbed medicines are really the ones that are preferred to use. On the other hand, rapid absorption also equates with more rapid onset of action against anxiety. So if a patient's got a panic attack and they really need a rapid effect, then something like Xanax may serve them better. Now what about half-life, shorter half-life equals greater risk of withdrawal effects. So benzodiazepine withdrawal resembles alcohol withdrawal. It can conclude seizures and it can include delirium, and seizures you can see particularly with the more rapidly metabolized, shorter half-life medications like alprazolam, and lorazepam, and possibly clonazepam. So benzodiazepine withdrawal is a serious matter. It can be severe, and of course, withdrawal also drives drug-seeking patients going through withdrawal means they try to seek more drugs, so that is common with withdrawal. Alprazolam as I'm sure many listeners have experienced is the most popular elicit or abused benzodiazepine. The patients will often talk about benzodiazepine sticks, and those are these elongated, oval shaped blue pills and the two milligram benzodiazepines pills, and they are quite popular sell on the street. Of course nowadays, you also have counterfeit pills selling them on streets and so on, which are quite concerning because you're not sure what's in them. Okay. Benzodiazepine sleep medications. You've got the "Z drugs" like Zolpidem or Ambien. They have different profile of activity at the GABA receptors and supposedly, they have less abusive potential. But the rule of thumb is that at the end of the day from a clinical perspective, they're more similar to benzodiazepines than not. They have rapid absorption, they have pretty short half-life. You can get rebound insomnia, you can get sleepwalking and strange other strange nighttime side effects. You can get withdrawal effects. So my advice is to use these Z meds with caution in patients with opiates or other substance use disorders, and they've also been implicated in overdose deaths. So they're marketed as being less problematic. But I think one has to have a high index of suspicion that they would be equally problematic for patients compared to the other densities. So what are the alternatives to benzodiazepines for sleep? Insomnia is a very common complaint among our opiate use disorder patients. So first of all, sleep hygiene and CBT for sleep, sleep habits. Counsel the patients about their sleep habits. This isn't a quick fix, but if it can sometimes be very helpful to patients over time if they can improve their sleep habits. Treat the underlying causes of sleep disturbance, mood or anxiety disorders, opioid withdrawal, stimulant intoxication, drinking too much coffee, caffeine, sedating antidepressants are good alternatives to tranquilizers like benzodiazepines, and they don't have abuse potential. There's trazodone, although in men you do have to be aware of the rare occurrence of priapism. It's rare, but it's a very serious side effect if it occurs. Mirtazapine remeron is sedating at low doses and it's often quite helpful. Tricyclic, the old-fashioned tricyclic antidepressants at low doses like doxepin and Amitriptyline or antihistamines like Benadryl, it can be bought over the counter. There's melatonin, and the melatonin agonists like Ramelteon which are useful, they're more useful in signaling the body when it's time to go to sleep. So they can be helpful, most helpful I think in conjunction with efforts to correct a patient's sleep hygiene, you get a patient going to bed at a reasonable hour and at the same hour every night. Then more recently there's an erection antagonists Spike super exons. So these are alternatives to benzodiazepines for sleep with less abuse potential, it should be thought about. So evaluation of benzodiazepine use disorder, look at the quantity and pattern of the use and the type of Benzo is one to one for Xanax that has higher abuse potential, and evaluate the DSM-5 criteria, bearing in mind that the patients may deny excessive use or impairment, and certainly, it's useful to obtain collateral information from reliable significant others. Is the patient observed to be intoxicated, sedated, uncoordinated? Probably tons of patients won't tell you this. But the family member will say, "He's a sloth, we have trouble picking him up off the floor, he's clearly out of it." This part, why it's often very helpful to get input from the family as to what's going on, and of course check the prescription monitoring program for prescriptions from multiple prescribers, and of course those monitoring programs tell you exactly how much and what drugs the patient has been getting. So evaluation of benzo use, there's the urine toxicology. The thing to remember about this is that the standard immunoassays in the urine tests are not so sensitive to all the benzodiazepines. So the standard assays test for nordiazepam and oxazepam, these are the main metabolites of many benzos, including the older medications like diazepam and Chlordiazepoxide. But some of the newer high-potency benzodiazepines, like Alprazolam and Clonazepam have different structures, different metabolic end products. The assays are less sensitive. So just because the patient's urine is negative for benzos, they still could be using one of those more high-potency ones. You can request lower thresholds for detection or more sensitive assays if this is suspected. How you treat benzodiazepine use disorder? The evidence on specific studies looking at treatment of benzodiazepine use disorders are limited. So as I mentioned, a lot of what we know is by-extension from other substance use disorders that have been more extensively researched, like alcohol use disorder, cocaine use disorder. Advice to quit or cut down can be effective. You just say to the patient, "I think you're using too much of these benzos, it's dangerous. It would be important for you to try to cut them." If you have a trusting relationship with the patient, good relationship, the patient will be open to hearing your advice. They may not go with it right away, but they'll hear you. That's motivational intervening. CBT, there's a few studies that have looked at CBT for benzo use disorder. Evaluate for mood and anxiety disorders. Treat the mood or anxiety disorder with a SSRI depressant, for example, if that's there. Think about the levels of care. Sometimes if you got really severe high-use benzodiazepine use, you may need to think about a medically supervised detoxification on an inpatient unit, or if the patient's really using a lot of benzos and they may be at risk for opioids overdose. So benzodiazepine discontinuation is basically a substitution and taper strategy. Substitute a benzodiazepine with lower abuse potential and long half-life like Clonazepam, particularly Chlordiazepoxide, which has a very long half-life. Phenobarbital can also be used. Choose an equivalent starting dose and there are tables for this that determine dose equivalencies. Taper the dose slowly over a period of weeks or even months. Oxazepam is a good choice if there's lot of liver impairment because oxazepam is eliminated mainly by the kidneys and through the stool. Then anticonvulsants like Carbamazepine or Pregabalin can be useful adjuncts in a benzodiazepine taper because they have a cross tolerance. Benzodiazepine Equivalency Table, this is a way of determining if you have patients taking six or eight milligrams of alprazolam a day. How much chlordiazepoxide do you need to start them on? You use a equivalency table like this. So here's a case vignette, again, to keep us clinically grounded. A Buprenorphine patient with benzodiazepine and alcohol use. A 35-year-old man with opioid use disorder on bupenorphine 16 milligrams a day, illicit opioid abstinent, urine intermittently positive for benzodiazepine, describes drinking alcohol twice per week. Same picture we talked about before. On further history, he's been under financial stress, maybe he's depressed. He buys Alprazolam. Sticks, he calls them, from his former heroin dealer. Takes half a stick at night, one milligram, if you can believe that what he's getting from the dealer is actually Alprazolam to sleep at night. Drinks 2-4 beers to relax. Acknowledges feeling high when he drinks the beers. His wife who does not drink or take drugs and also seems reliable, so she's aware of his Alprazolam use for sleep. She's worried about his alcohol use, but she has not witnessed any severe intoxication or loss of consciousness while he's drinking. He's holding down a job, he had no lateness or absences. He wants to stop drinking and he wants to stop buying drugs from the dealer. But he says he's tried and he's been unable to stop either the alcohol or the Alprazolam though. Question, which medication would be the most appropriate first-choice to help him stop drinking? Naltrexone, Disulfiram, Acamprosate, or Gabapentin? Now, what do we think? Well, I would answer disulfiram, although you could make arguments for others. I think the Disulfiram would prevent drinking if the patient takes it. If the patient drinks they'll get sick. If there's a significant other in the picture, it's a good strategy to have a significant other witness the daily ingestion of the Disulfiram. It sounds like this patient's wife could do that, and of course, you need to educate the patient and the spouse about the Disulfiram. Naltrexone would be contraindicated because the patient is on Buprenorphine and that would precipitate withdrawal. Acamprosate, it has been shown to be modestly effective in reducing relapse after drinking. It's not been shown to be effective among outpatients, interestingly. Although you could try it as a second line of treatment and probably wouldn't do any harm. Gabapentin is not FDA-approved for treatment of alcohol or benzodiazepine use disorder, but it's a good thought. Has low abuse potential. Only been a few occasional reports of misuse. It may help with anxiety and sleep. There's one clinical trial at least that's shown that it's helpful for treatment of alcohol use disorder. I would guess the effect is probably not as powerful as the effect of Disulfiram if you could get the patient to take Disulfiram, but Gabapentin is not a bad thing. So another question. What would be the most appropriate next step in managing these patient's benzodiazepine use? Alternatives, admit for inpatient benzo detoxification. Prescribe alprazolam, one milligram at bedtime with a taper schedule. Prescribe Clonazepam, one milligram at bed time and continue until the cause of the insomnia is better understood, or prescribe a low dose of Doxepin, 10 or 25 milligram, and tapering doses of Clonazepam. Here, I would start with a low dose of Doxepin and tapering doses of Clonazepam because you're substituting a non-addictive, possibly helpful medication to help with sleep in the form of the low dose antidepressant Doxepin. Tapering off the benzodiazepine using Clonazepam, which is a slowly absorbed and slowly eliminated medication to try to prevent the emergence of withdrawal symptoms. Let's move on now to talk about cocaine, methamphetamine, and prescription stimulants. So cocaine and amphetamines are indirect acting sympathomimetics. They promote the release of dopamine, norepinephrine, and serotonin from their respective neurons in the central nervous system. Cocaine works by blocking the reuptake pump on the cell surfaces. It also happens to be a local anesthetic. Amphetamines promote release of catecholamines in serotonin, partly by blocking the reuptake of these transmitters into their storage vesicles. But anyway, the net effect of both of these is they yield a rapid outflow of dopamine and norepinephrine, serotonin from their cells. Many patients will experience a rewarding effect or high, and there's addictive potential stemming from this. Addictive potential system mainly stem from the release of dopamine in the ventral striatum or the brain reward system. So there are some milder stimulants with lower abuse potential. These include these we see, antidepressant bupropion, which acts mainly on norepinephrine but also pretty small, modest dopamine release. It's mildly energizing, but it is rarely abused. It is a widely used, effective antidepressant, and it's one of the things that one might think about in the treatment of a patient with cocaine use disorder. Let's say he's got depression and might help us solve cocaine use disorder as well. There's modafinil or provigil and r-modafinil or nuvigil. These are FDA approved for treating daytime sleepiness, sleep apnea, narcolepsy, shift work, and mild stimulus. They used off label for ADHD and for chronic fatigue and for depression to some extent, and also relatively low abuse potential. I'm at prescription stimulants. So you've got dexedrine, you've got mixed, which is d-amphetamine, you've got mixed d and l-amphetamine, which is marketed as Adderall, you've got methylphenidate, which is more similar to cocaine. It blocks dopamine re-uptake, norepinephrine re-uptake. These are effective treatments for ADHD, and they're also used as adjunctive medicine in the treatment of depression. There are extended release formulations like Adderall XR, and Concerta, and Vyvanse, which is a pro-drug of amphetamine. These have slow absorption and they scarcely produce less high and they have less abuse potential. So it's the same principle as we talked about with the benzodiazepines. Look for the swirl absorption medication if you need to prescribe one's medication to a patient. Methamphetamine. Methamphetamine is a variant on amphetamine. It's readily synthesized in elicit laboratories, and it is highly prevalent in some sectors of the United States including the West and the Mid-west. It is associated with risky sex because of its sexually stimulating effect. It can be taken by mouth, but it's also smoked and injected. There's been quite a bit of evidence about the toxicity of this drug if it's taken in large amounts over a long period of time including neurotoxicity. Perhaps more so in other stimulants and multiple physical and psychological adverse effects. It's a very bad addiction. You can see severe substance use disorder stemming from methamphetamine. So what about stimulants in combination with opioid use disorder? Stimulants and cocaine commonly co-occurs with opioid use disorder. Everything co-occurring from casual use, the speed balling, which is the combination of cocaine and opioid leads to a full out use disorder. The stimulants may also be observed among patients with opioid use disorder like amphetamines, methamphetamines. Stimulants sometimes prescribed for ADHD, the diagnosis is not always so clearly established. So you need to get a good history and try to be convinced that the patient truly has ADHD. What are some red flags for misuse of prescribed stimulants? This is pretty similar to what we talked about with benzodiazepines. Symptoms of intoxication or withdrawal, often helpful to get family or significant other input on these. Demands for a particular medication, usually immediate release. So the patient says, "Now, extended-release Adderall, XOR Adderall doesn't work for me, doc. I need immediate release. 20 milligrams please. That's all that works for me." So red flag. Repeatedly loss prescriptions, discordant pill counts, preoccupation with securing the medications supply, and of course, multiple prescribers. Evaluation of cocaine and other stimulant use disorders. Cocaine can be intranasal, intravenous, or smoked, freebased, cracked. Methamphetamine may be taken by mouth, or intranasal, or smoked, or injected. It's difficult to quantify the doses of these. Patients talk about grams or bags or different units that they sell by on the streets. The query how many days per week. The route of use, intravenous being the most severe. How many hours per day using. Evaluate the DSM-5 symptoms of the use disorder. Ask about the dollar value of what's being consumed. That's a way to quantify use. Look for stimulant and cocaine stimulant withdrawal, which consists of fatigue, depression, which may be quite severe insomnia, then hypersomnia, you get functional impairment for several days or even a week from substantial stimulant cocaine withdrawal. Treatment. So there's a lot of research on behavioral treatments, motivational interviewing, contingency management, cognitive behavioral therapy, 12-step facilitation. There's evidence for the effectiveness of many of these. There's been a lot of research on medications for cocaine use disorder, although very little in the way of mere indications. Some hints that noradrenergic antidepressants like tricyclic antidepressants, or bupropion may be helpful. Some studies show while others don't. Disulfiram, topiramate, some studies show it, others don't. Cocaine use disorder. Identifying ADHD seems to be a helpful treatment strategy. Doctor Levin and her colleagues at Columbia University have done a study showing that Adderall extended release is effective in helping patients stop using cocaine if they have attention deficit disorder. So look for attention deficit disorder. Amphetamine, methamphetamine use and treatment. Again, there's evidence on contingency management, cognitive behavioral therapy, 12-step facilitation. Medications, none clearly effective, FDA approved or effective. Although there are hints of effectiveness from some trials including naltrexone, bupropion, and one study with mirtazapine. So this is an ongoing effort. But naltrexone and buproprion are medications that one might think of trying. Levels of care. Really limited evidence on how to assign patients to levels of care. Most patients with cocaine or stimulant use disorder are treated as outpatients. If they show severe psychosocial impairment, you might think about inpatient or residential treatment really to try to enforce a period of abstinence and reset things for the patient and try to get a long-term treatment plan going. It would help the patients with sustained abstinence. Another case vignette, a same patient on buprenorphine and benzodiazepine and alcohol use. We talked about this patient before doing well on buprenorphine but using other benzos and some alcohol. Now, the patient shows up and starts to produce cocaine positive urines. He says he takes cocaine in the morning to combat fatigue and to get to work on time. He also said his work is often tedious. Cocaine helps them stay focused. He denies all symptoms of a cocaine use disorder. He asked for a prescription of Adderall immediate relief. Mentioned that several years ago, a doctor diagnosed him with ADHD and treated him with Adderall. His childhood history yields no indication of problems with performance or behavior at school. What do you think would be the most appropriate next step in his treatment? Institute Contingency Management where cocaine positive urines trigger reductions in his buprenorphine dose. B; prescribe Adderall, immediate release. C; prescribe Adderall, extended release. D; counsel that ongoing alprazolam and alcohol use may contribute to his fatigue, or E; Obtain collateral history from his mother about his childhood history. So I think both D and E are good answers. Counsel the patient that the ongoing alprazolam and alcohol use may be contributing to his fatigue and if he would fix that, he might feel less need to use stimulants. Then of course, obtain collateral history from mum about the childhood years. Did he really have ADHD? Maybe he did. He doesn't remember clearly. So I don't think you want to prescribe Adderall right away, there is not eno ugh evidence for it. You certainly don't want to punish the patient by reducing their opioid use disorder medication treatment, even though there are some clinics in the United States that will discharge a patient from buprenorphine and methadone treatment, if they don't stop using other drugs. I think most experts would agree now that that's a bad strategy. Cannabis use and use disorder. Cannabis is interesting stuff. It contains multiple potentially active compounds including THC, which is the cannabinoid receptor partial agonist. It's what is mainly responsible for the high and it does that by promoting dopamine release. This cannabidiol which does not release dopamine, does not have abuse potential, does not bind on cannabis receptors in the cannabinoid receptors in the typical way. It is a potential anticonvulsant and analgesic. The different strains of cannabis that contain different concentrations of these different compounds and contemporary strains, may be highly potent with high concentrations of THC. You may see severe intoxication, greater risk of use disorder, and cognitive impairment amotivational syndrome. Cannabis and opioid use disorder; cannabis is very commonly used by patients with an opioid use disorder, including people being treated with methadone, or buprenorphine, or naltrexone. Cannabis and THC have got shared neuropharmacological mechanisms with opiates. Cannabis withdrawal looks similar to opioid withdrawal in many respects. There's irritability, insomnia, anxiety. Cannabis seems to have analgesic properties and patients often report taking cannabis to help with sleep. Of course, medical cannabis is now legal in many states, as it is being prescribed. So how do you evaluate this? How do you quantify cannabis? Patients talk about joints. They also talk about blunts, a blunt is where you cut a cigar open and fill it in with a bunch of cannabis. Rough rule of thumb, one blunt is approximately equal to three joints. But you know quantification is difficult because of variations in the potency of the cannabis. Trial elicit DSM-5 symptoms of substance use disorder, and patients often deny impairment. Again, it's useful to get collateral history from family members. There's often failure to perform in school or career, trouble with motivation. It's a clinical problem. It's tough to motivate patients that are heavy cannabis users. It can be. To try to get them to acknowledge, "Maybe I should really try to cut down or quit. Maybe I would do better." Treatment; behavioral treatment is the mainstay, advice to quit, motivational interviewing, CBT, contingency management, some evidence for these. Medications; various ones have been tested. None proven effective yet. Levels of care; most cannabis use can be managed on an outpatient basis. Rarely, inpatient care would be needed to relieve apparent use. Co-occurring opioid and other substance use disorders conclusions. So just the main points. Co-occurring substance use is common among patients with opioid use disorder including alcohol, benzodiazepines, cocaine, and other stimulants, and cannabis all of which we've talked about today. Again, general principles; the first step is an evaluation. Ask the patient, use motivational interviewing principals, quantify the use, seek collateral reports from reliable significant others, and apply the DSM-5 criteria. Look for co-occurring psychiatric disorders including depression, anxiety, PTSD, ADHD, problems with sleep, and pain. Consider behavioral or pharmacological treatments for the other substance use disorders. Much of co-occurring substance use, mild to moderate, it can be managed in the office or in an outpatient setting. There are certainly indications for intensive outpatient or inpatient care, including serious risks, overdose, gross intoxication, severe psychosocial impairment, failure to improve at lower level of care. These are some of the references that underlie the material that I've presented today. I would just like to highlight that the PCSS program has a mentor program, that is, it makes available to anyone who requests one, a mentor who is an experienced addiction clinician. Mentor program is designed to offer general information and advice to clinicians, about evidence-based practices and prescribing opioid medications. It's a nationwide network of providers with experience treating addictions and pain, and experienced in evidence-based treatments, including medication-assisted treatments and behavioral treatments. It's a three-tiered approach that allows every mentor-mentee relationship to be catered to the specific needs. There's no cost, it's freely provided through the PCSS program. There's also a PCSS discussion forum, which is comprised of our PCSS mentors and other experts in this field, which helps provide prompt answers to clinical question. We also have a mentor on college month. It's available to address any submitted questions through the discussion forum. You can create a new login account by clicking into the image on the slide and access to the registration page. This is the contact information, including the website for PCSS, and we encourage you to access these freely available resources. That concludes the webinar for today. Thank you for your attention and we certainly hope that it's been helpful overview.
