Treatment of co-occurring psychiatric and substance use disorders

By: Douglas M. Ziedonis, Ed. Day, Erin L. O’Hea, Jonathan Krejci, Jeffrey A. Berman and David Smelson

The co-morbidity of a concurrent substance use disorder and a non-substance major psychiatric disorder is quite common. Yet there is very little data available to inform the clinician as to what treatment(s) might be best for this particular group of patients with this particular set of substance abuse plus non-substance psychiatric co-morbidity.

In general, the limited research available, consensus recommendations and clinical experiences all suggest that integrated treatment, i.e. treatment by the same group of providers that addresses both the substance misuse and the other major mental illness is most effective. However, there are exceptions to this rule and providers must be flexible and offer a combination of services regarding what works best in treating the mental disorder plus what works best in the treatment of the specific substance abuse disorder. While on the surface this appears to be logical and pragmatic, this kind of reasoning does not always work. For example, there is some evidence that lithium is less effective in people with bipolar disorder complicated by substance abuse than it is in bipolar disorder alone. Furthermore, some pharmacological agents used to treat some psychiatric disorders have an increased liability for abuse and dependency, suggesting greater caution in using these interventions when substance abuse is a comorbid issue.

The most efficacious treatment approach is probably integrated multi-modal treatment which involves the same group of caregivers providing treatment to both the mental illness and the substance misuse disorder. These integrated treatments draw from and utilize a wide variety of psychosocial interventions that are combined with more specific psychopharmacological strategies that address the specific psychiatric disorder and some of the craving and withdrawal symptoms of the substance misuse. However, much more research needs to be done in this important and common area of practice.

Introduction

Co-occurring mental illness and addiction is common and worsens patient clinical course, treatment compliance, and outcomes (McLellan et al., 1998; SAMSHA, 2003; Westermeyer et al., 2004). Co-occurring disorders are so common that the phenomenon has become the expectation in addiction, mental health, and medical treatment settings. Recent research and clinical experience has improved the system, programme, and clinical interventions that can help these individuals.

Despite being common, the co-occurrence of mental illness and substance use presents a diagnostic and treatment challenge for clinicians and treatment services. The term ‘dual diagnosis’ is often used to describe this problem, although it lacks precision in describing a very heterogeneous problem. The pattern of co-morbidity may vary between co-morbid mood, anxiety and personality disorders in patients attending substance misuse treatment services, and co-morbid alcohol, cannabis and cocaine misuse in patients accessing general psychiatric services (Abou-Saleh, 2004). Therefore, we prefer the term co-occurring disorder as opposed to dual diagnosis.

The high rate of co-occurring severe mental health and substance use problems has been increasingly recognized in the international research literature over the past 20 years (Maslin, 2003). The National Co-morbidity Study (NCS) and the Epidemiological Catchment Area (ECA) Study both demonstrated that co-occurring mental illness and addiction are very common in the general population, criminal justice system, and treatment system. In the NCS, individuals with alcohol dependence had high rates of clinical depression during their lifetime (24% major depression and 11% dysthymia for men and 49% major depression and 21% dysthymia for women), and individuals with bipolar disorder had high rates of alcohol (61%) and other drug (41%) dependence. High rates of personality disorders have also been reported in patients with substance use disorders, particularly antisocial, narcissistic, and borderline personality disorders (Ross et al., 1988; SAMSHA, 2003; Ziedonis et al., 1994). Personality disorders in substance abuse treatment settings have a poorer response to treatment and a greater risk of suicide (American Psychiatric Association, 1994; SAMSHA, 2003). Finally, tobacco dependence is the most common substance of abuse in the United States and often occurs among individuals being treated for other forms of addiction and mental health problems (Ziedonis & Williams, 2003).

Despite methodological problems such as differences in sampling methods, populations and diagnostic systems, these co-morbidity trends appear to be consistent across treatment settings in the USA (Mueser et al., 2000), the UK (Graham et al., 2001; Menezes et al., 1996), Germany (Krausz et al., 1996), and Australia (Fowler et al., 1998).

Individuals with co-occurring mental illness and addiction have more cravings, withdrawal symptoms, cognitive impairment, depressive symptoms, relapses, and poorer responses to traditional treatments compared to individuals with addictive disorders alone (Carol et al., 2001; Smelson et al., 2001, 2002a, 2002b 2003). These individuals often have wide fluctuations in mental status, increased suicide risk, poorer medication compliance, increased hospitalizations and emergency room visits, and increased HIV rates, hepatitis C rates, physical trauma, and other co-existing medical morbidity/mortality.

Finally, individuals with dual diagnosis have higher rates of homelessness, greater chances of perpetrating violence and being the victim of traumatic events, and greater incidence of illegal activities compared to individuals with mental illness or addiction alone (SAMHSA, 2003).

Summary and conclusions

Psychiatric and substance use disorders commonly co-occur and require the clinician to have additional knowledge and skills in assessing and treating both types of disorders. There are many subtypes of co-occurring mental illness and addiction disorders based on the different types of disorders, the severity of each disorder, and the motivation to address either disorder.

Due to the chronic and often long-standing nature of co-occurring disorders, precise and detailed history taking is critical to accurate diagnoses. The use of collaborative sources of information cannot be overemphasized.

Previously clinicians thought it appropriate to withhold treatment for the psychiatric symptoms until a patient was abstinent for a long period of time. However, now treatment is often initiated much earlier. While each disorder impacts the other, the clinician is often faced with the need to treat withdrawal, intoxication, affective, psychotic and cognitive symptoms without a clear understanding of the exact cause and effect relationships of the presenting symptoms.

More research is needed to study and develop improved treatment approaches for the wide range of co-occurring disorder subtypes in all treatment settings. The use of more than one psychosocial therapy could facilitate better outcomes. For example, the alcoholic with major depression may require motivational enhancement therapy, 12 step facilitation and relapse prevention for the substance abuse or dependence and cognitive behavioural, interpersonal, brief psychodynamic or supportive psychotherapy for the depression. Regular reassessment of the patient will facilitate a more precise diagnosis and better targeted interventions.

References

Peter Tyrer and Kenneth R. Silk, Cambridge Textbook of Effective Treatments in Psychiatry, Cambridge University Press 2008.

Read Also

Cambridge Textbook of Effective Treatments in Psychiatry 

Evidence-Based Practice in Psychology

Introduction to Empirically validated psychological therapies for drug dependence

Educational interventions for alcohol use disorders

An Introduction and Conclusions to Psychological treatments of alcohol use disorders

Psychological therapies and amphetamine and methamphetamine dependence

Psychological therapies and cocaine dependence

Goals of psychological therapies in treating drug dependence

Evidence-based cognitive-behavioral and behavioral treatments for drug dependence

Psychological therapies and cannabis dependence

Complex interventions for alcohol use disorders

Alcoholics Anonymous

The Minnesota model of care for alcohol use disorders

Therapeutic communities for alcohol use disorders

Combined pharmacotherapy and psychotherapy for alcohol use disorders

An Introduction to Pharmacotherapy of alcohol misuse, dependence and withdrawal

Treatment of sedative-hypnotic dependence
Treatment of nicotine dependence

Treatment of nicotine dependence

By: Andrea H. Weinberger, Pamela Walters, Taryn M. Allen, Melissa M. Dudas, Kristi A. Sacco and Tony P. George

Nicotine dependence is found in at least a billion people worldwide and in millions in the United States and Great Britain. It is a major cause of morbidity and mortality in all countries, and both active smoking and exposure to passive smoke has significant health care consequences.

There currently are public health campaigns in both the UK and USA to combat smoking, and laws against smoking in public places are just one, if not one of the most visible, of the various public and community campaigns against smoking. While these campaigns are effective, most smokers wishing to quit will utilize pharmacological treatments which involve primarily nicotine replacement therapy (NRT) or the use of bupropion. Both have substantial evidence as to effectiveness, though there are other secondary pharmacological treatments that also are beginning to find some support such as vareniciline, clonidine and nortriptyline. The NRTs come in various forms from patches to nasal sprays to gum, inhalers, and lozenges. All have substantial support for their effectiveness. Cognitive-behavioural therapies, especially multimodal interventions that are tailored to the specific patient, have a good deal of success and support for that success as well. Despite these effective interventions, smoking remains a major public health problem.

Introduction

Cigarette smoking is the single largest preventable cause of substantial morbidity and mortality in developed countries. In the United States, approximately 23% of the general population reports cigarette smoking, which is the most common (> 98%) method of tobacco use (Center for Disease Control (CDC), 2002; Giovino, 2002). Approximately 430 000 people in the USA die each year as a result of smoking-attributable medical illnesses such as lung cancer, chronic obstructive pulmonary disease, cardiovascular disease and stroke (Giovino, 2002). It is estimated that 29% of adults in the United Kingdom smoke (Lader & Meltzer, 2000). This equates to approximately 16 million British smokers. Worldwide, it is estimated that approximately 1.1 billion people use tobacco on a regular basis (CDC, 2002).

In the UK, the proportions of men and women who currently smoke are similar. Over the past 5 years the overall proportion of smokers in the UK population has stabilized, although in some groups, such as adolescents, there has been an increase. It is thought around 25% of 15-year-olds are regular smokers (NICE, 2002; Lader & Meltzer, 2000). As a result of the implementation of tobacco control policies in the USA (e.g. tobacco excise taxes, advertising health dangers), the prevalence of cigarette smoking was reduced from 45% in the 1960s to about 22.9% in 2002 (CDC, 2002). However, it appears that many of these remaining smokers have more difficulty quitting smoking, and today’s smoker has often failed multiple quit attempts despite using behavioural therapies combined with pharmacological interventions such as nicotine replacement therapies (NRTs) and sustained-release bupropion. In fact, quit rates with NRTs over the past 15 years in controlled clinical trials appear to be declining (Irvin et al., 2003). The remaining population of smokers has characteristics associated with smoking persistence and quit attempt failures such as lower education attainment, less interest in behavioural treatments to assist with cessation, and medical, substance abuse and psychiatric co-morbidities (Hughes, 1996b). In addition, women are smoking at higher rates than in the past, may have more intense nicotine withdrawal and depressed mood during quit attempts than men (Gritz et al., 1996), and may be less responsive to quitting with NRTs (Perkins et al., 1999).

Smokers who have failed initial quit attempts generally embrace pharmacotherapies, and given that a large proportion of remaining smokers do not respond to conventional pharmacotherapies, the development of novel and more effective medication treatment for smoking cessation is critical in our efforts to treat nicotine dependence.

Recent advances in our understanding of nicotine’s effects on central neurotransmitter systems are guiding basic and clinical pharmacologists to develop medications for new pharmacological targets to treat nicotine dependence.

The hazards of smoking are important and well established. Smokers have a larger number of chronic respiratory diseases and have a substantially higher risk of cancers and cardiovascular disease. They are twice as likely as nonsmokers to suffer from fatal ischemic heart disease and four times as likely to suffer a fatal aortic aneurysm (Parrott et al., 1998). The National Institute for Clinical Excellence (NICE) has estimated that treatment for smoking related disease cost the National Health Service (UK) around £1.5 billion (Edwards, 2004).

Nicotine addiction is closely linked to socio-economic disadvantage. Smoking prevalence is higher and nicotine use heavier amongst poorer smokers. The socio-economic gradient in smoking behaviour accounts for about two-thirds of the excess premature mortality associated with deprivation.

Smoking is now increasing rapidly throughout the developing world, and it is estimated that current cigarette smoking will cause about 450 million deaths worldwide in the next 50 years. Reducing current smoking by 50% would prevent 20–30 million premature deaths in the first quarter of this century and 150 million in the second quarter (Doll et al., 1994). For most smokers, quitting is the single most important thing they can do to improve their health.

Clinical features of nicotine dependence

Most tobacco users (> 98%) are smokers of cigarettes, and while there are a subset of cigarette smokers who do not smoke every day, most cigarette smokers are daily users and have some degree of physiological dependence on nicotine (Rigotti, 2002). Determination of nicotine dependence is typically accomplished clinically by historical documentation of daily smoking (typically 10–40 cigarettes per day) for several weeks, evidence of tolerance (e.g. lack of aversive effects of nicotine such as nausea and excessive stimulation) and the presence of symptoms of nicotine withdrawal upon smoking cessation. These withdrawal symptoms include dysphoria, anxiety, irritability, decreased heart rate, insomnia (waking in the middle of the night), increased appetite and craving for cigarettes (American Psychiatric Association, 2006). In addition, most dependent smokers state that they smoke their first cigarette of the day within thirty minutes of awakening. Scales such as the Fagerstrom Test for Nicotine Dependence (FTND) allow assessment of the evel of nicotine dependence with scores of 4 on a scale of 0–10 consistent with physiological dependence to nicotine. These scales have been empirically validated (Heatherton et al., 1991).

Interestingly, the positive effects of cigarette smoking (e.g. taste, satisfaction) appear to be mediated by non-nicotine components of tobacco such as tar (Dallery et al., 2003). Besides positive reinforcement, withdrawal and craving, there are several secondary effects of nicotine and tobacco use that may contribute to both maintenance of smoking and to smoking relapse including mood modulation (e.g. reduction of negative affect), stress reduction, and weight control. In addition, conditioned cues can elicit the urge to smoke even after prolonged periods of abstinence. Specific effects might be most relevant to individuals high on dietary restraint (weight reduction), and psychiatric disorders (mood modulation, stress reduction). These secondary effects may present additional targets for pharmacological intervention in certain subgroups of smokers (e.g. schizophrenic, depressed, or overweight smokers).

National guidelines

There are clinical practice guidelines available in both the USA and UK. The US Public Health Service published the monograph Treating Tobacco Use and Dependence in 2000 (Fiore et al., 2000), and the American Psychiatric Association recently updated its Practice Guidelines for the treatment of nicotine dependence (APA, 2006). In the UK, a series of guidelines and key documents were published in the late nineties. The paper ‘Smoking kills’ (DOH 98) outlined the government’s plan of action to stop people from smoking. This plan included proposals for abolishing tobacco advertising and promotion. It also looked at ways of altering public attitudes, preventing tobacco smuggling and supporting further research into this important area of public health. Partnerships with other agencies such as businesses were pivotal in order to start the restriction of smoking in public places.

The Royal College of Physicians published smoking cessation guidelines in 1998 which were updated in 2000 (West et al., 2000). Expert committees such as the Cochrane Tobacco Addiction review group were set up to operate in much the same manner as its American equivalent, The Agency for Health Care Policy Research.

As a direct result of the change in priority given to the management of smoking, smoking cessation services were launched in a variety of health action zones throughout England and Wales in 1999–2000. In the 3 years up to and including 2001–2002, £53 million was made available for these services with further substantial amounts earmarked for the years 2003–2006, £41 million, £46 million and £51 million, respectively. Quarterly reports are fed back to the government by these services so that progress towards specified targets can be audited. The government’s guidance on management of smoking cessation is implemented through The National Institute for Health and Clinical Excellence (NICE). This organization is part of The National Health Service (NHS) and its role is to provide guidance for both the NHS and patients on medicines, medical equipment, and diagnostic tests. It was specifically asked to review the available evidence on nicotine replacement therapy (NRT) and bupropion and provide guidance that would inform the NHS about effective evidence-based treatments for smoking cessation.

Before we proceed to examine the treatments for smoking, a quick glance at these official guidelines suggests the manner and context in which, in the UK, smoking cessation treatment should take place. Nicotine replacement therapy or bupropion should normally only be prescribed as part of an abstinent contingent treatment (ACT) programme in which the smoker makes a commitment to stop smoking. Smokers should be offered advice and encouragement to aid their attempt to quit. Ideally, initial prescription of NRT or bupropion should be sufficient to last only until 2 weeks after the target stop date. Normally, this will be after 2 weeks of NRT and 3–4 weeks for bupropion to allow for the different methods of administration and mode of action. Second prescriptions should be given only to people who have demonstrated that their quit attempt is continuing on reassessment. If a smoker’s attempt to quit is unsuccessful with treatment using either NRT or bupropion, the NHS should normally fund no further attempts within 6 months. It is thought that there is insufficient evidence to recommend a combination of bupropion and NRT.

It is recommended that smokers who are under the age of 18 years, who are pregnant or breastfeeding, or who have unstable cardiovascular disorders should consult a health care professional before either treatment is prescribed. Bupropion is not recommended for smokers under the age of 18 years as its safety and efficacy have not been evaluated for this group. Women who are pregnant or breastfeeding should not use bupropion.

Conclusions

It is important to identify smoking in health care settings, particularly populations that are high risk for smoking (e.g. individuals with psychiatric and addictive disorders). Identifying and urging people to stop smoking and making sure they are aware of the medical consequences of smoking is important. Many smokers are able to quit with minimal therapeutic interventions. Simple advice to give up smoking is one of the most cost effective interventions we can make in medicine, and yet this is not part of routine health care delivery in many settings both in the US and the UK. Initial attempts to assist individuals with smoking cessation should utilize stepped-care approaches, reserving more intensive behavioural therapies and pharmacological interventions for treatment-resistant smokers. More intensive therapies may be needed for smokers who have had multiple failed quit attempts and smokers with co-morbid psychiatric, alcohol or drug, or medical disorders.

There are a number of empirically validated pharmacotherapies for the treatment of nicotine dependence in the USA, including five NRT formulations, varenicline and sustained-release bupropion, as well as a number of non-approved pharmacotherapies which appear promising. Nicotine replacement therapy may be the most cost effective, and it is the treatment that has the largest data base supporting its effectiveness. Bupropion is currently the best non-nicotine treatment, although in a single head-to-head trial, varenicline was superior to bupropion and to placebo. Intensive behavioral support from a trained counsellor is the most effective non-drug treatment for smokers, and it appears equally effective in both an individual and a group setting. Given that 80% of adult smokers start as teenagers, we should target this age group in order to have a significant impact on smoking cessation. Little real research has taken place with this group.

The issue of passive smoking has received less attention in the UK than in the US in the past, though the recent ban on smoking in pubs and other public places reveals that this issue is taking hold in the UK. Efforts need to continue to be made to make government and business leaders aware of the impact of active as well as passive smoking on morbidity and mortality.

In ever increasing pharmacologic dependent societies, additional research on medications that target neurotransmitter systems involved in nicotine dependence (e.g. selective GABA and DA receptor agonists) may be important for treatment-resistant smokers. If people thought that a simple pill with minimal side effects could help them avoid the discomfort of withdrawal that accompanies smoking cessation, then perhaps greater progress could be made on this important public health issue.

References

Peter Tyrer and Kenneth R. Silk, Cambridge Textbook of Effective Treatments in Psychiatry, Cambridge University Press 2008.

Read Also

Cambridge Textbook of Effective Treatments in Psychiatry 

Evidence-Based Practice in Psychology

Introduction to Empirically validated psychological therapies for drug dependence

Educational interventions for alcohol use disorders

An Introduction and Conclusions to Psychological treatments of alcohol use disorders

Psychological therapies and amphetamine and methamphetamine dependence

Psychological therapies and cocaine dependence

Goals of psychological therapies in treating drug dependence

Evidence-based cognitive-behavioral and behavioral treatments for drug dependence

Psychological therapies and cannabis dependence

Complex interventions for alcohol use disorders

The Minnesota model of care for alcohol use disorders

Therapeutic communities for alcohol use disorders

Combined pharmacotherapy and psychotherapy for alcohol use disorders

An Introduction to Pharmacotherapy of alcohol misuse, dependence and withdrawal

Treatment of sedative-hypnotic dependence
Treatment of co-occurring psychiatric and substance use disorders

Treatment of sedative-hypnotic dependence

by: Karim Dar and Manoj Kumar

Misuse and dependence upon benzodiazepines, despite much greater awareness of the dangers of these drugs, still appear to be growing problems. Misuse occurs because of dependency upon these drugs that have been prescribed for extended periods with some increasing tolerance on the part of the patient. Misuse also occurs by people who purchase or obtain these drugs by means other than prescription. The growing emphasis on insomnia and the increasing competition among various drug companies to capture the prescription sleeping pill market appears to exacerbate this problem. At the moment, a gradual tapering of the prescribed or illegally used drug, especially by substituting a longer-acting drug for a shorter-acting drug, appears to have the most supporting evidence. Little research has been done on hypnotics compared with the benzodiazepines, and this is a bit of a puzzle.

Introduction

Sedative hypnotic drugs are central nervous system depressants traditionally used to reduce anxiety and induce sleep. The sedatives under consideration in this chapter are benzodiazepines, the Z-drugs (zopiclone, zolpidem and zaleplon) and barbiturates. After their introduction in 1903, barbiturates were supplanted by the benzodiazepines which were introduced in the early 1960s. This was primarily due to concerns about the obvious toxicity of barbiturates, particularly in overdose, and knowledge of their propensity for dependence. After reaching a peak in the early 1980s, prescriptions for benzodiazepines in the UK have shown a substantial reduction; however, while annual prescriptions for benzodiazepines in England fell from 10 million to around 6 million between 1993–2003, those for the Z-drugs rose from 0.3 million to over 4 million over the same time period, mainly in older people (DoH, 2003), and this is a worldwide phenomenon.

Expert bodies have long advised that use of all these group of drugs be limited to short periods and should be generally avoided in elderly people (BNF, 2004; CSM, 1988; Priest & Moutgomery, 1988). Around 80% of all such prescriptions in England are for those aged 65 years or over (Curran et al., 2003), and many patients remain on the drugs for months or years (Taylor et al., 1998). This prescribing is likely to lead to development of dependence and many other adverse effects on health (Ashton 1995). All currently marketed hypnotics have been associated with at least some features of dependence and have demonstrated a potential for misuse and dose escalation in at least a minority of patients (Ashton, 1995; Hajak et al., 2003; Lader, 1999).

Manifestations of anxiety and of sedative-hypnotic abstinence syndromes

It is important to note that the symptoms of anxiety and withdrawal syndromes from benzodiazepines overlap greatly. The psychological manifestations of anxiety include irritability, restlessness, insomnia, agitation, nightmares and difficulty in concentration. Physiological symptoms include tremors, shakiness, profuse sweating, palpitations and lethargy. In addition, in withdrawal syndromes in particular, there is hyper-excitability of voluntary musculature and hyperacuity of sensation leading to muscle twitching, aches and pains, hypersensitivity to light, smell and sounds, a metallic taste in one’s mouth and, very rarely, convulsions (Tyrer et al., 1990). Other physical reactions include nausea, loss of appetite, weight loss and feeling like one has a ‘flu-like’ illness. Other mental status changes can involve dysphoria, impaired memory and possibly confusion, depersonalisation and derealisation, psychotic reactions, and hallucinations (APA Task Force, 1990).

Summary and Conclusions

The treatment of tranquilliser dependence is not especially satisfactory, with only gradual withdrawal, often using a different benzodiazepine, over a variable time scale, showing satisfactory levels of efficacy in almost all studies. Other forms of pharmacological substitution are of limited value, with only carbamazepine showing some hint of real benefit, and psychological treatments such as cognitive-behaviour therapy are disappointing. The best evidence for a psychological intervention is for brief self-help packages and other forms of bibliotherapy, which also have the advantage of being accessible for booster purposes at all times. However, the evidence for efficacy is better in those who are in primary care and with less intractable dependence. Interestingly, these approaches
do not seem to differ in effectiveness for those who are dependent through prolonged therapeutic prescription or though deliberate misuse. The lack of information about the dependence problems of the Z-drugs (zopiclone, zolpidem and zaleplon) is troubling.

References

Peter Tyrer and Kenneth R. Silk, Cambridge Textbook of Effective Treatments in Psychiatry, Cambridge University Press 2008.

Read Also

Cambridge Textbook of Effective Treatments in Psychiatry

Evidence-Based Practice in Psychology
Introduction to Empirically validated psychological therapies for drug dependence
Educational interventions for alcohol use disorders
An Introduction and Conclusions to Psychological treatments of alcohol use disorders
Psychological therapies and amphetamine and methamphetamine dependence
Psychological therapies and cocaine dependence
Goals of psychological therapies in treating drug dependence
Evidence-based cognitive-behavioral and behavioral treatments for drug dependence
Psychological therapies and cannabis dependence
Complex interventions for alcohol use disorders
The Minnesota model of care for alcohol use disorders
Therapeutic communities for alcohol use disorders
Combined pharmacotherapy and psychotherapy for alcohol use disorders
An Introduction to Pharmacotherapy of alcohol misuse, dependence and withdrawal
Treatment of nicotine dependence
Treatment of co-occurring psychiatric and substance use disorders

An Introduction to Pharmacotherapy of alcohol misuse, dependence and withdrawal

By: George A. Kenna, Kostas Agath and Robert Swift

While there is a large volume of research on alcohol misuse, dependence and withdrawal, the pharmacologic solutions are not as directly evident as this amount may suggest. There are widespread cultural determinants as to what constitutes alcohol misuse though the definitions for dependence are much clearer. Yet we do not have good solid pharmacologic treatments to prevent or decrease alcohol usage in the alcohol-dependent individual, though results from the recent COMBINE study suggest a more prominent and effective role for naltrexone in conjunction with medical management. Acamprosate did not fare as well in this trial even though it has been approved for alcohol dependence, and questions of heterogeneity among patient populations might explain conflicting findings. The effectiveness of disulfiram appears to rely heavily upon the patient’s determination to remain abstinent. Anticonvulsants may have a role here, but more data is needed. Benzodiazepines remain the gold standard for treatment of symptoms of alcohol withdrawal, while a number of studies also support the use of some anticonvulsant drugs in assisting with withdrawal, especially in cases of mild-to-moderate severity.

There is a large volume of research on the pharmacological treatments for alcohol misuse, dependence and withdrawal. Part of that research is marred by methodological difficulties (Moncrieff & Drummond 1997), necessitating increasingly sophisticated means of grading the available evidence to allow generalizability of findings (Mayo-Smith, 1997, Garbutt et al., 1999, Scottish Intercollegiate Guidelines Network –SIGN, 2003, Lingford-Hughes et al., 2004).

Harmful use of alcohol

Harmful use refers to physical and/or mental damage due to a pattern of alcohol use in the absence of a diagnosis of another specific form of alcohol disorder (such as dependence). It is an ICD-10 diagnosis without a direct equivalent in DSM-IV, and its diagnosis depends upon the accurate reporting of alcohol-related physical or mental health problems (Babor, 1992). Harmful alcohol use (problem drinking) is believed to play a role in behavior associated with a pattern and amount of alcohol use considered hazardous such as decreased worker productivity, increased unintentional injuries, aggression and violence against others, and child and spouse abuse (Gmel & Rehm, 2003). Additionally, many individuals may periodically abuse alcohol at harmful levels, yet not be alcohol dependent.

While the frequency and intensity of these markers increases with increased amounts and frequency of alcohol use, there is no firm quantitative definition for harmful alcohol use in the United States. For example, data from the National Health Interview Survey (Dawson, 1994), suggests that the risk of occupational injuries increases with the frequency of five or more drinks per occasion. Older workers who normally drink one or two drinks (equivalent to 1.5 ounces of 80 proof liquor) a day report the lowest risk of injuries contrasted with people who drink five or more drinks a day, who report more than a fivefold increase in risk (Zwerling et al., 1996). Heavy drinking is alcohol consumption exceeding 14 drinks per week for men (or more than four drinks per drinking occasion), more than seven drinks per week for women (or more than three drinks per occasion), and greater than seven drinks per week for all adults 65 years and older (National Institute on Alcohol Abuse and Alcoholism (NIAAA), 2000). Heavy alcohol use has also been defined (Office of Applied Studies, National Survey on Drug Use and Health (NSDUH), 2004) as drinking five or more drinks at the same time on at least five separate occasions during the previous month.

Appropriate pharmacological treatment is largely dependent on the health problem addressed (depression, anxiety, cardiovascular, endocrine, gastrointestinal abnormalities). Naltrexone has been tried but the research evidence has not supported its use in harmful use (Davidson et al., 2004, Kranzler et al., 2003, Davidson et al., 1999, Rubio et al., 2002). In the United Kingdom no official guidelines for the pharmacological treatment of harmful alcohol use exist. Research on the use of NTX for non-dependent problem drinkers is limited. Kranzler et al. (2003) compared the effects of 50 mg of NTX or matching placebo in a sample of early problem drinkers who received NTX either daily or in targeted high-risk situations for drinking, in addition to brief coping skills therapy. Participants in the targeted group received a diminishing number of tablets (started at 1 tablet daily for week one, then 1 less tablet per week) over an 8-week treatment period. While NTX was better than placebo in reducing heavy drinking frequency, NTX did not significantly reduce the number of drinking days. Regardless of whether participants received NTX or placebo, there was a reduction in the likelihood for any drinking by participants in the targeted condition. However, as the number of tablets declined to fewer than three per week in the targeted NTX group, this group no longer exhibited a decreased risk for heavy drinking.

Davidson et al. (1999) found no differences in heavy drinkers between NTX and placebo in either drinking days or drinks per drinking day over a 7-day period in the home environment, but did find advantages of NTX for reducing craving and decreasing the reinforcing effects of alcohol. Moreover, Davidson et al. (2004) reported that placebo-treated hazardous drinkers fared better than those treated with NTX in terms of abstinence, drinks per drinking day and craving, although the results may have been confounded by gender and family history of alcoholism. Rubio et al. (2002) in an open randomized trial with mildly dependent drinkers found delayed effects at 12 months after 12 weeks of a controlled drinking program either alone or in combination with NTX. The NTX group had fewer drinking days, heavy drinking days and less craving.

The dosing strategy for the use of naltrexone for harmful drinking in non-dependent alcoholics is unclear at present. But presently, there is insufficient evidence at this time to support daily or targeted use of NTX for harmful alcohol use, and its use is best reserved for moderate-to-severe alcohol dependence.

Alcohol dependence

The pharmacological treatments of alcohol dependence focus on relapse prevention once detoxification is complete. They are intended as an adjunct to psychosocial treatments (Slattery et al., 2003; Lingford-Hughes et al., 2004) and not as a monotherapy.

Alcohol withdrawal

For many alcohol-dependent individuals with significant physical dependence, a cluster of withdrawal symptoms known as ‘alcohol withdrawal syndrome’ (AWS) may occur upon cessation or reduction of alcohol consumption or reaching a level of such significant tolerance that individuals cannot consume enough alcohol to delay withdrawal. Estimates suggest that as many as 2 million Americans may experience symptoms associated with alcohol-related withdrawal annually (Abbott et al., 1995).

Depending directly on the degree of physical dependence, this syndrome can range from creating significant discomfort to mild tremor to alcohol withdrawal-related delirium, hallucinosis, seizures, and potentially death (Kozak et al., 2000; Bayard et al., 2004). Though most alcohol-dependent persons do not fit the stereotypical image of an alcoholic, individuals who are nutritionally compromised, dehydrated, or have other organ deficiencies are at more risk for withdrawal. Repeated withdrawal episodes may contribute to the development of alcohol dependence and to negative consequences associated with excessive alcohol consumption (Finn & Crabbe, 1997). Predictors for AWS complications include the duration of alcohol consumption, total number of prior detoxifications from alcohol, and previous withdrawal-related seizures and episodes of alcohol withdrawal delirium (AWD) (Asplund et al., 2004).

Withdrawal-related seizure is considered a more severe manifestation of AWS, as is AWD or ‘delirium tremens’ as traditionally called. The incidence of seizures in alcohol dependent individuals waiting for detoxification ranges from 1% to 15% (Chan, 1985). AWD is estimated to have a mortality rate of approximately 1 in 20 patients who go into alcohol withdrawal (Trevisan et al., 1998).

The pharmacological treatment of alcohol withdrawal aims at reducing the severity of non-specific features (such as elevated blood pressure, high pulse, tremor, agitation, anxiety, depression), and avoiding the occurrence of specific features (such as seizures, delirium tremens). The distinction between specific and non-specific symptoms is reflected in differential efficacy of the various pharmacological agents employed for the treatment of alcohol withdrawal.

Several reviews agree that benzodiazepines reduce both the specific and non-specific symptoms of alcohol withdrawal and are the treatment of choice for alcohol withdrawal syndrome (Mayo-Smith, 1997, Lingford Hughes et al., 2004), and the only recommended monotherapy for it (Franck, 2003). Amongst benzodiazepines there is no evidence to support one agent over another, although longer half-life seems to be better in preventing specific symptoms (Mayo-Smith, 1997) with chlordiazepoxide the most popular choice in the absence of liver failure (Lingford-Hughes et al., 2004), even in the elderly (Mayo-Smith, 2004) albeit with a reduced dosage (Franck, 2003).

Apart from benzodiazepines, a few other agents were found to be superior to placebo in treating non-specific symptoms of alcohol withdrawal syndrome, although there is no consensus about their place in treatment because of either non-proven efficacy in treating specific symptoms or because of dangerous side effects. For example, chlormethiazole, a popular alternative first-line treatment of alcohol withdrawal, although superior to placebo, has no proven efficacy in the prevention of seizures and its outpatient use is marred by potentially serious side effects such as respiratory depression and increased airway secretion (Williams & McBride, 1998).

Carbamazepine is also superior to placebo in treating nonspecific symptoms of alcohol withdrawal (Franck, 2003), and more recent evidence shows that it is as effective as benzodiazepines in seizure prevention during withdrawal (Hilbom et al., 2003), a finding that was disputed in previous reviews (Mayo-Smith, 1997, Franck, 2003).

Benzodiazepines are frequently administered in a fixed-schedule tapering regime, where clients are assigned to an initial dosage in a predetermined reduction program (Mayo-Smith, 1997). Fixed-schedule tapering regimes do not take into account the great variation of withdrawal severity apart from the onset of the regime, but their acceptability is based on the minimal need of specialist monitoring during detoxification (MayoSmith, 1997). Alternative benzodiazepine regimes consist of administration of a variable dose titrated against the Clinical Institute Withdrawal Assessment Alcohol revised (CIWA-Ar) scale (Sullivan et al., 1989) that is administered either at set intervals during the day (such as hourly), or at the request of a client when they experience withdrawal features. Although the use of the alternative regimes is preferable in reducing the total amount of benzodiazepine administered, they need availability of trained staff and they are not suited for clients with a seizure risk (Mayo-Smith, 1997; Lingford-Hughes et al., 2004).

References

Peter Tyrer and Kenneth R. Silk, Cambridge Textbook of Effective Treatments in Psychiatry, Cambridge University Press 2008.

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