Biomedical subjects

J Walden

Publications and source records attributed to J Walden.

At least 55 records · Page 3Linked to original sources

PubMed1999

Tiagabine appears not to be efficacious in the treatment of acute mania.

BACKGROUND: Because a GABAergic hypofunction has been implied in the pathophysiology of mania, we have tested the antimanic properties of the GABA transporter 1 inhibitor tiagabine. METHOD: An open trial was conducted in 8 acutely manic inpatients with DSM-IV bipolar I disorder, 2 of them with tiagabine monotherapy and 6 with tiagabine as an add-on to previously insufficient mood-stabilizing medication. The study duration was 14 days. Changes in psychopathology were assessed by the Bech-Rafaelsen Mania Rating Scale. RESULTS: None of the patients showed clear-cut relief from manic symptoms during the 2-week observation period. In 2 patients, we saw pronounced side effects (nausea and vomiting in one and a generalized tonic-clonic seizure in the other). CONCLUSION: The results from this open trial suggest that tiagabine seems to have no pronounced antimanic efficacy compared with standard treatments such as valproate, lithium, or neuroleptics. It also appears that rapid dosage increases for antimanic treatment can cause potentially severe side effects.

Acute Disease↗

PubMed1998

Lamotrigine may limit pathological excitation in the hippocampus by modulating a transient potassium outward current.

Actions of the new antiepileptic drug lamotrigine were characterised using whole cell patch clamp recordings from rat CA1 pyramidal cells in vitro. The results suggest that lamotrigine, besides its previously described effect on the fast sodium inward current and calcium currents, modulates the transient potassium outward current ID. This may be an effective mechanism to inhibit pathological excitation.

Animals↗

PubMed1998

[Significance of hepatic cytochrome P450 enzymes for psychopharmacology].

Nearly all psychotropic drugs are metabolized by hepatic cytochrome P450-enzymes. In humans, there are 5 isoenzymes involved in this process. The activity of these enzymes can be modulated by a number of commonly used drugs, yielding potentially hazardous interactions. Most of the recently introduced selective serotonin reuptake inhibitors are potent inhibitors of cytochrome P450 enzymes. Thus, the plasma concentrations of tricyclic antidepressants or clozapine might be elevated into toxic levels. In contrast, carbamazepine induces most of the isoenzymes. This potentiates the elimination of tricyclics and antipsychotics and might cause a serious risk for the recurrence of depressive or psychotic symptoms. Moreover, 5-10% of the population are slow metabolizers of CYP2D6. This group is prone to increased adverse effects of moderately dosed medication. This review systematically points out the reported or predicted pharmacokinetic drug interactions in psychopharmacology focussing on clinical significance.

Cytochrome P-450 Enzyme Inhibitors↗

PubMed1998

Effects of the atypical antidepressant trimipramine on field potentials in the low Mg2+-model in guinea pig hippocampal slices.

Trimipramine has been classified as an atypical tricyclic antidepressant, because only weak inhibitory effects on serotonin and/or noradrenaline reuptake have been found. Since some antidepressive drugs (e.g. imipramine) and other agents used in the treatment of affective disorders (e.g. carbamazepine) modulate neuronal calcium channels, trimipramine was tested on field potential changes (fp) in the low Mg2+-model of epilepsy which has been shown to be affected by calcium antagonists. Trimipramine reduced the frequency of occurrence of fp in a dose dependent manner (5-100 microM). The threshold concentration of trimipramine which did not decrease the firing rate was approximately 1 microM. Simultaneous application of subthreshold concentrations (2 microM) of the organic calcium antagonist verapamil with trimipramine decreased the firing rate to 37.0+/-22.7% (means+/-SEM, n=7) with respect to baseline values. In contrast, no additive effects of N-methyl-D-aspartate antagonists and trimipramine were observed. In conclusion, the data suggests that the antidepressive effects observed with trimipramine treatment may be due to its inhibitory action on neuronal calcium channels.

2-Amino-5-phosphonovalerate↗

PubMed1998

The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices.

Little is known about the mechanisms of action of kava pyrones which are the pharmacological active compounds of the plant Piper methysticum Forst. We investigated the effects of the synthetic kava pyrone (+/-)-kavain on long-term potentiation (LTP) in the CA1-region of guinea pig hippocampal slices. (+/-)-Kavain reduced the amplitudes of extracellular field potential changes evoked by electrical stimulation in a concentration dependent manner. These effects were reversible. In experiments with LTP no changes were found in the presence of (+/-)-kavain. In conclusion, our findings suggest (+/-)-kavain to be an effective drug in modulating excitatory signals in the hippocampus of guinea pigs. Additionally, no alterations on synaptic plasticity in hippocampal neurons for this kava pyrone can be presumed.

Action Potentials↗

PubMed1998

Delirium and persistent dyskinesia induced by a lithium-neuroleptic interaction.

We report the case of a bipolar patient developing severe delirium and extrapyramidal signs shortly after initiation of a lithium-neuroleptic combination therapy. Clinical presentation, EEG changes and lithium plasma levels showed a close correlation. The delirium was reversible when all drugs were stopped; however, dyskinesia was found to be persistent after a period of 6 months. This rare syndrome is difficult to differentiate from lithium intoxication and neuroleptic malignant syndrome. Given the additional use of valproate and biperiden in this patient, valproate encephalopathy and anticholinergic delirium are further differential diagnoses. To avoid this serious pharmacodynamic drug interaction, patients should be closely monitored when lithium-neuroleptic comedication is started.

Antimanic Agents↗

PubMed1998

[Adjuvant treatment of schizophrenic illness with carbamazepine].

Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy.

Anticonvulsants↗

PubMed1998

[Calcium antagonistic actions of drugs used in treatment of affective disorders].

Disturbances of intra- and extracellular calcium levels are often reported during the course of affective disorders. In this review calcium antagonistic properties of drugs used in the treatment of affective disorders are discussed. The effects of calcium channel blockers in animal models of depression and in clinical trials are compared to established treatment strategies. Knowledge on changes in calcium homoeostasis during the treatment of affective disorders may increase the scope of therapeutic options.

Animals↗

PubMed1998

Modulation of calcium and potassium currents by lamotrigine.

Actions of the new antiepileptic drug lamotrigine (LTG) were characterized using extracellular and whole cell patch clamp recordings from rat CA1 and CA3 pyramidal cells in vitro. The results suggest that LTG, beside its previously described effect on the fast sodium inward current, also modulates - presumably voltage-gated - calcium currents and the transient potassium outward current ID. These may be effective mechanisms to inhibit pathological excitation in epilepsy and may be of potential benefit in treating underlying cellular disturbances in bipolar disorder.

Action Potentials↗

PubMed1998

Differential treatment of bipolar disorder with old and new antiepileptic drugs.

Although lithium remains the preferred medication for bipolar disorders, new investigations suggest that only 60 to 80% of patients have a good response with a classical presentation. The antiepileptics carbamazepine and valproate are important alternatives. Several studies have shown that lithium, carbamazepine and valproate are effective in pure mania. Mixed mania and rapid cycling respond, however, well to valproate. One disadvantage of carbamazepine is its enzyme inducing property with the consequence of a decrease of plasma levels of other psychotropic medications and a worsening of psychopathology. First data indicate a good antimanic and antidepressive efficacy of the new antiepileptic drug lamotrigine.

Anticonvulsants↗

PubMed1998

Acetazolamide in the treatment of acute mania. A case report.

Several antiepileptic drugs are also being used in affective disorders. There are some hints that also the carbonic anhydrase inhibitor acetazolamide might be useful in the treatment of bipolar affective disorder. We report a 39-year-old male patient with a history of bipolar affective disorder who presented with his second manic episode. Acetazolamide was added to a low dose of valproic acid and to perazine. A marked decrease of the BRMAS score was achieved. The implications of this case are discussed.

Acetazolamide↗

PubMed1998

Lamotrigine in the treatment of schizoaffective disorder.

There is accumulating evidence for the efficacy of lamotrigine in the treatment of bipolar disorder, including bipolar depression, both as monotherapy and in combination with sodium valproate. We present the cases of 3 female patients admitted to our hospital with the diagnosis of schizoaffective disorder who were treated with lamotrigine. While dosages up to 200 mg/day, resulting in serum concentrations of less than 5 mg/l, were only partially effective, 400 mg/day (with serum concentrations >10 mg/l) led to considerable mood stability, with complete remission from paranoid symptoms. We suggest that lamotrigine might be helpful in the treatment of schizoaffective disorder, probably with serum concentrations of more than 5 mg/l.

Adult↗

PubMed1997

Effects of kawain and dihydromethysticin on field potential changes in the hippocampus.

1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg2+, recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 mumol/l and 10 to 40 mumol/l, respectively. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 mumol/l kawain and 10 mumol/l dihydromethysticin indicated additive actions of both drugs. 5. Since the serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic serotonin-1A agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.

Animals↗

PubMed1997

A calcium antagonistic effect of the new antiepileptic drug lamotrigine.

The new antiepileptic drug lamotrigine (LTG; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine) has been shown to be effective in the treatment of focal epilepsies with or without secondary generalization. Furthermore, some case reports indicate an efficacy in the treatment of bipolar affective disorders. It has been suggested that the main mechanism of action of LTG is the inhibition of glutamate release through blockade of voltage sensitive sodium channels and stabilisation of the neuronal membrane. Since some antidepressant drugs and the antiepileptic substance carbamazepine have calcium antagonistic properties, which may be of significance in the pathophysiology of epilepsies and affective disorders, the interaction of lamotrigine with carbamazepine and the organic calcium channel blocker verapamil was analyzed in the low Mg(2+)-induced model epilepsy which has been shown to be suppressed specifically by organic calcium antagonists. Lamotrigine reduced the frequency of occurrence of low-magnesium induced field potentials in CA1 and CA3 areas of the hippocampus slice preparation (guinea pigs) in a dose-dependent manner. The subthreshold concentrations which yielded no effect were 1 mumol/l for lamotrigine, 10 mumol/l for carbamazepine and 2 mumol/l for verapamil. Combinations of these subthreshold concentrations elicited a reduction in the repetition rate of field potentials. The results indicate that lamotrigine behaves additive with verapamil and carbamazepine what can be due to a common action on the same subtype of calcium channels. It can be assumed that lamotrigine may have besides its action on high-frequency sodium dependent action potentials also effects on calcium channels.

Animals↗

PubMed1997

Psychosis during chronic levodopa therapy triggered by the new antidepressive drug mirtazapine.

We report the case of a patient developing psychosis after the addition of mirtazapine, a novel antidepressant enhancing serotonergic neurotransmission, to a chronic levodopa regimen. There was complete and rapid recovery upon low-dose clozapine treatment. To our knowledge, this is the first published case of a mirtazapine-levodopa interaction and the second case report of a psychosis induced by a serotonergic antidepressant in a patient with Parkinson's disease (PD). This phenomenon might be due to a postsynaptic serotonin receptor supersensitization caused by low central serotonin levels in treated PD.

Adult↗

PubMed1997

Reduction of the frequency of occurrence of low magnesium induced field potentials in the hippocampus slice preparation of guinea pigs: a good screening tool for calcium antagonistic effects of anticonvulsant and antipsychotic drugs.

An ideal model for in vitro research purposes of epilepsies should reflect the different clinical aspects of epileptic seizures, both in vivo and, as far as comparisons are possible, in vitro. It should induce long-term changes on a cellular level analogous to what is observed in epileptic patients, and should be triggered by varying endogenous physiological processes without additional exogenous drugs. These criteria are satisfied in the low magnesium model of epilepsy. Reducing Mg2+ below physiological concentrations or omitting it from artificial cerebrospinal fluid in vitro induces synchronized depolarization shifts in limbic-cortical networks which can be easily recorded extracellularly with a basic electrophysiological set up. These depolarization shifts resemble an increase of the calcium flux into the cell. Multiple depolarizing mechanisms such as NMDA receptor activation or prevention of presynaptic adenosine action converge onto this central pathway. It is hypothized that disturbed calcium homeosthasis is not only a characteristic of epilepsies, but also of affective disorders. Thus, the low magnesium model enables us to screen substances in vitro not only for antiepileptic, but also potential psychiatric use by testing them for calcium antagonistic properties.

Animals↗

PubMed1996

Darier's Disease and psychosis.

There are some reports in the literature about the comorbidity of Darier's Disease (keratosis follicularis) and psychiatric illness (e.g. mental retardation or affective disorders). Here we present evidence that schizophreniform psychosis may also be associated with Darier's Disease.

Adult↗

PubMed1996

Carbamazepine inhibits the potentiation by adenosine analogues of agonist induced inositolphosphate formation in hippocampal astrocyte cultures.

Carbamazepine (CBZ) resembles lithium in its beneficial effects in therapy and prophylaxis of affective disorders. Since lithium is presumed to act via an attenuation of the inositolphosphate/Ca(2+)-second messenger system, it is of particular interest whether or not CBZ might also have inhibitory effects on this type of signal transduction. CBZ is an antagonist of adenosine A1-receptor subtypes. We show here that activation of adenosine A1-receptors potentiates the phenylephrine induced formation of inositolphosphates in hippocampal astrocytes and that this potentiating effect is inhibited by CBZ at a therapeutically relevant concentration. These results indicate that CBZ can by antagonism of adenosine A1-receptors inhibit the inositolphosphate/Ca(2+)-signalling in neural pathways regulated by adenosine.

Adenosine↗