Dual Diagnosis

Dual Diagnosis

Dual diagnosis is a term generally defined as applying to a substance use disorder with a co-occurring psychiatric disorder (Duckworth & Freedman, 2013). However, clearly, patients with a substance use disorder are often being evaluated and treated for a long list of medical, neurological, endocrinological, nutritional and other diseases (Blum, Trachtenberg & Ramsey, 1988). Comorbidity is another commonly used synonym. Although the term dual diagnosis is the most commonly used unifying term, it actually refers to a very heterogeneous spectrum of disorders.

The concept of dual diagnosis was introduced in the early 1980’s in the U.S. (Dackis & Gold, 1984). We have worked with cigarette smokers who tried to quit and relapsed because of depression. The question was, if you could treat depression and cigarette dependence, would outcomes improve? Narcotic or cocaine addicts were also found to have anxiety disorders, depression and other major psychiatric comorbidities. Still, most experts thought that it was the old “is it a chicken or egg?” paradox. Naturally, alcohol and other drugs caused depression. But it was a toxic, chemically-induced state that would disappear once the offending agents were gone. In this model, detoxification and treatment for chemical dependency was an antidepressant.

Subsequently, there were some early models attempting unified treatment. Most of these began in academic medical centers. Eventually pilot programs utilizing the emerging treatment models started up through the efforts of government agencies. In 1987, an article appeared in Time magazine reporting on the treatment programs in New York state. Through this article, for the first time, the public was introduced to the problem (Gorman, 1987). In many ways, the chicken or egg paradox divided the field with addiction medicine saying that drugs caused depression so treat the addict, and addiction psychiatry saying one person had two or more diseases at the same time. Both, it appears, are correct but for different addicts.

Thirty years later, there still is much work to be done on validating best treatment models. But dual disorder, concurrent treatment requires a sophisticated approach with testing and trained addiction medicine specialists. Both are in short supply. Many other barriers remain to the integration of substance use treatment and co-occurring mental disorders.

An example of the problem with using the chicken or egg paradox in dual diagnosis is in consideration of the possibility that maternal smoking prenatally and childhood exposure to secondhand smoke may increase the incidence of schizophrenia later in life (Gold, 2007; Gold & Frost-Pineda, 2005). Such changes may be epigenetic in nature. Epigenetic changes are caused by environmental factors altering the shape of the supporting network of DNA that results in alterations in the way genes are expressed. The most common example of this is fetal alcohol spectrum disorder, which is the most common preventable cause of mental retardation in the United States (Green, Singh, Zhang, et al., 2007).

The “egg” side of the smoking issue is the well-known phenomenon of very high rates of nicotine dependence in those with mental illness. It is estimated that 80 to 85% of patients with schizophrenia are smokers.

This article reviews some of the key points that are of importance when working with dual diagnosis clients and suggests ways to optimize services to these individuals. We will also discuss treatment modalities and discuss avenues for further research and development of treatment models for this challenging clinical problem.

Epidemiology

Co-occurring substance use disorders and psychiatric illness are extremely common. Clinically, we expect that over 50% of treatment seekers (for mood, anxiety or addiction) will present with a serious co-occurring problem (Kessler, McGonagle, Zhao, et al.,1994). Depression, anxiety and hypomania are the most common clinical presentations with addiction. Fifty to sixty percent of all patients with schizophrenia and bipolar disorder have a lifetime occurrence of a substance abuse problem, not including nicotine.

Conversely, 37% of alcohol abusers and 53% of other substance abusers, not including nicotine, will be diagnosed as having at least one mental disorder during their lifetime.

Risk factors for dual diagnosis disorders include male gender, young age, poor education, low socioeconomic status, general medical illnesses and military veteran status as well as those with conduct disorders (Kessler, McGonagle, Zhao, et al., 1994; Regier, Myers, Kramer, et al., 1984). The interested reader is referred to detailed statistics given in the Kessler and Regier articles.

Relationship Between Substance Abuse and Mental Illness

It is convenient to think of the etiology of dual diagnosis in the context of the chicken or the egg paradox. However, experience and research has revealed that this is an overly simplistic paradigm as previously indicated.

Psychiatric disorders may predate a substance use disorder. Many individuals with a mental health disorder either self-medicate with alcohol or other substances (DuPont& Gold, 2008). Examples of this are legion. Eighty to ninety percent of schizophrenics smoke cigarettes (Drake & Mueser, 2000). This may be therapeutic for them in that nicotine appears to “dampen” extraneous noise and auditory hallucinations through inhibition of a gating mechanism in the brain (Leonard, Adler, Benhammou, et al., 2001).

The old synonym for alcohol as “courage in a bottle” is well known to those suffering from various anxiety disorders since alcohol initially blunts anxiety and millions of people know of its utility as a “social lubricant.”

Likewise, sedatives, particularly short-acting benzodiazepines, may be prescribed or diverted for anxiety. Without proper monitoring, this frequently results in physical dependence, which is often very difficult to treat.

Many patients with co-occurring pain and resultant depression are prescribed opiates and rapidly discover that opiates in the short term are an extremely effective antidepressant as well—until they become dependent on them (Berrocoso, Sanchez-Blazquez, Garzon & Mico, 2009). Anecdotally, many patients with attention deficit disorders may self-medicate with cannabis because they feel that it reduces hyperactivity.

It is also theorized that severe mental illness increases the likelihood that the sufferer will be exposed to increased opportunities for substance use. The social isolation that many experience, the general decrease in economic status and the resultant dissociation from the mainstream of society, greatly increases the chance that the mentally ill person will encounter drug using opportunities. This concept has been termed downward drift (Fox, 1990).

Substance use disorders may cause or potentiate mental illness. For many years, it has been known that alcohol can cause permanent psychosis, which is very resistant to treatment (Smith & Hillman, 1999). Cocaine and amphetamines may cause psychosis that can last even after the drug is stopped (Bramness, Gundersen, Guterstam, et al., 2012). Panic attacks and even psychotic reactions are being seen with increasing frequency as the potency of cannabis increases (Zvolensky, Lewinsolm, Bernstein, et al., 2008). There is good evidence to indicate that marijuana smoking may provoke the earlier onset of schizophrenia in predisposed individuals. Acute psychotic events are even more common in smokers of “synthetic marijuana,” which is sold under the common names of Spice, K2, as well as many others. This is most likely due to the lack of antipsychotic components in these chemicals as opposed to their presence in natural cannabis. Inhalation of a variety of hydrocarbon solvents frequently results in a permanent organic brain syndrome and other psychiatric disorders (Wu & Ringwalt, 2006).

Methamphetamine and the methamphetamine analog, MDMA, commonly known as Ecstasy, produce permanent alterations in neuronal structure similar to those seen in traumatic brain injury (TBI) (Gold, Kobeissy, Wang, et al., 2009).

Finally, it is becoming apparent that alterations in the human genome may increase the risk for both substance use disorders and mental illness. Although detailed genetic mapping is still in its infancy, it appears that some of the gene alterations that increase risk for substance use disorders, and mental illness, may reside very close to or be identical to each other (Kendler, Chen, Dick, et al., 2012).

Adverse Consequences of Dual Diagnoses

It is clear that having a co-occurring substance use disorder and psychiatric disorder is significantly worse than having either alone.

The long-term prognosis for those with a dual diagnosis is much worse than a single diagnosis. Dually diagnosed individuals are less likely to achieve long lasting sobriety. Because of the increased destabilization of their lives, they are less likely to be compliant with treatment plans. They are much less likely to adhere to a regimen of medications with resultant relapse of their psychiatric illness and more frequent and prolonged psychiatric hospitalizations. The access to general medical care in the dually diagnosed is frequently delayed and as a result, illnesses tend to be more severe and premature death more likely. Violent and impulsive acts are much more likely in the dually diagnosed. Perhaps most concerning is that people who abuse drugs and alcohol are more likely to both attempt suicide and to die from their suicide attempts (Dumais, Lesage, Alda, et al., 2005; Pirkola, Marttunen, Henriksson, et al., 1999).

Adverse encounters with the criminal justice system are more common in the dually diagnosed and their rate of incarceration is higher, often leading to delayed or substandard care for their disorders. There is a high rate of co-occurring disorders among the prison population in the United States (Lehman, Myers, Thompson & Corty, 1993).

Diagnostic delays in individuals with co-morbidities are extremely common and result more from a deficiency in our mental health treatment systems than from the nature of dual diagnoses themselves. Many treatment providers are not conversant with both substance use issues and psychiatric disorders. Primary care providers are much more likely to make a diagnosis of mental illness than to correctly diagnose substance abuse (Pagano, Graham, Frost-Pineda& Gold, 2005). The reasons for this are multiple. First, substance abuse training, while improving in graduate training programs, is still woefully deficient so the provider may not be sufficiently trained to make the diagnosis. Second, mass screening on routine visits is not universally done. This may be due to issues such as time factors or embarrassment on the part of the provider. Many primary care providers, additionally, are frustrated by the lack of appropriate specialist care both for substance abuse and for mental illness in their communities (Drake, Essock, Shaner, et al., 2001).

Specialty care is likewise frequently deficient. Some providers of mental health services may be inadequately trained in substance abuse treatment and have little knowledge of, or access to those that are. And many nonpsychiatric addiction medicine specialists are inadequately trained in the identification and treatment of psychiatric disorders (Woody, 1996).

As can be readily seen, all of these considerations belie the importance of identifying and implementing appropriate evaluation and treatment models.

Treatment Models (After Detoxification and Early Stabilization)

Whatever treatment model is eventually utilized, initial evaluation and treatment must address acute substance abuse and psychiatric emergencies. It is beyond the scope of this article to discuss such treatment interventions, which may include detoxification and/or aggressive use of various psychotropic medications.

Three basic treatment models have been proposed and utilized in managing dually diagnosed individuals. These are parallel, serial and integrated. We will discuss each treatment model separately.

Parallel Model

In the parallel model a client is treated for both the substance use disorder and the psychiatric disorder concurrently but by two separate entities that operate independently. Interfacility communications are frequently deficient or nonexistent and may rely upon the client to facilitate. An additional barrier to effective information transfer in the United States is the stringent requirements by regulatory agencies that were established to protect the confidentiality of the patient, but in practice frequently impede the smooth flow of information.

Additionally, it is difficult in the early phases of treatment to motivate the patient into following up with more than one treatment provider and this often results in patients receiving less than optimal care or in many cases, creates enough frustration on the part of patients that they drop out of care altogether. It also is frequently difficult to synchronize care between agencies because of such issues as waiting lists, third party payer constraints and scheduling conflicts.

Serial Model

The serial approach involves treating what is considered to be the primary condition first and then addressing the secondary disorder. This has been described as being akin to the popular arcade game Whack-a-Mole in which one tries to hit the most obvious moles sequentially but other moles keep popping up with increasing speed and frequency. There are very obvious flaws in this approach. It assumes that one can accurately identify the primary disorder, which is very difficult to do. It also makes the assumption that each disorder is an entity unto itself, when, in fact, the two may interact with each other and have a synergistic effect. Without addressing both disorders simultaneously, it is unlikely that optimal treatment can be given to either the substance use problem or the psychiatric disorder.

This treatment approach also frequently fails to address other client needs such as housing problems, joblessness and isolation from support sources. Too often, one treatment entity assumes that the other one will address these problems and as a result, the client suffers.

In 2001, in an effort to address the ongoing problem of unsatisfactory treatment models, the American Society of Addiction Medicine (ASAM), proposed the concept of Dual Diagnosis Capable (DDC) and Dual Diagnosis Enhanced (DDE) programs. This simple concept essentially proposed that facilities offering care should be capable of both diagnosing and treating dually diagnosed clients. A link to the ASAM statement is provided in the reference section of this article.

Integrated Model

This leads us to what is arguably the most efficacious treatment model; the integrated approach. Although intuitively this would seem to be the best treatment model, and peer-reviewed trials would seem to indicate success in several parameters, some studies have shown little or no improvement in outcomes. The ambiguities in outcome data may be due to methodological difficulties in study design, which has somewhat impeded the progress of starting more integrated programs (Brunette, Asher, Whitley, et al., 2008; Drake, O’Neal & Wallach, 2008).

The integrated model is a holistic model incorporating all of the best features of both substance abuse treatment and mental health care. The details of this will be discussed in the next section of this article. It assumes that all treatment providers will have the same philosophy in their approach to treatment. It utilizes physicians and advanced care practitioners who are skilled in treatment of both substance use disorders and psychiatric disorders, or at the very least, are conversant with the challenges of both realms and able to communicate effectively with other colleagues to address their clients’ needs.

All treatment is delivered in the same geographic site to reduce the need for travel of clients who must frequently depend on less than adequate mass transportation. It also makes it more efficient for clients to maximize their treatment time by avoiding long trips to other facilities.

The ideal integrated facility will also have all ancillary personnel to effectively address psychosocial issues. This includes mental health/ substance abuse counselors, social workers, legal advocates and occupational therapists.

A dual diagnosis enhanced (DDE) facility should be able to provide seamless treatment to the client from detoxification services to inpatient treatment (at a partner facility) to outpatient services and may include opiate treatment programs as well.

An extremely important element that is frequently missing in even the best programs and has been shown to be a very important element in optimizing outcomes is outreach. This includes outreach to patients and families, outreach in the form of education to the community and outreach to the professional community (Ley, Jeffery, McLaren & Siegfried, 2000).

Treatment Methods

Treatment methods can be divided into three broad groups: biologic therapies, professional psychosocial therapies and self-help groups.

Biologic Therapies

Biologic therapies play a greater role in psychiatric disorders than they do in substance use disorders. Most of the mood disorders and psychoses are best treated with a combination of medication and psychotherapeutic methods. Initially, in order to engage the patient in therapy, it is necessary to stabilize his or her psychiatric disorder quickly; and psychotropic medications are generally the most expedient way to accomplish this.

Medications play a less significant role in treatment and relapse prevention of substance use disorders. While several medications have been approved for prevention of alcohol relapse, opiate abuse relapse and nicotine abuse, all are adjunctive and rely heavily on concurrent psychotherapeutic methods (Patel, Feucht, Reid, et al., 2010; SAMHSA, 2005; Miller, 1995).

Studies are ongoing to identify older medications and develop new ones to simultaneously treat both psychiatric disorders and substance use disorders and prevent relapse. As our understanding of brain mechanisms and chemistry is expanded, undoubtedly new psycho-pharmaceuticals will be introduced.

I will briefly mention several other biologic, nonpharmacologic modalities that are being explored primarily for addiction treatment and relapse prevention. These include deep brain stimulation, transcranial magnetic stimulation and ECT. All of these modalities involve stimulating areas in the brain that have been identified as being concerned with various factors in chronic addiction. None of these modalities are currently indicated for addiction treatment and the few clinical trials that have been done are extremely small. The interested reader is referred to review articles on these emerging techniques (Herremans & Baeken, 2012; Münte, Heinze & Visser-Vandewalle, 2013; Sankar, Tierney & Hamani, 2012; Barr, Farzan, Wing, et al., 2011; Wing, Bacher, Wu, et al., 2012).

Psychosocial Therapies

Professional psychosocial therapies remain the mainstay of most dual diagnosis disorders. These can be broken down into separate methods.

Motivational interviewing attempts in a supportive, directed way to utilize the client’s own beliefs to motivate change and action. It is a nonthreatening, nonconfrontational approach that was initially developed for substance users and as such is especially useful in dual diagnosis. It relies on a skilled interviewer being able to identify potential areas of ambiguities in the client’s thought processes and by restating these ambiguities to motivate the client into action. There are multiple sources available to learn motivational interviewing skills both in hands-on courses and online lectures (Miller & Rollnick, 1991).

Cognitive behavioral therapy (CBT) attempts to change the learned responses to difficult situations by the client and alter them to a healthier more appropriate response. CBT may be done individually or in groups. Group therapies are generally more common and enlist the power of group dynamics as well as maximizing therapist time. Patients with social phobia disorder, which is commonly seen in substance users, may have great difficulty participating effectively in groups and initially usually do better in either smaller groups or individual sessions. Likewise, adolescents may have difficulty in groups in that they tend to “feed” upon each other’s inappropriate coping mechanisms (Macgowan & Wagner, 2005).

Family education is a very important component to effective dual diagnosis therapy. The purpose of family education and involvement in the treatment process is twofold: (1) The family may not understand the nature of the dually diagnosed family member’s problems. Educating family members may increase their comfort level, which is beneficial to the client and the family; (2) A supportive family is in a very good position to encourage medication compliance and treatment compliance and to monitor progress and identify early signs of relapse (Platter & Kelley, 2012).

Self-help Groups

Self-help groups such as Alcoholic’s Anonymous (AA) and Narcotics Anonymous (NA), based upon the 12-Step philosophy can be very useful to the recovering client. Such groups are readily available in almost all communities, are free and provide social support, mentoring and a generally healthy environment compared to the client’s previous social groups. A frequent criticism that is leveled at 12-Step groups is that they are “medication nihilists” and inappropriately advise clients to stop their medications. This, however, is not the official stance of Alcoholics Anonymous. A brief review of AA literature finds such statements as: “A.A. is not a medical organization, does not give out medicines or psychiatric advice” (AAWS, 1972).

And more specifically:

Some of us have had to cope with depressions that can be suicidal; schizophrenia that sometimes requires hospitalization; manic depression; and other mental and biological illnesses . . . Some members have taken the position that no one in A.A. should take any medication. While this position has undoubtedly prevented relapses for some, it has meant disaster for others . . . A.A. members and many physicians have described situations in which depressed patients have been told by A.A.s to throw away the pills, only to have depression return with all its difficulties, sometimes resulting in suicide . . . Unfortunately, by following a layman’s advice, the sufferers find that their conditions can return with all their previous intensity. On top of that, they feel guilty because they are convinced that “A.A. is against pills.” . . . It becomes clear that just as it is wrong to enable or support any alcoholic to become re-addicted to any drug, it’s equally wrong to deprive any alcoholic of medication which can alleviate or control other disabling physical and/or emotional problems (AAWS, 2011).

In addressing such concerns with patients, it is paramount to direct them toward official AA literature and encourage them to be honest in meetings but to discuss the specifics of their disorder and treatment only with the appropriate sponsor and their treatment providers. If a sponsor turns out to be a drug nihilist, we will recommend that they get another sponsor.

Additionally, Dual Diagnosis Anonymous groups based upon the 12-Step approach are starting to appear in many communities. Dual Recovery Anonymous is one of the larger organizations with meetings in many states. Their web link is: www.draonline.org, and interested clients should be referred to their site and other similar ones

Other self-help resources include training in meditation techniques, “urge” surfing, guided imagery and other similar techniques. We have found the tapes produced by Belleruth Naparstek and others to be especially useful for a wide variety of psychiatric diagnoses. Ms. Naparstek was one of the earliest proponents of guided imagery and has produced a wide series of tapes on many subjects

Self-administered mindfulness techniques may enhance neuroplasticity and speed the development of new neuronal circuitry.

Conclusions

Dual diagnosis should be considered the expectation rather than the exception in dealing with clients for evaluation or treatment. As such, the recommendations of ASAM as discussed previously should be put into place as much as possible.

There are obvious roadblocks to an integrated, comprehensive DDE approach. Not the least is the reality that such ventures are very expensive. Third party payers have been slow to embrace dual diagnosis treatment. They pay for crisis but not for ongoing support and monitoring. This problem may be somewhat ameliorated when the Affordable Care Act (ACA) is fully implemented. It will address such issues with enhanced training in screening and brief intervention (SBIRT), and by incentivizing such approaches by the primary care provider. There is a general realization that dual diagnosis treatment facilities are much more cost effective than acute care hospitalization.

Professional training is another significant impediment to integrated treatment models. Relatively few medical providers are skilled in treating such disorders. While residency training programs are devoting more time to substance use disorders, many burgeoning primary care physicians (internists, family physicians, pediatricians), still receive inadequate training in screening techniques and even the fundamentals of substance use disorders. This is even more pronounced in medical specialists. As an example, the American Board of Addiction Medicine notes that there are less than three dozen physicians jointly board certified in Obstetrics and Gynecology and Addiction Medicine in the United States (personal communication).

The LCSW and mental health counseling curriculum, likewise, has been deficient in substance use disorders, both in the area of evaluation and treatment (personal communication).

In addition to the lack of enough well-trained providers and the paucity of dual diagnosis capable and dual diagnosis enhanced facilities, there remains the problem of evidence-based validation of treatment techniques and treatment models. Although at this point it appears that a comprehensive, integrated approach is the most efficacious one in treating dually diagnosed individuals, methodological problems in many studies continue to plague the field (Petersen, Jeppesen, Thorup, et al., 2005).

We are very optimistic that as more trained providers come online and more primary care providers become familiar with basic screening and intervention techniques, and as evidenced-based outcomes continue to demonstrate the superiority of the integrated model, this will become the standard of care for dually diagnosed patients.

References

AAWS. (1972). A Brief Guide to Alcoholics Anonymous. NY: Alcoholics Anonymous World Services, Inc., 10.

AAWS. (2011). The A.A. Member—Medications & Other Drugs. NY: Alcoholics Anonymous World Services, Inc., 13.

Barr, M. S., Farzan, F., Wing, V. C., George, T. P., Fitzgerald, P. B., & Daskalakis, Z. J. (2011). Repetitive Transcranial Magnetic Stimulation and Drug Addiction. International Review of Psychiatry, 23(5), 454–466.

Berrocoso, E., Sanchez-Blazquez, P., Garzon, J., & Mico, J. (2009). Opiates as Antidepressants. CPD (Continuing Professional Development), 15(14), 1612–1622.

Blum, K., Trachtenberg, M. C., Ramsey, J. (1988). Improvement of Inpatient Treatment of the Alcoholic as a Function of Neuronutrient Restoration: A Pilot Study. International Journal of the Addictions, 23, 991–998.

Bramness, J. G., Gundersen, Ø. H., Guterstam, J., Rognli, E. B., Konstenius, M., Løberg, E. M., . . . Franck, J. (2012). Amphetamine-induced Psychosis: A Separate Diagnostic Entity or Primary Psychosis Triggered in the Vulnerable? BMC Psychiatry, 12(1), 221.

Brunette, M. F., Asher, D., Whitley, R., Lutz, W. J., Wieder, B. L., Jones, A. M., & McHugo, G. J. (2008). Implementation of Integrated Dual Disorders Treatment: A Qualitative Analysis of Facilitators and Barriers. Psychiatric Services, 59(9), 989-995.

Dackis C.A., & Gold M.S. (1984) Depression in Opiate Addicts. In Mirin, S. M. (Ed.)., Substance Abuse and Psychopathology (pp. 20–39). Arlington, VA: American Psychiatric Press, Inc.

Drake, R. E., & Mueser, K. T. (2000). Psychosocial Approaches to Dual Diagnosis. Schizophrenia Bulletin, 26(1), 105–118.

Drake, R. E., Essock, S. M., Shaner, A., Carey, K. B., Minkoff, K., Kola, L., . . . Rickards, L. (2001). Implementing Dual Diagnosis Services for Clients with Severe Mental Illness. Psychiatric Services, 52(4), 469–476.

Drake, R. E., O’Neal, E. L., & Wallach, M. A. (2008). A Systematic Review of Psychosocial Research on Psychosocial Interventions for People with Co-occurring severe Mental and Substance Use Disorders. Journal of Substance Abuse Treatment, 34(1), 123–138.

Dumais, A., Lesage, A. D., Alda, M., Rouleau, G., Dumont, M., Chawky, N., . . . Turecki, G. (2005). Risk Factors for Suicide Completion in Major Depression: A Case-Control Study of Impulsive and Aggressive Behaviors in Men. American Journal of Psychiatry, 162(11), 2116–2124.

DuPont, R. L., & Gold, M. S. (2008). Comorbidity and “Self-Medication.” Journal of Addictive Diseases, 26(S1), 13–24.

Fox, J. W. (1990) Social Class, Mental Illness, and Social Mobility: The Social Selection-Drift Hypothesis for Serious Mental Illness. Journal of Health and Social Behavior, 31(4), 344–353.

Gold, M., & Frost-Pineda, K. (2005). Substance Abuse and Psychiatric Dual Disorders: Focus on Tobacco. Journal of Dual Diagnosis, 1(1), 15–36.

Gold, M.S. (Ed.). (2007). Dual Disorders, Nosology, Diagnosis and Treatment Confusion. Binghamton, NY: Haworth Medical Press.

Gold, M. S., Kobeissy, F. H., Wang, K. K., Merlo, L. J., Bruijnzeel, A. W., Krasnova, I. N., & Cadet, J. L. (2009). Methamphetamine- and Trauma-Induced Brain Injuries: Comparative Cellular and Molecular Neurobiological Substrates. Biological Psychiatry, 66(2), 118–127.

Gorman, C. (1987). Bad Trips for the Doubly Troubled. TIME magazine. Accessed April 12, 2013. Retrieved from at: http://www.time.com/time/magazine/article/0,9171,965144,00.html. Accessed April 12, 2013.

Green, M. L., Singh, A. V., Zhang, Y., Nemeth, K. A., Sulik, K. K., & Knudsen, T. B. (2007). Reprogramming of Genetic Networks During Initiation of the Fetal Alcohol Syndrome. Developmental Dynamics, 236(2), 613–631.

Herremans, S. C., & Baeken, C. (2012). The Current Perspective of Neuromodulation Techniques in the Treatment of Alcohol Addiction: A Systematic Review. Psychiatria Danubina, 24(S1), S14–20.

Kendler, K. S., Chen, X., Dick, D., Maes, H., Gillespie, N., Neale, M. C., & Riley, B. (2012). Recent Advances in the Genetic Epidemiology and Molecular Genetics of Substance Use Disorders. Nature Neuroscience, 15(2), 181–189.

Kessler, R .C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., . . . Kendler, K. S. (1994). Lifetime and 12-Month Prevalence of DSM-III-R Psychiatric Disorders in the United States: Results from the National Comorbidity Survey. Archives of General Psychiatry, 51(1), 8–19.

Lehman, A. F., Myers, C. P., Thompson, J. W., & Corty, E. (1993). Implications of Mental and Substance Use Disorders. Journal of Nervous and Mental Disease, 181(6), 365–370.

Leonard, S., Adler, L. E., Benhammou, K., Berger, R., Breese, C. R., Drebing, C., . . . Freedman, R. (2001). Smoking and Mental Illness. Pharmacology Biochemistry & Behavior, 70(4), 561–570

Ley, A., Jeffery, D. P., McLaren, S., & Siegfried, N. (2000). Treatment Programmes for People with Both Severe Mental Illness and Substance Misuse. Cochrane Database of Systematic Reviews (4), CD001088. doi: 10.1002/14651858.

Macgowan,  M. J., & Wagner,  E. F. (2005). Iatrogenic Effects of Group Treatment on Adolescents with Conduct and Substance Use Problems: A Review of the Literature and a Presentation of a Model. Journal of Evidence-Based Social Work, 2(1‒2), 79–90.

Miller, N. S. (1995). Pharmacotherapy in Alcoholism. Journal of Addictive Diseases, 14(1), 23‒46.

Miller, W. R., & Rollnick, S. (1991). Motivational Interviewing: Preparing People to Change Addictive Behavior. NY: Guilford Press.

Münte, T. F., Heinze, H. J., & Visser-Vandewalle, V. (2013). Deep Brain Stimulation as a Therapy for Alcohol Addiction. Current Topics in Behavioral Neurosciences, 13, 709–727.

Pagano, J., Graham, N. A., Frost-Pineda, K., & Gold, M. S. (2005).The Physician’s Role in Recognition and Treatment of Alcohol Dependence and comorbid Conditions. Psychiatric Annals, 35(6), 473–481.

Patel, D. R., Feucht, C., Reid, L., & Patel, N. D. (2010). Pharmacologic Agents for Smoking Cessation: A Clinical Review. Clinical Pharmacology, 2, 17–29

Petersen, L., Jeppesen, P., Thorup, A., Abel, M. B., Øhlenschlaeger, J., Christensen, T. Ø., . . . Nordentoft , M. (2005). A Randomised Multicentre Trial of Integrated Versus Standard Treatment for Patients with a First Episode of Psychotic Illness. BMJ, 331(7517), 602.

Pirkola, S. P., Marttunen, M. J., Henriksson, M. M., Isometsa, E. T., Heikkinen, M. E., & Lönnqvist, J. K. (1999). Alcohol-Related Problems Among Adolescent Suicides in Finland. Alcohol and Alcoholism, 34(3), 320–329.

Platter, A. J., & Kelley, M. L. (2012). Effectiveness of an Educational and Support Program for Family Members of a Substance Abuser. American Journal of Family Therapy, 40(3), 208–213.

Regier, D. A., Myers, J. K., Kramer, M., Robins, L. N., Blazer, D. G., Hough, R. L., . . . Locke, B. Z. (1984). The NIMH Epidemiologic Catchment Area program. Historical Context, Major Objectives, and Study Population Characteristics. Archives of General Psychiatry, 41(10), 934–941.

SAMHSA. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. DHHS Publication No. (SMA) 05-4048. Rockville, MD: Substance Abuse and Mental Health Services Administration.

Sankar, T., Tierney, T. S., & Hamani, C. (2012). Novel Applications of Deep Brain Stimulation. Surgical Neurology International, 3(S1), S26–33.

Smith, I., & Hillman, A. (1999). Management of Alcohol Korsakoff Syndrome. Advances in Psychiatric Treatment, 5(4), 271–278.

Wing, V. C., Bacher, I., Wu, B. S., Daskalakis, Z. J., & George, T. P. (2012). High Frequency Repetitive Transcranial Magnetic Stimulation Reduces Tobacco Craving in Schizophrenia. Schizophrenia Research, 139(1–3), 264–266.

Woody, G. (1996). The Challenge of Dual Diagnosis. Alcohol Health and Research World, 20(2), 76–80.

Wu, L. T., & Ringwalt, C. L. (2006). Inhalant Use and Disorders among Adults in the United States. Drug and Alcohol Dependence, 85(1), 1–11.

Zvolensky, M. J., Lewinsohn, P., Bernstein, A., Schmidt, N. B., Buckner, J. D., Seeley, J., & Bonn-Miller, M. O. (2008). Prospective Associations Between Cannabis Use, Abuse, and Dependence and Panic Attacks and Disorder. Journal of Psychiatric Research, 42(12), 1017–1023.