I would like to welcome you today to another webinar in the Pain Curriculum Series sponsored by the PCSSO. Today we will be discussing managing patients with pain and psychiatric comorbidity. I'm Dr. John Renner, I'm affiliated with the Division of Psychiatry at Boston University School of Medicine. The objectives for today's talk are the following. At the conclusion of this activity, participants should be able to recognize the prevalence of co-occurring psychiatric disorders in patients with chronic pain, review the impact of psychiatric comorbidity on chronic pain, describe the assessment of patients with chronic pain who suffer with co-occurring psychiatric disorders, and finally compare treatments for co-occurring psychiatric disorders in patients with chronic pain. Before we start, I'd like to look at some of the statistics on the prevalence of psychiatric comorbidity and chronic pain. This slide lists the most common co-occurring psychiatric conditions. In the middle column, it shows you the current incidence in patients with chronic pain compared to the column on the right, which is the incidence in the general population. Here we can see that with depression, the incidence in patients with chronic pain is 45% as compared to 5% in the general population. Anxiety disorders, it's 25% in patients with chronic pain, compared to a range of 3% to 8% in the general population. Similarly with personality disorders, it's 51% compared to 10% to 18% in the general population. If we look at the numbers for PTSD, we can see a significant difference between the general population and the veteran population. In the general population, PTSD rates are about 1%. In general population with pain, it's about 2%. However, when we look at veterans, that number rises to 49% in veterans with chronic pain compared to 20% in veterans with no pain injuries. The numbers with civilians with trauma in the general population is 3.5% to 15%. Substance use disorders are also higher in individuals with chronic pain. In the general population, it's 10%. In the population with chronic pain, it's 15% to 28%. And lastly, somatoform disorders, the numbers are unknown in the general population, but in the chronic pain population, it runs about 97% with patients having chronic low back pain in inpatient rehab programs. Now, this slide basically presents the same numbers. You'll see in the center the same percentages of co-occurring disorders in patients with chronic pain. On the right-hand side, you just see a list of the references for each of these numbers. So this slide is really included if you'd like to get more details on this information. Now what about psychiatric co-morbidity and chronic pain? How do we summarize the information we've just looked at? The prevalence of co-occurring psychiatric disorders is significantly higher in individuals with chronic pain. It's two to three times higher in patients with chronic pain than in the general population. The most common co-occurring disorders are depression, anxiety, and substance use disorders. And interestingly, the incidence of PTSD is very high in combat veterans with chronic pain. The prevalence of co-occurring psychiatric disorders and chronic pain, the next topic, we've covered that. We will now move to our next topic, which is the impact of psychiatric co-morbidity on chronic pain. How does this affect the presentation and severity of the illness? Is there a relationship between chronic pain and depression? Depression is the most common co-occurring psychiatric disorder in patients with chronic pain. It occurs in 45% of patients, as we just noted. Among patients with major depressive disorder, a significantly higher proportion are reporting chronic, that is, non-disabling or disabling pain, than those without major depressive disorder. The percentages here are 66% versus 43%, respectively. Disabling chronic pain was present in 41% of those with major depressive disorder versus in 10% of those without major depressive disorder. Is there a difference in treatment response in patients with chronic pain with co-occurring depression? There certainly is. There's poor adherence to treatment. There's worse satisfaction with treatment. There's a higher likelihood of relapse, and there's less chance of functional improvement. The reference for this is included at the bottom of the slide. Now the question is, how common are co-occurring depression and anxiety disorders in patients with chronic pain? That is, how often do we see both disorders presenting at the same time? All depressed patients with pain should be assessed for an anxiety disorder. There's a 16% prevalence of co-occurring disorders. Most anxiety disorders are present before the onset of pain. Most depressive disorders appear after the onset of pain, so the sequence is different between the two conditions. Psychiatric comorbidity is associated with increased pain intensity. How about the issue of PTSD and chronic pain? PTSD is relatively infrequent in civilian populations with chronic pain, averaging about 2%. However, the incidence in combat veterans can be as high as 49%. It is also important to recognize that these patients often present with depression and other anxiety disorders. These are often multi-problem patients. You should also anticipate that substance use disorders are likely to be present in these patients who present with pain and PTSD. What is the impact of this comorbidity? Patients with chronic pain and PTSD had higher levels of maladaptive coping strategies, greater catastrophizing, greater emotional impact of their pain. They felt less control over their pain, and there were poorer outcomes for injury recovery. All in all, this is a very negative impact on the response to treatment. I'd now like to just summarize the issues of these co-occurring conditions. Depression and anxiety are the most common psychiatric disorders seen in patients with chronic pain. These patients report severe pain and disability, are less likely to adhere to treatment, and have poorer outcomes. Adhering to assessment and treatment of chronic pain and co-occurring psychiatric disorders is therefore critical to improve treatment outcomes. The next topic that we are going to consider is the assessment of patients with chronic pain and with co-occurring psychiatric disorders. The initial assessment of all patients with chronic pain should include a review of psychiatric symptoms and previous treatment and a mental status exam. Be sure to include questions regarding substance use and abuse, early childhood abuse and current domestic violence, PTSD, suicidal ideation, medications from multiple providers, and any litigation or compensation issues that are involved in the case. If the diagnosis is unclear, such patients should be referred for a full psychiatric evaluation. What is the critical first step in the patient assessment? The most important thing is to screen for depression with suicidal ideation and any plans for self-harm. Suicidal patients should be referred for a psychiatric evaluation and or hospitalization. You also want to screen for a substance use disorder. Patients with substance use disorder may require inpatient detoxification before pain management can proceed. Patients who are currently abusing opioids may require detoxification or stabilization on methadone or buprenorphine before any additional treatment may proceed. How do you rule out substance-induced psychiatric disorders? The high incidence of substance use and abuse in this population requires special attention to rule out substance-induced psychiatric disorders. It is important to understand whether or not the patient has a primary psychiatric disorder along with co-occurring chronic pain or whether their psychiatric disorder is simply induced by their substance use. Substance-induced disorders can mimic depressive disorders, anxiety disorders, psychotic disorders, and personality disorders. What are the DSM-5 criteria for substance-induced psychiatric disorders? In these circumstances, symptoms occur during or within 30 days of substance intoxication or withdrawal. The symptoms may be reasonably assumed to be substance-induced in the following cases. Alcohol frequently causes depression, anxiety, and hallucinations. Stimulants often cause depression, mania, and paranoid psychosis. Psychedelics may cause psychosis or somatic delusions. Marijuana may cause psychosis. The important thing here to understand is that if the symptoms are induced by the substance use disorder, they will remit with sobriety. According to DSM-5 criteria, you can expect that symptoms may be present for 30 days while the patient is using or after they've stopped using. If you go beyond the 30-day window and the symptoms are still present, then by DSM-5 definition, they cannot be considered to be substance-induced. What criteria suggest that substance-induced psychiatric disorders are less likely? That is, what criteria suggest that an independent psychiatric disorder is present? First, the symptoms were present prior to the substance use. The symptoms are present during extended periods of sobriety. We normally require a minimum of three months' sobriety in order to apply this criteria. There's a family history of a similar disorder. If the symptoms are diagnosed while the patient is using the substance or immediately following detoxification, they should be reassessed after three to four weeks of sobriety beyond the 30-day window to make a definitive diagnosis. How do you make the diagnosis of substance-induced psychiatric disorders? You do not attempt to confirm the diagnosis while the patient is intoxicated or immediately following substance use or detoxification treatment. You need to verify the drug's free state with laboratory tests and assess psychiatric status when the patient is sober. I would also add that you would consider the patient sober if they are not using illicit substances and are now stable on methadone or buprenorphine treatment. You want to obtain a careful longitudinal history that tracks the course of both the patient's substance use and their psychiatric symptoms. You want to track two parallel symptom courses and then look at how these courses interact with each other and their relationship. You want to confirm the patient's history with relatives or significant others, and you want to review the family history for psychiatric disorders. Now we will complete the psychiatric assessment. If you are able to rule out a substance-induced psychiatric disorder, you should proceed on the assumption that the current symptoms reflect an independent psychiatric disorder, and that psychiatric treatment will be required. We will go through this in detail in the following section. If symptoms are substance-induced, treatment for substance use or abuse or dependence must be part of the treatment plan. A repeat psychiatric assessment should be part of the annual treatment plan review for all chronic pain patients. To summarize the assessment section, all patients with chronic pain should be screened for psychiatric disorders, including PTSD and substance use disorders. Suicidal ideation requires a careful psychiatric assessment and may require immediate treatment and hospitalization. A patient with a current substance use disorder may require detoxification before pain treatment can proceed. It is also very important to distinguish substance-induced disorders from independent psychiatric disorders. We'll now proceed to the final section of this talk. We're going to look at treatment of co-occurring psychiatric disorders in patients with chronic pain. What are the general principles? How do you manage psychiatric disorders in patients with chronic pain? The basis for successful management of chronic pain and co-occurring psychiatric disorders is a biopsychosocial treatment approach. If screening identifies the presence of an active substance use disorder and or any substance-induced psychiatric disorder, patients must first be referred for detoxification if required. An ongoing addiction treatment must be integrated into their ongoing chronic pain management program. You really have to have a more complex treatment plan that pays attention to both conditions, their substance use problem and their chronic pain problem. The biopsychosocial model for chronic pain includes the following. Evidence-based pharmacotherapy for both chronic pain and any co-occurring psychiatric disorder. Cognitive behavioral therapy. This should address pain issues and any relevant psychiatric symptoms, including substance use disorders. And finally, a graded education program. We now want to focus specifically on chronic pain self-management. This is an important concept and is a critical element in managing patients with chronic pain and reducing their reliance on pharmacotherapy. Treatment should always begin with a chronic pain self-management program. The patient will require careful education on the physiologic mechanisms that underlie their pain and details about the efficacy of all recommended treatments. The patient must take responsibility for compliance with any recommended pharmacotherapy. This includes medications for pain and for any psychiatric disorder. I would put stress on the word responsibility. Pharmacotherapy is not going to be effective unless the patient complies with the medication requirements. And it has to be stressed that the patient needs to take that responsibility and seriously own their role in this aspect of their treatment. In addition, the patients must take responsibility for implementation of any graded exercise program. If the patients do not take that responsibility and do not implement a degraded exercise program, as similarly they do not implement indicated pharmacotherapy, it is unlikely that a chronic pain self-management program will be effective. What is the evidence for the efficacy of this type of self-management treatment program? This approach has been found to be highly effective for diabetes and asthma. Data for chronic pain self-management is marginal and compliance has been a problem. We are relying to some degree on the success we have seen with other chronic disease conditions. We need to work with the patient to try and achieve similar levels of success in chronic pain management. A successful chronic pain management program requires strong support from the family, strong support from the primary pain treatment clinician, and clearly requires that the patient understands the problem and takes responsibility for implementing the treatment plan. What is the role of cognitive behavior therapy? CBT is well established as an effective evidence-based therapy for chronic pain, depression, anxiety, PTSD, and substance use disorders. CBT typically includes skill acquisition, relaxation therapy, cognitive restructuring, effective communications, and stress management. This is followed by skill consolidation and rehearsal. The patient will need training to generalize their new skills. They need support for maintenance of behavioral change. They need to continue to practice these skills until they become very comfortable and routine. And they need to learn strategies to avoid relapse. What are the benefits of early implementation of CBT in chronic pain treatment? McCracken and Turk reviewed comprehensive program outlines and reported that patients who complete a chronic pain program based on the biopsychosocial CBT model demonstrate an improved return to work, reduction in pain, increased activity, reduced use of medications, and they noted that these benefits were maintained at five-year follow-up. So this review, the references at the bottom of the slide, clearly showed that this approach can be effective and will improve treatment outcome. Another option is acceptance and commitment therapy, also known as ACT. This is a new development in the CBT field that has proven to be particularly useful for patients with chronic pain. It can be provided by a therapist either individually, in groups, or in couples. It is not guided by a specific manual, but rather the therapist is going to individualize their own mindfulness techniques, or they may work with the patient to develop a particularly unique program. It is helpful because it covers a broader area than we usually deal with in many areas of psychiatry. Things like spirituality, community relationships, marriage, parenting, employment, physical well-being, the whole range of value systems that can be brought into this system to help a patient learn how to deal with things. For example, patients may be helped to see that when they are afraid that they can't tolerate certain pain, the system will teach them to understand that their mind is telling them that they're afraid of certain pain, not that they do have the pain. This helps them put some distance between themselves and their symptoms, and it makes it easier for them to learn how to accommodate and live with some of these more distressing symptoms. If you wish more information, I would refer you to McCracken and Volz as a good article that covers this subject. Can pain be managed without opioids? This is a clearly important question as we are facing a national epidemic of opioid abuse, and physicians need to be more skilled and more careful in the use of opioids in all conditions, particularly in chronic pain management. Optimized antidepressant therapy and pain self-management in depressed primary care patients with musculoskeletal pain. This is a randomized clinical trial. Optimized antidepressant therapy, along with pain self-management program, produce significant reductions in depressive symptoms and severity, and moderate reductions in pain severity and disability after 12 months. The reductions in depression and pain were seen early in the treatment, at one month following initiation, and they were sustained throughout the 12 months. Again, we have another study here looking at depressed primary care patients with musculoskeletal pain and showing the benefits of treatment for depression and treatments with the self-management program for chronic pain. What are the guidelines for pharmacotherapy of psychiatric disorders in patients with chronic pain? First of all, and most important, you must begin with a chronic pain management program, and stress the importance that the patients take responsibility for implementation of the self-management program, and that they also take responsibility for participation in the other elements of the program. You then want to add CBT and a graded exercise program. In most cases, standard psychiatric medications for depression, anxiety disorders, and PTSD can be used. There is little research available to guide medication and choices with chronic pain, so your use of standard medications, the drugs that the primary care physician is comfortable with, will probably be useful and effective in this patient population. You want to avoid medications, however, that have any abuse potential. The side effect profile can guide medication choice, and we'll explain this in more detail, and you need to frequently monitor the patients for medication compliance. How do you manage pharmacotherapy of psychiatric disorder in these chronic pain patients? You want to begin with non-abusable medications. The SSRIs are a good choice because they will treat both depression and anxiety, and as we noted before, these conditions are commonly co-occurring in these patients. You need to make sure the patient is receiving adequate doses and that the trial is of adequate length, that is, six to eight weeks. If there's no response to the initial choice of an SSRI, consider Defazodone, SNRIs, or dual action agents. CBT will improve the response to medications, so we need to be looking at a program that includes both CBT and pharmacotherapy. Benzodiazepines have no role as a primary treatment for depression or PTSD. Even though patients will request these medications, it is very important that their use be avoided in these patients. Benzodiazepines can be used with caution and for short term in some anxiety disorders, but I would stress they're not recommended for depression or for PTSD. In some cases, if the patient has not responded to CBT for anxiety disorders and antidepressant medications have been ineffective, and the patient has no history of the abuse of benzodiazepines, then the clinician may proceed with caution with a benzodiazepine trial. Now this slide lists the standard pharmacotherapy recommendations for psychiatric pharmacotherapy in patients with chronic pain. First of all, depression. SSRIs, venlafaxone, duloxetine, tricyclic antidepressants, Defazodone, and bupropion. For generalized anxiety disorder, SSRIs, tricyclics, buspirone, duloxetine, and escitalopram. For panic disorder, SSRIs or Defazodone. For anxiety disorder, paroxetine. For PTSD, SSRIs, tricyclic antidepressants, extended release venlafaxone, or parazepine, which is specifically valuable for treating the nightmares and PTSD. And for bipolar disorder, valproate. This slide compares the efficacy and some of the side effects for some of the common antidepressants that we have mentioned. You can see, first of all, that all of the drugs listed across the top of this slide are effective. If you then ask the question, how many of these drugs not only treat depression but also help with sleep, you will see that Defazodone is the only one of the listed drugs that is helpful for sleep. If you ask the question for effectiveness with co-occurring anxiety disorders, not all of these medications have good effects on anxiety. Defazodone, fluoxetine, sertraline, and paroxetine have been prescribed. Fluoxetine and sertraline are specifically helpful for generalized anxiety disorder. What about problems with sexual dysfunction? This is a major issue with most of the SSRIs. It's minimal with Defazodone and bupropion. What about weight gain problems? Again, common problem with most of the SSRIs, but minimal or no weight gain problems with Defazodone or bupropion. What are the risks for substance abuse in depressed patients on chronic opioid therapy? Patients with moderate to severe depression are 1.8 and 2.4 times more likely, respectively, to misuse opioid medications to relieve these symptoms. So one needs to be extremely careful in prescribing opioids to patients who are also depressed. Such patients may benefit from pharmacotherapy with standard antidepressant medications. There are no clear guidelines to guide the choice of medication, though consideration should be given to venlafaxine and duoxetine because of their efficacy in chronic pain management. Both of these drugs have separate indications for pain management and should be considered when you have depressed patients with chronic pain problems. What are the evidence-based pharmacotherapies for anxiety disorders? A recent systematic review of randomized controlled trials, including a Cochrane database review, reported on data from trials demonstrating greater than 50% reduction in baseline scores on the Hamilton anxiety scale in generalized anxiety disorder. Fluoxetine was ranked first for response and remission. Sertraline was ranked first for tolerability. In a sub-analysis for generalized anxiety disorder, duloxetine was ranked first for response, escitalopram was ranked first for remission, and pregabalin was ranked first for tolerability. Now let's go back to the question of the use of benzodiazepines. What are the risks for using benzodiazepines in the treatment of other anxiety disorders? This slide refers to a comprehensive literature review by Posternak and Mueller. Efficacy was demonstrated for generalized anxiety disorder, panic disorder, and agoraphobia with the use of benzodiazepines. There was probable efficacy seen for social phobia. There was little evidence of added risk for medication abuse or increased relapse, but it was important to avoid use in primary sedative hypnotic use disorder or in other individuals with substance use disorders. What this research tells us is that for individuals who have no history of substance use disorder and no history of primary abuse of benzodiazepine or other substances, it is safe to prescribe benzodiazepines for treating anxiety disorders or generalized anxiety disorder. However, if an individual has any history of sedative hypnotic abuse or any history of substance use disorder, then it is highly risky to prescribe benzodiazepines for anxiety disorders and other medications should be the first choice. What about treating co-occurring pain and PTSD? This slide refers to a 12-session integrated treatment for chronic pain and PTSD. This was done by John Otis and was published in 2009 in Pain Medicine. It included CBT for PTSD and CBT for chronic pain. The elements of this program were relaxation training, activity goal setting, cognitive restructuring, and relapse prevention. CBT for PTSD was not recommended until the patients had achieved stable sobriety. So with this complex group of patients, the first goal was to make sure that they were sober and did not have an active substance use problem. And then we see here a study which combined CBT for both the PTSD and the chronic pain. When you're treating these patients, you want to avoid opioids whenever possible. Preferred pharmacotherapy options for chronic pain with co-occurring PTSD are NSAIDs, anticonvulsants, and tricyclic antidepressants. Similarly, if you're treating chronic pain, PTSD, and now patients with traumatic brain injury, and this triad of problems is seen frequently in combat veterans, CBT is helpful for pain management. Prolonged exposure therapy and cognitive processing therapy have been demonstrated to have good efficacy for the treatment of PTSD. Traumatic brain injury may make it more difficult for patients to invest in these cognitive approaches. However, these highly structured approaches may also aid the TBI directly in these individuals. Now I want to look at practice guidelines for PTSD pharmacotherapy that were published by Matt Friedman in 2010. This is from his handbook of PTSD. Biopsychosocial approach was recommended. SSRIs and SNRI venlafaxin are the first-line medications. Extended release venlafaxin may be more tolerable because of fewer or less intense side effects. Parazisin is helpful for nightmares. This is an off-label use of this medication. The drug has to be titrated up slowly, beginning with 1 milligram at bedtime, gradually increasing to as high as 20 milligrams if needed. However, once you begin to see an effect of reduced or significantly eliminated nightmares, the medication increases can be stopped. You want to add CBT if there's no response to these medications alone. Prolonged exposure therapy, cognitive processing therapy, will be helpful for the PTSD. Second-line medications include mirtazapine, tapiramide, amitriptyline, imipramine, venalzine, and nifazidone. And again, caution is urged against the problems or against using any benzodiazepines. Now, to summarize treatment recommendations for psychiatric comorbidity and chronic pain management. Number one, develop a biopsychosocial treatment plan. Number two, begin first with a chronic pain self-management program. Do not begin first with pharmacotherapy. Incorporate cognitive behavior therapy. Then add, if necessary, standard pharmacotherapy for depression, anxiety disorder, and PTSD. Always begin first with non-abusable medications. Make sure that the patient receives an adequate dose and for an adequate period of time, that is 6 to 8 weeks. Warn patients that psychiatric medications are unlikely to work if combined with illicit drugs and that the combination can be lethal. Now, the next two slides include a list of all the references that were covered in this presentation. So this is here for your detailed education if you wish to pursue more information. Finally, I would like to discuss the PCSSO Colleague Support Program and our LISTSERV. The PCSSO Colleague Support Program is designed to offer general information to health professionals seeking guidance in their clinical practice in prescribing opioid medications. PCSSO mentors comprise a national network of trained providers with expertise in addiction medicine, addiction psychiatry, and pain management. Our mentoring approach allows every mentor-mentee relationship to be unique and catered to the specific needs of both parties. This mentoring program is available at no cost to providers. For further information on requesting or becoming a mentor, visit www.pcss-o.org slash colleague-support. The LISTSERV is a resource that provides an expert of the month who will answer questions about educational content that can be presented through the PCSSO project. To join, email pcss-o at aaap.org. Finally, just some general comments on the PCSSO Providers Clinical Support System for Opioid Therapy. This is a collaborative effort led by the American Academy of Addictions and Psychiatry in partnership with a large number of other academic and medical groups, including the American Academy of Neurology, the American Academy of Pain Medicine, the AMA, and other groups listed on this slide. For more information, visit www.pcss-o.org and questions are available by email at the PCSSO at aaap.org or at our Twitter listing. I want to thank you all for participating. I hope you will follow up by connecting with the PCSSO system for both expert mentors and for additional information. Again, thank you very much.

Dr. John Renner

patients with pain

psychiatric comorbidity

chronic pain

depression

PTSD

treatment outcomes