[Complex therapy of schizophrenia]. / A szkizofrénia komplex terápiája.

Schizoprenia is not a consistent illness, but the symptoms free state do may achive with different methods. During the last fifty years the clinical psychopharmacology improved very quickly, but the psychotherapy and sociotherapy as well. The complex therapy of schizophrenia is a new method: the psychopharmacons together with psychotherapy (first of all with cognitive one), sociotherapy and psychiatric rehabilitation. During the acute or chronic phase of schizophrenia the psychopharmacons are the first line treatment, but the complex therapy is better. In the last forty years we tested this new therapy, finally conducted a clinical trial: with one psychopharmacon (monotherapy), with two or three psychopharmacons (combination) and with the complex therapy (one psychopharmacon together with psychotherapy, sociotherapy and psychiatric rehabilitation). The antipsychotics, first of all the second generations have a very good efficacy. Risperidone is proven to be an efficient product. Fields of indication: first psychotic episode, acut schizophrenic exacerbation, chronic schizophrenia, the treatment of behavior disorder in dementia, maniac phase of bipolar disorder, treatment of behavioral disorders.

Culturally-sensitive complaints of depressions and anxieties in women.

BACKGROUND: Current classifications of Mental Disorders are centered on Westernized concepts and constructs. "Cross-cultural sensitivity" emphasizes culturally-appropriate translations of symptoms and questions, assuming that concepts and constructs are applicable. METHODS: Groups and individual psychiatrists from various cultures from Asia, Latin America, North Africa and Eastern Europe prepared descriptions of main symptoms and complaints of treatment-seeking women in their cultures, which are interpreted by clinicians as a manifestation of a clinically-relevant dysphoric disorder. They also transliterated the expressions of DSM IV criteria of main dysphoric disorders in their cultures. RESULTS: In many non-western cultures the symptoms and constructs that are interpreted and treated as dysphoric disorders are mostly somatic and are different from the Western-centered DSM or ICD systems. In many cases the DSM and ICD criteria of depression and anxieties are not even acknowledged by patients. LIMITATIONS: The descriptive approach reported here is a preliminary step which involved local but Westernized clinicians-investigators following a biomedical thinking. It should be followed by a more systematic-comprehensive surveys in each culture. CONCLUSIONS: Westernized concepts and constructs of mental order and disorders are not necessarily universally applicable. Culturally-sensitive phenomena, treatments and treatment responses may be diversified. Attempts at their cross-cultural harmonization should take into consideration complex interactional multi-dimensional processes.

[Clinical observations with aripiprazole in schizophrenia]. / Klinikai megfigyelések aripiprazollal szkizofréniában.

The atypical antipsychotic aripiprazole was administered once a day by peroral dose--10-15 mg--in 103 schizophrenics; they were hospitalized or in day-hospital or outpatient department. During the simple blind clinical trial it was compared by 70 schizophrenics administered by haloperidol treatment (9-15 mg/day dose). The aripiprazole had good therapeutic effect at the positive and negative symptoms of acute schizophrenia, and at the other antipsychotic non-responder patients, and had no serious side-effects. The hypothesis, that of aripiprazol had good effect on the mesolimbic dopamine system as dopamine antagonist, causes improvement on positive symptoms; also good effect on the mesocortical dopamine system as partial agonist, causes improvement on negative symptoms of schizophrenia. The patients had good compliance with aripiprazol.

Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane.

Because of the high number of therapy-resistant depressions and the growing number of suicides, there is still a great need for the development of antidepressants with a new pharmacological spectrum. The finding that phenylethylamine and tryptamine are endogenous enhancers of the impulse propagation mediated release of catecholamines and serotonin in the brain, and the development of synthetic enhancer substances opened the possibility to stimulate catecholaminergic and serotonergic neurons in the brain stem via a previously unknown mechanism. (-)-Deprenyl, a prototype of the phenylethylamine-derived synthetic enhancer substances, stimulates the catecholaminergic neurons in the brain but is almost ineffective on the serotonergic neurons. R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, (-)-BPAP, the recently developed tryptamine-derived selective synthetic enhancer substance, is a hundred times more potent enhancer of the catecholaminergic neuronal activity than (-)-deprenyl, and is also a highly potent stimulant of the serotonergic neurons. Evaluation of the peculiar pharmacological profile, the high potency and unusual safeness and tolerability of (-)-BPAP cherish the hope that this compound by itself and in combination with uptake inhibitors may improve the effectiveness of drug therapy in major depression and diminish the number of therapy resistant cases.

Comparison between genes of Alzheimer's disease and brain tissue of others.

We have examined samples from 14 donors that were prepared from 44 different anatomical regions of the brain. These samples were prepared both as frozen formalin-fixed, paraffin embedded. There were 310 frozen samples and 367 fixed samples. A total of 265 of the frozen samples were tested for RNA quality. A very high quality was obtained with 122 of these frozen samples (44%). The sample numbers were not large enough to draw conclusions about RNA quality for individual brain regions. Silver staining was performed on some samples and 5 of 7 samples tested from one donor diagnosed with Alzheimer's like dementia showed evidence of Alzheimer's disease by this method.

Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence.

Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution.

[About the curability of schizophrenia]. / A szkizofrénia gyógyithatóságáról.

The curability of schizophrenia is not clear, but in this case report we describe a paranoid schizophrenic patient who has remained symptom-free during three decades of treatment with clozapine. During this time he has had a very successful career which points to the possibility of the long-term curability of schizophrenia. From his mother's side he inherited genes for multiple mental disorders and his psychosis started at age 27, after two years of therapeutic resistance he received clozapine and became symptom free. His compliance has been perfect, clozapine has no side effects.

[Pharmacovigilance as new direction of research]. / Farmakovigilancia mint új kutatási terület.

Pharmacovigilance: permanent collection and assessment of the safety data of the drug, in the interest of precise knowledge of the safety profile of the pharmacon; permanent collection of unexpected adverse drug reactions, effects on special patient populations, drug interactions, adverse drug reactions of long-term treatment, adverse drug reactions of long latency. Our study was performed under the tutelage of the Drug Safety Programme in Psychiatry (AMSP), 2004. We review the side effects occuring in the different organ systems; side effects during the use of antidepressive and antipsychotic therapy. We review how the danger of polypharmacy can be avoided by reducing the dose of the current drug; by using therapeutic drug; or just by monitoring therapeutic and adverse effects.

About the menopausal depression.

BACKGROUND: According to studies performed in the last some years, several factors may increase the risk for depression during menopause to occur. Perimenopause, the period mostly associated an increase in the rate of depressive symptomatology, is characterised by decline of estrogen level. But the other changing reproductive physiology, as progesterone, inhibin level, CNS activity of gonadal steroids may have role in depression during menopause. METHODS: We enrolled 40 patients with major depression (women's age range 39-51 years). In the open label clinical trial 10-10 of them had fluoxetine, estrogen, the combination of fluoxetine and estrogen or fluoxetine and cognitive psychotherapy. The measurement was made by the Clinical Global Impression Scale. Duration of the treatment was six weeks. RESULTS: From the 10-10 depressed patients 4 improved by estrogen, 6-6 by the combination of antidepressant and estrogen or fluoxetine alone, but 8 with combination of antidepressants cognitive psychotherapy. CONCLUSIONS: The combination of antidepressant and psychotherapy the best solution for the treatment of menopausal depression, but the therapy must be individual.

Clozapine maintenance therapy in schizophrenia.

Long-term pharmacotherapy with antipsychotic agents is an important aspect of the management of schizophrenia. In patients responsive to the chosen treatment, maintenance therapy is usually conducted by halving the drug dose that has proven effective during the acute phase. This strategy is suitable for maintaining remission; moreover, it can improve the patients' quality of life. Records from over 1000 patients treated with clozapine during the past 22 years were examined; 782 of these patients were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria (with the modification in early years). From this group, 181 patients were treated with clozapine for at least a year. The mean duration of long-term maintenance treatment with clozapine was 12.2+/-4.25 years (range: from 14.5 months to 18 years). Clozapine was administered in a daily dose of 50-200 mg (mean: 71.5+/-14.12 mg). In 76 schizophrenics, treatment was initiated with clozapine, whereas 105 patients were switched over from other treatments after their failure. The control group comprised 152 patients on long-term maintenance therapy with haloperidol. Clozapine administered for long-term maintenance therapy was effective both in paranoid and in catatonic schizophrenia. It also accomplished good results in patients with disorganized or residual schizophrenia, as well as in individuals with schizoaffective psychosis. Relapse rate was similar to that observed in the haloperidol group; however, patient compliance, side-effect profile, and therapeutic efficacy were all superior in the clozapine group. Long-term maintenance therapy with clozapine is successful. Compliance is good; schizophrenic patients are willing to take this atypical antipsychotic for years on end. Clozapine treatment is associated with a low relapse rate and a favorable safety profile.

[Schizoid psychosis during cannabis intake (case report)]. / Szkizoid pszichózis kannabisz fogyasztás után (esetbemutatás).

UNLABELLED: Three young people developed psychosis during/ after cannabis intake. The 17-year-old male after only a few marihuana cigarettes, the 22-year-old patient after two years of addiction developed schizoid psychosis; the 20-year-old patient after six years of cannabis addiction had schizoaffective psychosis. The first two patients become symptom-free on the antipsychotics and during the drug-free period. The third patient, who had cannabis during the psychotic symptoms, still has the schizoid psychosis. CONCLUSIONS: The connection between cannabis and psychosis is clear in our three patients. Marihuana is working on the dopamine system and may cause schizoid psychosis, sometimes permanent psychosis. Cannabis, this light drug might not be a "safe" agent.

The use of the synthetic enhancer substances (-)-deprenyl and (-)-BPAP in major depression.

There is still a great need for the development of antidepressants with a new pharmacological spectrum. The finding that phenylethylamine and tryptamine are endogenous enhancers of the impulse propagation mediated release of catecholamines and serotonin in the brain, and the development of synthetic mesencephalic enhancer substances opened the possibility to stimulate catecholaminergic and serotonergic neurons in the mesencephalon via a previously unknown mechanism. (-)-Deprenyl, a prototype of the phenylethylamine-derived synthetic enhancer substances, stimulates the catecholaminergic neurons in the brain but is almost ineffective on the serotonergic neurons. R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, (-)-BPAP, the recently developed tryptamine-derived selective synthetic mesencephalic enhancer substance, a hundred times more potent compound than (-)-deprenyl, acts also on the serotonergic neurons. The evaluation of the special pharmacological profile of the synthetic mesencephalic enhancer substance, especially the high potency and the unusual safety and tolerability of (-)-BPAP provide hope that this compound may in the future significantly improve the effectiveness of drug therapy in major depression and its combination with uptake inhibitors may substantially diminish the number of therapy resistant cases.

Agranulocytosis during clozapine therapy.

Granulocytopenia and agranulocytosis are considered among the most dangerous adverse effects of clozapine. During the last 15-year period, this atypical antipsychotic agent has been administered to 750 patients managed at the Emergency Psychiatry Services and Clinical Pharmacology Unit of the National Institute of Psychiatry and Neurology (NIPandN; Budapest, Hungary). Granulocytopenia was ascertained in seven, whereas agranulocytosis was diagnosed in two patients of this population. The latter two comprised a 42-year-old female with schizoaffective psychosis and a 35-year-old male with paranoid schizophrenia. The female patient received clozapine in a daily dose of 400 mg, which induced agranulocytosis after 2 months. The male patient was treated with 225-mg/day clozapine and the time to the diagnosis of agranulocytosis was 6 weeks. These adverse reactions were recognized early and the appropriate treatment of agranulocytosis resulted in complete recovery in both cases.