Antiepileptic drugs and depression during pregnancy in women with epilepsy.

OBJECTIVES: To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy. MATERIALS AND METHODS: Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end. RESULTS: Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate. CONCLUSIONS: Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.

The Effect of Formulation, Dose, and Adjuvants on Uptake of Phosphite Into Pine Foliage.

The aim of this investigation was to determine the effect of dose and adjuvant on uptake of two phosphite products (Phos-A and Phos-B) into Pinus radiata needles. In experiment 1, uptake of 6 kg ha-1 phosphite, applied as Phos-A, in 100 liters of water, together with an organosilicone superspreader (0.2%), was high (>60%). Uptake at doses greater than 6 kg ha-1 (12, 15, 18, and 24 kg ha-1) and applied in volumes less than 100 liters of water (75 and 50 liters) was poor (1 to 30%). Using stability tests and NMR spectroscopy in experiment 2, this appeared to be linked to a concentration dependent reaction resulting in the degradation of the organosilicone adjuvant that facilitated uptake of Phos-A. In experiment 3, uptake of phosphite applied as Phos-B, between 6 and 24 kg ha-1 in 100 liters of water, was tested alone and with four adjuvants (an organosilicone, alcohol ethoxylate, lecithin, and esterified seed oil). Uptake of Phos-B without any adjuvant was high (>50%) across all doses, indicating the formulation was optimized for P. radiata needles. Uptake of Phos-B increased with concentration up to 72% at 24 kg ha-1 in 100 liters of water. Symptoms of phytotoxicity were observed at rates of ≥12 kg ha-1. This study highlighted the effect of formulation, dose, concentration, and adjuvant on the uptake of phosphite into P. radiata needles.

The prescribing of antiepileptic drugs for pregnant Australian women.

BACKGROUND: It is not clear how widely it is appreciated in Australia that certain antiepileptic drugs, particularly valproate, are teratogenic. AIM: The aim of the study is to assess trends in the pattern of antiepileptic drug prescribing for pregnant women in Australia to determine whether drug use is optimal, particularly from the fetal viewpoint. METHODS: Analysis of data contained in the Australian Register of Antiepileptic Drugs, assessing trends in antiepileptic drug use correlated with pregnancy outcomes. RESULTS: Valproate was the only significant teratogen among the antiepileptic drugs in common use. There was a fetal malformation rate of 14.5% associated with its use in monotherapy, as compared with a rate of 3.15% in antiepileptic drug-unexposed pregnancies in women with epilepsy (OR = 5.23, 95% CI = 1.81, 15.09). The highest malformation rate associated with any other antiepileptic drug used in monotherapy was 5.0%, for carbamazepine. Neurologists had progressively prescribed valproate less frequently and in lower dosage than other classes of practitioner over the 10-year study period, with a parallel decrease in occurrence of fetal malformations in pregnancies referred to the Register. Other prescribers of valproate did not seem to have adopted these practices to the same extent and had not obtained similar degrees of reduction in the occurrence of fetal malformations. CONCLUSIONS: Contemporary Australian obstetricians, even though they may not be valproate prescribers, when managing pregnancies in women taking valproate, need to be alert to the possibility that it may not be being used optimally from the fetal point of view, especially when not prescribed by neurologists.

Combination antidepressants - use by GPs and psychiatrists.

BACKGROUND: Current treatment of depression fails to achieve remission in 50% of patients. Combinations of two antidepressants are used by some Australian psychiatrists. OBJECTIVE: This article investigates the pros and cons of combination antidepressant therapy and provides suggestions for when to consider their use, which combinations to choose, and how to introduce combination antidepressant therapies. DISCUSSION: Combining two antidepressants is a controversial strategy, with supporters and critics arguing its efficacy and safety from opposing perspectives. The use of combination antidepressant therapies may facilitate remission from depression. However, there is limited evidence supporting these treatments, and safety concerns are often cited. There is some support for combination therapies in selected cases from international bodies. After considering risks and benefits on a case-by-case basis, careful use of selected combination antidepressant therapy may be one of a range of effective treatments for some individuals suffering from depression.

Effect of dose and adjuvant on uptake of triclopyr and dicamba into Pinus contorta needles.

Management of dense infestations of wilding Pinus contorta in New Zealand requires high doses of herbicides; 18 kg active ingredient (a.i.) ha-1 triclopyr and 5 kg a.i. ha-1 dicamba are used in combination with a complex mix of adjuvants (methylated seed oil, non-ionic surfactant and ammonium sulfate) and other active ingredients. From the perspective of cost and environmental impact there is a need to reduce the complexity of this tank mix and the rates of active ingredients. Using radiolabelled herbicides, this study evaluated the effect of dose and adjuvants (crop oils, non-ionic surfactants, and organosilicones) on needle injury and uptake of triclopyr and dicamba into P. contorta needles at 24 hr or 7 days after treatment (DAT). The uptake of triclopyr decreased significantly with increasing concentration (0.75%-6%) resulting in the highest uptake dose at the equivalent of 18 kg a.i. ha-1 triclopyr at 7 DAT. When applied at 18 kg a.i. ha-1, none of the adjuvants tested significantly increased the uptake of triclopyr (applied as Grazon®), with ~50% uptake occurring at 7 DAT. The uptake of dicamba (applied as Kamba® at 5 kg a.i. and 10 kg a.i. ha-1) was significantly affected by dose and adjuvants. The uptake of dicamba applied at 5 kg a.i. ha-1 was low at 7 DAT with no adjuvant (31%); however, use of a methylated seed oil doubled the uptake. When triclopyr and dicamba were applied together, there was no evidence that either active ingredient negatively affected uptake of the other, with triclopyr enhancing uptake of dicamba. These results show potential to reduce the amount of herbicide used for conifer control without compromising efficacy.

To combine or not to combine? A literature review of antidepressant combination therapy.

OBJECTIVE: Treatment resistant depression is a common clinical problem and a major public health concern. The use of antidepressant combinations to overcome treatment resistance, while somewhat controversial, is a popular strategy in practice. This paper reviews published trials on combination antidepressants with a view to inform clinical practice. METHOD: A systematic but selective review of the published literature was conducted using EMBASE, PSYCHLIT and MEDLINE with relevant search terms. RESULTS: A number of trials suggesting efficacy of combination antidepressants were found. These are incorporated into a number of treatment guidelines for the management of treatment refractory depression. Clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, however combination strategies are an effective option. CONCLUSIONS: Many antidepressants can be usefully combined especially if they engage separate mechanisms of action. Clinically, antidepressant combinations provide a useful resort in otherwise treatment resistant individuals. However, much further research is needed to determine relative efficacy and determine long term outcome.

Practical management of the suicidal patient.

BACKGROUND: Suicide is nearly always due to untreated depression, causes widespread distress, and is a waste of life years. Eighty percent of suicides are male, mainly in the age range of 25-44 years. Nearly every person who commits suicide has talked about it before the event. OBJECTIVE: This article focusses on teaching some 'tricks of the trade' used by the author in treating suicidal patients. DISCUSSION: General practitioners should ask the patient to indicate on a scale of 0-10, the stresses, emotional suffering and suicidal intensity they are feeling. They should offer understanding, very frequent contact, antidepressants, discussion, guarantees of improvement, and benzodiazepines for relief from pain during the process.

Lamotrigine in epilepsy, pregnancy and psychiatry--a drug for all seasons?

Lamotrigine has been demonstrated to be effective as both an antiepileptic drug and a mood stabiliser. For epilepsy it is less efficacious than valproate in primary generalised epilepsy, but it is comparable to some traditional drugs in partial epilepsy. In psychiatry it has significant advantages over other mood stabilisers for the treatment and prevention of depressive phases of bipolar illness, but not for the treatment of mania. It has a more benign adverse effect profile than older antiepileptic agents and is not a proven teratogen. Risk of adverse reactions is reduced by commencing treatment at a markedly reduced dose that is gradually increased.

A survey of combination antidepressant use in Australia.

OBJECTIVE: The aim of this study was to survey doctors working in psychiatry in Australia about the practice of using two antidepressants simultaneously. METHOD: A postal survey was sent to all doctors in psychiatry in Australia enquiring about their prescribing history and their attitudes to combination antidepressants and related issues. RESULTS: Seventy-nine percent of respondents had used combination antidepressants. The most frequently reported combination was a selective serotonin reuptake inhibitor combined with a tricyclic antidepressant. Combinations of mirtazepine with venlafaxine and other antidepressants were the next most frequently used. Seventeen percent of respondents reported having seen a complication from combination antidepressants, 75% believed that Australian GPs should be given information on the use of combination antidepressants, 89% wished for more information on this topic, and 88% believed patients had a right to be informed of this option in their treatment. Use of combination antidepressants was more frequent than exceeding the recommended maximum dose of an individual antidepressant. CONCLUSION: Combination antidepressants are used far more frequently in Australia than suspected previously. Research into safe and evidence-based practice is strongly indicated.

Defective receptor expression and dendritic cell differentiation of monocytes in glioblastomas.

OBJECTIVE: Better characterization of the changes that occur in the circulating monocytes of patients with glioblastoma has become more important recently as monocyte-derived dendritic cells are used as adjuvants in the development of glioma vaccines. This study seeks to develop understanding of the phenotypic changes that occur in circulating monocytes of patients with intracranial cancer and to assess the ability of these cells to differentiate into mature dendritic cells. METHODS: Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were compared between three cohorts: patients with intracranial glioblastoma (n = 15), patients with intracranial metastases (n = 9), and a group of healthy controls (n = 10). Monocytes were then tested for their ability to differentiate into mature dentritic cells based on morphology, CD83 expression and high levels of co-stimulatory molecules. RESULTS: Comprehensive analysis of monocyte receptor expression demonstrated significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma but not in patients with intracranial metastases compared with a group of healthy controls. GMCSFR expression was significantly reduced in both patients with glioblastoma and intracranial metastases. Additionally, the monocytes of patients with glioblastoma showed a reduced capacity to differentiate into mature dendritic cells as identified by CD83 expression, receptor expression, and morphology. CONCLUSION: Peripheral monocytes are phenotypically altered in the setting of glioblastoma and display a reduced functional capacity to differentiate into mature dendritic cells.