Is the prophylactic antidepressant efficacy of lithium in bipolar I disorder dependent on study design and lithium level?

In the 1970s, several randomized controlled trials demonstrated significant antimanic and antidepressant properties of lithium in the prophylactic treatment of bipolar disorder. However, a recent meta-analysis of randomized, placebo-controlled trials of lithium in bipolar disorder found that its protective effect against depressive relapse/recurrence was equivocal. By examining potentially relevant parameters of recent randomized controlled trials with regard to lithium's prophylactic antidepressant efficacy, we try to identify factors which might help to explain these discrepant results across the different trials. Lithium's efficacy against manic relapse/recurrence appears rather robust at plasma levels between 0.8 and 1.2 mmol/L, whereas lithium's efficacy against depressive relapse/recurrence may be more modest and dependent on whether a response during the preceding acute episode was achieved by lithium treatment. Furthermore, it might be advisable to continue lithium without interruption at the same dose/plasma level, which yielded the initial response. A lithium level between 0.5 and 0.8 mmol/L may be equally efficacious against overall relapse and associated with equal or even superior efficacy regarding depressive relapse/recurrence. To provide evidence-based guidelines on this issue, large prospective, randomized, double-blind, placebo-controlled trials are needed comparing the efficacy of lithium at different plasma levels against manic and depressive relapse/recurrence. In these trials, factors previously associated with predicting response to lithium should also be assessed.     

Are experiences of sexual violence related to special needs in patients with substance use disorders? A study in opioid-dependent patients

A history of sexual violence has been related to more complex treatment needs in patients with substance use disorders (SUD). Most of the existing studies, however, included patients with various types of SUD, did not examine gender differences and focused on a small range of clinical domains. Our sample consisted of opioid-dependent outpatients treated during a three-year period in a German metropolitan region. The analysis was based on a local case register and included all patients for whom information on lifetime sexual violence was available (N = 3531; 68.3% males). In a case–control design, patients with a history of sexual violence were compared to patients without these experiences regarding a wide range of clinical and social factors indicative of potential needs. Almost two thirds (65.6%) of the female patients and 10.9% of the males reported experiences of sexual violence. Victims differed from non-victims across a variety of domains, including more psychiatric symptoms and suicide attempts, more legal problems, financial and family problems, as well as a higher use of services. In contrast to a previous study among alcohol-dependent patients, no gender differences became apparent. Our findings suggest that experiences of sexual violence are an indicator for more complex needs in opioid-dependent patients of both genders. In addition to integrated trauma-informed approaches, an effort needs to be made to link addiction facilities to further institutions to meet these complex needs.     

Isolation of Helicobacter pylori from patients enrolled in a clinical trial in the Philipines

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Decreased drinking in adults with co-occurring cannabis and alcohol use disorders in a treatment trial for marijuana dependence: Evidence of a secondary benefit?

The purpose of the present study was to investigate whether cannabis dependent users who met criteria for a secondary diagnosis of alcohol use disorder (AUD) would increase their use of alcohol in response to decreasing their use of marijuana in a behavioral treatment trial for cannabis use disorder (CUD). This phenomenon is commonly known as “substance substitution.” Participants were randomly assigned to one of four 9-session treatment conditions with cannabis and alcohol use measured at baseline, posttreatment, and at 4 follow-ups through 14 months. Of those enrolled (n = 198), 27 (13.6%) also met criteria for AUD. Linear mixed models were used to analyze alcohol use over time with cannabis use and time as predictors. Findings demonstrated that there were no associations between declines in cannabis use and changes in alcohol consumption in the full sample. However, among those with CUD who also had AUD, declines in cannabis use significantly predicted concurrent declines in alcohol use (p < .05). This study did not find evidence of substance substitution among individuals receiving treatment for CUD. Contrary to expectations, the results indicated that individuals with AUD were more likely to decrease, rather than increase, their alcohol use when they reduced their marijuana use. Treatment for CUD in this study appeared to result in improvements in substance use generally, at least for those with comorbid AUD.     

Are differences in population prevalence of alcohol's harm to others related to survey administration mode?

Introduction and Aims. This study assessed the comparability of estimates of alcohol's harm to others across different administration modes in Swedish general population surveys. Harm was categorised as harm from strangers' drinking and harm from heavy drinkers known to the respondent. Design and Methods. Three surveys were conducted in 2011/2012 (n = 6841), including identical questions. One was based on self‐administered postal or Web questionnaires, and two were based on computer‐assisted telephone interviews of which one included a more ambitious procedure in terms of for example monetary incentives to the respondents. Pearson χ²‐tests were used to compare differences in the prevalence of harm. To estimate potential effects of survey mode, the samples were pooled, and multivariate Poisson regression models with mode as explanatory variable were used, adjusting for socio‐demographic and behavioural factors. Results. Respondents in the two computer‐assisted telephone interviews were more likely to report harm from strangers' drinking compared with respondents in the self‐administered postal or Web questionnaires. However, no significant differences were found between survey modes concerning reports of harm from known people's drinking. Discussion and Conclusions. A survey mode based on interviews seems to facilitate reports of harm from strangers' drinking. This does not apply to reports of harm from known people's drinking. Therefore, the comparability of estimates of alcohol's harm to others between survey modes depends on the type of harm being studied. [Sundin E, Landberg J, Galanti MR, Room R, Ramstedt M. Are differences in population prevalence of alcohol's harmto others related to survey administration mode?     

Are cannabis users who participate in a randomized clinical trial different from other treatment seekers?

Randomized controlled trials (RCTs) provide the most convincing evidence for clinical questions concerning the efficacy of interventions. When participants in RCTs are characteristically different to those in usual clinical practice, it may be difficult to generalize findings. This study compares profiles taken from a centralized intake process for those presenting with cannabis as their main drug, which were then separated into three categories, (a) those who were offered a specialist assessment for cannabis dependence over the phone but did not attend their appointment, (b) those who presented for their initial appointment, and c) those attending and subsequently recruited into an RCT. To explore whether issues such as severity of cannabis use and co-occurring disorders acted as a barrier to attending treatment or to inclusion in an RCT, we examined basic triage information. Results indicated that there were no statistically significant differences on selected characteristics between groups, suggesting that RCT participants were representative of treatment seekers, and that the filtering that occurs between those who make phone contact with professional services and those who present to treatment are not necessarily due to presence of patient characteristics such as coexisting medical, psychological issues, or severity of their cannabis use.     

Are nanomaterials a threat to the immune system?

Nanoparticles can enter into the human body through several routes and interact with components of the immune system. This interaction leads to enhanced release of different cytokines that include both proinflammatory and inflammatory cytokines as shown by several laboratories. The use of different types of materials may have different effects on the immune system; for instance, cobalt and nickel nanoparticles have inflammogenic effects while hydroxyapatite crystals stimulate TNFa secretion from macrophages which subsequently activate other phagocytes. Nanoparticles used in cosmetics and skin care products cause low systemic toxicity on skin. Carbon nanoparticles produce allergic symptoms, while fullerene is useful in mitigating allergy. Thus, nanoparticles have immunomodulatory potential as these can stimulate or suppress the immune system. However, both the conditions are undesirable and the successful nanoparticle-based therapeutics should avoid immunostimulatory or immunosuppressive reactions to the nanomaterials once administered into the body. The interaction of nanoparticles with the immune system alters its bioavailability and prolongs exposure time. Therefore, more data should be generated through in vivo studies.     

Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A retrospective naturalistic study

In bipolar disorder the discontinuation of lithium prophylaxis is associated with early episode precipitation. Is this ;rebound' phenomenon peculiar to lithium? This naturalistic retrospective case note review investigated the frequency of immediate recurrence after discontinuation of any prophylactic treatment. Bipolar patients who stopped at least one medication after at least 6 months of remission were studied. A total of 310 case notes were examined in a systematic search. A total of 53 cases of discontinuation in 48 subjects were found. Discontinued medications included lithium, valproate, carbamazepine, typical and atypical antipsychotics and antidepressants. Recurrence occurred within 3 months of medication withdrawal in 39 cases (74%). Over half of the discontinuation episodes involved lithium: recurrence occurred in 86% of these cases. In the groups stopping other prophylactic agents, a majority of subjects suffered recurrence: anticonvulsants (89%), antipsychotics (64%) and antidepressants (58%). However, these groups were small and the clarity of the data was undermined by the simultaneous withdrawal of other agents. Manic and hypomanic episodes were the most common form of recurrences. Depressive episodes occurred proportionately most frequently following antidepressant withdrawal. More than half of recurrences required hospital admission. This study provides preliminary naturalistic evidence that early episode recurrence in bipolar disorder is not peculiar to lithium withdrawal but may occur following withdrawal of medication from all classes recommended in prophylaxis. These findings, if replicated, have important implications for clinical practice and for research.     

Are results from pharmaceutical-company-sponsored studies available to the public?

Purpose  

Only 53% and 63% of studies and clinical trials results presented at congresses are published. Company-sponsored trial results are being posted on publicly accessible Web sites. We analyzed the public availability (publication or posting on a Web site) rate, time to publication, and factors predicting public availability of results of studies sponsored by a pharmaceutical company.     

The role of p-glycoprotein in psychiatric disorders: a reliable guard of the brain?

A major component in the protection of the brain against blood-borne toxic influences is the multispecific efflux pump P-glycoprotein. This pump, a 170 kD protein, located at the luminal side of the capillary endothelial cells, has a large capacity and is capable of extruding a wide array of structurally divergent substrates. The brain uptake of the majority of antidepressants and antipsychotics, as well as many other psychotropic drugs and endogenous compounds is hampered by the activity of P-glycoprotein. In this review we discuss the current state of knowledge concerning the role of Pglycoprotein on pharmacokinetics of psychiatric drugs and the impact of modulation of P-glycoprotein on major psychiatric disorders. Relevant issues in reference to the function of P-glycoprotein and other efflux pumps in the blood-brain barrier related to mood disorders and schizophrenia are addressed, such as a possible role of P-glycoprotein as a susceptibility factor in depressive disorders and psychotic disorders.     

Are typical human serum BPA concentrations measurable and sufficient to be estrogenic in the general population?

Mammalian estrogen receptors modulate many physiological processes. Chemicals with structural features similar to estrogens can interact with estrogen receptors to produce biological effects similar to those caused by endogenous estrogens in the body. Bisphenol A (BPA) is a structural analogue of estrogen that binds to estrogen receptors. Exposure to BPA in humans is virtually ubiquitous in industrialized societies, but BPA is rapidly detoxified by metabolism and does not accumulate in the body. Whether or not serum concentrations of BPA in humans are sufficiently high to disrupt normal estrogen-related biology is the subject of intense political and scientific debate. Here we show a convergence of robust methods for measuring or calculating serum concentrations of BPA in humans from 93 published studies of more than 30,000 individuals in 19 countries across all life stages. Typical serum BPA concentrations are orders of magnitude lower than levels measurable by modern analytical methods and below concentrations required to occupy more than 0.0009% of Type II Estrogen Binding Sites, GPR30, ERα or ERβ receptors. Occupancies would be higher, but ⩽0.04%, for the highest affinity receptor, ERRγ. Our results show limited or no potential for estrogenicity in humans, and question reports of measurable BPA in human serum.     

Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models

Background and rationale  Epidemiological evidence suggests that people who begin experimenting with drugs of abuse during early adolescence are more likely to develop substance use disorders (SUDs), but this correlation does not guarantee causation. Animal models, in which age of onset can be tightly controlled, offer a platform for testing causality. Many animal models address drug effects that might promote or discourage drug intake and drug-induced neuroplasticity. Methods  We have reviewed the preclinical literature to investigate whether adolescent rodents are differentially sensitive to rewarding, reinforcing, aversive, locomotor, and withdrawal-induced effects of drugs of abuse. Results and conclusions  The rodent model literature consistently suggests that the balance of rewarding and aversive effects of drugs of abuse is tipped toward reward in adolescence. However, increased reward does not consistently lead to increased voluntary intake: age effects on voluntary intake are drug and method specific. On the other hand, adolescents are consistently less sensitive to withdrawal effects, which could protect against compulsive drug seeking. Studies examining neuronal function have revealed several age-related effects but have yet to link these effects to vulnerability to SUDs. Taken together, the findings suggest factors which may promote recreational drug use in adolescents, but evidence relating to pathological drug-seeking behavior is lacking. A call is made for future studies to address this gap using behavioral models of pathological drug seeking and for neurobiologic studies to more directly link age effects to SUD vulnerability.     

Assessing the cost-effectiveness of switching from a β-blocker to latanoprost in the treatment of ocular hypertension

Glaucoma is a pathological condition whose most important risk factor is increased intraocular pressure (IOP). The medical treatment of glaucoma essentially consists of compounds that are able to decrease the IOP. The compounds discussed in this review act in a different way, β-blockers mainly inhibit the production of aqueous humor, whereas latanoprost decreases the resistance in the outflow channels. β-Blockers are compounds with a well-known efficacy and safety profile and they are fairly inexpensive. Their systemic and local side effects are mainly cardiovascular and pulmonary adverse events, dry eye and keratopathy. Latanoprost, which has recently been introduced into the market, has been shown to be equally as effective, or better in lowering IOP in patients than timolol, although it is more expensive. Systemic reported side effects are anecdotal; local hyperaemia, keratopathy, hypertrichosis, increased pigmentation of eyelashes and iris, uveitis and cystoid macular oedema have been reported. A comparison of costs reveals that a 1-year therapy with timolol ophthalmic solution starts from €11.00 and can reach €146.00 for the most expensive preservative-free 1-day dispenser packages (～ 13.5 times higher). For latanoprost once-daily administration, the cost for 1years therapy is €98.55, approximately six times higher than generic or brand 0.5% timolol applied twice-daily. What are the factors influencing a change in therapy from β-blockers to latanoprost? The only good reason is represented by a further deterioration in the visual field. This may occur, despite a significant reduction in IOP, because the reached IOP is not sufficient enough to avoid further deterioration because the patient’s work or social activities do not allow a correct daily dosage of the compound (bad compliance); or as a result of treatment suspension, because of the development of systemic and/or local side effects. Changes in therapy must always be related to a failing control of the disease, as any therapeutic modification leading to an increase in the number of visits and additional examinations, consequently enhances the costs.