Gary K. Hulse

Assessing motivation to quit smoking in people with mental illness: a review

BACKGROUND People with mental health (MH) disorders smoke at higher rates, are more nicotine-dependent and suffer greater morbidity and mortality from smoking-related illnesses than the general population. Helping these people to quit smoking is a public health priority; however, many MH professionals assume that those with mental illness are not motivated to quit. OBJECTIVES To use predetermined criteria to identify, review critically and evaluate empirically all English language, peer-reviewed data on motivation to quit smoking in MH populations. METHODS A systematic search was conducted and key data on subject characteristics, measures of motivation and other variables abstracted. chi(2) analyses were used to compare motivation between MH and general populations, between in-patients and out-patients and between people with depression and people with psychotic disorders. RESULTS Evidence suggests that people with MH disorders are as motivated to quit smoking as the general population, although those with psychotic disorders may be less motivated than individuals with depression. Although readiness to cease smoking was assessed in 14 studies, only two evaluated motivation to quit smoking in in-patient populations. CONCLUSIONS People with MH disorders are motivated to quit smoking, although more research is needed looking at in-patient populations. The commonly held false belief that people with MH disorders are not motivated to cease smoking means that opportunities to encourage smoking cessation among this disenfranchised group are being missed.

Validity and Psychometric Properties of the General Health Questionnaire-12 in Young Australian Adolescents

Background: The General Health Questionnaire (GHQ) is a measure of current mental wellbeing that has been extensively validated with adults. The instrument has also been used with adolescents. Objective: (i) To assess the psychometric properties of the GHQ-12 among school students in grades 7–10; (ii) to validate it against other psychological tests; and (iii) to suggest a threshold score. Method: The survey was conducted in single sex and mixed schools from the state and private system in Perth, Western Australia. The survey contained the GHQ-12 and measures of anxiety, depression, self-esteem, stress, generalized self-efficacy, social desirability and negative affectivity. Results: There were 336 students (female 55%) with an age range of 11–15 years (median 13). The GHQ showed good internal consistency (alpha 0.88). Girls had higher mean GHQ-12 scores than boys (F (1,326) 15.0, p < 0.001) and scores for both genders increased with school grade (F (3,326) 4.2, p < 0.01). Multiple linear regression showed that depression, anxiety, self-esteem and stress were significant independent predictors of GHQ scores. The model accounted for 68% of the variance (adjusted R 2). Screening indices were calculated by comparison with a combined depression and/or anxiety category. Threshold scores of 13/14 for males and 18/19 for females appeared optimal. General Health Questionnaire scores were compared with two criterion groups: adolescents in hospital with alcohol or drug (AOD) related problems and those with problems not related to AOD use. Only the former group had significantly higher total scores. Conclusions: The GHQ-12 showed good structural characteristics and was appropriately correlated with other measures of related traits. Overall, the GHQ-12 appears to be a valid index of psychological wellbeing in this population and was considerably shorter than some of the other instruments.

Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease.

OBJECTIVES The results of observational studies suggest that smoking increases the risk of Alzheimer disease (AD). The authors designed this study to determine if older people who smoke have decreased gray matter density in brain regions associated with incipient AD. METHODS The authors recruited 39 pairs (N = 78) of smokers/never-smokers 70 to 83 years of age who were matched for age, sex, education, and handedness. Participants were free of clinically significant cognitive impairment, depression, stroke, or other serious medical conditions. Gray matter density was determined by voxel-based morphometry using statistical parametric mapping of T1-weighted magnetic resonance images. RESULTS Smokers had decreased gray matter density in the posterior cingulum and precuneus (bilateral), right thalamus, and frontal cortex (bilateral) compared with never-smokers. CONCLUSIONS Smoking is associated with decreased gray matter density in brain regions previously associated with incipient AD. Longitudinal investigations are required to clarify whether these changes are progressive in nature.

Improving Clinical Outcomes in Treating Heroin Dependence: Randomized, Controlled Trial of Oral or Implant Naltrexone

CONTEXT Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation. OBJECTIVE To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily oral naltrexone treatment. DESIGN Seventy heroin-dependent volunteers entered a randomized, double-blind, double-placebo controlled trial with a 6-month follow-up period. PATIENTS Eligibility criteria were DSM-IV opioid (heroin) dependence; age 18 years or older; willingness to be randomized; residing in the Perth, Western Australia, metropolitan area; and completion of preclinical screening and written consent. A total of 129 eligible participants were identified, and 70 (54%) provided informed consent and were randomized as per the study design. INTERVENTION Participants received oral naltrexone, 50 mg/d, for 6 months (plus placebo implants) or a single dose of 2.3 g of naltrexone implant (plus placebo tablets). MAIN OUTCOME MEASURES (1) Maintaining therapeutic naltrexone levels above 2 ng/mL; (2) return to regular heroin use (>or=4 d/wk); (3) other heroin use and abstinence; (4) use of illicit nonopioid drugs; (5) number of opiate overdoses requiring hospitalization; (6) treatment-related unexpected and expected adverse events; and (7) blood naltrexone levels (ie, pharmacokinetic profile) for recipients of active naltrexone implants. RESULTS More participants in the oral vs the implant group had blood naltrexone levels below 2 ng/mL in months 1 (P < .001) and 2 (P = .01); in addition, more oral group participants had returned to regular heroin use by 6 months (P = .003) and at an earlier stage (median [SE], 115 [12.0] days vs 158 [9.4] days). There were 10 trial-related, unexpected adverse events. One serious adverse event, a wound hematoma, was associated with surgical implantation. Naltrexone blood levels in implant recipients were maintained above 1 and 2 ng/mL for 101 (95% confidence interval, 83-119) and 56 (39-73) days, respectively, among men and 124 (88-175) and 43 (16-79) days among women. CONCLUSIONS The naltrexone implant effectively reduced relapse to regular heroin use compared with oral naltrexone and was not associated with major adverse events. Clinical Trial Registration anzctr.org.au Identifier: ACTRN12606000308594.

The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a κ-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term.

Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse.

Objective:  To determine the obstetric and perinatal outcomes of women using illicit drugs during pregnancy by substance group.

Suicide and attempted suicide among older adults in Western Australia

BACKGROUND Suicide rates are high in later life. Risk factors include male sex and depressive illness. This study investigated the relationship between suicidal behaviour and contact with mental health services among the elderly in Western Australia. METHODS Record linkage was used to obtain records of hospital admissions and mental health service contacts for all suicide attempts and deaths in the period 1980-95. Standardized incidence ratios were calculated for the elderly, general population and people with mental health service contacts. Cox regression was used to evaluated potential risk factors for elderly people who were in contact with mental health services. RESULTS People over 60 years of age accounted for 15% of suicides and 4.6% of attempted suicides. Suicide rates were 3.3 times higher in males and 4.4 times higher in females when compared to the general population of elderly people. For attempted suicide, the rate was 5.8 times higher in males and 6.6 times higher in females with prior contact with mental health services. Highest risk of suicide was found in patients with diagnoses of affective psychoses (RR = 3.7), adjustment reaction (RR = 3.2) or depressive disorder (RR = 2.8). The diagnosis of cancer was associated with decreased risk of suicide (RR = 3.6) and attempted suicide (RR = 1.9). CONCLUSIONS Suicide rates are high among the elderly in Western Australia. Suicide is significantly associated with the diagnosis of mood disorder. Suicide attempts are less common, and are associated most strongly with mood and personality disorders. The decreased risk of self-harm behaviour among patients with cancer warrants further investigation.

Blood naltrexone and 6-β-naltrexol levels following naltrexone implant: Comparing two naltrexone implants

The aim of this study was to profile and compare blood naltrexone and 6‐ β‐ naltrexol levels with time following treatment with two sustained‐release naltrexone preparations produced by GoMedical Industries, Australia at a community heroin treatment clinic in Perth, Western Australia. A sample of 10 patients who each received a 1.7 g naltrexone implant were compared to 24 patients who each received a 3.4 g naltrexone implant as treatment for heroin dependence. Blood naltrexone levels following treatment with the 1.7 g naltrexone implant remained above 2 and 1 ng/ml for approximately 90 and 136 days, respectively. Use of the 3.4 g naltrexone implant extended the period of coverage to approximately 297 (1 ng/ml) or 188 (2 ng/ml) days. Blood 6‐ β ‐naltrexol levels remained above 10 ng/ml for approximately 18 and 83 days, respectively, following use of the 1.7 g and 3.4 g naltrexone implants. The current study data indicate that blood naltrexone and 6 ‐β‐ naltrexol levels following treatment with either the 1.7 g or 3.4 g naltrexone implant are greater than those reported in other published data on other sustained‐release naltrexone preparations. Furthermore, duration of blood naltrexone and 6 ‐β‐ naltrexol levels achieved following use of the 3.4 g implant were superior to those achieved with the 1.7 g naltrexone implant, with naltrexone blood levels maintained above 2 ng/ml for a period of approximately 6.3 months compared to 3 months, respectively. The implications of this in managing the heroin‐dependent patient, especially those who find it difficult to shift away from dependent use patterns, are discussed.

24-month effect of smoking cessation on cognitive function and brain structure in later life

BACKGROUND Observational studies investigating the association between smoking, cognitive decline and dementia have produced conflicting results. We completed this trial to determine if smoking cessation decreases the progression of cognitive decline in later life. METHODS We recruited older smokers (n=229) and never smokers (n=98) and invited smokers to join a smoking cessation trial. The primary outcome of interest was change in Alzheimers Disease Assessment Scale cognitive subscale (ADAS-cog) scores over 24 months. Secondary measures included the Logical Memory test and changes in gray matter density. Successful smoking cessation was defined as a minimum of 547 smoking free days during follow up. RESULTS The ADAS-cog scores of unsuccessful quitters (UQ) increased (i.e., became worse) 1.1±0.3 and 1.2±0.4 points more than the scores of never smokers (NS) (p=0.001) and successful quitters (SQ) (p=0.006) respectively over the 24 months of follow up. Similarly, the scores of UQ declined (i.e., became worse) relative to NS on measures of immediate (p=0.004) and delayed recall (p=0.029). All analyses were adjusted for age, years of education, baseline cognitive performance, alcohol use, depression scores, and the presence of chronic respiratory disease. Thirty-six NS, 18 SQ and 48 UQ completed the imaging substudy. Compared with NS, UQ showed a disproportional loss of gray matter density in the right thalamus, right and left inferior semi-lunar lobule, as well as left superior and inferior parietal lobule over 24 months. SQ showed loss of gray matter compared with NS in the right middle and inferior occipital gyri, right and left culmen, and the left superior frontal gyrus. We did not find any brain regions in which UQ had lost more gray matter than SQ over 2 years. CONCLUSION These results are consistent with the hypothesis that smoking causes cognitive decline and loss of gray matter tissue in the brain over time.

Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants

The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear. Patients attending a community‐based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy. The first 50 patients to commence HCV therapy and complete at least 6 months follow‐up were prospectively studied. ETR response (HCV PCR negative) was 34/50 (68%) and SVR 6 months post‐treatment was 31/50 (62%). Viral eradication was maintained in those 22 patients that have had 12 months or more post‐treatment follow‐up. Eleven (22%) patients stopped therapy early due to side effects or poor compliance. Only two patients with an ETR likely reinfected due to unsafe injection practices. One was re‐treated and achieved an SVR. Of the patients achieving a 6‐month SVR, 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation. 46% of patients received antidepressant and/or antipsychotic medication during treatment. Conclusion: This study of HCV treatment in a community‐based subcutaneous naltrexone implant clinic found antiviral therapy resulted in a 62% SVR. This result is comparable to that reported in hospital‐based clinics in non‐IDU patients. The side effect profile and compliance was also similar. HCV antiviral therapy should be offered to this large and currently under treated group. (HEPATOLOGY 2007;45:111–117.)