[M Adli, T.Bschor, B. Canata. S. Döpfmer, M. Bauer: Lithium in the treatment of acute depression. Fortschr Neurol Psychiat 199866: 43].
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Depressive Disorder↗
Biomedical subjects
H Grunze
Publications and source records attributed to H Grunze.
[Predictors of response to phase prophylactics (mood stabilizers) in bipolar affective disorders].
Since the introduction of lithium ions in the acute treatment and in the prophylaxis of bipolar disorders the antiepileptic drugs valproate and carbamazepine have been in use for several years as mood stabilizers. In a number of open and controlled clinical studies predictors of response for the single drugs were investigated. These studies indicated that valproate was a predictor of good response in mixed (dysphoric) mania and bipolar rapid cycling. Moreover, valproate has a better response than lithium in secondary mania (organic origin) and atypical mania (episode sequence: depression-mania-euthymia rather than mania-depression-euthymia). The preferential efficacy in the spectrum of bipolar disorders of the new antiepileptic drugs lamotrigine and gabapentin must be analysed in more detail in future studies.
Affect↗
[Gabapentin in the treatment of mania].
We present the case of a 60-year old bipolar-I-patient showing a rapid antimanic response to gabapentin after having been non-responsive to lithium and perazine. This case encouraged us to further evaluate the antimanic potency of gabapentin in an open label trial. 20 patients with acute mania were treated for up to 21 days with gabapentin in a dose range from 1200 to 4800 mg/day. Ten patients were treated with gabapentin as add-on medication and ten patients were treated with a high dose of gabapentin alone. The BRMAS score declined significantly in patients with moderate mania, whereas gabapentin alone was not efficacious in patients with very severe mania. Keeping in mind the limitations of an open study, it can still be said that gabapentin as add-on medication with other effective mood stabilizers appears to be safe and efficacious in the treatment of moderate mania.
Acetates↗
Intravenous valproate loading in acutely manic and depressed bipolar I patients.
Recently, valproate has emerged as a drug of primary choice for the treatment of acute mania, especially mixed mania and, partially, rapid cycling. Because of its relative safety, it can be administered in high doses as an oral loading therapy, with approximately 60% to 70% of patients showing a favorable response. Here we report on seven bipolar I patients, two of which have euphoric mania, three have a mixed manic state (including one patient with ultra-rapid cycling and one with very prominent depressed features), and two have solely depressed mood. All but one of the manic patients showed a rapid and favorable response to intravenous valproate loading, which built up sufficient blood levels that were maintained by subsequent oral treatment. Of the two patients with solely depressed mood, however, one experienced only minor benefits and the other showed no change in the depressive symptomatology. Intravenous valproate was tolerated without problems and also led to a drastic reduction in and eventual withdrawal of benzodiazepine treatment in two cases. All of the patients showed a drastic remission of mania with valproate blood levels at or only slightly above 50 microg/mL (blood drawn 12 hours after last application). It is interesting to note that one patient who was previously nonresponsive to oral valproate loading responded well to intravenous valproate. Besides the obvious efficacy and safety of this treatment regimen, these findings may also imply that a difference in pharmacokinetics with intravenous loading may result in a quick saturation of plasma-binding proteins, and hence, peak concentrations of valproate may be reached rapidly, which could contribute to the beneficial action, even in patients previously nonresponsive to oral valproate.
Acute Disease↗
Treatment of acute mania with topiramate.
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Adult↗
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↗
[Severe therapy refractory depression as initial manifestation of Parkinson disease].
A 60-year old female patient was referred to our University hospital with the diagnosis of severe treatment-resistant major depression to perform electroconvulsive therapy (ECT). For almost two years the patient had been treated with several antidepressants and, temporarily, neuroleptics. After showing no favourable response to ECT, the diagnosis of idiopathic Parkinson's disease was made and the patient was treated with L-dopa plus benserazide and pergolide in combination with the monoamine oxidase inhibitor moclobemide. Both depressed mood and motor symptoms showed dramatic improvement under this therapy.
Aged↗
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↗
New perspectives in the treatment of acute mania: a single case report.
1. There is increasing evidence that standard treatment of mania with lithium or neuroleptics fails in many subtypes of mania, e.g. dysphoric mania or rapid cycling, and new strategies are needed. 2. This single case report reports on possibilities and pitfalls in alternative attempts to tackle a severe manic syndrome successfully. 3. In this patient, lamotrigine and valproate, the latter only in an i.v. formulation, led to a relief from mania. 4. It is concluded that the success of this treatment may be due to a common underlying mechanism of action of these drugs, most likely on the level of ion channel regulation, and that further experience with alternative formulations of standard treatments such as valproate i.v. should be collected.
Anticonvulsants↗
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↗
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↗
Renal impairment as a possible side effect of gabapentin. A single case report.
A bipolar I manic patient was treated successfully by adding gabapentin to perazine and clonazepam. Also initially tolerated well, an increase of creatinine after several weeks of GP (2000 mg) was observed which was reversible after discontinuation of GP. It is suggested that the possibility of renal dysfunction should be kept in mind with the usage of gabapentin.
Acetates↗
Female genital disorder as adverse symptom of lamotrigine treatment. A serotoninergic effect?
The new anticonvulsant, lamotrigine, is becoming an important tool in the treatment of bipolar disorder, including bipolar depression. Its efficacy in bipolar depression might be linked to its inhibition of serotonin uptake. We present the case of a female schizoaffective patient successfully treated with 400 mg of lamotrigine developing considerable genital disorder, a side effect well known from the treatment with selective serotonin reuptake inhibitors (SSRIs). We suggest that female genital disorder induced by high doses of lamotrigine is a serotoninergic side effect.
Adult↗
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↗
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↗
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↗
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↗
Combined treatment with lithium and nimodipine in a bipolar I manic syndrome.
1. The benefit of a combined treatment with the calcium antagonist nimodipine and lithium in a bipolar I disorder (currently manic, DSM IV 296.44, ICD 10 F 31.1) was explored and documented in a longitudinal single case study. 2. Nimodipine (270 mg/d) was added to lithium (900 mg/d), substituting for previously administered neuroleptics, in an up to then unsatisfactorily treated manic patient. 3. A clear-cut improvement in the patient's condition was achieved within a fortnight, and lasted over the continuation period of this drug regimen. This combined treatment was discontinued after eight weeks and lithium alone was then administered. Within three months another manic episode appeared. 4. Side-effects and changes of lithium blood levels were not observed during the combined treatment with nimodipine and lithium. 5. Further research on the benefits of adding a calcium antagonist, instead of neuroleptics, to lithium therapy for bipolar manic disorder patients who do not respond sufficiently to lithium is recommended. In addition, the benefits of a long term prophylaxis of nimodipine alone or in combination with lithium should be evaluated in those bipolar patients who still show a high relapse frequency on lithium alone.
Adult↗