Matthias Dose

The Use of Sodium Valproate, Carbamazepine and Oxcarbazepine in Patients with Affective Disorders

During recent years alternatives to lithium prophylaxis have been developed using primary dipropylacetamide and, later on, sodium valproate, as a mono-therapy as well as in combination with low-dosage lithium treatment. It has been shown in a placebo-controlled ABA design that sodium valproate exerts an acute antimanic effect and a prophylactic action of sodium valproate has also been established. Carbamazepine represents another important contribution to the arsenal of drugs to be used as alternatives for the prophylactic treatment in patients not responding to lithium and/or experiencing too many side effects. The keto-derivative of carbamazepine, oxcarbazepine, has been shown to exert acute antimanic effects in a similar way to carbamazepine itself.

Carbamazepine as an adjunct of antipsychotic therapy

The effect of low-dose haloperidol combined with the anticonvulsant carbamazepine was investigated in a 5-week placebo-controlled, double-blind study in acute schizophrenic patients. Weekly ratings showed a clinically pronounced and statistically significant improvement in both the carbamazepine and placebo groups. However, the patients on carbamazepine needed less neuroleptic and anticholinergic medication and experienced fewer side effects compared to the patients on placebo. Moreover, patients in the carbamazepine group showed a clear deterioration after discontinuation of carbamazepine (but maintenance of neuroleptic medication), while the placebo group did not change after discontinuation of placebo. Concomitant treatment with carbamazepine in psychotic patients may help to reduce neuroleptic dosages and unwanted side effects.

Therapeutic effects of GABA-ergic drugs in affective disorders. A preliminary Report

A possible antimanic efficacy of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind, placebo-controlled ABA design. A marked improvement was observed after valproate medication in a group of 5 acutely ill manic patients. Similar results were obtained in 7 trials examining the antimanic property of the keto-derivative of carbamazepine (oxcarbazepine) in 6 patients with acute mania, whereas no antimanic effect could be observed in a treatment with diazepam and with THIP. Combination of THIP and diazepam in another patient showed a slight antimanic effect. Additionally, a possible prophylactic effect of long-term treatment using valproate was examined. In 8 of 9 patients exhibiting a bipolar affective or schizoaffective psychosis, who did not properly respond to lithium treatment, a prophylactic effect of valproate medication could be demonstrated. The results point to the view that anticonvulsants, possibly due to GABA-ergic effects, may be beneficial in affective disorders.

Use of calcium antagonists in mania

The organic calcium antagonist verapamil in doses of 320-480 mg/day reduced manic symptomatology in seven of eight patients manifesting a manic or schizomanic syndrome in a placebo-controlled, double-blind study. The delayed onset of antimanic effects parallels the action of lithium in acute mania. Common pharmacological profiles of lithium, certain anticonvulsants, and neuroleptics with regard to calcium dependent processes are discussed.

Process Analysis in Behavioral Family Therapy

Process research in behavioral family therapy (BFT) is a hitherto neglected area with the notable exception of the work of Alexander and Patterson with their colleagues. However, the development of instruments to assess therapists behavior during the treatment session seems timely for the following reasons: (a) to investigate the relationship between therapist behavior and out-come, (b) to improve therapist training/supervision, (c) to establish treatment integrity in comparative outcome studies, and (d) to monitor treatment progress. For these purposes two sets of instruments were developed: (a) a category system to describe the content of a session, which is rated every 30 seconds and (b) several rating scales to evaluate therapist behavior, including relationship competency, ability to structure a session, didactic competence, ability to initiate behavioral probes, use of appropriate intervention strategies, use of reinforcement, and dealing with uncooperativeness. Scales are described, and data on their reliability and utility are presented.

Acute Mania: Practical Therapeutic Guidelines

SummarySeveral psychoactive drugs have been shown to be effective in the treatment of acute manic syndromes. In clinical practice, antipsychotics are the most commonly used medications, although they are associated with several adverse effects, namely extrapyramidal symptoms, which may interfere with patient compliance. Therefore, their use should be restricted to severe cases of mania, in which patients have a lack of insight and concomitant psychotic features.Alternative antimanic drugs [lithium and anticonvulsants such as carbamazepine and, in some cases, valproic acid (sodium valproate)] can effectively be used in compliant patients, especially at the beginning of manic episodes or in hypomania. However, anticonvulsants lack sedative effects and lithium has a delayed onset of antimanic effects. Nevertheless, these disadvantages can be overcome by the short term concomitant use of low potency antipsychotics or benzodiazepines. This provides effective sedation with minimal unpleasant adverse effects and (with short term use of benzodiazepines) risks for the development of dependency.Previously untreated outpatients in the early stage of hypomania should be treated with slowly increased doses of lithium or carbamazepine, assisted by low potency antipsychotics or benzodiazepines to provide sedation and improve sleep. In noncompliant patients or those with manic syndromes with pronounced psychotic features, high potency antipsychotics (oral or depot formulations) may have to be used. In outpatients who relapse into mania while receiving prophylactic lithium or carbamazepine, the dosage of either drug should be increased in parallel with the measures suggested for previously untreated patients.Inpatients can be effectively treated with rapidly increasing doses of carbamazepine suspension and the use of higher doses of sedative medication. In some patients with treatment-resistant mania, the combination of lithium with antipsychotics may augment therapeutic efficacy, while a minority of patients may require electroconvulsive therapy.

Calcium Antagonists in Mania: A Preliminary Clinical Report

Manic syndromes can be treated successfully by use of different psychoactive drugs, e.g. neuroleptics, lithium, high doses of beta-receptor blocking agents or anticonvulsants. On the other hand, the biochemical basis of manic excitement has so far not been elucidated and the establishment of the “psychopharmacological bridge” is complicated by the heterogeneity of substances apparently useful in the treatment of mania. One proposal which has been made in this context is derived from the therapeutic action of neuroleptic drugs: the hypothesis of an over-activity of dopaminergic neurons in mania (Post et al., 1980). From a clinical point of view, however, manic patients treated with neuroleptic drugs appear unspecific- ally sedated and the kernel symptoms of mania are often not reached by these agents. Lithium (Gershon et al., 1960), high-dosage propranolol (Emrich et al., 1979) and anticonvulsants like carbamazepine and valproate (cf. this symposium) have been shown to possess more specific antimanic (and partly antidepressant) effects in affective psychoses. To explain the similarity of therapeutic action of these different kinds of compounds, the hypothesis has been made that a central deficiency of GABA-ergic transmission may play a crucial role in the pathogenesis of mania (Emrich et al., 1983) reflecting a state of imbalance of excitatory and inhibitory neuronal networks. Such a model is generally accepted for epileptic-form activity. Here, an excessive intracellular movement of calcium ions is assumed to be involved in th6 pathogenesis (Lux, 1980).

Medikamentöse und psychologische Behandlung schizophrener Psychosen

Medicinal and Psychological Treatment of Schizophrenia Besides tormenting symptoms and a corresponding decline of performance, schizophrenic psychoses entail a bad social prognosis for the patient. Relatives, who mostly carry the burden of care for schizophrenic patients, are often overstrained. Pharmacological and psychological treatment strategies of scientifically well established efficacy have been developed from the vulnerability- stress model of schizophrenic psychoses. The present paper critically summarizes the history, neuropharmacology, classification, wanted and unwanted effects, and clinical use of antipsychotic drugs (neuroleptics). It also presents relevant psychological treatment modalities: psychoeducation, cognitive therapies, social skills training, and psychoeducative family programs. In conclusion it is demonstrated that behavioral therapy is effective in combination with antipsychotic medical treatment, and that psychological techniques can improve the efficacy of standard neuroleptic maintenance treatment.

Zur klinischen Pharmakologie von Carbamazepin in der Psychiatrie

Bei der Rezidivprophylaxe affektiver Psychosen ist Carbamazepin (CBZ) als Alternative bzw. Adjuvans zu Lithium in den letzten Jahren in verstarktem Mase in das Zentrum des Interesses geruckt. Die Grunde hierfur sind einerseits theoretischer, andererseits klinischer Natur. In theoretischer Hinsicht sind die aus pathophysiologischen Erwagungen gespeisten Versuche, die phasenprophylaktischen Wirkungen von Lithium, CBZ und Valproat „auf einen Nenner zu bringen” von grosem Interesse. In klinischer Hinsicht ist CBZ als Alternative zu Lithium von Interesse, da CBZ ein anderes Nebenwirkungs-Profil als Lithium hat und da Lithium-Non-Responder CBZ-Responder sein konnen (und vice versa), und da insbesondere Lithium-CBZ-Kombinationen bei Non-Respondern wirksam sein konnen.

The Use of Valproate and Oxcarbazepine in Affective Disorders

Lithium prophylaxis which, undoubtedly, represents a great breakthrough in the pharmacopsychiatry of affective disorders contains two disadvantages: 1st There is a sizable number of patients not responding to this therapy, and 2nd in some patients there is a great number of side effects leading to non-compliance or discontinuation of lithium prophylaxis.