Katayama et Al.: therapeutic window of lamotrigine for mood disorders: a naturalistic retrospective study. Pharmacopsychiatry 2014; 47: 111-114.

Katayama and colleagues proposed in their article a therapeutic window for lamotrigine in affective disorders between 5 and 11 µg/mL. Despite potential differences in lamotrigine metabolism, the results of their retrospective study in a Japanese population match nicely with what we have previously reported in a Caucasian population with rapid cycling bipolar disorder. It is suggested that not only in epilepsy, but also in mood-disordered patients clinicians should rather consider lamotrigine plasma levels than dosage when in doubt about the efficacy of treatment.

Sildenafil-induced cervical spinal cord infarction.

We present a patient with an acute cervical spinal cord infarction resulting from the use of sildenafil (Viagra) in combination with his hypertension medication. Symptoms were acute and rapidly progressive, and MR imaging with DWI was crucial in confirming the diagnosis.

[Clinical standing of valproate treatment of bipolar disorders]. / Klinischer Stellenwert der Valproat-Therapie bei bipolaren Störungen.

During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.

Gait variables differentiating fallers from nonfallers.

PURPOSE: This study examined the qualitative and quantitative differences between 2 groups of older adults, fallers and nonfallers. We compared walking differences during overground walking to a task of obstacle clearance. METHODS: Forty-eight community dwelling older adults (18 fallers and 30 nonfallers) participated. The mean age of the participants was 78.1 +/- 7.2 years (fallers) and 75.8 +/- 5.1 years (nonfallers). Walking differences within and between fallers and nonfallers during a single visit for 6 conditions were examined: (1) baseline walking, (2) slow walking, (3) fast walking, and (4) 5 cm obstacle clearance - approach, during, and exit. Quantitative differences of temporal-spatial walking measures were analyzed using a multifactorial ANOVA adjusted for age, gender, height, and BMI with a Scheffe correction (p < 0.05) applied for multiple testing. Qualitative data were analyzed using Chi-square fisher's exact test. RESULTS: There were interaction effects for group by walking condition for single support (p = 0.002) and step length (p = 0.05), while 1st double support approached significance (p = 0.06). Main Group effects were found during the comfortable walk (p < 0.001-0.05) for all 7 gait variables. Qualitatively, the fallers demonstrated increased knee flexion during both over ground walking (c2 = 9.01 ; p < 0.006), and the fallers consistently took several small steps immediately prior to the obstacle clearance (c2 = 8.42 ; p = 0.007). CONCLUSION: There were significant differences in quantitative and qualitative walking characteristics differentiating fallers from nonfallers during over-ground walking at different velocities and during obstacle clearance.

Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline.

BACKGROUND: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. AIMS: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. METHOD: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. RESULTS: A total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. CONCLUSIONS: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.

Use of mineral magnetic concentration data as a particle size proxy: a case study using marine, estuarine and fluvial sediments in the Carmarthen Bay area, South Wales, U.K.

Compositional (non-magnetic) data can correlate strongly with particle size, which deems it appropriate as a particle size proxy and, therefore, a reliable means of normalising analytical data for particle size effects. Previous studies suggest magnetic concentration parameters represent an alternative means of normalising for these effects and, given the speed, low-cost and sensitivity of the measurements may, therefore, offer some advantages over other compositional signals. In this work, contemporary sediments from a range of depositional environments have been analysed with regard to their mineral magnetic concentration and textural characteristics, to observe if the strength and nature of the relationship identified in previous studies is universal. Our data shows magnetic parameters (chi(LF), chi(ARM) and SIRM) possess contrasting relationships with standard textural parameters for sediment samples collected from marine (Carmarthen Bay), estuarine (Gwendraeth Estuary) and fluvial (Rivers Gwendraeth Fach and Gwendraeth Fawr) settings. Magnetic concentrations of sediments from both the marine and estuarine environments are highly influenced by the magnetic contribution of finer particle sizes; Gwendraeth Fawr River sediments are influenced by the magnetic contribution of coarser particle sizes, while sediments from the Gwendraeth Fach River are not influenced significantly by any variations in textural properties. These results indicate mineral magnetic measurements have considerable potential as a particle size proxy for particular sedimentary environments, which in certain instances could be useful for geochemical, sediment transport, and sediment provenance studies. However, the data also highlight the importance of fully determining the nature of the relationship between sediment particle size and magnetic properties before applying mineral magnetic data as a particle size proxy.

Pilot study of correlation of pulp stones with cardiovascular disease.

We propose that calcification of dental pulp may have a similar pathogenesis as calcified atheromas and could lead to use of routine dental radiographs as a rapid screening method for early identification of potential cardiovascular disease (CVD). Fifty-five dental patients ages 20 to 55 were chosen because pulp stones in pulpally noninflamed teeth were not expected in this age group. They completed a questionnaire regarding their CVD status and that of their parents and siblings. Entry criteria included at least one asymptomatic, minimally restored, noncarious molar and no history of gout, renal disease, or renal lithiasis. Patients' periapical radiographs of record were viewed to determine the presence of pulp stones. There was a significant relationship between pre-existing CVD and pulp stones (odds ratio of 4.4 with a 95% confidence interval of 1.1, 18.7), but no relationship was found for family history of CVD and pulp stones (odds ratio of 1.7 with a 95% confidence interval of 0.5, 5.5). Seventy-four percent (14/19) of patients with reported CVD had detectable pulp stones while only 39% (14/36) of patients without a history of CVD had pulp stones. This pilot study demonstrates that patients with CVD have an increased incidence of pulp stones in teeth with noninflamed pulps compared to patients with no history of CVD. No relationship was found between presence of pulp stones and family history of CVD. The findings suggest that dental radiographic determination of the presence or absence of pulp stones may have possibilities for use in CVD screening.

Meteorological normalisation and non-parametric smoothing for quality assessment and trend analysis of tropospheric ozone data.

Despite extensive efforts to ensure that sampling and installation and maintenance of instruments are as efficient as possible when monitoring air pollution data, there is still an indisputable need for statistical post processing (quality assessment). We examined data on tropospheric ozone and found that meteorological normalisation can reveal (i) errors that have not been eliminated by established procedures for quality assurance and control of collected data, as well as (ii) inaccuracies that may have a detrimental effect on the results of statistical tests for temporal trends. Moreover, we observed that the quality assessment of collected data could be further strengthened by combining meteorological normalisation with non-parametric smoothing techniques for seasonal adjustment and detection of sudden shifts in level. Closer examination of apparent trends in tropospheric ozone records from EMEP (European Monitoring and Evaluation Programme) sites in Finland showed that, even if potential raw data errors were taken into account, there was strong evidence of upward trends during winter and early spring.

Serum levels of substance P and response to antidepressant pharmacotherapy.

Substance P (SP) is possibly involved in the etiopathology of affective disorders. Here we investigated the relationship of SP serum levels and response to antidepressant drug therapy. SP serum levels were determined before and during a 9-week drug trial in 40 depressed patients treated with paroxetine in combination with either lamotrigine (n = 20) or placebo (n = 20). Responders (n = 18) and non-responders (n = 22) significantly differed in SP serum levels: responders started with higher SP levels that decreased during drug therapy, whereas non-responders had lower SP levels that increased at the beginning. There were no differences between patients with adjunct lamotrigine or placebo. These preliminary data indicate that SP serum levels might be related to response to antidepressant drug therapy. Further studies have to substantiate this finding.

St John's wort (Hypericum perforatum) modulates evoked potentials in guinea pig hippocampal slices via AMPA and GABA receptors.

The effects of an ethanolic extract of the plant Hypericum perforatum L. (St John's wort) (HYP) and its hydrosoluble fraction (HYPWS) on electrically evoked population spikes and fEPSP were investigated in this study. Concentration dependent (10(-6) to 10(-4) g/l) excitatory effects were found. Above concentrations of 10(-3) g/l, HYP reduced the evoked responses, whereas HYPWS further increased them. Paired pulse facilitation was unaffected with HYPWS (10(-4) to 10(-2) g/l). The excitatory effects of HYPWS were amplified by the GABA(A) and GABA(B) receptor antagonists bicuculline and phaclofen, respectively. These excitations were antagonised by the AMPA receptor antagonist CNQX. Excitations caused by hypericum were not antagonised by the NMDA receptor antagonists D-APV and MK801, the metabotropic glutamate receptor (type I and II) antagonist MCPG, or the L-type calcium channel blocker verapamil. Hypericin and hyperforin, two components of H. perforatum, were found not to be responsible for the excitatory effects of the extract.

[Psychopharmacotherapy of bipolar affective diseases]. / Psychopharmakotherapie bipolarer affektiver Erkrankungen.

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

[Comorbidity of depressive disorders and cardiovascular diseases. Implications for diagnosis, pharmaco- and psychotherapy]. / Komorbidität von depressiven Störungen und kardiovaskulären Erkrankungen. Implikationen für Diagnostik, Pharmako- und Psychotherapie.

Controlled studies and meta-analyses show not only that depression and cardiovascular disease often occur together, but that depressive illnesses are an independent risk factor in the development and the progression of coronary heart disease. It can be difficult to distinguish between reactive mood disturbance after myocardial infarction and depressive episodes that may have preceded the infarction and which require treatment. Due to this difficulty, depressive disorders are rarely diagnosed, and only a minority of patients receive adequate treatment. However, owing to the introduction of new antidepressants in recent years, the number of treatment options has increased. Specifically, selective serotonin reuptake inhibitors (SSRI) offer a valuable alternative to tricyclic antidepressants, which are problematic in heart disease. The authors describe on the one hand controlled studies of SSRIs and discuss differential therapeutic consequences. On the other hand, studies of psychotherapeutic interventions in comorbid patients with depression and coronary heart disease are reported. Finally, the authors discuss which psychotherapeutic interventions may be suitable.

Clinical relevance and treatment possibilities of bipolar rapid cycling.

Bipolar rapid cycling (RC) is defined as 4 or more affective episodes within 1 year. It has been postulated that RC is related to a poor response to lithium, to the same extent as mixed episodes or other atypical symptoms of the illness. This article reviews the current status of alternative pharmacological or otherwise supportive therapies of RC. Biological parameters and characteristics of the illness associated with RC like gender prevalence in women, hyperthyroidism, catecholamine-O-methyltransferase allele, the influence of sleep, different subtypes of bipolar disorder and the risk of antidepressant-induced cycling will be discussed in detail.

Comparison of long-term monitoring methods for bipolar affective disorder.

Long-term monitoring is a clinical necessity in bipolar affective disorder. The most important requirements are usability and value for clinical decisions. Four methods of long-term monitoring - (1) the Adjective Mood Scale by von Zerssen, (2) Kraepelin's early life charts, (3) the NIMH Life Chart Method by Leverich and Post and (4) the Social Rhythm Metric by Monk - were compared regarding the acceptance by patients, the time commitment needed for documentation and training as well as the usability for the clinician regarding psychotherapy and decision support in pharmacotherapy. The Adjective Mood Scale is easiest to learn, Kraepelin's life chart offers the best graphical presentation, the NIMH life charts offer the best clinical decision support and the Social Rhythm Metric integrates a psychotherapeutic approach.

The Stanley Foundation Bipolar Network: results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres.

The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in the SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar II disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean +/- SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration over time. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapid-cycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history.

Electronic diary for bipolar patients.

Long-term monitoring methods providing an overview of the course of bipolar disorder of individual patients are a clinical necessity at least for patients who require a combination therapy with drugs that have only proven their efficacy for monotherapy. The Life Chart Method (LCM) of the NIMH is an adequate method for this purpose. Unfortunately, due to data entry and management requirements, it is too expensive for everyday clinical use. The 'electronic diary for patients with bipolar disorder' is meant to provide a method to minimize the effort for detailed long-term monitoring of patients with bipolar affective disorder and thus make it available for the everyday clinical use for every bipolar patient.

Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review.

1. Antiepileptic drugs that are successful as mood stabilizers, e.g. carbamazepine, valproate and lamotrigine, exhibit a characteristic pattern of action on ion fluxes. As a common target, they all affect Na+- and Ca2+ inward and K+ outward currents. 2. Furthermore, they have a variety of interactions with the metabolism and receptor occupation of biogenic amines and excitatory and inhibitory amino acids, and, by this, also influence long- term potentiation (LTP) to different degrees. 3. The kava pyrones (+/-)-kavain and dihydromethysticin are constituents of Piper methysticum. Anticonvulsant, analgesic and anxiolytic properties have been described in small open trials. 4. In the studies summarized in this article the effects mainly of (+/-)-kavain were tested on neurotransmission and especially on voltage gated ion channels. It is assumed that effects on ion channels may significantly contribute to clinical efficacy. 5. Experimental paradigms included current and voltage clamp recordings from rat hippocampal CA 1 pyramidal cells and dorsal root ganglia as well as field potential recordings in guinea pig hippocampal slices. 6. The findings suggest that (i) kava pyrones have a weak Na+ antagonistic effect that may contribute to their antiepileptic properties (ii) that they have pronounced L- type Ca2+ channel antagonistic properties and act as an positive modulator of the early K+ outward current. These two actions may be of importance for mood stabilization. (iii) Furthermore, kava pyrones have additive effects with the serotonin-1A agonist ipsapirone probably contributing to their anxiolytic and sleep- inducing effects. (iv) Finally, they show a distinct pattern of action on glutamatergic and GABAergic transmission without affecting LTP. The latter, however, seems not to be true for the spissum extract of Kava where suppression of LTP was observed. 7. In summary, kava pyrones exhibit a profile of cellular actions that shows a large overlap with several mood stabilizers, especially lamotrigine.

Reversal of chloroquine resistance in Plasmodium falciparum using combinations of chemosensitizers.

Research into chloroquine resistance reversal in Plasmodium falciparum has revealed a widespread range of functionally and structurally diverse chemosensitizers. However, nearly all of these chemosensitizers reverse resistance optimally only at concentrations that are toxic to humans. Verapamil, desipramine, and trifluoperazine were shown to potentiate chloroquine accumulation in a chloroquine-resistant (CQ(r)) strain of P. falciparum, while progesterone, ivermectin, and cyclosporin A were not shown to potentiate chloroquine accumulation. The simultaneous use of two or even three of these chemosensitizers at concentrations within their therapeutic ranges in humans displayed an additive effect in potentiating chloroquine accumulation in the CQ(r) strain. The levels of resistance reversal achieved with these multiple combinations were comparable to those achieved with high concentrations of the single agents used to enhance the activity of chloroquine. No chemosensitizer, whether used singly or in combination, potentiated any change in chloroquine accumulation or a shift in the 50% inhibitory concentration for the chloroquine-sensitive strain. The use of combinations of chemosensitizers at concentrations not toxic to humans could effectively reverse chloroquine resistance without the marked toxicity from the use of a single agent at high concentrations. This cocktail of chemosensitizers may serve as a viable treatment to restore the efficacy of chloroquine in patients with malaria.

Effects of Hypericum perforatum L. on evoked potentials in guinea pig hippocampal slices.

Therapeutic uses of Hypericum extracts have been demonstrated as safe and effective in treating mild to moderate depression in numerous clinical trials. To date, however, no definitive statements on their mode of action can be made, and little information on their electrophysiological effects is available. The present communication summarises the results of our efforts directed towards clarifying the effects of an ethanolic Hypericum extract (HYP) and its hydrosoluble fraction (HYPWS), and two of its constituents hypericin and hyperforin on electrically evoked population spikes in guinea pig hippocampal slices. In higher concentrations (>10 microM), the two extract constituents tested revealed inhibitory effects only, whereas concentration-dependent (between 10(-6) to 10(-4) g/l) excitatory effects were observed for HYP and HYPWS. The excitatory effects were strongly amplified by the GABA(B) antagonist phaclofen, whereas the effects of bicucullin, a GABA(A) antagonist, were marginal. The excitations were completely blocked by the AMPA antagonist CNQX, but not by the NMDA antagonists APV and MK801 or the L-type calcium-channel blocker verapamil. This kind of excitatory effect on the hippocampus is unknown in other antidepressants and; indeed, many of the latter reduce neuronal excitability. We conclude, therefore, that the mechanisms involved in the antidepressant activity of Hypericum extracts are different from those of conventional antidepressants, and that identifying their excitatory components may facilitate their more rational standardisation.