All types of antidepressants have been found to be effective for major depression with comorbid substance dependence.
CME credit for this article is now expired. It appears here for informational purposes only.
At the end of this article, readers should be able to:
1. Delineate evidence-based principles of successful assessment and treatment.
2. Translate these principles into applications for real-world practice.
3. Develop treatment strategies for patients who have comorbid mental illness and substance use disorder.
During the past 10 to 15 years, psychiatrists have increasingly recognized the importance of successfully engaging and treating individuals with comorbid psychiatric and substance use disorders. National epidemiological studies and surveys have clearly indicated that “co-occurring disorders are an expectation, not an exception.”1 In particular, data from the Epidemiology Catchment Area survey showed that of people living in the community, 55% of those with schizophrenia and 62% of those with bipolar disorder had a lifetime diagnosis of substance use disorder.2
The National Comorbidity Survey replicated and expanded these results, and findings of high prevalence of comorbid mental illness and substance use disorders have been further demonstrated in more recent national epidemiological reports.3-6 Epidemiological studies have indicated higher odds ratios for comorbid substance use in adults and adolescents with nearly every psychiatric disorder, compared with those for the general population. Conversely, individuals (adults and adolescents) with diagnosed substance use disorders have higher odds of having a comorbid mental health condition than individuals with no substance use disorder. Furthermore, findings indicate a high prevalence of substance use disorders comorbid with trauma-related pathology.7
In the past decade, there has been increasing research on evidence-based integrated treatment approaches for individuals with comorbid disorders. This research includes specific program models, such as Integrated Dual Disorder Treatment, as well as a range of integrated practices and approaches based on that model.8 These approaches have been condensed into instructions for integrated practice for clinicians and include an array of guidelines (eg, assessment, service planning, treatment).9,10 On the basis of this and other research, the Comprehensive, Continuous, Integrated System of Care incorporates universal integrated practice (termed “co-occurring capability”) as a fundamental system design feature and utilizes research-based principles that inform integrated practice.11,12
There has also been a growing body of research on the effectiveness of psychotropic medication for mental illnesses in individuals with psychiatric disorders and co-occurring active substance use. Whereas active substance users were previously excluded from psychopharmacological research, resulting in limited data on the effectiveness of psychotropic medications in this population, current research makes it clear that active psychopharmacological intervention for mental illness produces significantly better treatment outcomes in these individuals, even when active substance use continues. It is now best practice for psychiatric prescribers to work within an integrated treatment framework, in which appropriately matched psychopharmacological and non-psychopharmacological interventions for both mental illness and substance use disorders are integrated into patient care.
In addition, as understanding of the “brain disorder of addiction” has increased, there has been a steady expansion of pharmacological options specific for treatment of substance use disorders.13 The previously limited armamentarium of psychopharmacology for addiction has been expanded to include an array of anticraving agents that directly intervene in the neurotransmitter mechanisms that support continuing addiction.14 In addition, opiate maintenance treatment, formerly restricted to licensed methadone programs, can now be provided more readily in office-based settings by practitioners who prescribe buprenorphine. Many common psychotropic medications are being shown to also have a potential direct effect on improving substance use disorders. For nicotine dependence, the most prevalent and most potentially lethal of comorbid substance use disorders, there are a range of psychopharmacological agents that have specific and potentially lifesaving indications.
Principles of treatment
The psychopharmacological principles outlined in this article are based on 3 publications:
• The Centers for Mental Health Services (CMHS) Managed Care Initiative Report15 that includes treatment principles and practice guidelines (including psychopharmacology guidelines) for individuals with co-occurring psychiatric and substance use disorders
• An updated version of the CMHS Managed Care Initiative Report co-occurring disorder psychopharmacology practice guidelines that incorporates more current information16
• An even more recent document issued by the Substance Abuse and Mental Health Services Administration that references and builds on the previous work17
Because comorbidity is highly prevalent, all practicing psychiatrists are likely to see patients with co-occurring mental illness and substance use disorders, including patients with active use. The first principle of treatment is therefore to purposefully welcome these individuals-who are most likely to be at risk for poorer outcomes if not successfully engaged in care. A welcoming approach facilitates the creation of an empathic, hopeful relationship, screening for co-occurring substance use, building trust to allow the patient to share information, and working in partnership with the patient over time to make progress on both disorders.12,15
Welcoming and engagement are the cornerstones of treatment success, yet some practitioners may find that their own attitudes make genuine welcoming difficult. Practice how you will welcome individuals with active co-occurring conditions:
Hi, there. As a person with both mental health symptoms and active substance use, you’re likely to be having a hard time. I know it’s difficult for you to come here, asking for help. Thank you for coming, and for sharing the information about your substance use. You are in the right place. I’m glad you’re here. My job is not to fix you or control you, but to get to know you, inspire you with hope, and work with you over time to help you address all of your issues in order to help you achieve your goals.
Successful psychopharmacological interventions for patients with comorbid psychiatric and substance use disorders are more likely to be successful when the clinician is a collaborator in the recovery process. Partnership and shared decision making about multiple issues are critical features of this type of relationship and facilitate the application of a range of non-medication evidence-based strategies (such as motivational engagement, skills training, and contingency management) in addition to identifying the best medication regimen for the individual. The clinician engages in continual assessment and re-assessment, and focuses on small steps of success and progress over time.
Research on patients with serious mental illness and co-occurring substance use disorders receiving Integrated Dual Disorder Treatment has shown that it commonly takes about 3 to 4 years for approximately half of the patients to achieve stable sobriety. Most of the rest are making significant progress in improving their lives, although they continue to abuse substances.6 Thus, it is important to work in the integrated relationship to take small steps forward for each issue, rather than feel frustrated that the patient is not sober after a few weeks or months.
Screening and assessment
The practice of delaying assessment of a patient pending a minimum duration of sobriety-usually 30 days-is incorrect. There should be no arbitrary barrier to the initiation of screening, psychiatric assessment, or psychopharmacological intervention based on substance levels or duration of sobriety.
Diagnostic assessment, whether for psychiatric disorders, substance use disorders, or both, primarily involves obtaining a good patient history. The assessment process I recommend is Integrated Longitudinal Strength-based Assessment.8 The first principle of this assessment process is that with a long-standing established psychiatric diagnosis, the diagnosis persists regardless of whether the person is using substances. Similarly, if the patient has substance dependence, that disorder persists over time regardless of the presence of comorbid mental health conditions or periods of being in or out of remission.
The second principle of the assessment process is a careful integrated and longitudinal (or chronologic) evaluation of persistent mental health conditions and substance use, looking at the overlap between both conditions at any point. The third principle is to pay particular attention to periods of 30 days or longer in the history when the patient was either abstinent or using substances below the threshold that would affect the symptoms. A careful analysis of baseline mental status, level of functioning, and previously successful medication response-during those periods of strength or success-helps in diagnostic decision making, because baseline persistence of mental health conditions during past periods of sobriety is predictive of current persistence. The integrated longitudinal strength-based assessment can begin immediately and will enable you to establish a provisional diagnosis of persistent mental illness (and initial treatment recommendations) based on history, even in individuals with current or recent substance use.
The integrated assessment process should attempt to distinguish persistent mental illness with associated disability at baseline from persistent mental illness without disability. Integrated assessment should also distinguish between substance use, abuse, and dependence (per DSM-IV-TR). Finally, a careful history can delineate which past mental health conditions may have been substance-induced, because they can be shown to have cleared up completely within 30 days of discontinuing use.
Integrated interventions and treatment
When mental illness and substance use disorders are comorbid, both disorders should be considered primary, and treatment of both should be integrated and simultaneous. Interventions, including medications if prescribed, should be specific to each disorder. In addition to being matched to diagnosis or problem, interventions must be matched to treatment readiness (often termed “stage of change”). Stage of change is issue-specific, not person-specific. Consequently, integrated interventions must be stage-matched for EACH issue. A common example is a patient in the action stage for a mental illness but in the contemplation stage for making changes regarding active substance use. In this case, an “integrated prescriber” might provide appropriately matched medication for the mental illness and use motivational interviewing strategies to help the patient think more clearly about decisions regarding substance use in relation to personal recovery goals.
During the action stage, interventions may include skill building for symptom or illness management or relapse prevention. In addition, providing patients with practical skills, such as refusing drugs from a dealer, can be very helpful in supporting small steps of progress. With practice, psychiatrists can learn to provide targeted integrated interventions within the context of the brief medication visit. Brief motivational interviewing and brief focused skill-building conversations are readily integrated into the short visit.
Contemplation: What is your current plan for using alcohol, and how is that plan working for you in relation to your goals?
Action: Where are you having trouble in your efforts to not use substances? Can we role-play one skill you can use in that situation?
Maintenance of necessary psychotropic and other medication
Integrated psychopharmacology begins by providing appropriate psychopharmacological interventions for each of the concurrent primary disorders, just as in any other type of comorbidity. The first step is simply to use the best medication (if any) for the patient for each disorder concurrently, being aware of potential medication interactions.
Next, be sure to initiate and maintain necessary (non-addictive) medication needed for stabilization and treatment of a known serious mental illness or medical condition even when the patient is actively using substances. Discontinuing necessary medication is associated with greater risk of symptom relapse and re-hospitalization than is continuing medication with closer monitoring.12,17
This does not mean that abstinence from substances should not be recommended for individuals for whom psychotropic medication is being prescribed. It is important to discuss openly (and document) the recommendation of abstinence and that continuing substance use when taking a prescribed medication is associated with greater risks of adverse effects. However, if (as is likely) the patient chooses not to follow those recommendations, it is critical to continue necessary psychotropic medication treatment, to maintain an empathic and hopeful relationship, to monitor the patient closely, and to work in partnership with the patient to help the patient talk openly about his substance use and make better decisions regarding substance use over time.
Clinical strategies and guidelines
Because comorbid disorders are to be expected, it is important for all prescribers to develop-and practice-artful approaches for working in partnership with patients who present challenges. In particular, it is important to be proactive in the prescribing relationship to avoid what might be termed an “unholy alliance,” which can emerge when patients approach prescribers with the goal of obtaining medications to “feel better,” and prescribers feel their job is to provide medications for that purpose. In that situation, we may feel that saying yes is inappropriate but do so to accommodate the patient, or we may say no and jeopardize the relationship. Either way, it feels like we lose. To avoid this, it is helpful to practice routine strategies and messages based on the expectation that these types of encounters will occur and on the desire to use these encounters purposefully to support positive engagement and progress.
When patients request (or demand) medications for symptom relief, it is important to take time to get a good integrated, longitudinal, strength-based history, not of the symptom, but of the person’s life: goals, current and past functioning, previous experiences with treatment, and evidence of disorders and syndromes beyond particular symptoms. It is important to be calm and in control of the assessment, letting the person know that you will get to know her well and will figure out the best medication strategy to help her in the context of what is actually happening in her life. The more that you can keep the conversation away from a focus on “symptoms” or “feelings” (which can often be exaggerated for the purpose of convincing you to prescribe), the more accurate will be your assessment. This will enable you to more clearly determine what aspects of the patient’s painful experiences are related to possible disorders that may respond to medication and what aspects of the patient’s pain relate to issues in her life (experiences of trauma, for example) that require other types of intervention.
Explain your medication decisions in relation to the likelihood (based on the assessment) that the diagnosis is a treatable psychiatric disorder, and the risks and benefits of medication in relation to that disorder. It is often difficult in any assessment (with or without comorbidity) to fully distinguish depression (for example) as a result of “life circumstances” from major depression; nevertheless, it is important to communicate any uncertainty accurately so that the patient has a clear idea of the potential benefits and limitations of medications.
It is helpful to point out clearly and empathically that medication is not intended to relieve normal painful feelings, so much as to correct any “biological imbalance” that may lead the patient to experience real feelings inaccurately. Consequently, it is important for the patient not to expect medications to simply make him feel “better” in the face of a painful life. The prescriber should simultaneously emphasize-very positively-the importance of receiving appropriate levels of empathic support and treatment (including residential addiction treatment if needed) to help the patient learn to manage painful feelings successfully, without using substances inappropriately, to achieve his recovery goals. This approach shifts the relationship from “withholding” to “offering the help that is truly needed.”
The appropriate use of benzodiazepines in patients with comorbid disorders is extremely controversial. This one issue created the greatest conflict in our CMHS Managed Care Initiative Panel project. After much debate, the group came up with the following recommended guidelines for prescribing benzodiazepines for anxiety disorders or opiates for chronic pain for individuals with known substance dependence.
For patients with known substance dependence (active or remitted), the routine continuation of prescriptions of benzodiazepines, addictive pain medications, or nonspecific sedative/hypnotics is not recommended, with or without comorbid psychiatric disorder. On the other hand, medications with addictive potential should not be automatically withheld for carefully selected patients with well-established abstinence who demonstrate specific beneficial responses to them without signs of misuse, merely because of a history of addiction.
However, consideration of continuing prescription of potentially addictive medications for consumers with diagnosed substance dependence is an indication for both (a) careful discussion of risks and benefits with the patient (and, when indicated, the family) and (b) documentation of expert consultation or peer review.9,12
During the past decade, there has been detailed investigation of anticraving agents and other medications for treatment of substance use disorders, including in patients with co-occurring psychiatric disorders, as well as investigation of various psychopharmacological agents for the treatment of mental illness in individuals with comorbid active substance use disorders. Consequently, there is emerging knowledge that all prescribers should be aware of. Some of the new information is ahead of what has been formally approved and recognized by the FDA. The following is a selected list of tips regarding psychopharmacological practice with comorbid disorders.
More routine prescription of anticraving agents such as acamprosate or naltrexone for alcohol dependence (naltrexone-as an opiate blocker-is also an appropriate treatment for opiate dependence), and varenicline or bupropion for nicotine dependence is now being encouraged.18 Studies have demonstrated that both oral and long-acting injectable naltrexone are effective in reducing alcohol use, even in individuals who are actively using, including those with comorbid psychiatric disorders.19 While the data are not fully clear, on average, naltrexone is probably more effective than acamprosate for alcohol use disorders, although some individuals respond better to the latter.20
Varenicline has currently been recommended as a first-line treatment for nicotine dependence in individuals with comorbid schizophrenia and possibly bipolar disorder as well.21-23 Findings suggest better outcomes than with bupropion, and re-analysis indicates that prior concerns about symptom exacerbation is not well founded. Disulfiram continues to be viable for alcohol dependence in select motivated patients with comorbid psychiatric disorders (psychotic or nonpsychotic); it may also reduce cocaine craving as a result of dopamine beta hydroxylase inhibition, although it is not approved for the latter indication.24,25
There are numerous reports of alcohol anticraving effect for anticonvulsant mood stabilizers such as valproate, topiramate, and gabapentin. In a recent study, gabapentin combined with naltrexone improved drinking outcomes compared with naltrexone alone.26
These early findings are important to be aware of, although these anticonvulsant medications are not approved specifically for substance use disorders.
Emerging medications that may have anticraving potential for stimulants include baclofen, vigabatrin, and modafinil for cocaine and methamphetamine; tiagabine and topiramate for cocaine; and mirtazapine and bupropion for methamphetamine.27-34
Clozapine has a differentially positive effect in reducing substance use in individuals with psychosis, beyond its direct effect in reducing positive and negative psychotic symptoms.35,36 For individuals with comorbid bipolar disorder and addiction, it is important to remember that lithium is still an important front-line treatment for bipolar I disorder, even though it is not effective for substance use. However, for many patients who have comorbid substance use and bipolar disorders, especially those with atypical or rapid cycling mood disorders, the anticonvulsant mood stabilizers such as valproate may have beneficial effects for both conditions.37
Atomoxetine is currently recommended as a first-line treatment for clearly diagnosed ADHD in individuals who also have active substance dependence, for whom initial prescription of stimulants would usually not be advised. However, many patients with substance dependence in remission may be successfully and safely treated with long-acting stimulants for ADHD when atomoxetine is inadequate.38
All types of antidepressants have been found to be effective for major depression with comorbid substance dependence. Recent findings indicate that with co-occurring alcohol use disorder and major depression, mirtazapine uniquely appears to improve depression and to function as an anticraving agent for the alcohol use disorder.39
Finally, adolescents with comorbid mental health and substance use disorders have been shown to have better outcomes for their mental health disorders when treated with appropriate psychotropic medications, even with continuing active substance use, compared with those who were not so treated.40 In addition, N-acetylcysteine has been recently shown to have a positive effect in reducing marijuana abuse in adolescents.41
Note: This article was originally published as a CME in the April 2013 issue of Psychiatric Times. Portions of it may have since been updated.
Kenneth Minkoff, MD, has no disclosures to report.
Mark J. Albanese, MD (peer/content reviewer), has no disclosures to report.
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