Introduction
Opioid use disorder (OUD) with injection drug use has reached epidemic levels with endocarditis as a major potential medical complication increasing the risk of mortality. There has been an increase in the number of hospitalizations, particularly among patients who are younger, white non-Hispanic, and from rural areas [ ]. In one study, among hospitalized patients, 42% were uninsured or had Medicaid coverage, suggesting the high cost and need for prevention and harm reduction strategies [ ]. Treatment for patients with endocarditis secondary to OUD is complex, often involving long hospitalizations, lengthy treatment with intravenous (IV) antibiotics, postacute care at nursing facilities, high rates of readmission, and comorbid mental health illness.
Stigma from both the medical staff and patient can impact the delivery of care and contribute to poor clinical outcomes. One qualitative study enrolled medical staff and patients with both describing stigma leading to delay in treatment as well as fragmented care within institutions [ ]. A systematic review revealed general negative attitudes of health-care professionals toward patients with substance use disorders (SUDs) with perceived violence, low motivation, and manipulation as main themes [ ]. Many patients describe social determinants of health as a barrier to treatment, highlighting the need for a patient-centered approach with integration of treatment across levels of care as well as increase in training in medical staff.
SUDs and psychiatric diagnoses are common co-occurring illnesses. The United States Department of Health has cited 37.2% of patients afflicted with SUDs also have a history of one serious mental illness [ ]. Given the high prevalence of comorbidity, some have argued that dual diagnosis treatment should be the standard of care. For this reason, all guidelines recommend screening for both and a multidisciplinary approach that addresses case management, family interventions, education, self-help groups, pharmacotherapy, and housing. Additionally, treatment strategies of contingency management, relapse prevention, motivational interviewing, and assertive community treatment are recommended [ ]. However, only a small percentage of this population receives this integrated treatment [ ].
In this chapter, we present the common psychiatric illnesses that occur with SUDs with specific considerations for OUD when data are available. Screening, workup, and management for each illness will be reviewed followed by a discussion of clinical approach in special populations.
Depression
Depression is the most common co-occurring psychiatric disorder in patients with SUDs [ ]. Patients with OUDs and depressive symptoms have been found to have lower rates of treatment completion, poorer psychosocial functioning, and higher likelihood of relapse compared to those without depressive symptoms [ ]. The relationship between depression and opioids is complex, bidirectional, and multifactorial.
Epidemiology
Rates of depression in patients with OUD are high across studies and settings. Among patients with OUDs, 27% of treatment-seeking individuals who use opioids meet diagnostic criteria for major depressive disorder (MDD); this number increases to 57% when considering depressive symptoms that do not meet full criteria for MDD [ ]. From 1999 to 2016, there has been more than a 30% increase in overdose deaths [ ], and suicides involving opioids have tripled from 1999 to 2014 from 640 to 1825 [ ]. A study of military veterans with an OUD found that these individuals have the highest rates of suicide (120/100,000 person-years) compared to veterans with other psychiatric conditions [ ]. In another military study drawn from a pain clinic, depression and OUD were found to be additive for suicide risk. Patients with OUD should be screened carefully for current suicidal ideation, recent suicidal behaviors, and history of suicide and self-injury.
Diagnostic criteria and workup
The Diagnostic and Statistical Manual version 5 (DSM-5) defines MDD as a 2-week period with at least five symptoms of depression. These symptoms include: depressed mood; markedly diminished interest or pleasure in activities; significant weight loss when not dieting or weight gain or decrease or increase in appetite; a slowing down of thought and a reduction of physical movement observable by others; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt nearly every day; diminished ability to think or concentrate; recurrent thoughts of death or suicide with at least depressed mood or loss of pleasure being one of symptoms [ ]. Other DSM-5 depressive disorders include disruptive mood dysregulation disorder, persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, substance/medication-induced depressive disorder, unspecific depressive disorder, and depressive disorder due to another medical condition.
Numerous validated tools have been developed for depression screening across settings. The Patient Health Questionnaire (PHQ) is validated for depression screening in patients with SUDs, specifically in patients with injection drug use [ ]. The Center for Epidemiologic Studies Depression Scale (CES-D) and the Beck Depression Inventory are also screening tools that can be used in this population; however, a clinical evaluation is recommended by SAMHSA as a follow-up to any positive screen [ ].
Additionally, medical conditions that cause or present with depression should be considered and include infection (e.g., spinal abscess, pneumonia), cardiac events (e.g., myocardial infarction), nutritional deficiencies (e.g., B12), and endocrine conditions (e.g., hypothyroidism). Hypoactive delirium from an acute medical condition may appear to staff and physicians as depression. Anoxic brain injury from overdose and a major neurocognitive disorder from chronic substance use may also present with apathy or amotivation, mimicking depressive illness. See Table 11.1 for more information.
| Medical mimics | Infection (e.g., spinal abscess, pneumonia) Cardiac events (e.g., myocardial infarction) Nutritional deficiencies (e.g., B12) Endocrine conditions (e.g., hypothyroidism) Oncological conditions (e.g., pancreatic cancer) Rheumatological conditions (e.g., lupus) Medication induced (e.g., steroids) Neurologic conditions (e.g., multiple sclerosis, frontal tumors or stroke, frontal seizures) |
| Hypoactive delirium | Numerous etiologies |
| Anoxic brain injury | Overdose (e.g., opioids) Drug induced (e.g., cocaine-induced vasospasm; progressive leukoencephalopathy from opioid inhalation) |
| Major neurocognitive disorder | Secondary to chronic substance use (e.g., opioids; alcohol; inhalants; cocaine/methamphetamines) |
Treatment
The Four Quadrant Clinical Integration Model developed by the National Council for Community Behavioral Healthcare in conjunction with SAMHSA recommends management of patients with mental health needs across psychiatric, primary care, and other health-care settings. For psychiatric comorbidity, ASAM recommends a comprehensive evaluation to determine stability, direct questioning around suicidal ideation/behaviors to reduce and monitor suicide risk, and pharmacotherapy and other psychosocial interventions as needed [ ].
Selective serotonin reuptake inhibitors (SSRIs) are the first-line recommended pharmacological treatment for patients with depression of all levels of severity. Serotonin–norepinephrine reuptake inhibitors (SNRIs) and other antidepressants (e.g., bupropion, mirtazapine) are also appropriate to use in the first-line management of depressive symptoms in patients with OUDs. While there is good evidence for the use of TCAs in the management of depression, these medications should be avoided in patients with high impulsivity and who are at overdose risk. Choice of antidepressant should rely on the individual profile of the patient, including consideration of drug–drug interactions, personal history of medication use, family history of treatment response, side effect profile, and pharmacokinetic considerations. Appropriate titration of medications should be undertaken with medication trials of at least 4–8 weeks at the maximum tolerated dose [ ].
Psychotherapy can also be considered as monotherapy for patients with mild depression or in conjunction with an antidepressant in patients with moderate to severe depression. Cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) in patients with SUDs have strong evidence to support their use. Use of motivational interviewing techniques can enhance engagement to treatment and facilitate behavioral change. Mindfulness-based interventions have also been found to be effective [ ].
Anxiety disorders
Similar to depressive disorders, anxiety disorders are highly comorbid with OUDs and interfere with coping [ ], achieving, or maintaining abstinence from opioids, and may perpetuate the cycle of addiction [ ]. The lifetime prevalence of an anxiety disorder has been associated with early onset of heroin use and is also a factor associated with rapid transition to addiction [ ]. Moreover, patients experiencing opioid withdrawal or undergoing opioid detoxification may experience significant symptoms of anxiety [ ].
Epidemiology
A review found that 26%–35% of patients with OUDs had a lifetime prevalence of anxiety disorders [ ]. The lifetime comorbidity rates for patients with opioid, sedative, and tranquilizer use with anxiety disorders are cited at 60% (not including PTSD or OCD), higher than with other substances of misuse [ ]. In one study of 90 patients with prescription opioid misuse, panic disorder was the most common comorbid psychiatric disorder (13.9%), followed by generalized anxiety disorder (10.7%) [ ]. Kidorf et al.’s study of over 200 patients with injection drug use found women more likely to have diagnoses of most anxiety disorders [ ].
Diagnostic criteria and workup
The DSM-5 anxiety disorders include separation anxiety disorder, selective mutism, specific phobia, social anxiety disorder, panic disorder, agoraphobia, generalized anxiety disorder, substance/medication-induced anxiety disorder, and anxiety disorder due to another medical condition.
Validated screening tools for anxiety disorders include the generalized anxiety disorder (GAD 7) and the Hamilton Anxiety Rating Scale. The workup for an anxiety disorder in a patient with an OUD includes ruling out medical mimics of anxiety, such as infection, metabolic abnormalities, cardiac conditions (e.g., endocarditis, atrial fibrillation), pulmonary conditions (e.g., pulmonary embolism, asthma), and endocrine disorders (e.g., hypo- or hyperthyroidism).
Treatment
First-line treatment of anxiety disorders in patients with OUDs includes psychotherapy (e.g., CBT, mindfulness-based interventions) and antidepressant medications (e.g., SSRIs and SNRIs). An appropriate trial of an antidepressant is 4–6 weeks at maximum tolerated dose. Patients with anxiety sensitivity may have a lower tolerability of associated side effects, necessitating a slower titration. Adjunctive agents that may be considered in the management of anxiety disorders include buspirone, hydroxyzine, clonidine, propranolol, and less commonly antipsychotics [ ].
While benzodiazepines are commonly prescribed for acute anxiety, these medications are not recommended for chronic treatment, especially in patients with co-occurring SUDs. In a survey of patients seeking opioid withdrawal management, 44% had used benzodiazepines in the previous month; of these patients, 42% used these for anxiety and 27% to enhance euphoria from another substance [ ]. Due to the high potential for misuse, prescribing benzodiazepines to patients with OUDs is discouraged [ ].
Bipolar disorder
Bipolar disorder (BD) is a serious mental illness marked by alternating intervals of elevated and depressed mood [ ]. Affecting approximately 2.6% of the national population, BD is a complex condition characterized by a range of negative outcomes including poor quality of life, reduced overall functioning, increased medical burden, and heightened mortality [ ].
Epidemiology
BD is highly comorbid with SUDs. In the National Epidemiologic Survey on Alcohol and Related Conditions, lifetime mania was present in 8.9%–33.4% of patients with substance use or dependence while hypomania was present in 3.7%–13.4% [ ]. A meta-analysis examining the prevalence rates of SUDs in treatment-seeking bipolar patients within both inpatient and outpatient settings found alcohol use in 42%, cannabis use in 20%, and other illicit drug use in 17% of patients [ ]. In a separate sample of opioid-dependent treatment-seeking patients referred from needle exchange, 12% were found to meet criteria for bipolar I disorder in the past 12 months [ ].
Diagnostic criteria and workup
The DSM-5 defines bipolar I disorder to comprise a history of a manic episode. Although typically associated with depression, a major depressive episode is not required for diagnosis of bipolar I disorder. A manic episode is defined as a 1-week period (or any duration if hospitalized or treated) of abnormally and persistently elevated, expansive, or irritable mood and increased energy with three or more associated symptoms including grandiosity, decreased need for sleep, pressured speech, racing thoughts, distractibility, increased goal-directed activity, or reckless behaviors. Bipolar II disorder requires a history of a major depressive episode (as defined in depression section above) and a hypomanic episode. Hypomania should be observable by others but should not be severe enough to cause impairment in social or occupation functioning. Other DSM-5 bipolar and related disorders include cyclothymic disorder, substance/medication-induced bipolar and related disorder, bipolar and related disorder due to another medical condition, other specified bipolar and related disorder, and unspecified bipolar and related disorders [ ].
For screening, SAMHSA recommends using the Composite International Diagnostic Interview (CIDI)-based screening scale for Bipolar Spectrum Disorders in patients with SUDs. CIDI-based screening scale identifies between 67% and 96% of BD cases [ ]. The Mood Disorder Questionnaire has been evaluated as a screen for BD in SUD populations but has not been found to be useful [ ].
Diagnosis of BD in patients with SUDs can be challenging as acute intoxication, particularly with cocaine or amphetamines, or withdrawal from alcohol or benzodiazepines may also be mistaken for mania or hypomania. When a patient presents with an apparent mania or hypomania, medical conditions that cause or present with mania (or agitation) should be considered (see Table 11.2 ). Further, medications such as steroids may induce mania. Phenomenological considerations associated with SUDs may also confound the clinical picture such as disruptions in sleep–wake cycle, risk-taking behaviors to procure drugs/alcohol, and distractibility/increased goal-directed behavior related to cravings.
| Medical mimics | Infection (e.g., spinal abscess, pneumonia) Cardiac events (e.g., myocardial infarction) Nutritional deficiencies (e.g., B12) Endocrine conditions (e.g., hypercortisolism, hyperthyroidism) Oncological conditions (e.g., pancreatic cancer) Rheumatological conditions (e.g., lupus) Medication induced (e.g., steroids) Neurologic conditions (e.g., multiple sclerosis, seizures, stroke, traumatic brain injury) Autoimmune conditions (e.g., systemic lupus erythematosus) |
| Hyperactive delirium | Numerous etiologies |
| Substance use disorders | Acute intoxication (e.g., cocaine or amphetamines) Withdrawal syndromes (e.g., from alcohol or benzodiazepines) |
Treatment
Treatment of BD can be complex and is individualized according to a patient’s symptoms, needs, preferences, and responses to treatment. Suspected BD should trigger referral to a psychiatrist as treatment involves both pharmacological and psychosocial therapy. Choice of treatment can target mania, bipolar depression, or maintenance of a euthymic state. Mood stabilizers (e.g., lithium, valproic acid, carbamazepine, and lamotrigine) as well as antipsychotics are the mainstay of treatment [ ]. Psychosocial treatments for BDs include CBT, family-focused therapy, and interpersonal and social rhythm therapy (IPSRT) [ ].
Psychotic disorders in patients with SUDs
Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis and is characterized by hallucinations, disorganized thoughts and speech, negative symptoms, and cognitive impairment [ ]. Schizophrenia is ranked by the World Health Organization as one of the top 10 illnesses contributing to the global burden of disease [ ].
Epidemiology
The lifetime prevalence of SUDs among patients with schizophrenia has been estimated to range from 47% to 59% in the United States compared with 16% in the general population [ , ]. A 2018 systematic review and meta-analysis by Hunt et al. estimated prevalence rates of OUDs in patients diagnosed with schizophrenia or first-episode psychosis as 4.8% [ ].
Diagnostic criteria and workup
The DSM-5 defines schizophrenia as a 1-month period with two or more of the following: delusions, hallucinations, disorganized speech; grossly disorganized or catatonic behavior; negative symptoms (affective flattening, alogia, or avolition). Further, there must be a 6-month period of continuous signs of disturbance that do not need to meet the above criteria (e.g., negative symptoms only or attenuated forms of above symptoms). Substance/medication-induced psychotic disorder is the presence of delusions and/or hallucinations during or soon after intoxication, withdrawal, or exposure to a substance, with the disturbance not being better explained by another type of psychotic disorder. Other DSM-5 schizophrenia spectrum and other psychotic disorders include schizoaffective disorder, delusional disorder, brief psychotic disorder, schizophreniform disorder, psychotic disorder due to another medical condition, other specified schizophrenia spectrum and other psychotic disorder, and unspecified schizophrenia spectrum and other psychotic disorder [ ].
Workup for psychosis, particularly for patients who do not have an established diagnosis of schizophrenia, should be broad and includes ruling out contributions from medical conditions that cause or present with psychosis (See Table 11.2 ). Acute intoxication, particularly with cocaine or amphetamines, or withdrawal from alcohol or benzodiazepines may be mistaken for or present with psychosis. Further, medications such as steroids may cause psychosis.
Treatment
Treatment of schizophrenia involves both pharmacologic and psychosocial components. Antipsychotics are the mainstay of pharmacologic treatment. No antipsychotic has been shown to be more effective than another in the treatment of schizophrenia aside from clozapine in the treatment-refractory population. As such, antipsychotic choice is guided by the tolerability, past response, side effect profile, medical comorbidities, and patient preference [ ]. Psychosocial interventions that have efficacy in treating schizophrenia include skills training, family-based education intervention, cognitive remediation, and CBT [ ]. A 2013 Cochrane systematic review and meta-analysis of patients with co-occurring severe mental illness and substance use did not show clear evidence of the efficacy of psychosocial interventions or evidence to recommend any one intervention over another [ ]. Despite this review, guidelines continue to support the use of psychosocial interventions in addition to pharmacotherapy for patients with co-occurring schizophrenia and SUDs [ , ].
Trauma in patients with SUDs
Since the adverse childhood experiences study illustrated the additive, detrimental effects of trauma on physical and mental health outcomes, more attention has been paid to individuals with a history of trauma. Evidence has shown that traumatic experiences in childhood have negative impacts on neurobiological development which in turn predisposes individuals to develop later psychiatric illnesses such as posttraumatic stress disorder (PTSD) and SUDs [ ]. As comorbid PTSD and SUD result in poorer health outcomes and social functioning when compared to either disorder alone [ ], it is critical that individuals with an identified SUD are screened for PTSD.
Epidemiology
The co-occurrence of SUD and PTSD is well established with a lifetime prevalence of PTSD estimated at 26%–52% in individuals carrying an SUD diagnosis [ ]. As it pertains to OUD specifically, data from multiple studies support the high rate of coexisting OUD and PTSD. Furthermore, specific populations including women with a history of sexual trauma have higher rates of nonmedical use of prescription drugs including opioids [ ]. Veterans with a history of PTSD, when compared to those without an underlying psychiatric illness, were more likely to receive prescription opioids as well as demonstrate higher-risk opioid use as marked by higher doses, receiving more than one type of opioid and/or concurrent sedative-hypnotic, as well as refilling opioid prescriptions early [ ]. Finally, while a history of trauma and PTSD increases an individual’s risk of developing an OUD, individuals who engage in IV drug use are often exposed to further traumatic experiences in the context of acquiring or using illicit substances [ ].
Diagnostic criteria and workup
The DSM-5 defines PTSD as a trauma and stressor-related disorder resulting from exposure to a traumatic event as defined by actual or threatened death, serious injury, or sexual violation [ ]. Exposure can take the form of direct experience, witnessing the traumatic event, learning that the event happened to a family member or friend, or experiencing repeated or extreme exposure to details of the traumatic event. Diagnosis of PTSD requires that symptoms from the following four clusters are present for at least 1 month after a traumatic exposure: reexperiencing, avoidance, negative cognitions and mood, and hyperarousal. Examples of screening tools for PTSD include The Abbreviated PTSD checklist–civilian (PCL-C), a shortened version of the PTSD checklist, and The Life Events Checklist (LEC).
Treatment
Treatment of comorbid PTSD and SUD depends upon an integrated approach utilizing psychosocial interventions, evidence-based psychotherapies, and pharmacotherapies [ , ]. Trauma-focused therapy is the gold standard treatment for PTSD alone, and other available modalities include prolonged exposure, cognitive processing therapy, eye movement desensitization and reprocessing (EMDR), and CBT. Research pertaining to the effectiveness of psychotherapy for PTSD in the context of a comorbid SUD is limited [ ]; however, Seeking Safety: A Treatment Manual for Trauma and Substance Use is an evidence-based treatment to address both PTSD and SUDs and has been found to be effective in numerous settings with measurable improvements in overall functioning [ ].
First-line pharmacological treatment for PTSD includes SSRIs with recommended trial of 4–6 weeks. While research regarding the effects of alternative antidepressants such as SNRIs and TCAs in patients with co-occurring SUD is lacking, these medications can also be considered to target PTSD-related symptoms. Prazosin, an alpha-1-antagonist, has been shown to mitigate trauma-related nightmares [ ]. However, a recent study in veterans with chronic PTSD did not find prazosin improved trauma-related nightmares [ ].
Cognitive and capacity concerns in patients with SUDs
Opioids can affect cognition at therapeutic doses and can lead to deficits across a range of neuropsychological domains [ ]. These effects on cognitive function center on the presence of opioid receptors in the brain that modulate attention, memory, and learning. In a systematic review, opioid use affected delayed episodic memory, attention, language, verbal working memory, cognitive impulsivity, and verbal fluency [ ]. Additionally, overdose of opioids can lead to hypoxic brain injury resulting in chronic cognitive deficits. Acquisition of opioids can expose patients to dangerous situations and increase the risk of traumatic brain injuries, which can result in diffuse axonal injury, chronic attention and memory deficits, emergence of impulsivity, and disinhibition. Chronic OUD and its impact on cognition are understudied.
The effects of opioid use on cognition may affect a patient’s medical decision-making capacity. For this reason, assessment of cognition through formalized screening tools may be needed and can include the Montreal Cognitive Assessment, Mini-Mental State Exam, or other validated cognitive scale in quantifying the level of impairment. Prior to evaluation of medical decision-making capacity, the patient should be provided the relevant clinical information to make an informed decision. The four-factor model for assessing decision-making capacity includes: (1) ability to communicate a clear and consistent choice, (2) demonstration of a clear understanding of relevant clinical information, (3) assessment of the risks and benefits of each treatment option, and (4) appreciation of the consequences of the clinical scenario and decision made [ ]. This assessment is contingent upon the specific risk to benefit ratio of the medical decision.
A common question in the hospitalized patient with OUD is decision-making capacity to leave against medical advice (AMA) as patients with SUDs are up to three times more likely to make this request [ ]. Recommendations are based on the specific medical risks of stopping inpatient treatment and available strategies to mitigate risks. If the patient is deemed to lack decision-making capacity, treatment should focus on approaches to restore capacity when possible, assessment of the underlying reason and motivation for leaving the hospital, mitigation of risk, and identification of a surrogate decision-maker. Data from an inpatient unit specializing in substance withdrawal found that admission from the emergency department (ED), younger age, and higher withdrawal scores were associated with AMA discharges [ ]. In a qualitative study, the main themes by patients’ for leaving prematurely center on undertreated withdrawal and cravings for substance use, inadequate pain control, perceived stigma from hospital staff, and hospital restrictions (e.g., restrictions to leave the unit) [ ]. Understanding the patient rationale for request to leave AMA can prevent negative health outcomes, and a thorough evaluation to identify potential causes is essential to prevent premature discharge and suboptimal care. See the example clinical scenario and assessment below for more information.
Clinical Vignette: Ms. X is a 20-year-old woman with a past medical history significant for opioid use disorder who presented to the medical hospital for chest pain and was diagnosed with endocarditis of the tricuspid valve. Vital signs notable for blood pressure of 135/90, heart rate of 108, respiratory rate of 14, temperature of 37.0. IV antibiotics were initiated as well as consultation with cardiothoracic surgery. On hospital day 2, the patient requested to leave against medical advice. The medical team notes high risk of sepsis without treatment. See Table 11.3 for assessment of decision-making capacity .
