Welcome to the American Osteopathic Academy of Addiction Medicine's Learning Management System. This presentation is on two closely intertwined psychiatric disorders, co-occurring disorders and substance-induced disorders. My name is Dr. Gregory Landy and I will be your narrator throughout this presentation. In preparing and narrating this particular presentation, let me assert that I have no financial or ethical disclosures to make. As I mentioned at the outset, this particular presentation will explore two common clinical entities, co-occurring disorders and substance-induced disorders, both of which are closely related and intertwined. This presentation will also explore the factors contributing to co-occurring and substance-induced disorders. And finally, after the conclusion of this presentation, you will have a better understanding of the diagnostic criteria for both. So why should we spend any time reviewing co-occurring disorders? Well, this slide gives the broadest understanding of why this particular presentation is worth your clinical time. So as it states, compared with the general population, individuals with a substance use disorder are roughly twice as likely to suffer from mood and anxiety disorders. And the opposite is also true. This picture graphically illustrates the epidemiology of co-occurring disorders. This SAMHSA illustration looks at past year substance use disorder and mental illness among adults aged 18 or older. As you can see, the large round circle, 36.4 million individuals, mental illness with no substance use disorder. The smaller pale yellow circle, these are individuals with a substance use disorder and no diagnosed mental illness, constitutes 10.8 million. The overlapping orange area is the subject of this presentation. These are individuals diagnosed with a substance use disorder and mental illness. And this constitutes 8.2 million individuals based, again, on this SAMHSA data. This slide once again illustrates the importance the American Osteopathic Academy of Addiction Medicine places on understanding co-occurring disorders. Comorbid psychiatric illness and substance use disorders, when combined overall, have a much more poor prognosis. In particular, there are worse treatment outcomes for both disorders, higher relapse rates for the substance use, shorter time to relapse of substance use, and overall more hospitalizations, which of course has both social and economic implications. Those with co-occurring disorders also have a poor quality of life. And let's not forget that there's a high risk of suicide magnified when both a co-occurring mental disorder and a substance use disorder exist in the same individual. And this is particularly true among those with a bipolar disorder diagnosis. The epidemiology of co-occurring disorders, situations where your patient has both a substance use disorder and a mental illness, clearly implies that clinicians should keep in mind that both disorders necessitate a comprehensive approach that would help identify and evaluate both of them. But the clinical realities also suggest that even with the most prudent, careful, and thoughtful evaluation, it can be very difficult to differentiate co-occurring disorders from independent and substance-induced disorders. In some cases, the only way to do this is to recommend, encourage that the individual reduce or abstain from their preferred substances, which can not only be very difficult, but it can also lead to delays in treatment for the psychiatric symptoms that can, of course, have some serious consequences. So what contributes to the incidence of co-occurring disorders? Well, of course, there are many possible ideologies. And in this presentation, we will discuss in detail many of them. But from the broadest perspective possible, from a stratospheric viewpoint, these two statements on this slide sum it up. Drug abuse may bring about symptoms of another mental illness. For example, there appears to be an increased risk of psychosis, invulnerable marijuana using young people, which suggests this possibility. And on the other hand, mental disorders can lead to drug abuse, sometimes posited as a means of self-medications. Patients suffering from anxiety or depression may rely on alcohol, tobacco, and other drugs to temporarily alleviate their symptoms. And again, we'll be discussing this in more detail. Teasing apart the differential diagnosis among individuals with a substance use disorder and a mental illness and adding in a substance use disorder is a particularly difficult situation, particularly when the individual is still actively using a substance. Further complicating the differential diagnosis is that the symptoms of intoxication and withdrawal may resemble the symptoms of mood and anxiety disorders, causing further confusion. The DSM-5 provides diagnostic criteria for substance-induced disorders, which adds a level of clarity and distinction. And one important point to remember is that to diagnose a mood or anxiety disorder, the full syndrome must be established prior to the use of a particular substance. So let's take a moment and drill down into one common scenario where psychiatric disorder and substance use overlap and commingle. And this is with trauma. According to the National Center for PTSD, seven or eight out of every 100 people will experience post-traumatic stress disorder in their lifetime. Some studies indicate a particular high co-occurrence of PTSD and opioid use disorder. The study cited here found that nearly a third of those with opioid use disorder have PTSD. And people with PTSD develop drug addiction at three times the national average. Now again, there may be many reasons for this, but for the clinician, it's important to keep these numbers in mind. Among veterans, it's been estimated that up to 30% of combat veterans suffer from PTSD. Among veterans, psychiatric diagnoses, particularly PTSD, were associated with an increased risk of receiving opioids for pain, and that high-risk opioid use can have adverse clinical outcomes. It's also been noted that 60% to 80% of veterans with PTSD also have an alcohol use disorder diagnosis. The importance of clinicians recognizing the relationship between individuals having a post-traumatic stress disorder and a co-occurring opioid use disorder was recognized by SAMHSA when they assembled an expert consensus panel to develop pharmacologic guidelines for treating individuals with PTSD and co-occurring opioid use disorders. The resulting widely available pharmacologic guidelines for treating individuals with PTSD and co-occurring opioid use disorders was empaneled with three osteopathic members, including the narrator of this presentation. The American Osteopathic Academy of Addiction Medicine encourages clinicians to routinely screen for tobacco use among their patients. And this slide gives some indication of why that's important. Among individuals with an alcohol use disorder, those individuals find nicotine more reinforcing, and they will have more nicotine dependence criteria and withdrawal symptoms. There's also evidence that many people in substance abuse treatment are interested in smoking cessation, and they're interested in doing that simultaneously with their other treatments. But there remains, in the clinical literature and in clinical practice, a debate about the best time for tobacco treatment to begin in the context of the individual's other substance use disorders. But the bottom line should be, there should be, at some point in the clinical continuum of care, a serious conversation between the parties about the time to quit tobacco use. And it's also interesting that in outpatient treatment programs, the incidence of smoking can be rather high. So let's now pivot to a far more detailed discussion of substance-induced disorders. And let's begin with the DSM-5 criteria for helping us differentiate these disorders. This disorder represents clinically significant symptomatic presentation of a relevant mental disorder. And you have developed from your history in physical or labs or a combination of both that the disorder developed during or within one month, let me repeat, during or within one month of substance intoxication or withdrawal or taking a medication. It must be kept in mind that the involved substance or medication is capable, independently of producing the mental disorder that you're looking at. And finally, DSM-5 always has kind of a footnote that the disorder that you're looking at is not better explained by an independent mental disorder. It's important to keep in mind that the full mental disorder persisted for at least one month after cessation or acute withdrawal or intoxication or taking the medication. The disorder did not occur exclusively in the context of delirium. And as always with all psychiatric disorders, there must have been significant distress or impairment in function to qualify as a psychiatric disorder. This slide provides a useful overview of diagnoses that are associated with a particular class of substance. I standing for intoxication, W for withdrawal, and P for persisting effects. As you can see, both alcohol and use of sedatives can have persisting neurocognitive disorder diagnoses. And anxiety, depression are common in both the intoxication and withdrawal state of many substances. So again, refer to this particular slide just as an overview of the particular diagnoses that can be associated with particular substances. An individual with an alcohol use disorder may also have depression, which can result from two potential scenarios. One, it can be substance induced. The second, it may be an independent psychiatric disorder. As difficult as it might be, it's important for clinicians to make every effort to differentiate between these two situations because they have different prognoses and different clinical pathways for treatment. Intoxication and withdrawal, if they are contributing to or the etiologic origin of the depression, for example, those may resolve without resort to any medications. Antidepressant disorders, an independent major depressive disorder, of course, may very well require antidepressant medications. So as you can see, errors in diagnosis can lead to medical mismanagement, particularly with regards to the implementation of pharmacotherapy, which may or may not be necessary, along with its intended side effects. A study cited on this slide was a longitudinal research of 250 patients with alcohol, cocaine, or heroin use disorders that were followed for up to 18 months. What the researchers reported is that individuals with substance induced depression significantly predicted a post-discharge use of alcohol, cocaine, and heroin. And of those achieving remission, independent major depression predicted relapse to alcohol and cocaine. So let's now transition to a more in-depth discussion of substance induced disorders. And we'll begin that journey with substance induced depressive disorders. So as always, let's begin with a review of the diagnostic criteria for both the primary psychiatric disorder and its counterpart, its close cousin, if you will, the substance induced version. So on this slide, let's look at the major depressive disorder diagnostic criteria as enumerated in DSM-5. As you recall, diagnosis requires five or more of the following symptoms that have been present during the same two week period, which represent a change from previous functioning. At least one of the symptoms is either a depressed mood or a loss of interest or pleasure or anhedonia, as it's sometimes referred to. Those five criteria include depressed mood most of the day, markedly diminished interest or pleasure in activities, a significant weight loss, which DSM-5 goes on to further explain as a change of more than 5% of body weight in a month. Of course, not due to conscious effort of the person to lose weight. Changes in the individual's sleep patterns that can include insomnia or hypersomnia for nearly every day during that two week period. There should be some change in motor activity. It can be psychomotor agitation or retardation, change in their energy levels, cognitive feelings of worthlessness or guilt, diminished ability to think or concentrate, and recurrent thoughts of death. And again, as always, the symptoms cause distress or impairment. So let's compare that with the diagnostic criteria for a substance-induced depressive disorder. And again, there are some similarities. First, there's a prominent and persistent disturbance in mood characterized by depressed mood or diminished interest or pleasure. And there's evidence from your history and physical or laboratory findings or both that the symptoms in criterion A of a major depressive disorder developed during or soon after substance intoxication or withdrawal, and that the substance that you're concerned about can actually produce those symptoms in the criterion A. Of course, the disturbance is not better explained by a depressive disorder that is not substance-induced. And there are some typical clues that may help you differentiate a substance-induced disorder. The symptoms preceded the onset of the substance use. The symptoms persist for a substantial period of time after cessation or withdrawal, typically a month. Or there is evidence of an independent depressive disorder, for example, a history of recurrent non-substance-related episodes. And of course, the disturbance does not occur in the presence of a delirium. For the sake of redundancy, let's review, again, from a slightly different perspective, some of the factors to keep in mind when diagnosing substance-induced depressive disorders. You will need evidence from your history in physical or labs or both indicating the individual has used a substance, may be intoxicated, or in the throes of withdrawal. Substance-induced disorders typically start within days to weeks after substance use or withdrawal. Those symptoms may last for days after use and can persist for weeks, much of which is related to the half-life of the particular substance that you're looking at. Of course, primary depressive disorders may precede the onset of substance intoxication or withdrawal, and they may occur during periods of abstinence. And depressive symptoms may continue while the substance use continues, which of course adds a degree of confusion to your diagnostic picture. So what is the prevalence of a substance-induced depressive disorder? Well, it boils down really to the research methodology employed to answer that particular question. In the first cited study on this slide, the lifetime prevalence of substance medication-induced depressive disorder is less than 0.5%, just barely over 0.25%. NESARC, which uses a different sampling methodology, looked at the 12-month prevalence of independent mood disorders and reported 9.21% in their sample, while the prevalence of substance-induced mood disorders was less than 1%. A study conducted in 2013 by Langus and others looked at patients with substance use disorder and reported different conclusions. In their study, they found that 42 had both a substance use disorder and a major depressive disorder. Nearly half had a lifetime history of an independent major depressive disorder. Slightly a quarter had a history of substance-induced depressive disorder only. And slightly over a quarter had a history of independent major depressive disorder and a substance-induced depressive disorder. Now if we look at those with independent major depressive disorder, in contrast to those with a substance-induced depressive disorder only, we find that they had fewer years of education. And once again, tobacco use disorder rears itself. They smoke more cigarettes per day. And they had shorter duration of their particular depressive episodes. Again, differentiating a substance-induced depression from a primary diagnosis of major depressive disorder is difficult. But there are some research clues that can give some guidance. Individuals with substance-induced depression only did not have an increased family history of major depressive disorder. And major depressive episodes are not observed at higher rates in their children, which of course underscores the importance of a focused social family history. And patients with substance use disorder, both primary and substance-induced major depressive disorder, unfortunately predict future episodes of depression. A research study reported certain demographics that are associated with substance-induced depressive disorders. This particular study identified that being male, African-American, having at most a high school education, lacking health insurance, lower family income, a greater family history of substance use disorders and antisocial behavior, stressful events in their life, and reported feelings of worthlessness, sleep problems, and thoughts of death were more likely among those with a substance-induced depressive disorder. And unfortunately, they are less likely to report their mood, which means they are less likely to receive treatment. So let's now turn our attention to substance-induced bipolar disorders, again, following the same format, looking at the diagnostic criteria and certain other related epidemiologic factors. So let's begin by reviewing DSM-5's diagnostic criteria for a bipolar I disorder, the manic episode. Here we have a distinct period of abnormally and persistently elevated expansive or irritable mood and abnormally or persistently increased activity or energy lasting at least one week and present most of the day nearly every day or any duration if hospitalization is necessary. During the period of mood disturbance and increased energy or activity, you need three or more of the following symptoms. You need four of the following symptoms if the mood is primarily irritable. Those criteria include inflated self-esteem or grandiosity, a decreased need for sleep, more talkative than usual or pressured speech, flight of ideas, or they feel their thoughts are racing, they're easily distractible, they have an increase in goal-directed activity, and they have an excessive involvement in activities that have a high risk potential. And as always, the mood disturbance is severe enough that it causes marked impairment in the individual's social or occupational functioning or in the need to hospitalize them to prevent harm to themselves or others. And of course, the event is not attributed to the effects of a substance. Now, the bipolar II disorder is a lighter version of bipolar I, hypomania. So let's look at the criteria. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, an abnormally and persistently increased activity or energy lasting four consecutive days. Keep that number in mind, it's a differential point from bipolar I. During the period of mood disturbance and increased energy and activity, three or more of the following symptoms are required, or four if the mood is only irritable. The episode is associated with an unequivocal change in functioning that is uncharacteristic of that individual when they are not symptomatic. Their change in mood can be observed by others, but the episode is not severe enough to cause marked impairment in social or occupational functioning, or to require hospitalization. And once again, of course, the episode cannot be attributed to the use of a substance. Now at this point, you might begin to see some similarity in how DSM-5 approaches substance-induced diagnoses. So in terms of a substance-induced bipolar disorder, DSM-5 requires that there be a prominent and persistent disturbance in mood that's characterized by elevated, expansive, or irritable mood with or without depressed mood, remarkably diminished interest or pleasure in almost all activities. And here we see that there must be evidence from the history and physical examination or laboratory findings or both that the symptoms in Criterion A of bipolar disorder develop soon or during substance intoxication or withdrawal. And the involved substance can actually produce those symptoms listed in Criterion A. The disturbance is not better explained by a bipolar or related disorder that is not substance-induced. Such evidence of an independent bipolar or related disorder could include the following. Symptoms precede the onset of substance use. The symptoms persist for a substantial period of time, about a month, after the individual stops using the particular substance or the withdrawal phase is passed. And of course, the disturbance does not occur exclusively during a delirium. In terms of prevalence, there is really nothing to indicate substance-induced mania or bipolar disorder. However, it's important to keep in mind that persons with an alcohol use disorder have about a 3% risk for bipolar disorder compared to a 1% risk in the general population. As might be expected, different substances have different courses when it comes to how they manifest themselves. PCP-induced mania initially may present as a delirium. And then as the course progresses, become manic or mixed state. It typically happens within hours to days. On the other hand, a stimulant-induced mania or hypomania can have its development within minutes to hours after the use of the particular stimulant. And there are typically brief episodes that resolve in one to two days. Less commonly reported substances that can induce mania are listed on this slide. We have reports of methylphenidate, for example, or brazelam, or lorazepam, opioid withdrawal, and even high-dose caffeine. The authors of a study examining substance use and antidepressants and bipolar disorder are summarized on this slide. The authors of this report looked at 53 patients diagnosed with bipolar disorder. They conducted retrospective interviews to identify lifetime effective episodes, what particular medications the individuals had tried previously, and they did corroborative interviews to help make their research design more substantial. They found that antidepressant-induced mania or hypomania was evident in nearly 40% of their study group. 17 patients had a substance use disorder, and you can see the breakdown on the slide. The history of substance use disorder was associated with a substantially increased risk for antidepressant-induced mania. And the substance use preceded the antidepressant-induced mania by greater than one year in almost all of the cases the authors reported. So let's turn our attention now to substance-induced psychotic disorders. And we'll follow the same format as we did with the previous substance-induced disorders, looking at the established diagnostic criteria first. So let's review the diagnostic criteria for schizophrenia. There must be two or more of the following criteria, each present for a significant portion of time during a one month period, or less if successfully treated. At least one of these must be either one, two, or three, meaning delusions, hallucinations, or disorganized speech, two which can be added, grossly disorganized or catatonic behavior, and negative symptoms, such as decreased emotional expression or withdrawal from social activities. The decrease in functioning in at least one area since the symptoms started, and there must be continuous signs of the disturbance persisting for at least six months. And of course, as a clinician, you would have ruled out schizoaffective disorder, bipolar disorder, substance use, and autism. So the diagnosis of a substance-induced psychotic disorder, again, bears similarity to the manner in which DSM-5 has described the previous substance-induced disorders. In the case of a substance-induced psychotic disorder, there must be the presence of one or both of the following symptoms, meaning delusions or hallucinations. And there must be evidence from your history and physical or laboratory findings, or both, that the individual has criteria A that develops soon or during substance intoxication or withdrawal or after exposure to a medication. Involved substance can actually produce those symptoms that are listed in criteria A. And the disturbance is not better explained by a psychotic disorder that is not substance-induced. Evidence of an independent psychotic disorder could include the following. The symptoms preceded the onset of the substance use. The symptoms persist for a substantial period of time after the individual has stopped using the particular substance or after withdrawal. And of course, the disturbance does not occur exclusively during the course of a delirium. And the disturbance does cause clinically significant distress or impairment in social, occupational, or other important areas of the individual's functioning. So keep these two points in mind as you're diagnosing a substance-induced psychotic disorder. It quite naturally follows that a history of a primary psychotic disorder will not rule out the possibility that the individual also has a substance-induced psychotic disorder. And consider primary psychotic disorder if there is a persistence of the psychotic symptoms for a substantial period of time at the end of that particular substance's intoxication or withdrawal phase, roughly meaning about a month. It's also important to keep in mind that individuals that are intoxicated or withdrawing from a particular substance may also experience, as a part of that process, certain perceptual disturbances. They may recognize them as drug effects and they're reality testing, meaning that they can differentiate them as real. This is not a substance-induced psychotic disorder, but instead regard this as a manifestation of substance intoxication or withdrawal with perceptual disturbance. Now, naturally, if the perceptual disturbances occur in the course of withdrawal delirium, these then become part of a delirium diagnosis and not a substance-induced psychotic disorder. As with many of the substance-induced disorder diagnoses, in the general population, the prevalence is unknown. And in general, it is related to research studies that have provided at least some idea about what the prevalence may be. In those presenting with the first episode of psychosis, Krebin et al. found that psychosis in different treatment settings, the prevalence was 7% to 25%. In another study, Behides and others, in 2015, looking at 198 methamphetamine users, they reported that 51% of the participants had a lifetime psychotic disorder. 80% were determined to be substance-induced. 20% were determined to be primary psychotic disorders. And 39% had current psychotic disorder. And of those, 49 were substance-induced. Here we have another research study that helps provide some guidance and some light on the relationship between the use of a substance and its subsequent development into a psychotic disorder. In this particular study by Cannon and others, 386 patients were studied as they presented to an emergency department. Among that group, 44% of the cases were determined to be a substance-induced psychosis. And the table extracted from that study shows the type of substance that induced the psychosis, with cannabis leading the list, followed closely by alcohol and cocaine and lesser amounts of hallucinogens, sedatives, heroin, and stimulants. So take a moment and study this slide. This particular table is taken from Cannon and others' research as reported on the clinical characteristics of substance-induced and primary psychotic disorder groups. As you can see, there were substantial differences, statistically significant differences, between individuals with a primary psychotic disorder and those that were substance-induced. In terms of their PANS scores, their positive and negative subscale scores, and also their awareness of their symptoms and the misattribution of their symptoms, an interesting slide that provides some insight into those clinical characteristics of those two groups. Cannon included a longitudinal arm to his study, examining 319 subjects out of the original 386. Those individuals were re-interviewed at six and 12 months. And interestingly, at follow-up, 34 subjects, or 11%, changed from substance-induced psychosis to primary psychosis. And another 25 had their diagnosis change in the first six months to persistent psychotic symptoms in the absence of substance use. The last topic that we're going to explore in this series is substance-induced anxiety disorders. And we will follow the same format that we have when looking at the other substance-induced disorders. So let's begin with a review of the diagnostic criteria as listed in DSM-5 for a panic disorder. Criterion A, recurrent unexpected panic attacks. A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes and during which time four or more of the following symptoms occur. These can include palpitations, pounding heart, accelerated heart rate, sweating, trembling or shaking, sensations or shortness of breath or smothering, feelings of choking, chest pain or discomfort, nausea or abdominal distress, feeling dizzy, unsteady, lightheaded or faint, chills or heat sensations, parathesias, numbing or tingling, derealization or depersonalization, fear of losing control or going crazy, and fear of dying. And criterion B, at least one of the attacks has been followed by one month of one or both of the following. Persistent concern or worry about additional panic attacks or their consequences or going crazy, for example. And a significant maladaptive change in behavior related to the attacks, such as significant time devoted to avoiding panic attacks. According to DSM-5, a generalized anxiety disorder occurs when excessive anxiety and worry occurs more days than not for at least six months about a number of events or activities such as work or school performance. The individual, as a consequence, finds it difficult to control their worry. The anxiety and worry in a generalized anxiety disorder are associated with three or more of the following six symptoms. With at least some symptoms having been present for more days than not for the past six months, although only one item is needed for children. The symptoms include feeling restless or feeling keyed up or on edge, being easily fatigued. They find it difficult to concentrate or they find their mind going blank. They're irritable, they have muscle tension, or they have some degree of sleep disturbance. So in contrast to the primary disorders, here we have the diagnostic criteria for substance-induced anxiety disorders, as described in DSM-5. Again, panic attacks or anxiety are the predominant nature of the clinical picture. As before, there's evidence from the history and physical or laboratory findings, or both, that the symptoms in criterion A of those previously discussed anxiety disorders develop during or soon after substance intoxication or withdrawal. And of course, the involved substance that we're looking at is fully capable of producing the symptoms in that criterion A. The disturbance is not better explained by an anxiety disorder that is not substance-induced. And we can look to the following items as evidence, such as the symptoms precede the onset of the substance use, the symptoms persist for a substantial period of time, consider a month, after the cessation of acute withdrawal or severe intoxication, or there is other evidence suggesting the existence of an independent, non-substance induced anxiety disorder. And as before, the disturbance does not occur primarily within the context of delirium, and the disturbance does cause clinically significant distress or impairment. Keep the following points in mind when you're considering a substance-induced anxiety disorder. The diagnosis should be made instead of substance intoxication or withdrawal only when the panic attacks or the anxiety are the principal focus in your patient's clinical picture, and they are severe enough that you are considering clinical treatment. The panic or anxiety must have developed during or shortly after exposure to a substance or withdrawal. And here, urine drug testing may be helpful. And it goes without saying that the substance must be fully capable of producing the anxiety symptoms. Panic or anxiety symptoms will usually improve or remit within a few days to a month, of course, always dependent on the half-life of the substance and the nature of the withdrawal. In terms of prevalence of substance-induced anxiety disorders, the NSARC data provides some insights. Here we see that the 12-month prevalence of an independent anxiety disorder is about 11%, while the presence of a substance-induced anxiety disorder is much, much smaller, less than 1%. So let's do a brief review of what we've covered as we come to the end of this particular presentation. Substance-induced disorders may have symptoms that overlap with independent psychiatric disorders, and that complicates the assessment of co-occurring disorders. It's important, as you begin to differentiate the situation, to get a timeline looking at the onset of substance use in relation to the psychiatric symptoms. Substance-induced disorders should typically clear within a month. There's a lower likelihood of need for psychiatric medications for substance-induced disorders, which is one of the principal reasons for making an effort to differentiate them. Abstinence from substance use is recommended for substance-induced disorders. Primary disorders may benefit from treatment with medications and abstinence from substance use. I would invite you to review the references in the slides that follow this summary and keep up with the literature in this rapidly changing area. As we come to a close, I would like to thank you for taking time to participate in the American Osteopathic Academy of Addiction Medicine's Learning Management System. And again, I'm Dr. Gregory Landy, your narrator.

psychiatric disorders

co-occurring disorders

substance-induced disorders

mood disorders

anxiety disorders

comprehensive evaluation

diagnosis

poor prognosis