Hi, I'm Derek Blevins. I'm an assistant professor of psychiatry at Columbia University in the New York State Psychiatric Institute. And the title of today's webinar is psychiatric comorbidities, diagnosis, and treatment of comorbid psychiatric disorders and opioids disorder. None of the planners, faculty, and others in control of content for this education activity have any relevant financial relationships that is closed within eligible companies whose primary business is producing, marking, selling, reselling, or distributing health care products used by or on patients. The overall goal of PCSS is to train health care professionals in evidence-based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorders. Today's educational objectives will be to recognize that psychiatric illnesses and substance use disorders commonly co-occur describe how to stream for identified co-orbit psychiatric disorders, identify the distinction between independent psychiatric illness and substance-induced disorders, demonstrate comfort in developing treatment plans when comorbidities are identified. And our overall outline-- so first, we'll talk some about epidemiology, then about comorbidity theories, the clinical relevance of those two things, and then we'll go through three different cases. One, about depression, a second about PTSD, a third about ADHD, and then finally, some conclusions. Substance use disorders and other psychiatric illnesses frequently occur. Among the 37.9 million U.S. adults with a past year substance use disorder, 45% had a co-occurring mental illness, according to the 2020 National Survey on Drug Use and Health. About a third of all U.S. adults with past year mental illness had a past year substance use disorder. So why does this matter? Co-occurring psychiatric illnesses and SUD have a worse prognosis. So worse treatment outcomes, higher risk of relapse, and more hospitalizations. Also have a poor quality of life and an increased risk of suicide, and particularly people with bipolar disorder. Effective treatment of co-occurring psychiatric disorders, like bipolar disorder or major depression, I actually improved outcome of the SUD. Look, a couple of the theories of co-morbidities. So why are they so commonly co-occurring? So one is thinking about developmental factors. So one of the illnesses causing the other contributing to the other. So substance use or misuse usually starts in adolescents when the brain is undergoing significant developmental changes. Early substance exposure can change the brain in ways that increase the risk for mental illness. And early symptoms of a mental disorder may increase vulnerability to substance use. Another idea is around shared risk factors. So shared genetic vulnerability or environmental stress is like stressful life events or trauma and they contribute to either psychiatric illnesses or substance use disorders. And then indirect risk factors, like self-medicating one psychiatric disorder, may actually transition then into a substance use disorder. And some of the diagnostic and treatment implications of this. So the de-segment, the stinglish is between independence like get rid of illness and one that is substance-induced or secondary. Evidence of an independent disorder, coding include things like symptoms that perceive the onset of the substance use, symptoms that persist for a substantial period, so at least a month after the cessation of substance use, or past episodes that are not substance-related. The prism or psychiatric interview for substance-ism mental diseases is a diagnostic tool designed to distinguish between the independent and secondary symptoms. The prism places a section on substance use disorders early in the interview and an effort to establish the age of onset of substance and psychiatric syndromes. When querying criteria for disorders such as major depression, prism asks the interviewer to judge whether each symptom of depression like insomnia is or is not better explained as a usual effect of a substance or substance use. When evaluating someone with both SUV and psychiatric symptoms, careful diagnosis and evaluation for substance-induced disorders are important. A different clinical course may be expected if psychiatric symptoms are substance-induced. Substance-induced symptoms should improve rapidly with abstinence, though may be more prolonged in sub-subsidences like cannabis. Other works suggest that both primary and substance-induced depression predict future depression, relapse, and suicidal ideation, warranting clinical attention and consideration for specific treatment. But it can be very difficult to differentiate independent from secondary disorders, particularly without a period of reduction or abstinence, even with a very improvement about evaluation. And it can also be difficult for patients to achieve reduction or abstinence and delaying treatment for specific psychiatric symptoms or syndromes can have potential consequences. For co-occurring independent depressive disorder and substance-induced disorder, it has been shown that antidepressant treatment improves depression. The improvements around drug and alcohol use are less clear. However, for co-occurring bipolar disorder and substance use disorder, lithium or other mood stabilizers do appear to improve both mood and substance use outcomes. Some reasonable clinical guidelines for managing co-occurring substance use disorders and other psychiatric symptoms include things like initiating treatment for the substance use disorder earlier on, encouraging abstinence or reduction of substance use, and then observing what happens to the co-occurring psychiatric symptoms. Do they resolve or do they persist despite their reduction or abstinence? If psychiatric symptoms are severe or until risks, so things like forefunctioning, violence or suicide, it may be better to initiate treatment for co-occurring psychiatric syndrome right away, rather than delay while avoiding for abstinence or reduction. So having considered now some of the epidemiology and the clinical relevance, let's think through one case. So Mr. K is a 55-year-old married man who is hypertension you've been treating for many years. He recently had a right hip replacement surgery and comes to you today for a routine checkup. He reports these have been feeling down since his surgery three months ago with low energy and poor sleep and appetite. You know that he was depressed before first in his 20s and then again at ages 33 and 46. It's really important here to obtain details about his prior depressive episodes to think about the severity of the year of fire hospitalization, whether suicidal ideation or suicide attempts, and then past treatments. You don't want to repeat a failed treatment trial in this case. But you believe based off of his current symptoms in his history that he might be depressed again. So the first question is what are the steps you take to evaluate for depression? So the DSM criteria for a major depressive episode are five or more of the following list of symptoms in a two week time period and at least one of those five symptoms has to be either depressed mood or anodonia. So beyond those two symptoms changes an appetite or weight and that it can be increased or decreased insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or low energy, guilt or worthlessness, changing concentration, and recurrent thoughts of death or suicidal ideation. So five or more of those symptoms in a two week period. It's also important that these symptoms cause some clinically significant distress or impairment to meet the diagnostic criteria. You also want to think about the possibility of a persistent depressive disorder or used to be described as the stymearic disorder. It's important to consider the duration, the severity and the frequency of the depressive symptoms as this will also help guide treatments. So thinking about therapy versus medication or combined treatment and then the location of that treatment is outpatient appropriate intensive outpatient or inpatient treatment. And with diagnosis, self-report scan assistant screaming for current symptoms severity, but a clinical history is really needed for the diagnosis. And ideally assisted by a diagnostic instrument like the prism or the structured clinical interview for the asset. The QIDS is an example of a self-report that can be helpful in this case, but certainly more clinical history is needed to give the diagnosis. You also want to ask about prior hypomanic or manic symptoms. Remember that bipolar disorder is highly comorbid with SUDs. The lifetime prevalence of any SUV in individuals with bipolar one disorder was 60.3% in the National Civil Mabilities Survey. So quite high. Treating bipolar disorder with antidepressants alone without the patient already being on a mood stabilizer can be destabilizing. So this is why it's important to ask about symptoms of hypomania or mania in the past. You also want to ask about psychosis. So psychotic symptoms can occur with severe depression. And this is going to have prognostic and treatment implications. And also ask about other psychiatric symptoms or disorders like anxiety. Beyond thinking about the psychiatric components, you also want to think about potential medical etiologies that mimic depression like hyperthyroidism. And are there any substances, whether prescribed medications, illicit drugs or alcohol that could be cause it, causing or contributing to the depressive symptoms? You definitely want to be screening for safety, screening for suicide. For its depression is a risk factor for suicide, but other risk factors include prior suicide attempts, substance use, family history of suicide, feelings of hopelessness and impulsivity. And the Columbia suicide severity rating scale can be used to assess suicidal ideation and behavior. And it can be found online in very different formats. And also a training is available online for how to complete the CSSRS. Back to our case, as you're asking about depressive symptoms, Mr. K asks for prescription for oxycodone. You find this surprising as his surgery was months ago. Upon further questioning, he reveals that he's been taking more oxycodone than prescribed. So up to 10 to 15, 10 milligram tablets per day has begun to purchase it on the street and recently began sorting it because he feels a more immediate effect. So this is an important point to remember to ask about substance use and substance use disorder when evaluating depressive symptoms. The lifetime prevalence of major depressive disorder in those with opioid use disorder is 45.6%. So about half of people with opioid use disorder have a lifetime prevalence of major depression. You ask more about his oxycodone use. And he tells you that before his surgery, he began feeling down, but this only works in the after surgery when he had trouble with mobility and concerns about returning to work as a construction worker. He found an oxycodone helped numb his emotional pain. Again, important to think about the motivation for substance use or substance misuse. And he reveals that in his 20s, he was physically dependent on hair when has been in remission for 30 years. You want to ask more about his prior substance use and think about this have potentially been avoided if his surgeon had known about his hair on use in his 20s. You guys could ask about other substance use which he denies, but probably substance use certainly is not uncommon. After further discussion, you diagnose Mr. K with opioid use disorder or OUD and discuss treatment options as he states he wants to stop using oxycodone. As terrible body aches, vomiting, diarrhea, and chills each time he's attempted to cut down on his own. After discussion about treatment options, you agree to treat his OUD with buprenorphine, not oxone, which I'll refer to from here on out as buprenorphine. You also discuss sending routine blood work to evaluate his liver function, but not as the condition of starting buprenorphine. You identify symptoms of depression ongoing for four months, including low daily mood, anhedonia, low energy sleep onset and insomnia, weight loss of 10 pounds and constant guilty reminations about past mistakes. He's been isolating himself at home and tells you that his family and friends have commented on this. He does not feel of his energy. He has the energy to return to work. He denies manic or hypomanic symptoms now are in the past or any psychophic symptoms. On mental status exam, you can found him to be depressed, dysphoric, and have evidence of some psychomotor slowing. As neurohomsidal or suicidal ideation, he says his wife and children hope that he can feel better and that he wants to get better so that they don't have to worry about him, which he identified as a protective factor against suicide. So our first question is, does the knowledge about Mr. K's OUD impact how you think about his mood symptoms? So keep in mind that both opioid intoxication and opioid withdrawal can look like depression. So you can see here some examples of common symptoms that may overlap with depression. Some reasons to suggest, in this case, a primary mood disorder are these prior episodes of depression that began in his 20s. Remember the mean age of onset of depression is mid-20s. About 30 to 50% of people with one episode of major depression will have a recurrence in their lifetime. And then the risk of future depressive episodes increases by 16% for each successive episode. So it's greater than 80% after three episodes. So much more likely after having three episodes to have her friends. Prior to depressive episodes occurred in the absence of substance misuse, incurrent depressive symptoms actually began prior to his reported onset of opioid misuse. So in this case, it's possible that he may have been self-medicating this recurrence of depression with opioids. After a lot of thought, he believed that he meets criteria for major depressive disorder with current and addition to a diagnosis of opioid use disorder. The second question then is, how should you treat his depression or should you treat his depression? So several clinical trials of a dilated pharmacotherapy for depression and patients with opioid use disorder. The data suggests that antidepressant treatment is effective for improving depressive symptoms. And some studies suggest both depression and substance use improve an improvement in substance use as less consistent across studies. Lack of depression treatment carries risks. So for functioning, and not being able to go to work or participate in his family activities, or things like serious risks like suicide. Doctors consider when weighing a risk versus benefits of initiating antidepressant medication include the severity of the depression. So if it's more severe, it may warrant a more intensive treatment or a different type of treatment environment, what sort of past treatment trials has he had and had a response or failures to go more but medical conditions and potential medication interactions. Treatment options for major depressive disorder include, and we'll think about this from two different perspectives. One is pharmacotherapy and psychotherapy. So selective serotonin reuptake inhibitors or SSRIs and select serotonin and neuropinephrine reuptake inhibitors or SNRIs are really the first line treatments for MDD. And this is primarily due to the favorable safety profile. They're generally well tolerated. Some do affect the hepatic P450 system. So there are some potential drug interactions with specific medications. And some medications you want to monitor blood pressure, especially with the SNRIs and particularly with phenyl vaccine. Press cyclic-inter presence or TCA's are another example of pharmacotherapy or depression. These medications though are conjure indicated in patients with cardiac induction delays and it can be fatal in overdose. There is some positive evidence for treating depression and patients with comorbid opioid use disorder if you were on methadone maintenance. Monomine oxidase inhibitors are another of their pharmacotherapy. These do require dietary restrictions and washout periods when switching to or from another antidepressants. And then there are several other antidepressants that don't fit into these categories like bupopreon, retasipine, trasidone and the phazidone, or volazidone. And then again, psychotherapy of course, a treatment option. Evidence-based psychotherapy is for depression include cognitive behavioral therapy and interpersonal psychotherapy. You consider having Mr. K return after four weeks with the assumption that you'll be absent from non-prescribed opioids and taking only buprenorphine as prescribed. But you decide not to wait on depression treatment. You give in your diagnosis of MGT in addition to OUT. He also reports that while he is never attempted to a Sci-Fi, he has had suicidal thoughts and this has been fights debilitating and prior to press of episodes. So the value of diagnostic clarity with abstinence should be way with the evidence for an independent disorder that is impacted in function and perhaps substance use. You decide to prescribe extended release buprenone as Mr. K has responded to this in the past. You check for potential medication interactions with buprenorphine and learn that there are none. Buprenorphine is metabolized by the three A4 isol enzyme. Some inhibitors of three A4 include Fluoxetine and fluoxamine but not buprenone. Due to the sealing effect of buprenorphine though, this with Fluoxetine and fluoxamine is not thought to be clinically significant, but it should be monitored and discuss with patients if prescribing at three A4 inhibitor as this may increase the blood level of buprenorphine. You discuss the possible side effects of buprenone with Mr. K and that it can take about four weeks to see the full treatment effect. You discuss plans for at home buprenorphine induction and follow up on appointments. You discuss involving his wife to maximize his support system and you discuss a therapy referral with Mr. K. And just as a note, in some cases, four psychiatric providers, the same provider, can sometimes provide the therapy, important depression and substance use, but sometimes individuals may need two different therapists. So may need a prescriber and then a therapist that's focused on depression and a therapist that's focused on substance use. All right, so it's thought about depression, co-morbidity and how to treat opioid use disorder and co-morbid major depressive disorder. And now we'll think about treating PTSD. So Ms. M is a 28 year old woman who comes to you requesting buprenorphine for the treatment of OUD. She reports that she was first prescribed oxycodone two years ago after a fall in which she fractured her arm requiring surgical intervention. About a month later, she fractured her jaw again after a fall receiving another, that which resulted in her receiving another prescription for oxycodone. And since then, she's had several other injuries and aches and pains for which she has taken oxycodone. She reports that initially the oxyes were magic pills, not only treating her physical pain, but helped her stay numb and checked out. However, she tells you that over time, she began to need increasing doses of oxycodone to achieve the same effect. She describes using more than she planned, trying to cut back being unable, symptoms of opioid withdrawal when she tried to stop, prebings that she describes as being impossible to resist, and says that she is in financial trouble because of the amount of money she spent on oxycodone. She's also recently fired from her jaw. However, she tells you that over time, she's began to need increasing doses of oxycodone to achieve the same effect. She describes using more than she planned, trying to cut back but then being unable to, symptoms of opioid withdrawal when she's tried to stop, prebings that are impossible to resist, and that she's in financial trouble because of the amount of money that she spent on oxycodone. She was also recently fired from a job due to repeated absences. She says I was out getting high. She's using about 150 milligrams of oxycodone per day, orally. She reports wanting to stop using oxycodone, saying that it's ruined her life, and that's her that you can prescribe you for noticing. So you diagnose her with OUD, and believe that Vuprenorphine is a good treatment option for treating her OUD. However, you begin to wonder about her aches and pains and the many fractures that she's purported, given that she's only 28 years old. You ask her more about the circumstances leading to her injuries. She opens up to you and a revealed that she's been in a domestic violence relationship for four years, and that her injuries are the result of her physical abuse. She says that with the help of friends, she was able to leave the relationship and is currently living with a friend in a safe environment. You begin to wonder though, if she might have post-traumatic stress disorder or PTSD. So PTSD and substance use disorder and commonly occur. The lifetime prevalence of PTSD and in patients with SUD has been found to be between 36 and 50%. Some studies indicate exceptionally high comorbidity of PTSD and OUD, and this is relative to alcohol and other drugs, with around the third of those with OUD also having PTSD. Among veterans, psychiatric diagnoses, particularly PTSD, were associated with increased risk of receiving opioids for pain, high risk of opioid use, and adverse clinical outcomes. Trauma and stress are risk factors for many forms of sexual pathology, including depression, anxiety disorders, and substance use. When evaluating with the substance use disorder always be alert for possible PTSD. So there are screening tools and while they're not diagnostic, they can be helpful in indicating the presence of symptoms consistent with PTSD. If positive and more thorough assessments should be conducted, the primary care PTSD screen is commonly used in primary care settings and has reported a sensitivity of between 70 and 78%, and a high specificity of 87-92%. A list of PTSD screens, including the PCPTSD, can be found on the US Department of Veterans Affairs website. So Mrs. M. Scring positive for PTSD on the PCPTSD screening. So you review that the SMBIC criteria for PTSD to see if she meets the criteria. So the DSMBIC criteria for PTSD include the following and they need to last longer than one month to meet the PTSD diagnosis, and also pause significant for the rest of our paradigm. So the first is exposure to actual or threatened death, serious injury or sexual violence, and at least one of the following ways. So directly experiencing the traumatic event, witnessing the event as it occurred to others, learning that the traumatic event occurred to a close family member or friend, experiencing repeated or extreme exposure to aversive details of the traumatic event. The second criteria is presence of one or more of the following intrusive symptoms, associated with that event. So recurrent involuntary and intrusive distressing memories, recurrent distressing dreams, associated reactions or flashbacks, intense or prolonged psychological distress at a exposure or internal or external cues that symbolize or resemble an aspect of the event and market physiological reactions to internal or external cues that symbolize or resemble that event. And then third is the persistent avoidance of stimuli associated with the traumatic event, beginning after that traumatic event, with one or more of them or both of the following. Avoidance of or efforts to avoid distressing memories, thoughts or feelings about the event, so it can be one or both of those. And then negative alterations and cognitions and mood, as it evidenced by two or more of the following, being unable to remember an important aspect of the event, persistent and exaggerated negative beliefs or expectations about oneself, others or others, and the other thing that is important is that the event is a very important aspect of the event, and the event is a very important aspect of the event. And the event is a very important aspect of beliefs or expectations about oneself, others or the world, persistent distorted cognitions about the cause or consequences of the traumatic event that lead to blaming self for others, persistent negative emotional state, markedly diminished interests or participation activities, feelings or detachment or estrangement from others, and persistent inability to experience positive emotions. So it needs to have two or more of those symptoms alterations in cognition and mood. And then last, market alterations in arousal and reactivity associated with the event, as evidenced by two or more of the following. Irritable behavior in angry outbursts, typically expresses verbal or physical aggression toward people or objects, right plus or destructive behavior, hypervigilance, exaggerated startle response, problems with concentration and sleep disturbance. There is overlap between symptoms of PTSD and symptoms of drug or alcohol intoxication or withdrawal. Hyperarousal symptoms of PTSD, like the problems with concentration, sleep disturbance and irritability, can be caused by opioid intoxication of withdrawal. Negative alteration in mood or cognition, like feelings of being detached, diminished interest in activities, could also be caused by opioid use. Inclusion, symptoms like recurrent dreams, images or flashbacks, though are relatively specific to PTSD. To distinguish those symptoms that may be common to both, you want to ask about the relationship of the signs to the actual traumatic event that occurred to the person or to post-family member or family. If the symptoms started shortly after traumatic experience or are linked to distressing reflections of that event, the symptoms are likely secondary to PTSD. So back to our patient Ms. M with PTSD, you diagnosed her with PTSD in addition to OUD. And now you screen her for suicide. She denies any thoughts that life is not worth living. She has never attempted suicide or made a plan or had any intent. And she's hopeful about the future has many protective factors, including her religion, family and friends. So you'd believe her are a cure for suicide slow. The prevalence of suicidal behavior in patients who have been exposed to trauma is significantly greater among those with a diagnosis of PTSD and comparison to other diagnosis. And PTSD is associated with an increased incidence of suicide, attempted suicide, and prior inference to a suicidal ideation. So controlling for other psychiatric disorders, including depression, weekend, this association, but it did not eliminate it. So now you want to think about how to treatment stem. So a few different questions, how is PTSD treated? Should you treat her opioid use disorder first? And while treating her PTSD worse than her opioid use disorder, some questions that you might have now that you have arrived at these two different diagnosis. So treatments for PTSD can include the following. So psychotherapy, there are evidence-based psychotherapy specifically for PTSD, including CBT, as well as exposure-based CBT, CBT for PTSD involves a combination of psychoeducation, relaxation and anxiety management techniques, cognitive techniques, and then imagined and real life exposure to trauma related stimuli, and then relapsed prevention. PTSD treatment can also include psychotherapy, meta-analysis and several randomized controlled trials generally to support the superiority of SSRIs and SNRIs over placebo for non-combat related PTSD. There has been less work done on the treatment of PTSD and concurrent substance use disorder in terms of pharmacotherapy. The data also for SSRIs and combat related PTSD is more mixed. The most recent APA practice guideline, though do recommend SSRIs as a first-line treatment for PTSD. TCAAs are tricyclic antidepressants and monomine, oxidase inhibitors show improvement in intrusive and depressive symptoms, but SSRIs are generally considered first-line and part at least due to their superior safety profiles. Praiseson has also been found to be effective for PTSD, especially when the patient experiences nightmares and sleep disturbances and in particular populations. Other medications with some efficacy, particularly in open-label trials or reports include medications like beta blockers, lithium, phonodine, benzodiazepines, retazopine and methazadone. And adjective treatments with second-generation antipsychotics and patients who've partially responded to an SSRIs and RIs have also shown to be effective. So relatively little data exists addressing the treatment of comorbid PTSD and OUP. Seeking safety is one of the most widely studied non-exposure-based treatments for co-occurring PTSD and substance abuse disorder. Seeking safety is a standard CBT treatment with both safety and trauma and substance use components in each session. Seeking safety has shown positive results and PTSD symptoms and SUV in several studies. It's been shown to be more effective than standard community care for both PTSD and SUV. However, it has not demonstrated better outcomes than relapse prevention, which is a substance use disorder only treatment, or superior outcomes compared to health education. In addition to non-exposure-based treatments like seeking safety, several treatment protocols have recently involved exposure-based treatments for those with comorbid PTSD and SUV. Six studies were found to have positive and notably no negative outcomes. The studies did modify the classic exposure for PTSD in different ways and the flexibility in classic exposure may be a key component. Evidence for pharmacologic approaches for treating PTSD and SUV is limited primarily to alcohol use disorder. So the second question then, should I treat her OUP first? So historically individuals were treated for a substance use disorder, and then treatment of PTSD was deferred until the substance use disorder has resolved or improved, but this approach is really problematic because symptoms of PTSD may derive relapse for the substance use disorder. So studies suggest that usual treatments for OUD are effective for OUD, but do not impact PTSD symptoms. And then the third question is, while treating her PTSD worse on her OUP, and more evidence has shown that treatments for PTSD like exposure therapy are not harmful to individuals with substance use disorder, and PTSD can lead to improvement in SUV outcomes. Integrative treatments for PTSD and SUV then are recommended. So after a discussion with Ms. M, you decided to refer her to a trauma treatment program specifically for women with SUV and a history trauma sequence A-P. In addition, if you weren't arguing, she just started on a search ruling 50 milligrams, which was titrated to 100 milligrams because she continued to have depressed mood and sleep troubles after the first six weeks of the 50 milligram treatment. She completes the treatment program and returns to you to manage her due to pornography, and while continuing weekly therapy and medication management with the psychiatrist, she also attends a weekly after-care group. All right, and now moving on to our third case. So Mr. C is a 38 year old divorce man without children living alone employed as a realtor. He comes to you seeking treatment for his substance use disorder. He says he's been misusing opioids for about eight years. He started using the combination oxycodone acetaminathan, but after almost two years, he transitioned a heroin because it was cheaper. He's now using five to seven bags of heroin intravenously daily. He describes tolerance and withdrawal, says he no longer enjoys using it that he's just using it to avoid withdrawal. He reports that his divorce was mainly due to his heroin use and he has isolated himself from his friends. He's been increasingly less productive at work. He denies other drug route while use and he has never had an opioid overdose. He's never received S2D treatment before. He denies any other psychiatric history, but he does report that he struggled in school growing up, noting that he never read a book cover to cover because he would get forward and distracted. He describes significant difficulty in school with sitting still and would often get in trouble with teachers. He says his family would always complain that he was impulsive, frequently interrupting and appearing to be driven like a motor. His mother used to complain that he was constantly losing things, which Mr. C says his ex-wife also used to say. He's been at his current job for 10 years and feels it suits him as he doesn't have to sit at a desk, all day he can make his own schedule, although he often forgets about appointments and then consequently has lost a few clients. He denies any past or present medical problems that is not taking any medications. He denies any medical complications related to IV drug use, like abscesses, but you do test him for HIV and hepatitis B and CD and he's negative for all three. He's interested in starting a buprenorphine maintenance. As his brother who's also used to misuse opioids has done very well on buprenorphine. You plan for an outpatient buprenorphine induction and Mr. C has ultimately maintained on 10 milligrams of the sibling role of buprenorphine daily. Three months in the treatment, he's doing well, not using other opioids and has begun to exercise and it's been more time than his family and friends. He says, "I feel like I'm getting back to him "to my old self." However, he tells you he's having trouble organizing his day, is still missing appointments and a recently lost potential client due to this organization. He asks you if there's anything you can do to help him. You recall he has this history of trouble in school and he wonder if you might have ADHD. So ADHD is a disorder that by definition presents before the age of 12. It's estimated that ADHD symptoms will persist into adulthood in about half, so 50 to 60% of cases. ADHD and substance use disorders do frequently co-occur and adults in SUD treatment have rates of ADHD raining, raining from eight to 33%. So here is a graph showing, so on the left, you see patients with, a substance use disorder with co-morbid ADHD, and on the right, the reverse, so patients with ADHD with co-morbid substance use disorder. A few things to think about why ADHD or why thinking about ADHD is important in this patient population. So for patients with substance use disorder coming in for treatment, why is it important to consider ADHD? So a few different things. There's an earlier onset of a substance use disorder when ADHD is present. There's also a reduced likelihood of going into remission from ADHD symptoms if there's a moderate or severe substance use disorder that develops. There are higher relapse rates for both adolescents and adults in terms of substance use. If from a patient from substance use is achieved, it takes a longer time to achieve it. With, there's more treatment exposure, but the patients do less well on treatment, and there are higher rates of other psychiatric vulnerabilities like conduct disorder and antisocial personality disorder. But how to diagnose ADHD? So the DSM-5 criteria are a persistent pattern of inattention and/or hyperactivity impulsivity that interferes with functioning or development as characterized by either one, so one on this slide and then two on the next slide, one or the other, and it can be both. So the first is inattention, and they need to meet six or more of the following criteria or five or more if it's older adolescents or adults for at least six months. So failing to get close attention to details or making careless mistakes, difficulties sustaining attention in tasks, not seeming to listen when spoken to, not following through on instructions and failing to finish worker duties, difficulty organizing tasks and activities, avoiding or disliking or being reluctant to engage in tasks that require to same mental effort, losing things necessary for tasks and activities being easily distracted by extraneous stimuli and being forgetful and daily activities. So five or more of those to meet the inattention criteria for ADHD for older adolescents or adults. And then the second hyperactivity impulsivity, same number of criteria need to be met, so six or more, but for older adolescents or adults at least five or six months or longer. So fidget with or taps, hands, or feet, or squarms and seats, leave seat when inappropriate, runs, or climbs, and inappropriate unable to play or engage in leisure activities quietly being on the go or acting as if driven by a motor, talking excessively, blurring out answers before a question has been completed, difficulty waiting his or her turn and interrupting or intruding on others. Several of the symptoms need to have been present before age 12 to meet ADHD criteria and several symptoms need to be present in two or more settings. So at work and at home, for example. In terms of screening and self-report instruments, there are some that are available for ADHD. They include the adult ADHD self-report scale or the ASRS. It has about a 67 to 88% sensitivity in 66 to 82% specificity and patients with substance use disorder. The Connor's adult ADHD ratings deal has a 94% sensitivity and 70% specificity in patients with cocaine dependence or cocaine use disorder. And then the Wender Utah rating scale has a 93% sensitivity and 70% specificity in patients with cocaine dependence or cocaine use disorder. Some challenges to diagnosing ADHD in patients with substance use disorder. So there are issues both related to under and over diagnosis. So factors leading to under diagnosis can include things like being unable to recall symptoms before age 12. And thinking about the potential impacts of substances, alcohol opioids and methamphetamine use disorders are all associated with cognitive deficits. Deficits are shown to persist with abstinence and alcohol use disorder. Early on-state cannabis use, so starting less than 17 years old, is also associated with poor, or cognitive performance compared to later on-set. And long-term cannabis use is associated with IQ decline from childhood to mid-life for learning and processing speed and memory and attention problems. Another issue with under diagnosis may be the lack of corroboration from older family numbers, so they may have strange relationships or they don't want their family to be contacted or involved in their treatment. Or their parents may not remember details of their symptoms younger than age 12. In terms of over diagnosis, ongoing substance use disorder can mimic ADHD. So both the acute effects and withdrawal effects may look like some of the symptoms of ADHD. Relying on screening instruments for computer testing alone will not consider the impact of ongoing substance use or other psychiatric diagnoses. The early childhood may have been chaotic and inattentive or impulsive symptoms may be secondary to difficulties at home or lack of structure. They may have undiagnosed learning disabilities that may again look like ADHD that be more of specific learning disabilities. And patients may have a desire to obtain stimulant medications. So some helpful tips from assessing ADHD and patients with SUD. One is to complete a timeline for ADHD symptoms. Think about the onset of symptoms, what types of symptoms and did they change over time? Completing then a timeline for substance use, the onset of use, heavy substance use, when was it problematic and periods of abstinence or reduced use? Determine the presence or absence of ADHD symptoms prior to drug abuse and during periods of abstinence. So if symptoms are not present during abstinence or if they come and go, that would not be consistent with an ADHD diagnosis. So you have Mr. C. E. R. Patient fill out the ADHD rating scale which shows that he has symptoms highly consistent with ADHD based off of his fore. You go through the DSM criteria for ADHD and he appears to meet the criteria for ADHD predominantly inattentive type. Meaning he has more of the intent of symptoms than the hyperactive and pulsed of symptoms. You review a timeline of his symptoms and substance use which reveals that symptoms of ADHD began long before his opioid misuse. He did have a period of daily heavy cannabis use and his mid teens as he felt that cannabis allowed him to slow down and sit still. His symptoms of ADHD also predate his cannabis use and occur during times of abstinence from all substances. So now you ask yourself, how should I treat his ADHD? So there are both non-pharmacological and pharmacological interventions for ADHD. Non-pharmacological interventions, there's a wide range that include behavioral therapies, academic interventions, family therapies, and care coordination, all of which are well studied in children, but not as well studied in adults. And then pharmacologic interventions can really be broken down into two categories, stimulants and non-stimulant medications. Stimulants are really first-line treatments because they demonstrated efficacy in numerous double-blind placebo control trials. And among the stimulant treatments, they're really two main categories. So medical, phenidate, and amphetamines. And among both of those categories, we have short-acting and longer-acting agents. Among non-stimulant medication treatments, we have ademoxetine and bolognesesine. They're both non-stimulant medications that are FDA approved for ADHD and adults. And other medications that have demonstrated some efficacy, but do not have FDA approval for ADHD treatment in adults like the propion, Alpha agonists, so one, thicine, clonidine, both of those are for for children and adolescents, but not for adults. And then adafinil tricyclic antidepressants and MAOIs have demonstrated some evidence for treating ADHD, but do not have FDA approval. The literature treatment for ADHD and SUD is still limited, but the emerging trend is that medications that are effective for adult ADHD are likely to be effective for adults with both ADHD and SUD. Though the therapeutic benefit may be less, the available evidence supports the use of stimulants over non-stimulants for adult and pediatric ADHD. So a few questions that we wanna ask ourselves at this point as we're thinking about treating our patient who has co-morbid opioid use disorder and ADHD. So the first question is, do we have to worry about making people high and precipitating relapse if we prescribe stimulants? How much do I have to worry about the version if I prescribe stimulants? What are the best medications or formulations to prescribe? And if I do prescribe a stimulant, how should I monitor for a misuse? So their first question, thinking about rate of drug uptake into the brain and how that affects the high. So these are some graphs that show. the uptake and the striatum of IV cocaine, the far left IV methylphenidate, and then oral methicinidate, methylphenidate on the far right. So we see that cocaine and IV methylphenidate both produce a high, but that oral methylphenidate does not or at least much less than the IV methylphenidate does. So this slow brain uptake of oral methylphenidate allows for effective treatments. It reduces that high and allows for more therapeutic effects. There was a systematic review of 21 studies that had more than 100,000 individuals, and it showed that non-prescribed started to start a brain. So then our second question is how much do I worry about the version? There was a systematic review of 21 studies that had more than 100,000 individuals, and it showed that non-prescribed stimulant use was about five to 9% among grade school age students for eternity or sorority members. Those were lower GPA, those who were prescribed immediate release as compared to extended release stimulants, and those who reported ADHD symptoms. The reasons for misuse or diversion in this large systematic review included to be able to concentrate and prove alertness to get high or to experiment with stimulants. Another survey of 10,000 adults, so age 18 to 49, showed about 8.1% reported lifetime non-medical stimulant use. This is less than pain medications, which sits at about 25% in the survey. Sedatives are tranquilizers around 16% and sleep medications around 10%. In this survey, the most likely non-medical stimulant use was actually immediate release methylphenidate, followed by mixed amphetamine salts, immediate release, followed by mixed amphetamine salt, exenter release, methylphenidate exenter release, and then last was Liz Decenthetamine, which is amphetamine prodrug, meaning it needs to be orally ingested to be active. In another study of more than 200,000 adult substance use disorder assessments, 1.8% reported prescription stimulant non-medical use, which was associated with increased methamphetamine and cocaine use, and appeared to have more biopsychosocial problems. 1.6% reported stimulant prescription medical use, which is associated with lower illicit stimulants. And in terms of thinking about what medication to choose, so there are no data on comorbid ADHD and OUD specifically to guide treatment. However, based on studies with ADHD and other substance use disorders, there are a few things that we should consider here. So maybe atomoxetine should be considered as a first line treatment. It has particularly shown to be helpful for absent individuals with alcohol use disorder and those with a tick disorder. There are high drop out rates in studies with comorbid cocaine use disorder and ADHD, looking at atomoxetine as a potential treatment. Repoprione, remember, is off label, but is sometimes used to treat ADHD. Has efficacy in cigarette smoking cessation, which has FDA approval for, may be useful in comorbid mood disorders, which is FDA for depression. And there are some open label studies that show improvement in the three, so ADHD, substance use disorder, and mood outcomes. One for seeing the daphnellin tricyclic antidepressants might also be considered if stimulants in particular are trying to be avoided, or if these other two medications that atomoxetine and bupoprione, that there is a particular reason why those would be avoided, or if they have been tried before and not well tolerated for phthalatremants. And when thinking about stimulants more specifically, so prescribing for patients with SUV is complex and requires close monitoring. Using extended release formulations of stimulants, like the Ouros, methylphenidate Ouros, is osmotic release oral system, the dextrometthalphenidate extender release, and make the methamphetamine salt extender release, or the methylphenidate sustained release. Those are all example of extender release formulations of stimulants, which have lower misuse or abuse liability. You wanna monitor closely both the ADHD symptoms and any patterns of alcohol or drug use. If the substance use disorder is severe, you may refer for intensive intervention before starting the stimulant medication. And you may need to avoid stimulants if they have a current use disorder on prescription stimulants, or have a high risk of diversion of medication. So if you know that they have sold their medication in the past, for example. And there are of course non-pharmacologic approaches like we talked about that we would wanna consider certainly using adjunctively at least. For substance use disorders specifically, there's group and individual psychotherapy, family therapy, four adolescents and young adults, and then four ADHD considering cognitive behavioral therapy and organizational coaches. So monitoring when prescribing medications with misuse potential. So I'm a use diversion or use disorder or inherent risk of prescribing all control medications. All patients prescribed controlled substances should be assessed that each visit for signs of misuse or addiction. And you wanna evaluate patients using a kind of matter of fact, tone or approach and a non-threatening manner. Some red flags in this situation where you're prescribing controlled substance for a patient with a substance use disorder would be symptoms of intoxication or symptoms associated with heavier use like more agitation, psychosis, panic attacks or palpitations, demands for specific and usually short acting medications like immediate release or methamphetamine. So saying that extended release doesn't work for me. Repeated loss pills or bottles, discordant pill counts, escalation of doses. It's a particularly quick escalation of doses, excessive preoccupation with securing medication and then having multiple prescribers. Those are all red flags when prescribing controlled substance in this patient population. So your treatment plan now for Mr. C. You discuss ADHD treatment options. Here, reports feeling a little nervous about the idea of stimulant medication given that misusing pills is what got me into this mess in the first place. What he says, so you discuss a trial of atomoxidine. You confirm there's no interaction between atomoxidine and his buprenorphine. You start Mr. C. D. on atomoxidine 40 milligrams orally once daily and plan at follow-up. All right, so some conclusions, substance use disorders and other psychiatric illnesses frequently occur. When treating someone for substance use disorder, it's important to be mindful of the likelihood of psychiatric comorbidities. Screening instruments can assist in identifying those that warrant further investigation of a psychiatric comorbidity. And data thus far support the need for concurrent therapy directly targeting the substance use disorder in addition to the treatment of the co-occurring psychiatric comorbidity. Then there are a few slides of references that I will put through. a few final things. So I'd like to inform you of two resources offered through PCSS that may interest you. First, PCSS's mentor program is designed to offer mentoring assistance to those in need of more one-on-one interactions with one of our colleagues to address clinical questions. You can request a mentor from our mentor directory or we're happy to pair you with a flag. To find out more information, please visit our website using the web link noted on this slide. Second, PCSS offers a discussion forum, which is comprised of our PCSS mentors and other experts in the field to help provide prompt responses to clinical cases or questions. We also have the mentor on call each month. This person is available to address any submitted questions through the discussion forum. You can create a new login account by clicking the image on this slide to access the registration page. And this slide simply notes the consortium of lead partner organizations that are part of the PCSS project. And finally, please reference this slide for our contact info, website and Twitter and Facebook

psychiatric comorbidities

diagnosis

treatment

substance use disorders

prognosis

major depressive disorder

post-traumatic stress disorder

ADHD

individualized treatment plans