2008, volume 24, issue 3

Only for Pharmacotherapy in Psychiatry and Neurology

Melatonergic concept of pathogenesis and treatment of depression

Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2008, 3, 133–140

The history of introducing antidepressant drugs into psychiatry has been up to 1990. associated mainly with agents acting in various way on serotonergic or/and noradrenergic neurotransmission. The process of recognizing novel pathogenic mechanisms of depression brought up an attention to a role of another neurotransmitters, the disturbances of stress system, as well as to abnormal neuroplasticity processes with a possibility of the therapeutic action of antidepressant drugs via these phenomena. In recent years, the interest has been raised for a concept of treatment of depression by means of regulation of disturbed biological rhythms in this illness. Sleep disturbances occurring in a vast majority of patients make the main clinical manifestation of disturbed circadian rhythms in depression, along with such biochemical abnormalities as altered secretion profiles of many hormones (cortisol, prolactin, thyreotropin and melatonin). These abnormalities may reflect dysfunction of “the biological clock” which main structure is bilateral suprachiasmatic nucleus (SCN). The regulation of SCN activity connected with lighting rhythms is performed mainly by melatonin, acting on M1 and M2 receptors in this brain structure and serotonin pathways from raphe nuclei. In recent years, the antidepressant efficacy of agomelatine has been evaluated, the drug with agonistic action on melatonergic receptors M1 and M2 and antagonistic on serotonergic receptors, type 5HT2C. It has been demonstrated that agomelatine makes an efficacious antidepressant drug with good tolerability. A conspicuous feature of agomelatine is a rapid regulation of sleep disturbances and its lack of effect on sexual functions. The evidence for antidepressant action of agomelatine can make a confirmation for the role of melatonergic system in the pathogenesis and treatment of depression.

Original article

Influence of antipsychotics on scholastic/academic difficulties after 1 year from the first episode of schizophrenia

Jolanta Rabe-Jabłońska, Tomasz Pawełczyk, Kamila Wojtczak
Farmakoterapia w Psychiatrii i Neurologii, 2008, 3, 141–148

Aim: The aim of the study was to establish relationship between kind of antipsychotic used in the treatment of I episode of schizophrenia, number of antipsychotic treatment necessary for improvement of mental state, time of uninterrupted treatment and quality of school/ academic functioning after 1 year from I episode of schizophrenia.
Method: 114 patients (14-23 years) after the I episode of schizophrenia diagnosed acc. to ICD-10 were consecutively enrolled in the study. Participants were recrruited among patients of the Department of Affective and Psychotic Disorders, Outpatient Department of Medical University of Lodz, and from the private psychiatric practice. Information regarding the kind, numer , and the uninterrupted duration of antipsychotic treatment were obtained by a thorough analysis of the medical records and questionnaire filled by patients anf his family.
Results: It was shown that the majority of patients demonstrated learning difficulties 1 year after I episode of schizophrenia. According to the subjective assessment nearly 90% of patients complained of learning difficulties, and theese were also observed objectively as educational results deterioration in nearly 80% of participants. Statistically significant relationships were found for the duration of uninterrupted treatment and the occurrence of the objective learning difficulties and indirectly for the farther and the treatment with second generation antipsychotics.
Conclusions: The results indicate the necessity for planning the suitable care for the group of patients with the first episode of schizophrenia.

Original article

Piracetam in the treatment of Mild Cognitive Impairment and Alzheimer Disease

Alina Borkowska, Marzena Ziółkowska-Kochan, Wiktor Dróżdż
Farmakoterapia w Psychiatrii i Neurologii, 2008, 3, 155–160

Aim: The purpose of the study was an assessment of cognitive functions in patients with Mild Cognitive Impairment (MCI) and Alzheimer Disease (AD) treated with piracetam in doses 2400 mg a day or 4800 mg a day for six months.
Methods: Twenty MCI patients, 21 patients with AD and 20 healthy persons matched for gender, age and education were recruited. The Hamilton Depression Scale, 17-item version, was applied to control for depression. Mini Mental State Examination (MMSE) assisted as a measure of global cognitive functioning. Neuropsychological assessment was done with the Verbal Fluency Test, the Clock Drawing Test and the Digit Span Test (forward and backward).
Results: MCI patients and AD patients performed significantly worse than control subjects on all cognitive tests. MCI patients had better results on all cognitive tests, except for backward digit span, as compared to AD patients. The neuropsychological performance of MCI patients was significantly better in those treated with daily dose of piracetam 4800 mg in comparison to those treated with 2400 mg of piracetam daily. Higher dose of piracetam correlated with better performance on all cognitive tests in patients with MCI and in AD patients such correlation was present with the MMSE score and with results of the Verbal Fluency Test.
Conclusions: Significant cognitive dysfunctions in MCI patients were observed. Working memory deficits in MCI patients are similar to the deficits in AD patients. Piracetam may be one of the therapeutic options in ameliorating cognitive abnormalities in MCI patients particularly in higher daily doses.

Original article

In the search of effective therapy of cocaine dependance – modulation of dopaminergic and GABAergic neurotransmission influences behavioral effects of cocaine

Małgorzata Frankowska, Małgorzata Filip, Edmund Przegaliński
Farmakoterapia w Psychiatrii i Neurologii, 2008, 3, 161–166

Cocaine dependence makes a big social and medical problem. Cocaine possesses euphoriant properties connected mostly with dopaminergic activation which lead to psychic addiction and to compulsive administration of the drug. Currently, many research focus on the neurobiological basis of cocaine dependence and on pharmacological methods of its treatment.
In experimental animal studies of cocaine dependence, various models and methods are used – locomotor activity, sensitization, self-administration of cocaine, place preference, and discrimination model.
In own studies we have found that the endogenous 1-methyl-1,2,3,4-tetrahydroizochinoline (1-MeTIQ , a compound having antidopaminergic properties) reduces rewarding action of cocaine and also prevents relapses of its use. We also demonstrated that drugs activating GABA-ergic system reduce expression of cocaine sensitization and rewarding properties of cocaine.
The results obtained point to a purposefulness of using 1-MeTIQ and drugs activating the GABA-ergic system in the treatment of cocaine dependence.

Review article

Augmentation with second generation antipsychotics or antiepileptic drug as a method of management in schizophrenic patients with poor response to clozapine

Jan Jaracz
Farmakoterapia w Psychiatrii i Neurologii, 2008, 3, 167–176

Clozapine is a potent antipsychotic drug recomended for patients with schizophrenia who did not respond to at least two other antipsychotics trials. It has been estimated that 36-67% of patients respond to clozapine however in a substantial proportion the therapeutic effect in not satisfactory. The aim of this paper is to review results of studies regarding the efficacy and safety of clozapine augmentation with other agents. A Medline search identified 8 randomised control trials (RCT) and 18 open studies and case reports on augmentation of clozapine with other antipsychotic or antiepileptic drug. The results of RCT suggest the efficacy of lamotrigine and sulpiride in clozapine- refractory schizophrenia. Only one RCT confirmed the efficacy of clozapine augmentation with risperidone but three other did not support its use. Open studies and case reports suggest that amisulpride, aripiprazole and ziprasidone may also be effective in the menagement of refractory schizophrenia, but results need a confirmation in large RCT. Combination of second generation antipsychotics or antiepileptic drugs and clozapine seem to be well tolerated. The augmentation with risperidone, and lamotrigine did not lead to significant changes of clozapine plasma level. Studies vary in terms of inclusion criteria, duration of previous treatment, dose of clozapine, severity of disease and outcome measures. In most studies conclusions are limited by small sample size.