Kenneth Thau

Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis

The mortality of patients suffering from affective disorders is much higher than that of the general population; this excess is due to both suicides and cardiovascular disease. During long-term lithium treatment, the overall mortality has not been found to differ significantly from that of the general population but the question remains whether this lowering, if it is in fact caused by lithium, is due to a reduction in suicide frequency or cardiovascular mortality, or both. We analysed data from 827 previously studied patients and used a procedure that estimated both overall mortality and cause-specific mortalities by single-case analysis. For overall mortality, the ratio of observed deaths (among the patients) to expected deaths (in the general population) was 1.14, which is not significantly different from 1.0; this was also found in our previous analysis. In the whole patient group, comprising 5600 patient years under lithium treatment, seven suicides were observed and 1.3 expected, resulting in a standard mortality ratio of 5.22; this is significantly > 1.0, but markedly lower than that found in patients with affective disorders not given lithium. Cardiovascular mortality was not found to be higher in our patients than in the general population. In view of the fact that a placebo-controlled mortality study under long-term conditions is neither ethically nor practically feasible, our findings cannot prove definitively that long-term lithium treatment counteracts factors responsible for the excess suicide and cardiovascular mortality of affective disorders. However, our observations are compatible with such a notion.

The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness*

Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic‐depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient‐years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic‐depressive patients is 2–3 times that of the general population. Our data show that the mortality of manic‐depressive and schizoaffective patients given long‐term lithium treatment does not differ significantly from that of the general population.

Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates

AIMS Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants. METHODS PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity. RESULTS Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes. RECOMMENDATIONS Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication. CONCLUSION Methodological flaws and inconsistencies confound interpretation of todays literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Lithium in drinking water and suicide mortality

BACKGROUND There is some evidence that natural levels of lithium in drinking water may have a protective effect on suicide mortality. AIMS To evaluate the association between local lithium levels in drinking water and suicide mortality at district level in Austria. METHOD A nationwide sample of 6460 lithium measurements was examined for association with suicide rates per 100,000 population and suicide standardised mortality ratios across all 99 Austrian districts. Multivariate regression models were adjusted for well-known socioeconomic factors known to influence suicide mortality in Austria (population density, per capita income, proportion of Roman Catholics, as well as the availability of mental health service providers). Sensitivity analyses and weighted least squares regression were used to challenge the robustness of the results. RESULTS The overall suicide rate (R(2) = 0.15, β = -0.39, t = -4.14, P = 0.000073) as well as the suicide mortality ratio (R(2) = 0.17, β = -0.41, t = -4.38, P = 0.000030) were inversely associated with lithium levels in drinking water and remained significant after sensitivity analyses and adjustment for socioeconomic factors. CONCLUSIONS In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.

Mortality during initial and during later lithium treatment : a collaborative study by the International Group for the Study of lithium-treated patients

We have previously shown that the mortality of patients with recurrent affective disorders in long‐term lithium treatment is not higher than that of the general population. In the present study on 471 patients from Denmark and Germany, we examined mortality during the initial year of lithium treatment and during later lithium treatment. During initial lithium treatment, the total mortality was twice as high as in the general population (difference not significant) and the mortality due to suicide 16 times higher. During later lithium treatment, the mortality rates did not differ from those in the general population. Our results indicate that patients with frequent, often severe recurrences, those chosen for prophylactic lithium treatment, are at risk of high mortality, which then diminishes as the prophylactic action of the treatment takes effect.

Association between Prenatal Tobacco Exposure and Outcome of Neonates Born to Opioid-Maintained Mothers

Background: Prenatal nicotine exposure is associated with increased neonatal mortality, low birth weight, and smaller head circumference. Opioid-dependent pregnant women show a particularly high prevalence of tobacco smoking and are at greater risk for additional adverse events. However, little is known about the impact of tobacco smoking on opioid-maintained pregnant women and neonatal outcomes. Patients and Methods: This study examined the effect of cigarette smoking on 139 opioid-maintained pregnant women and their neonates. Forty-five percent of the participants were maintained on slow-release oral morphine (SROM), 39% received methadone maintenance, and 16% received buprenorphine. Participants were divided into two groups: (1) women who reported a low cigarette consumption of ≤10 cigarettes/day (56.8%) and (2) those reporting heavy consumption of ≥20 cigarettes/day (43.2%). Neonatal outcome measures were assessed, and a standardized Finnegan score was applied to determine the neonatal abstinence syndrome (NAS). Results: Fifty-two percent of the newborns did not require treatment for NAS (54% of neonates born to methadone-maintained mothers, 30% born to SROM-maintained mothers, and 95% born to buprenorphine-maintained mothers; p < 0.001). Heavy cigarette consumption was associated with significantly lower neonatal birth weight (p < 0.001), smaller birth length (p = 0.017) as well as with the severity of NAS (p = 0.03). With regard to concomitant consumption of opioids (p = 0.54), cocaine (p = 0.25), amphetamines (p = 0.90) or benzodiazepines (p = 0.09), no significant differences between heavy or low nicotine consumption were noted. Conclusion: Heavy tobacco smoking in opioid-maintained pregnant women is associated with adverse medical and developmental consequences for the newborn. Future treatment programs for this target group should focus on an individualized approach to opioid maintenance therapy in addition to offering specially tailored counseling for smoking cessation.

[ 123 I]- β -CIT SPECT Imaging Shows Reduced Thalamus–Hypothalamus Serotonin Transporter Availability in 24 Drug-Free Obsessive-Compulsive Checkers

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus–hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane ([123I]-β-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [123I]-β-CIT brain binding was used (V″3=(thalamus and hypothalamus−cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38±0.19 vs 1.69±0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=−0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [123I]-β-CIT binding in the thalamus–hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.

INTRODUCTION Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. METHODS We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. RESULTS No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. CONCLUSIONS It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Becks theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.

Quality of Life in Patients Receiving Opioid Maintenance Therapy

Background/Aims: In recent years, quality of life (QoL) assessments have proved useful for evaluating and comparing drug treatment programs. To compare QoL of patients maintained on methadone versus slow-release morphine, a prospective, randomized, double-blind, double-dummy, cross-over study was conducted. Methods: Over two 7-week study phases, participants received either oral slow-release morphine capsules followed by methadone oral solution or vice versa. QoL status was assessed at baseline, week 7, and week 14 using the German version of the Lancashire Quality of Life Profile. Results: No statistically significant difference was found between methadone and slow-release morphine in any QoL domain. A significant time effect for nearly all QoL domains was observed after 14 weeks of opioid medication, independent of the chosen drug (general well-being, p < 0.001; mental health, p = 0.001; general state of health, p = 0.018; leisure time at home, p = 0.034; leisure time out of the home, p = 0.008). Furthermore, this study revealed that even short-term maintenance yields significantly higher QoL scores in the important domain of general well-being. Conclusion: These results indicate that slow-release morphine has effects comparable to methadone on patient-reported QoL data and is thus a promising option for treatment of opioid-dependent subjects.

Multiple substance use among young males

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.