The prospects for immunotherapy in smoking cessation

Context Smoking is a major preventable cause of death and disability that is maintained by dependence on nicotine. Smoking cessation reduces mortality and morbidity. Although existing pharmacological aids to smoking cessation and relapse prevention (nicotine replacement therapy and bupropion) improve on unassisted quitting and behavioural methods, they are only modestly effective. More effective pharmacological methods are required that improve compliance, reduce side-effects, and can be used in combination with existing cessation methods. Starting point A nicotine vaccine is a promising immunotherapeutic approach to smoking cessation and relapse prevention. Such a vaccine would induce the immune system to form specific antibodies to nicotine to prevent it from crossing the blood-brain barrier to act on receptor sites in the central nervous system. Recent studies in rats provide proof of principle by showing that nicotine-specific antibodies can prevent the reinstatement of nicotine self-administration (N Lindblom et al, Respiration 2002; 69: 254–60) and block dopamine release in the shell of the nucleus accumbens (Sde Villiers et al, Respiration 2002; 69: 247–53). A phase 1 trial of a human cocaine vaccine has also recently been successfully completed (T Kosten et al, Vaccine 2002; 20: 1196–204). A safe and effective human nicotine vaccine would potentially have fewer side-effects and better compliance than existing smoking-cessation pharmacotherapies. It could also be used in combination with some of them (eg, bupropion). Where next? The most promising clinical application of a human nicotine vaccine is likely to be in relapse prevention in abstinent smokers. A vaccine may also have a role in preparing smokers to quit. Clinical trials of safety and efficacy in human smokers and ex-smokers are warranted. If a nicotine vaccine proves to be safe and effective, the health-care system will need to ensure that it is registered for clinical use and that the poorer members of the community (among whom smoking prevalence is now highest in developed countries) have access to the vaccine. The community will need to be appropriately informed about the role of a nicotine vaccine to ensure that it is not prematurely used for preventive purposes in children and adolescents.

Outpatient cognitive behavioural therapy programme for alcohol dependence impact of naltrexone use on outcome

Objective: Cognitive-behavioural therapy (CBT) has been effectively used in the treatment of alcohol dependence. Clinical studies report that the anticraving drug naltrexone, is a useful adjunct to treatment. Currently, few data are available on the impact of adding this medication to programmes in more typical, outpatient, and rehabilitation settings. The objective of this study was to examine the impact on outcome of adding naltrexone to an established outpatient alcohol rehabilitation program which employed CBT. Method: Fifty patients participated in an established 12-week, outpatient, 'contract'-based alcohol abstinence programme which employed CBT. They also received naltrexone 50 mg orally daily (CBT + naltrexone). Outcomes were compared with 50 historical, matched controls, all of whom participated in the same programme without an anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence. Results: Programme attendance across the eight treatment sessions was lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone) compared with 18% (CBT alone) (p < 0.001). Conclusion: When employing the same outpatient rehabilitation programme and comparing outcomes using matched historical controls, the addition of naltrexone substantially improves programme attendance, programme completion and reported alcohol abstinence. In a typical outpatient programme, naltrexone addition was associated with significantly improved programme participation, better outcomes and was well tolerated.

The burden of major depression avoidable by longer-term treatment strategies

Background: Major depression is the largest single cause of nonfatal disease burden in Australia. Effective drug and psychological treatments exist, yet are underused. Objective: To quantify the burden of disease currently averted in people seeking care for major depression and the amount of disease burden that could be averted in these people under optimal episodic and maintenance treatment strategies. Design: Modeling impact of current and optimal treatment strategies based on secondary analysis of mental health survey data, studies of the natural history of major depression, and meta-analyses of effectiveness data. Monte Carlo simulation of uncertainty in the model. Setting: The cohort of Australian adults experiencing an episode of major depression in 2000 are modeled through "what if" scenarios of no treatment, current treatment, and optimal treatment strategies with cognitive behavioral therapy or antidepressant drug treatment. Main Outcome Measure: Disability-Adjusted Life Year. Results: Current episodic treatment averts 9% (95% uncertainty interval, 6%-12%) of the disease burden of major depression in Australian adults. Optimal episodic treatment with cognitive behavioral therapy could avert 28% (95% uncertainty interval, 19%-39%) of this disease burden, and with drugs 24% (95% uncertainty interval, 19%-30%) could be averted. During the 5 years after an episode of major depression, current episodic treatment patterns would avert 13% (95% uncertainty interval, 10%-17%) of Disability-Adjusted Life Years, whereas maintenance drug treatment could avert 50% (95% uncertainty interval, 40%-60%) and maintenance cognitive behavioral therapy could avert 52% (95% uncertainty interval, 42%-64%), even if adherence of around 60% is taken into account. Conclusions: Longer-term maintenance drug or psychological treatment strategies are required to make significant inroads into the large disease burden associated with major depression in the Australian population.

Beating the urge: Implications of research into substance-related desires

Despite the advent of improved pharmacological treatments to alleviate substance-related desires, psychological approaches will continue to be required. However, the current psychological treatment that most specifically focuses on desires and their management-cue exposure (CE)-has not lived up to its original promise. This paper argues that current psychological approaches to desire do not adequately incorporate our knowledge about the factors that trigger, maintain, and terminate episodes of desire. It asserts that the instigation and maintenance of desires involve both associative and elaborative processes. Understanding the processes triggering the initiation of intrusive thoughts may assist in preventing some episodes, but occasional intrusions will be inevitable. A demonstration of the ineffectiveness of thought suppression may discourage its use as a coping strategy for desire-related intrusions, and mindfulness meditation plus cognitive therapy may help in accepting their occurrence and letting them go. Competing tasks may be used to reduce elaboration of desires, and competing sensory images may have particular utility. The application of these procedures during episodes that are elicited in the clinic may allow the acquisition of more effective strategies to address desires in the natural environment. (C) 2004 Elsevier Ltd. All rights reserved.

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

Objective: Antidepressant drugs and cognitive-behavioural therapy (CBT) are effective treatment options for depression and are recommended by clinical practice guidelines. As part of the Assessing Cost-effectiveness - Mental Health project we evaluate the available evidence on costs and benefits of CBT and drugs in the episodic and maintenance treatment of major depression. Method: The cost-effectiveness is modelled from a health-care perspective as the cost per disability-adjusted life year. Interventions are targeted at people with major depression who currently seek care but receive non-evidence based treatment. Uncertainty in model inputs is tested using Monte Carlo simulation methods. Results: All interventions for major depression examined have a favourable incremental cost-effectiveness ratio under Australian health service conditions. Bibliotherapy, group CBT, individual CBT by a psychologist on a public salary and tricyclic antidepressants (TCAs) are very cost-effective treatment options falling below $A10 000 per disability-adjusted life year (DALY) even when taking the upper limit of the uncertainty interval into account. Maintenance treatment with selective serotonin re-uptake inhibitors (SSRIs) is the most expensive option (ranging from $A17 000 to $A20 000 per DALY) but still well below $A50 000, which is considered the affordable threshold. Conclusions: A range of cost-effective interventions for episodes of major depression exists and is currently underutilized. Maintenance treatment strategies are required to significantly reduce the burden of depression, but the cost of long-term drug treatment for the large number of depressed people is high if SSRIs are the drug of choice. Key policy issues with regard to expanded provision of CBT concern the availability of suitably trained providers and the funding mechanisms for therapy in primary care.

Adequate primaquine for vivax malaria

Background. Treatment of vivax malaria with primaquine prevents the relapse of infection from residual liver stages of the parasite. Inadequate dosage is related to a higher relapse risk. Methods: A comparison was made of vivax malaria relapse-prevention treatments with primaquine 22.5 mg or 30 mg daily for 14 days on 146 reports to the Australian Army Central Malaria Register. Results: The lower dose of primaquine was found to carry a relative risk of 6.63 for a relapse of vivax malaria compared with the higher dose. Conclusions:The available data presented here suggest that vivax malaria in this region is increasingly tolerant of the 22.5 mg daily treatment regimen of primaquine and that the greater dose of at least 30 mg daily is more effective.

Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: A single centres' experience with pharmacotherapy

Aims: To compare treatment outcomes amongst patients offered pharmacotherapy with either naltrexone or acamprosate used singly or in combination, in a 12-week outpatient cognitive behavioural therapy (CBT) programme for alcohol dependence. Methods: We matched 236 patients across gender, age group, prior alcohol detoxification, and dependence severity and conducted a cohort comparison study of three medication groups (CBT+acamprosate, CBT+naltrexone, CBT+combined medication) which included 59 patients per group. Outcome measures included programme attendance, programme abstinence and for those who relapsed, cumulative abstinence duration (CAD) and days to first breach (DFB). Secondary analyses compared the remaining matched 59 subjects who declined medication with the pharmacotherapy groups. Results: Across medication groups, CBT+ combined medication produced the greatest improvement across all outcome measures. Although a trend favoured the CBT+ combined group, differences did not reach statistical significance. Programme attendance: CBT + Acamprosate group (66.1%), CBT + Naltrexone group (79.7%), and in the CBT + Combined group (83.1%). Abstinence rates were 50.8, 66.1, and 67.8%, respectively. For those that did not complete the programme abstinent, the average number of days abstinent (CAD) were 45.07, 49.95, and 53.58 days, respectively. The average numbers of days to first breach (DFB) was 26.79, 26.7, and 37.32 days. When the focal group (CBT + combined) was compared with patients who declined medication (CBT-alone), significant differences were observed across all outcome indices. Withdrawal due to adverse medication effects was minimal. Conclusions: The addition of both medications (naltrexone and acamprosate) resulted in measurable benefit and was well tolerated. In this patient population naltrexone with CBT is as effective as combined medication with CBT, but the trend favours combination medication.

Improvement in measures of psychological distress amongst amphetamine misusers treated with brief cognitive-behavioural therapy (CBT)

This trial of cognitive-behavioural therapy (CBT) based amphetamine abstinence program (n = 507) focused on refusal self-efficacy, improved coping, improved problem solving and planning for relapse prevention. Measures included the Severity of Dependence Scale (SDS), the General Health Questionnaire-28 (GHQ-28) and Amphetamine Refusal Self-Efficacy. Psychiatric case identification (caseness) across the four GHQ-28 sub-scales was compared with Australian normative data. Almost 90% were amphetamine-dependent (SDS 8.15 +/- 3.17). Pretreatment, all GHQ-28 sub-scale measures were below reported Australian population values. Caseness was substantially higher than Australian normative values {Somatic Symptoms (52.3%), Anxiety (68%), Social Dysfunction (46.5%) and Depression (33.7%). One hundred and sixty-eight subjects (33%) completed and reported program abstinence. Program completers reported improvement across all GHQ-28 sub-scales Somatic Symptoms (p < 0.001), Anxiety (p < 0.001), Social Dysfunction (p < 0.001) and Depression (p < 0.001)}. They also reported improvement in amphetamine refusal self-efficacy (p < 0.001). Improvement remained significant following intention-to-treat analyses, imputing baseline data for subjects that withdrew from the program. The GHQ-28 sub-scales, Amphetamine Refusal Self-Efficacy Questionnaire and the SDS successfully predicted treatment compliance through a discriminant analysis function (p

Prevention of child behavior problems through universal implementation of a group behavioral family intervention.

The aim of this mental health promotion initiative was to evaluate the effectiveness of a universally delivered group behavioral family intervention (BFI) in preventing behavior problems in children. This study investigates the transferability of an efficacious clinical program to a universal prevention intervention delivered through child and community health services targeting parents of preschoolers within a metropolitan health region. A quasiexperimental two-group (BFI, n=804 vs. Comparison group, n=806) longitudinal design followed preschool aged children and their parents over a 2-year period. BFI was associated with significant reductions in parent-reported levels of dysfunctional parenting and parent-reported levels of child behavior problems. Effect sizes on child behavior problems ranged from large (.83) to moderate (.47). Positive and significant effects were also observed in parent mental health, marital adjustment, and levels of child rearing conflict. Findings are discussed with respect to their implication for significant population reductions in child behavior problems as well as the pragmatic challenges for prevention science in encouraging both the evaluation and uptake of preventive initiatives in real world settings.

Development, prevention and treatment of iron deficiency in women

Iron deficiency is the most common nutritional deficiency in the world. Women of childbearing age are at particular risk of developing iron deficiency due to the iron losses associated with menstruation and childbirth. Women in less developed countries are often unable to obtain adequate dietary iron for their needs due to poor food supplies and inadequate bioavailable iron. In this situation, fortification and supplementation of the diet with extra iron is a reasonable approach to the prevention and treatment of iron deficiency. In Western countries however, food supply is unlikely to be an issue in the development of iron deficiency, yet studies have shown that many women in these countries receive inadequate dietary iron. Research has shown that the form of iron and the role of enhancers and inhibitors of iron absorption may be more important than total iron intake in determining iron status. Despite this, very little research attention has been paid to the role of diet in the prevention and treatment of iron deficiency. Dietary modification would appear to be a viable option for the prevention and treatment of iron deficiency in Western women, especially if the effects of enhancers/inhibitors of absorption are considered. While dietary modification has the potential to address at least part of the cause of iron deficiency in women of childbearing age, its efficacy is yet to be proven. (C) 1998 Elsevier Science Inc.