Combining psychosocial treatment with pharmacotherapy for alcohol dependence

Pharmacotherapy for alcohol dependence is always delivered in a psychosocial context that may affect the outcome of the treatment. The rigorous study of different psychotherapeutic treatments for alcohol dependence has shown several distinct approaches to be effective. This article reviews the combination of alcohol dependence pharmacotherapies, including disulfiram, naltrexone, and acamprosate, with different psychosocial interventions. Many psychosocial interventions for alcohol dependence, including Alcoholics Anonymous, can be integrated successfully with pharmacotherapy. Psychosocial interventions, ranging from brief medical management to more intensive manualized psychotherapies, have all been shown to produce positive outcomes in certain studies, depending on the specific medication and the study context. Particularly successful combinations may include the use of behavioral marital therapy plus a disulfiram contract for patients taking that medication, and the combination of naltrexone or acamprosate with cognitive-behavioral therapy or psychosocial support. Ongoing research examining the optimal combinations of medications with different psychosocial treatments for alcohol dependence may further inform the field.     

The adoption of alcohol pharmacotherapies in the Clinical Trials Network: The influence of research network participation

Organizational participation in clinical research may lead to adoption of the intervention by treatment agencies, but it is not known whether research involvement enhances innovativeness beyond the specific interventions that are tested. The National Institute on Drug Abuse's Clinical Trials Network (CTN) is a platform for considering this research question. To date, the CTN has not conducted research on medications for alcohol use disorders (AUDs), so greater adoption of innovative AUD pharmacotherapies by CTN-affiliated programs would suggest an added value of research network participation. Using longitudinal data from a pooled sample of CTN and non-CTN publicly funded treatment programs, we investigate adoption of tablet naltrexone and acamprosate over a 2-year period. CTN-affiliated programs were more likely to have adopted tablet naltrexone and acamprosate at 24-month follow-up, net of the effects of a range of organizational characteristics. Research network participation may thus enhance organizational innovativeness to include interventions beyond the scope of the network.     

Using medication-assisted treatment for substance use disorders: evidence of barriers and facilitators of implementation

The use of medications to treat substance use disorders (SUDs) has emerged as a potentially central part of the treatment armamentarium. In this paper we present data from several recent US national surveys showing that despite the clinical promise of these medications, there has been limited adoption of pharmacotherapies in the treatment of SUDs. The data reveal variable patterns of use of disulfiram, buprenorphine, tablet naltrexone, acamprosate and injectable naltrexone. After examining the environmental and institutional context for the adoption of pharmacotherapies, the specific organizational facilitators and barriers of medication adoption are considered. The paper concludes with a discussion of the minimal clinical and administrative guidance available to enhance adoption, the lack of client and consumer knowledge of medications that puts a brake on their adoption and availability, and the difficulties that must be surmounted in bringing new medications to market.     

Pharmacotherapy of alcohol dependence: a review of the clinical data

Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.     

Naltrexone and disulfiram in patients with alcohol dependence and current depression

OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.     

Medication assisted treatment of drug abuse and dependence: global availability and utilization

Clinical trials and clinical studies, using patented drugs and drugs off patent, provide data that impact the best treatment practices for substance abuse and dependence. In the United States, medications have been approved for use in the treatment of both alcohol and opioid dependence. Medications are used in the detoxification from drug abuse and dependence in the symptomatic relief of withdrawal. For long term treatment or medical maintenance treatment, medications eliminate the physiological effects of drug use by blocking drug-receptor binding in the brain. Therefore, patented drugs showing interactions with neurotransmitters in the brain, are attractive candidates for treatment efficacy trials. An effective long term treatment paradigm for reducing drug dependence is the combinatorial use of medications that block the effects of drug use with behavior change counseling and psychotherapy. Medications used for the long term treatment of opioid dependence are methadone, buprenorphine, and naltrexone. Pharmacotherapies used in the treatment of alcohol dependence include acamprosate, antabuse and naltrexone. A reliable indicator for successful treatment of drug dependence is time in treatment. Patients remain in long term treatment when they perceive that their health care environment is supportive and non-stigmatizing and with a good patient-provider relationship where their needs are identified and met. Additional medications are needed for individual comprehensive substance abuse treatment plans, particularly for individuals who abuse stimulants. Patented drugs remain an important source of candidate pharmacotherapies comprising medication assistant treatment, part of a comprehensive treatment plan for drug dependence that addresses the medical, social, and psychological needs of the patient. Adapting this drug treatment paradigm globally requires identifying and testing new drug candidates while building and changing programs to patient centered treatment programs that promote access to care and treatment and integrate medical, psychological, and social services.     

Extended-release naltrexone for alcohol and opioid dependence: A meta-analysis of healthcare utilization studies

Through improved adherence, once-monthly injectable extended-release naltrexone (XR-NTX) may provide an advantage over other oral agents approved for alcohol and opioid dependence treatment. The objective of this study was to evaluate cost and utilization outcomes between XR-NTX and other pharmacotherapies for treatment of alcohol and opioid dependence. Published studies were identified through comprehensive search of two electronic databases. Studies were included if they compared XR-NTX to other approved medicines and reported economic and healthcare utilization outcomes in patients with opioid or alcohol dependence. We identified five observational studies comparing 1,565 patients using XR-NTX to other therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication refill persistence versus acamprosate and oral naltrexone. Healthcare utilization and costs was generally lower or as low for XR-NTX-treated patients relative to other alcohol dependence agents. Opioid dependent XR-NTX patients had lower inpatient substance abuse-related utilization versus other agents and $8170 lower total cost versus methadone.     

Acamprosate and naltrexone treatment for alcohol dependence: an evidence-based risk-benefits assessment

This paper provides an evidence-based risk-benefit assessment of acamprosate and naltrexone in the treatment of alcohol dependence. A risk-benefit assessment is based on the premise that the choice of treatment depends on a number of factors, notably the adverse event profile and efficacy. An evidence-based approach attempts to operationalize how such risk-benefit assessments are made to inform physician choices. This approach involves a systematic assessment of all published double-blind, placebo-controlled trials. Based on this review, we conclude acamprosate and naltrexone are both useful in the treatment of alcohol dependence. However, the two drugs act in different ways in the brain, and their clinical profiles are different. Treatment effects seem to be more reliable for acamprosate, and this drug is better tolerated. The safety of the two drugs in combination has been supported by two independent double-blind studies, and combination treatment may offer an advantage for some patients.     

Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients

Rationale Acamprosate is a proven effective intervention in the treatment of alcohol dependence. However, acamprosate prevents lapses or relapses only in a minority of patients. An important question, therefore, is whether there is a specific subgroup of patients who respond particularly well to acamprosate.Objectives To identify predictors of acamprosate efficacy. Based upon the available evidence and hypotheses about the mechanisms underlying acamprosates effects on drinking behavior, the following variables were considered to be potential positive predictors: high physiological dependence at baseline, negative family history of alcoholism, late age-of-onset, serious anxiety symptomatology at baseline, severe craving at baseline, and female gender.Method Potential predictors of acamprosates efficacy were analyzed in a pooled analysis of data from seven randomized placebo-controlled trials involving a total of 1485 patients with alcohol dependence. Outcome is measured in terms of cumulative abstinence duration (CAD), continuous abstinence (ABST), and time to first relapse (TFR).Results CAD and ABST were predicted by baseline measures of craving and anxiety, as well as by study and treatment condition. Acamprosate efficacy was not differentially associated with any of the predictor variables. Importantly, the hypotheses were rejected despite the large sample size and sufficient statistical power.Comment The most straight-forward clinical implication of this study is that acamprosate can be considered as a potentially effective pharmacotherapy for all patients with alcohol dependence. The effect size of acamprosate alone is, however, moderate. Some evidence indicates that the combination of acamprosate with naltrexone or disulfiram leads to substantially better outcomes.     

Rats on the grog: novel pharmacotherapies for alcohol craving

Current pharmacotherapies for alcohol dependence in humans (e.g., naltrexone, acamprosate) are meeting with only limited therapeutic success. The development of novel pharmacotherapies is urgently needed but is reliant upon the screening of large numbers of candidate "anticraving" drugs using appropriate animal models. The development of animal models is complex because (1) laboratory animals are often reluctant to consume large quantities of alcohol, (2) inducing a state of alcohol dependence, analogous to the human condition, may require many months of alcohol exposure, (3) concluding that a given drug selectively reduces alcohol craving requires very carefully controlled experiments, and (4) false positives and false negatives may result from the sometimes distinct physiology and psychology of the alcohol-addicted human and rat. To address some of these problems, our laboratory has recently developed the "beer model" of alcohol dependence and craving. Rats, like humans, have a prodigious appetite for beer and will drink much more beer than equivalent ethanol solutions in water. Beer consumption in rats leads to clear signs of intoxication, anxiety reduction, and signs of withdrawal when beer access is suddenly denied. We have found that beer craving in rats is selectively reduced by the cannabinoid receptor antagonist SR 141716 and the opioid receptor antagonist naltrexone. Combining these two drugs appears to have a synergistic anticraving effect. Other promising pharmacotherapies for the future are discussed.     

Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence treatment, Part 2.

PURPOSE: The neurobiological basis of alcohol dependence, established pharmacotherapies for alcohol dependence, pharmacotherapies under investigation, and obstacles to treatment are discussed. SUMMARY: Alcohol binds to hydrophobic pockets of proteins, changing their three-dimensional structure and their function. Proteins that are particularly sensitive to alcohol include ion channels, neurotransmitter receptors, and enzymes involved in signal transduction. Established pharmacologic treatments, notably disulfiram and naltrexone, combined with behavioral therapies, may reduce the amount of drinking, the risk of relapse, the number of days of drinking, and craving in some alcohol-dependent individuals. For many patients, however, these treatments are not effective. Recent advances in molecular and behavior genetics are guiding the development of new drugs; these efforts seek to identify pharmacologic pathways relevant to alcohol dependence and to more effectively match treatments to individuals according to their genetic characteristics. Efficacy and safety concerns for acamprosate have been satisfied; the drug was recently released for marketing in the United States. Medications such as sertraline, ondansetron, topiramate, and aripiprazole represent novel lines of research and are currently being tested for use in the treatment of alcoholism. Even with more efficacious medications, however, a transformation must occur in how alcoholism treatment is viewed, not only by the public but also by clinicians. CONCLUSION: In addition to existing drug treatments for alcohol dependence, many other medications are under investigation, particularly for specific types of alcoholism. Pharmacogenomics is expected to play an important role in this research effort.     

Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence treatment, part 1.

PURPOSE: The neurobiological basis of alcohol dependence, established pharmacotherapies for alcohol dependence, pharmacotherapies under investigation, and obstacles to treatment are discussed. SUMMARY: Alcohol binds to hydrophobic pockets of proteins, changing their three-dimensional structure and their function. Proteins that are particularly sensitive to alcohol include ion channels, neurotransmitter receptors, and enzymes involved in signal transduction. Established pharmacologic treatments, notably disulfiram and naltrexone, combined with behavioral therapies, may reduce the amount of drinking, the risk of relapse, the number of days of drinking, and craving in some alcohol-dependent individuals. For many patients, however, these treatments are not effective. Recent advances in molecular and behavior genetics are guiding the development of new drugs; these efforts seek to identify pharmacologic pathways relevant to alcohol dependence and to more effectively match treatments to individuals according to their genetic characteristics. Efficacy and safety concerns for acamprosate have been satisfied; the drug was recently released for marketing in the United States. Medications such as sertraline, ondansetron, topiramate, and aripiprazole represent novel lines of research and are currently being tested for use in the treatment of alcoholism. Even with more efficacious medications, however, a transformation must occur in how alcoholism treatment is viewed, not only by the public but also by clinicians. CONCLUSION: In addition to existing drug treatments for alcohol dependence, many other medications are under investigation, particularly for specific types of alcoholism. Pharmacogenomics is expected to play an important role in this research effort.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

The status of disulfiram: a half of a century later

For more than 55 years, disulfiram has been approved by the Food and Drug Administration for the treatment of alcohol dependence. It is a unique medication that relies on "psychological threat" to avoid disulfiram-ethanol reactions. This paper reviews the history of disulfiram treatment, the current status of disulfiram treatment, the ensuing developments in disulfiram use in treating various addictions, and future directions. Clinical trials using disulfiram for the treatment of alcohol, cocaine, or co-occurring alcohol + cocaine dependence were included in this review. Disulfiram efficacy studies focusing on supervised, implant, and combination pharmacotherapies were also examined. In clinical trials, disulfiram has demonstrated inconsistent results in helping patients to abstain from alcohol, and patients poorly adhere to a disulfiram-treatment regimen. This has raised questions about disulfiram's practicality in the treatment of alcohol dependence. Recently, however, disulfiram has gained attention as a complementary agent to newer pharmacological medications, such as an opiate antagonist that specifically reduces alcohol craving. One hypothesis is that disulfiram would assist patients in gaining psychological control over drinking when given in conjunction with an opiate antagonist that would act directly on reducing alcohol craving. Preliminary evidence also suggests that disulfiram treatment could be a viable treatment for cocaine dependence because it was shown to reduce cocaine use among nonalcoholic, cocaine-dependent patients.     

New achievements and pharmacotherapeutic approaches in the treatment of alcohol dependence

The treatment of alcohol dependence mainly consists of psychological, social, and pharmacotherapeutic interventions aiming to reduce physical withdrawal, craving, and alcohol relapse. During the last years, it has become increasingly clear that adjuvant pharmacotherapy is efficacious especially in rehabilitation programs for alcohol dependent patients. The development of alcohol dependence seems to involve adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are approved treatments for the management of abstinence maintenance treatment. New compounds are under investigation. This review discusses the neurobiological basis of alcohol addiction, pharmacological targets for relapse prevention treatment and pre-clinical and clinical results with the most promising drugs.     

Pharmacological treatment of comorbid PTSD and substance use disorder: Recent progress

Previous research has identified a strong association between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), necessitating the development of treatments that address both conditions. Some pharmacotherapies are effective for the treatment of PTSD and SUD alone, however; no medications have been proven to be effective for the combination of these conditions. We review the recent advances in pharmacological treatment of comorbid PTSD and SUD. A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI), did not show overall efficacy for comorbid PTSD and alcohol dependence (AD), although it may have efficacy among light drinkers. Another clinical trial demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. A more recent clinical trial suggested that norepinephrine uptake inhibitors may also have efficacy for the treatment of comorbid PTSD and AD. In animal and preliminary human studies, brain norepinephrine and glutamate/GABA have emerged as potential treatment targets for comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising glutamate/GABA medications include topiramate, memantine, acamprosate, N-acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications for the treatment of PTSD and SUD need to be tested in controlled clinical trials.     

Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.     

Pharmacotherapy of Alcohol Use Disorders

Therapeutic interventions to treat alcoholism have increased in number, including several pharmacotherapies. Aspects of epidemiology, gender, and psychiatric comorbidity as well as a brief overview of neurobiology are presented as an introduction. The medications used clinically for the treatment of alcoholism, disulfiram and naltrexone, approved by the Food and Drug Administration in the United States for the treatment of alcoholism and acamprosate, a medication used extensively in Europe that is currently being evaluated in the United States, are reviewed in detail. An overview of the serotonergic agents is also provided. Finally, future directions, including new medications and some clinical strategies that show promise but are not yet used extensively clinically, are mentioned.     

Pharmacotherapy of alcohol use disorders

Therapeutic interventions to treat alcoholism have increased in number, including several pharmacotherapies. Aspects of epidemiology, gender, and psychiatric comorbidity as well as a brief overview of neurobiology are presented as an introduction. The medications used clinically for the treatment of alcoholism, disulfiram and naltrexone, approved by the Food and Drug Administration in the United States for the treatment of alcoholism and acamprosate, a medication used extensively in Europe that is currently being evaluated in the United States, are reviewed in detail. An overview of the serotonergic agents is also provided. Finally, future directions, including new medications and some clinical strategies that show promise but are not yet used extensively clinically, are mentioned.     

Pharmacological management of alcohol dependence: From mono-therapy to pharmacogenetics and beyond

Almost 10% of the world's population is affected by alcohol use disorders, and the treatment of alcohol dependence (AD) still remains a challenge. Patients with AD can differ in many traits. Three drugs (disulfiram, naltrexone, and acamprosate) have been approved by the FDA for the treatment of AD, and in some European countries sodium oxybate is also approved for this purpose. Combined pharmacological therapy has not provided such convincing results. Considering the fact that the “ideal” and effective drug for all types of alcoholic patients does not exists, the future challenge will be to identify a personalized approach. Recent data has shown that this objective can be achieved by investigating the genetic variability of the patient. Moreover, the use of replacement molecules can probably be considered an advantageous therapeutic opportunity (i.e. sodium oxybate). In addition, reduction of alcohol consumption is increasingly accepted as a viable treatment goal, and the use of nalmefene “as-needed” (a pharmacological approach similar to naltrexone, but, possibly, with lower hepatotoxicity) may help in the treatment of AD. Thus, it is important to stress that a pharmacological approach to treat AD should be preceded by the definition of patient characteristics; this may help in the choice of the most appropriate drug and it can be done more easily when more pharmacological options approved for the treatment of AD are also available.