2004, volume 20, issue 3


The usefulness of the debrisoquine test in evaluating the efficacy and safety of treatment with antidepressants

Koszewska I., Bidziński A., Turzyńska D., Kalinowski A., Święcicki Ł., Dąbrowski M., Torbiński J., Burna-Drażkowic E., Fornal S., Grądzka D., Namysłowska M., Pużyński S., Płaźnik A.
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 279-292

The metabolic ratio coefficient of debrisoquine (MR) was determined in l02 persons hospitalized with depression. No relations were found between the value of this coefficient and such patients’ characteristics as age, gender, diagnosis type (unipolar, bipolar, first episode depression), and the family history of affective disorders. Further analyses were done on a group of 77 patients, who were subsequently treated with antidepressive drugs that are known to be metabolised chiefly, or to a large extent, by CYP2D6. The undesirable side effects of treatment were not found to be significantly more frequent in the group of poor metabolisers (MR> 12.6), nor in the group of "increased risk" (intennediate metabolisers; 4 < MR < 12.6). A statistically insignificant but clearly visible tendency was found however, for the prescribed dosages to follow the metabolic profile of patients, i.e. patients with low MR values were given higher doses of drugs while the persons with higher MR values were given lower doses. The efficacy of antidepressive treatment was similar in all of the MR value brackets but the clinical evaluation revealed that the narrow group (6 persons) of poor metabolisers posed relatively more therapeutic problems than others did. The usefulness of the debrisoquine test in everyday clinical practice rests therefore in the possibility of defining this group, and modifying its treatment.


Pharmacological treatment for aggressive patients with psychiatric disorders

Małgorzata Rzewuska
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 293-323

Impulsive, aggressive behavior is common in psychiatric disorders. However, little systematic treatment data exists from controlled trials for this symptom domain. Many of the studies in aggression had methodological limitations.
In this article the author comprehensively, critically review the available data on treatment for psychiatric condition with aggressive behaviors including bipolar, psychotic disorders, agitation associated with dementia and personality disorder. The author concludes with a brief summary of optimal treatment approach.


Mood-normalizing action of lamotrigine

Maryla Tuszewska, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 325-334

Lamotrigine belongs to the third generation of antiepileptic drugs. Lamotrigine, as an antiepileptic drug is mainly recommended for partial-onset seizures, however, its efficacy has been also documented for juvenile myoclonic epilepsy and Lennox-Gastaut syndrorne. Lamotrigine has been also used for the treatment of migraine, trigeminal neuralgia, and painful polyneuropathy. In recent years, due to demonstrated mood-normalizing activity, lamotrigine has been used in the treatment of bipolar affective illness. Mood-normalizing action of lamotrigine includes prevention of depressive and manic recurrences, stabilization of rapid cycling and in acute episode, mainly antidepressant activity. Ionic channel blocking by lamotrigine is important mostly for the antiepileptic action of the drug however, psychotropic activity of lamotrigine in bipolar affective illness is probably due to antiglutamatergic and neuroprotective mechanism. The most serious adverse effect of lamotrigine is skin rash, which risk can be prevented by slow titration of the drug dose.


Aripiprazol (Abilify), an antipsychotic with a novel mechanism of action, the first dopamine-serotonin system stabilizer

Małgorzata Rzewuska
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 335-349

Aripiprazole is a new antipsychotic that offers a novel mechanism of action and is effective in the treatment of schizophrenia. It is a D2 receptor partial agonist with partial agonist activity at 5HT1A receptors and antagonist activity at 5HT2A receptors. Aripiprazole may best be described as the dopamine-serotonin system stabilizer.
The results of clinical trials show good efficacy in treating positive and negative symptoms, and that aripiprazole also has certain effects on affective symptoms occurring as part a schizophrenic psychosis. Aripiprazole shows a favorable safety and tolerability profile with low potential for extrapyramidal symptoms, weight gain and sedation, prolactin elevations, or QTc interval prolongation. These properties make it an appealing drug for maintenance use, especially in patients not tolerating other antipsychotics.


Switching of atypical neuroleptics in hospitalized patients

Bartosz Łoza, Mariusz Bartyzel
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 351-366

Background: Starting as early as from newly-admitted patients, searching and staying on the antipsychotic medication that works best and has the fewest side-effects still remains a process of trial and error. Moreover, the clinical consequences of the antipsychotic switching are even less determined and differentiated between various compounds. In such a situation, the well-known benefits of the atypical antipsychotic treatment should be considered and influence the switching algorithms.
Aim: We investigated the patterns of switching from or to different atypical antipsychotics in a group of hospitalized patients.
Methods: In a retrospective follow-up study of 112 mostly schizophrenic patients (65.2%), hospitalized during 0l/Jan/2003 – 29/Feb/2004, we applied a case-control analysis. We tracked 141 episodes of switching, multiplied in some cases. Switched patients were administered clozapine, olanzapine (generic – Zolafren and original – Zyprexa), risperidone, and a depot form of classical neuroleptics. Side-effects and side-effect-related auxiliary treatment were rated. Only patients, who completed their hospitalization with a clinical improvement, were included to the study.
Results: Typical antipsychotics and risperidone were the most frequently exchanged compounds and patients were switched mostly to olanzapine. The average doses of olanzapine (in equivalents) could be elevated safely comparing to classical antipsychotics (before switch) and risperidone (after switch). The olanzapine treatment was associated with less frequently observed side-effects and less commonly co-administered auxiliary medicines as compared to the pooled risperidone and typicals data. Clozapine was administered successfully in a small group of switched treatment resistant schizophrenic patients.
Conclusions: Atypical antipsychotics were less frequently associated with switching in comparison with classical antipsychotics suggesting their overall better tolerance and efficacy. Switching to olanzapine appeared to be the most preferential pattern because of the inadequate efficacy of other antipsychotic agent s in a substantial proportion of patients or patients' inability to tolerate them. Cross-titrated original (Zyprexa) and generic (Zolafren) forms of olanzapine were indistinguishable across all variables.


The effects of adjunctive donepezil treatment to new atypical neuroleptics (risperidone, and olanzapine) on mental and cognitive state of schizophrenic patients

Jolanta Rabe-Jabłońska, Krzysztof Jęczkowski, Anna Śmiech, Anna Wyszogrodzka-Kucharska, Dominik Strzelecki
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 367-375

 Beneficial effect of new atypical antipsychotics on cognition is not returning most schizophrenic patients to normative standards of cognitive functioning. Therefore, other treatments need to be considered as augmentation therapy. Subtle changes in cholinergic function may contribute to the cognitive impairment associated with schizophrenia. Donepezil-cholinesterase inhibitor may act as augmenting agent that manages cholinergic dysfunction in patients with schizophrenia.
The aim of study: assessing results of 4, and 8-weeks treatment with donepezil (S-10 mg/day) and new atypical antipsychotics in schizophrenic patients.
Material: 30 subjects with schizophrenia (ICD-10) in stabilization phase, (in period or improvement of mental state during at least last 6 months, and with score in chosen items of positive symptoms subscale of PANSS: delusions, hallucinations, excitement, grandiosity, and suspicious/persecutory less than 4 points), aged 18-42, treated with risperidone or olanzapine.
Methods: Donepezil (S-l0 mg daily dose) was added to risperidone or olanzapine treatment. This treatment was continued for 8 weeks. Before start of the trial and after 4 and 8 weeks of pharmacotherapy subject were assessed with PANSS, ESRS and neuropsychological tests: TNT A and B, Stroop’s Test and WCST.
Conclusions: Treatment with new atypical antypsychotics and donepezil was safe and well tolerated. Neither the 5 mg nor 10 mg dose of donepezil produced significant improvements in any cognitive measure compared with baseline data (verbal function – Stoop’s Test, attention, psychomotoric functions, visuospatial working memory – TMT, and other aspects of working memory and executive functions – WCST).


The onset of acute symptoms of prostatic hyperplasia in the course of venlafaxine treatment

Agnieszka Permoda-Osip, Jan Jaracz, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2004, 3, 377-381

In this paper a case of 55-years male patient who suffered from urinary hesitancy, weak urinary stream, and a filling of incomplete emptying after administration of 150 mg of venlafaxine due to depressive episode was reported. The careful urologic examination confirmed the diagnosis of benign prostatic hyperplasia with asymptomatic course before the onset of treatment with venlafaxine. These symptoms disappeared after switching an antidepressant therapy to selective serotonin reuptake inhibitor. The possible mechanisms responsible for urinary hesitancy in the course of treatment with venlafaxine were discussed. The appearance of urinary hesitancy in male patients treated with noradrenergic antidepresive drugs is the indication for careful urologic evaluation to rule out or confirm the prostatic disease.