Addiction in Clinical Practice: Psychiatry
William M. Greene, MD; Mark E. Sylvester, MD; Lisa J. Merlo, PhD
University of Florida, Department of Psychiatry, Division of Addiction Medicine

Abstract
The substance-related disorders are underdiagnosed and frequently misdiagnosed in the clinical practice of psychiatry; however, the magnitude of their influence cannot be overstated. Substance use can complicate the diagnostic process as well as the recommended course of treatment for patients. It is common among patients with mental health problems, and symptoms of substance use disorders are often mistaken for other psychiatric conditions. Given the importance of accurate diagnosis to the success of treatment, many factors should be considered when evaluating patients for substance use and related disorders. The present review highlights key issues in the assessment and treatment of psychiatric patients with comorbid substance use.

Keywords: addiction; psychiatry; clinical practice; review

Introduction
Patient substance use is an important factor to consider in the clinical practice of psychiatry. Substance abuse and dependence are serious conditions in their own right; in addition, substance-induced mental disorders or comorbidity of a primary psychiatric disorder with an addiction disorder can complicate an otherwise seemingly straightforward diagnosis. When substance use disorders co-occur with other Axis I disorders, the clinician must determine whether the etiology of psychiatric symptoms stems primarily from substance use, endogenous neurochemistry, or other psychological or developmental factors. Clarifying the extent to which substance use contributes to the presenting problem will facilitate effective treatment planning and maximize the likelihood of successful treatment outcome. This paper reviews important considerations in the treatment of patients with substance use and primary psychiatric disorders in order to help clinicians optimize their care.

Epidemiology
Substance use disorders and other psychiatric disorders are relatively common. Almost 40% of Americans admit to using one or more illicit substances in their lifetime (1). Indeed, the lifetime prevalence of any substance use disorder in the general American population has been estimated at 26.6% (2), though the risk is estimated to be even higher among select groups (3). With regard to psychiatric disorders, according to the National Institute of Mental Health (NIMH), primary psychiatric illnesses make up 26.2% of medical illnesses in a given year (4), and mental disorders are the leading cause of disability among individuals between the ages of 15-44 in the U.S. and Canada (5).

Psychiatric disorders also frequently coexist with substance use disorders. In fact, in 2007, the Substance Abuse and Mental Health Services Administration (SAMHSA) approximated that 4.6 million individuals in the United States are affected by co-occurring mental and substance abuse disorders (6). Clinical studies and epidemiologic surveys consistently indicate that substance use disorders and mood and anxiety disorders have strong associations when considered on a lifetime basis (7). Other research has demonstrated that 70-80% of patients being treated in addiction clinics have a comorbid psychiatric disorder (such as depression, anxiety, or schizophrenia), and approximately 50-80% of patients being treated in a mental health clinic have a comorbid substance use disorder (8).

Unfortunately, there are relatively few research studies which have specifically studied the prevalence of the nine substance-induced mental disorders defined by the Diagnostic and Statistical Manual of Mental Disorders (9). Nevertheless, it is important to recognize how substance use can mimic a myriad of psychiatric symptoms. For example, three such disorders are referred to as “organic brain syndrome” (i.e., substance-induced delirium, substance-induced persisting amnestic disorder, and substance-induced persisting dementia). Four others include the substance-induced disorders of mood, psychosis, anxiety, and sleep. The remaining two are substance-induced sexual dysfunction and hallucinogen persisting perceptual disorder. In general, the literature regarding substance-induced mental disorders is limited to descriptions of the underlying symptoms or concurrent disorder and has served primarily to raise professional awareness of these conditions (10). However, some attempts have been made to estimate their prevalence (11-13).

Diagnostic Issues
Historically, patients with comorbid psychiatric and substance use disorders have been under-diagnosed or misdiagnosed. The challenge of differentiating concurrent substance use disorders from psychiatric disorders necessitates strict adherence to the diagnostic criteria in order to accurately distinguish between substance intoxication, withdrawal symptoms, and the symptoms of psychiatric disorders. Indeed, the diagnostic criteria for psychiatric disorders mandate that substance use must always be ruled out before assigning a diagnosis (9). In addition, attention to the temporal sequencing of symptom onset is critical to determining the appropriate diagnosis. These steps are necessary to properly classify the illness and to optimize treatment efforts. For example, to isolate an independent mood or anxiety disorder from a substance use disorder, the DSM-IV (9) requires either 1) evidence that the mood or anxiety syndrome was occurring before substance use, or 2) evidence that the mood or anxiety syndrome persisted for 4 weeks or more after the cessation of intoxication or withdrawal. Alternatively, isolation of a substance-induced disorder requires that the mood or anxiety symptoms coincide with periods of substance use or remit shortly thereafter.

Unfortunately, clinicians frequently overlook or underestimate the impact of substance use due to patient denial, lack of experience managing patients with substance-related problems, inadequate screening methods, or faulty value judgments regarding the “typical” alcohol or other drug user. As a result, clinicians may find it beneficial to order urine drug screening with new patients and to adequately survey all potential psychotropic chemicals which are not included in the urine toxicology. Confirmation of history through collateral sources such as family, friends, or other health care professionals may be valuable.

Finally, the distinction between behaviors caused by substance use versus mental illness can be difficult to make, particularly when there exists a great deal of overlap between the two. For example, depression and mood instability are relatively common among patients with substance use disorders (14); whereas, a strong association between schizophrenia and nicotine use exists (15). As a result, when substance use is suspected, the clinician should obtain a complete medical and psychiatric history (emphasizing substance use history) before attempting to identify or label the patient’s condition(s). Other addictive behaviors (e.g., compulsive gambling, sex addiction, eating disorders, or internet addiction) should be explored as well. Failure to identify such symptoms as a primary or contributing cause to the patient’s distress and/or impairment may increase the chances of a misdiagnosis.

Treatment Considerations
There are several important considerations in the treatment of addictive disorders, including how to most effectively approach the patient and build rapport, determination of the most appropriate level of treatment, decisions regarding whether or not to utilize therapeutic or prophylactic medications, and referral for psychological treatment and/or participation in mutual-help groups. Each of these factors plays an important role in treatment acceptance, success, and relapse prevention.

Building Rapport
The doctor-patient relationship affords a unique opportunity to have a major impact on patients’ lives with relatively little effort on the part of the physician. So-called “brief interventions,” which may last just a few minutes in a primary care setting, have consistently proven beneficial in changing addictive behaviors (16). Common elements of brief interventions include assessment, feedback, negotiating, behavioral modification techniques, self-help bibliotherapy, follow-up, and reinforcement (17). When approaching the potentially uncomfortable topic of problematic or illicit substance use with a patient, it is often helpful to assure confidentiality, take a non-judgmental stance, express empathy, and provide hope (18). Building a cooperative alliance with the patient is more effective in changing behavior than taking an authoritarian stance (19).

Level of Treatment Required
In general, evaluation to determine the appropriate recommended level of treatment is best conducted by following the American Society of Addiction Medicine’s publication, ASAM Patient Placement Criteria for the Treatment of Substance-Related Disorders, 2nd Edition-Revised (20). This approach evaluates the patient’s status on six different dimensions in order to stratify their risk in a meaningful and reliable way. The first dimension deals with the patient’s potential for experiencing significant withdrawal symptoms, whereas the second and third dimensions assess for the presence of medical and psychiatric comorbidities. The fourth dimension evaluates the patient’s current readiness for change. Finally, the fifth and sixth dimensions assess the patient’s potential for relapse and the presence or absence of a supportive environment. A trial of abstinence with outpatient psychotherapy may be considered initially if the patient has a strong support network, is in a safe environment, and there is no medical risk for withdrawal (10). However, if abstinence and outpatient psychotherapy are not adequate or appropriate, partial hospitalization or inpatient treatment at a medical hospital, psychiatric unit, or treatment center may be warranted.

Considerations in the Use of Pharmacotherapy
Regardless of the proper placement of the patient, there are several medication-related issues to consider when treating patients with substance use disorders. For example, although pharmacotherapy is a standard form of treatment for many psychiatric disorders, new evidence suggests that clinicians should consider the interaction of comorbid substance usedisorders in order to maximize the effectiveness of the treatment and minimize potential negative consequences (21). In addition, many medications that are commonly used for the treatment of psychiatric disorders should be avoided when possible in patients with co-occurring substance use disorders (22). However, in certain cases of medical necessity (e.g., alcohol withdrawal or trauma), potential drugs of abuse such as benzodiazepines or opiates may be used with caution (23).

In most cases, the goal of pharmacotherapy is to actively facilitate weaning from the substance of abuse as soon as tolerated and/or to reduce the likelihood of relapse to active use. In both cases, close monitoring of the patient is required. Substance dependence produces powerful cravings, which are experienced as distressing and may encourage patient efforts at self-medication (24). Given the potency of these medications and their potential lethality when combined with other substances, this is a serious concern. As a result, the choice of medication should be carefully considered before prescription. For example, in some situations it may be beneficial to utilize an agonist medication such as methadone as a maintenance treatment to facilitate abstinence from heroin or other opiates while minimizing withdrawal symptoms (25). Methadone is generally considered a safer alternative to short-acting opiates and can be used to promote elimination of illicit drug use and recruitment into a full detox and recovery program (25). In other cases, use of a combined agonist-antagonist medication such as buprenorphine (Suboxone, Subutex) may be preferable. These medications work to block the euphoric effects at the receptor level and to minimize withdrawal and subsequent drug seeking behavior (25). Finally, anticraving medications (naltrexone, acamprosate, etc.) can be very useful for patients who acknowledge their disease and are willing to actively participate in treatment (26). These medications are frequently used in treatment centers and early cessation programs. However, patients with a firm commitment to their recovery and/or a history of sustained sobriety may be successful without the assistance of these medications (10).

Other considerations in the use of pharmacotherapy relate to other symptoms commonly associated with substance use and negative side effects of the medications. For example, one common symptom in early abstinence is insomnia, but use of sedatives and sleep medications with potential for abuse (e.g., zolpidem, eszopiclone, zaleplon, diphenhydramine) should generally be avoided when treating patients with substance use disorders, due to the risk of instigating a relapse (27). Behavioral treatment methods are typically recommended (28); though use of sedating antidepressants such as trazodone or doxepin, which lack abuse potential, may be indicated for some patients (29). With regard to negative side effects of pharmacotherapeutics for substance use disorders, it is noteworthy that patients with comorbid pain can be particularly difficult to treat. Prescription of opiate medication may be contraindicated due to the potential for abuse (30), and dosing can be particularly challenging. Regular users of opiates will require a higher dose of medication for adequate acute pain management (30), as will individuals who are being treated with an opiate-antagonist medication (31). In either circumstance, the support of a pain management specialist familiar with both substance dependence and ancillary pharmacotherapy should be enlisted (30). Evidence shows that a relatively high rate of sobriety can be achieved through active participation in 12-step support groups (32).

Treatment of Specific Psychiatric Conditions with Comorbid Substance Use
The following section will explore individual psychiatric disorders and discuss which drugs may mimic psychiatric symptoms either in their use or withdrawal. Also discussed will be which drugs to avoid in the treatment of psychiatric symptoms or disorders in comorbid substance use disorders. Finally, a discussion of safe alternatives, goals, and protocols for therapy will be included.

Affective Disorders
The most common pathological psychiatric symptom from the use of central nervous system depressants is depression (10). Therefore, these chemicals (alcohol, benzodiazepines, barbiturates, etc.) can both mimic and exacerbate clinical depression during both active use and withdrawal. Acute depressed mood following cessation of stimulant, opiate, or sedative use is also extremely common (10). After appropriate detoxification efforts and abstinence from the drugs of abuse, the depressive symptoms will frequently ameliorate or remit within a short period of time. For example, alcohol-induced depression generally resolves within the first two or three weeks of abstinence (10). In a study of over 3000 alcoholics, researchers concluded that substance-induced depression (26%) was more prevalent than independent major depressive disorder (15%), that those with substance-induced depression had more severe alcohol and drug histories, and that those with independent depression had more first-degree relatives with affective disorders (33). In another study of male alcoholics, 42% displayed depressive symptoms upon admission, with rapid abatement of symptoms leaving only 12% symptomatic after two weeks (11). Other depressants, such as benzodiazepines and barbiturates, show similar periods of depressive symptom abatement. However, though substance-induced depression may dissipate rapidly, it is considered as dangerous as or more dangerous than major depressive disorder in terms of the risk of suicide and self-injurious behavior (10). In fact, some researchers report that alcoholic patients have up to a 120-fold greater risk of death by suicide than the general public (34).

Chemicals such as cocaine, amphetamines, and MDMA (Ecstasy) promulgate mania and may mimic and/or exacerbate bipolar disorder. The use of these chemicals provides an intense euphoria or “rush” with hyperactive behavior and speech, anorexia, insomnia, inattention, and labile moods (35). The dosage and route of administration of these drugs affect the intensity of the experience and its effect on mood (36). In addition, if several weeks of abstinence are maintained, many stimulant users report a dysphoric state marked by anhedonia which may persist for weeks (37).

Anxiety Disorders
Treatment of patients who have an anxiety disorder with comorbid substance use can be particularly challenging because several anxiolytic medications have high abuse potential. For example, the benzodiazepines are frequently used in the treatment of acute anxiety, but for patients predisposed to substance abuse and dependency (i.e., those with positive family history, early age of first use, etc.), iatrogenic addiction is a significant concern. Therefore, in treating patients with comorbid substance use and anxiety disorders, alternative agents such as serotonin or serotonin/norepinephrine reuptake inhibitors (SSRIs, SNRIs), buspirone, anticonvulsants, antihypertensives, and even neuroleptics should be considered (38). If treatment with a benzodiazepine is clinically indicated, the risk can be minimized by choosing long-acting benzodiazepines such as clonazepam instead of shorter-acting (and more addictive) agents such as alprazolam (14). Beyond medications, the adjunctive and primary role of psychotherapy in the treatment of anxiety disorders (especially cognitive-behavioral therapy) should not be underestimated. Strong evidence suggests that, for several anxiety disorders, cognitive-behavioral therapy is as effective, if not more effective, than any medication (39).
Treatment of substance-induced anxiety is also complicated. For example, acute withdrawal from virtually any drug can precipitate symptoms of anxiety (40). Once appropriate detoxification has been achieved (to minimize physiologic concerns), treatment of the anxiety symptoms should be initiated. As indicated previously, use of benzodiazepines may be particularly dangerous for the patient with substance dependence, not only due to their potential as drugs of abuse, but also because their use is associated with lowered inhibitions and accidents (41). Use of benzodiazepines may provoke relapse, which is particularly dangerous in the case of relapse to alcohol use. The interaction between alcohol and benzodiazepines can result in agitation or even death by respiratory depression. As a result, the use of benzodiazepines in alcoholics (after detoxification) remains controversial, even in the face of severe anxiety (10).

The relation between anxiety and cannabis use is complex. Marijuana use is known to trigger heightened levels of anxiety and/or panic attacks in certain individuals either with or without a substance use disorder (42-47). Furthermore, researchers have noted both a higher incidence of panic attacks as well as an earlier age of onset of attacks among cannabis users (19 years old for cannabis users vs. 28 years old in cannabis naïve) (48). On the other hand, some marijuana users report that the drug helps them to feel “more normal” and experience a decreased level of anxiety (49). Clinical experience suggests that these individuals may have an underlying anxiety disorder which they are self-treating. As a result, a careful history should be conducted in order to elicit enough information to distinguish the two disorders.

Psychotic Disorders
Symptoms associated with psychosis frequently result from the acute effects of various psychoactive drugs. As a result, many individuals are misdiagnosed with a psychotic disorder following the use of hallucinogens, cocaine, amphetamines, or anticholinergics. The effects of these chemicals may mimic psychosis in the healthy patient; in addition, the chemicals themselves are prone to cause or exacerbate psychotic behavior (50). Indeed, in a study examining substance-induced psychotic disorders, researchers prospectively observed admissions to an acute psychiatric inpatient unit over the course of a year. During that time they found that 30% of admitted patients met DSM-IIIR criteria for organic mood disorder, 8% for organic hallucinosis, and 6% for organic delusional disorder (51).

In addition to the concerns related to acute intoxication effects, individuals occasionally become delusional or paranoid after prolonged heavy use of cocaine or amphetamine (10). In the paranoid state, the user may maintain intact abstract reasoning and linear thinking; whereas, they generally display delusions that are poorly developed and of a nonbizarre nature. Some stimulant users report visual hallucinations such as “coke snow” or tactile hallucinations (e.g., “coke bugs”) (10). Sleep disturbances are prevalent among individuals who are under the influence of these drugs, which may contribute to psychotic behavior through sleep deprivation (52). Hallucinogens such as cannabis, LSD, PCP, Ketamine, dimethyltryptamine (DMT), dextromethorphan (DXM), mescaline, and psilocybin mushrooms produce visual distortions and overt hallucinations (53). First and second generation antipsychotics are frequently effective in controlling acute agitation and psychosis, but there is some indication that quetiapine may have some abuse potential and should be used with caution in the treatment of individuals with primary or comorbid substance use disorders (54).

Finally, the development of psychotic symptoms in individuals who suffer from alcohol dependence is a significant concern. Alcoholic hallucinosis is most notable in the withdrawal phase between 12 hours and 2 days (10). Both auditory and visual hallucinations are known to occur when the patient is alert and well oriented. The most common symptoms include command or threatening auditory hallucinations, which may cause the patient to become agitated and paranoid (23). Though the most typical time for emergence of psychotic symptoms is 2 days, some symptoms (particularly paranoia) have been reported to last for weeks to months and may be evidence of a predisposition to an independent psychotic disorder (55). Indeed, there can be tremendous similarity between alcohol-related psychotic symptomatology and symptoms of schizophrenia (50).

Attention Deficit Hyperactivity Disorder (ADHD)
Attention Deficit Hyperactivity Disorder is a common behavioral disorder in children and adolescents, which presents unique substance-related concerns. Behavioral disorders, such as ADHD, are frequently comorbid with substance use disorders (56-58). Evidence suggests that untreated ADHD is actually a risk factor for subsequent development of substance use disorders and that early intervention may serve as a protective measure (59). Since most drug use originates in adolescence or even childhood (60), some researchers conceptualize substance use disorders as similar to other developmental disorders. This would indicate that, like ADHD, the earlier treatment is initiated, the greater the likelihood of a successful treatment outcome (61). Since inadequate treatment of either disorder may potentially lead to poor outcome for the comorbid condition, many clinicians have suggested that treatment of both disorders should ideally be provided in an integrated fashion (62, 63).

On the other hand, stimulant treatment of a patient predisposed to substance use disorders may hasten the development of the disorder or cause an iatrogenic substance use disorder. Ironically, side effects of methylphenidate (Ritalin) can mimic the very disease it is designed to treat (i.e., hyperactivity, difficulty concentrating, etc.), as can other stimulants like cocaine or amphetamine derivatives (64). As a result, in order to optimize treatment, the first step should be to confirm the diagnosis and attempt treatment using behavioral therapy methods or a nonstimulant medication (e.g., atomoxetine) (65). If these efforts are unsuccessful, the clinician may recommend prescription of a stimulant medication with lower potential for abuse, such as the prodrug lisdexamfetamine (Vyvanse). This practice allows patients the greatest likelihood of having their disorder adequately treated with agents that have the lowest potential for abuse. If other therapeutic methods fail, and stimulant therapy is initiated in the patient with a substance use disorder, close monitoring must be maintained. In addition, adequate structure should be established to ensure proper compliance (including avoidance of drug diversion activities) with the medication (65). More research is needed to develop clinical practice guidelines regarding whether and when stimulant treatment may be appropriate for patients with comorbid ADHD and substance use disorders (59).

Cognitive Disorders
It is important to recognize that substance use disorders can afflict individuals of any race, gender, or age. Particularly among elderly patients, substance use disorders, withdrawal symptoms, and even appropriate use of prescription medications can mimic dementia and/or delirium. In addition, substance use and other mental health conditions have been associated with an increased prevalence of falls and higher mortality rates among elderly individuals (66). However, avoidance, early detection, and treatment of substance-related disorders improved morbidity and mortality. According to the American Geriatrics Society, the British Geriatrics Society, and the American Academy of Orthopaedic Surgeons Panel on Falls Prevention, there is a consistent association between the use of benzodiazepines and falls, regardless of setting (i.e., community, long-term care, hospital, or rehabilitation center). Furthermore, data suggest that there is no difference in the rate of falls between long-acting vs. short-acting class II benzodiazepines (67). As a result, it is recommended that use of these medications be avoided in elderly patients.

Conclusion
Due to the high prevalence of both psychiatric and addictive disorders, recent emphasis has been placed on the coexistence of psychiatric disorders with substance use disorders and other addictive behaviors. Substance use and the effects of psychotropic drugs (whether in their active use or withdrawal syndromes) have been referred to as “the great mimicker” of mental illness. Consequently, these disorders have frequently been misdiagnosed or correctly identified but treated inefficiently. New evidence suggests that integrating treatment for addictive and psychiatric disorders offers a more promising outcome.

Understanding the role that substance use, abuse, dependence, and withdrawal can play in the incidence, comorbidity, and exacerbation of psychiatric symptoms facilitates the diagnostic process and optimizes the chances for treatment success. Conducting a thoughtful and thorough interview, with ancillary acquisition of therapeutic markers such as urine drug screens, collateral information, and evaluation for other addictive behaviors and psychosocial dynamics, will also help to ensure accurate diagnosis. Relatively few epidemiological data exist on substance-induced mental disorders and organic brain syndromes, but new strategies are emerging for optimal treatment of these concurrent disorders. Knowing the available treatment options helps to minimize risk to patients while still achieving a safer and therapeutic outcome than treating the disorders without consideration of the potential for interaction effects. For example, it is generally advisable to avoid prescribing any drug with abuse potential to patients at risk for, or with a known history of, addiction. Proper placement of the patient based on risk stratification using the ASAM criteria allows the patient to receive the appropriate level care in which to address addictive and psychiatric disorders simultaneously.

Author Information
William M. Greene, MD, currently works as Assistant Professor of Psychiatry at the University of Florida in Gainesville, FL. The majority of his work is clinical, currently managing an inpatient detoxification unit, in addition to outpatient evaluations and follow-up. Dr. Greene’s main area of interest is in treating substance dependence as it relates to various psychiatric comorbidities. He is actively involved with evaluating and treating impaired healthcare professionals. He is also active in teaching medical students and residents. Dr. Greene received a BS in Biology from Wake Forest University in 1997 and completed medical school at the University of South Florida in 2003. Dr. Greene completed his psychiatric residency at University of Florida in 2007 and has been working in the field of addiction medicine since then. Dr. Greene serves on the University of Florida Alcohol and Drug Education Policy Committee, is a member of the American Society of Addiction Medicine, and has contributed to multiple publications related to substance abuse.

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