Lege Artis Medicinae



NOVEMBER 30, 2004

Lege Artis Medicinae - 2005;15(02 klsz)

[As many as 80% of patients with schizophrenia have serious problems with the compliance at some point during their course of their treatment. In most cases, patients are partially compliant, taking only a portion of their prescribed medication. Early warning signs of such partial compliance may confuse some clinicians with non-response to treatment and may result in switching these patients to alternative oral antipsychotic drugs. This review focuses on factors that can contribute to partial compliance such as poor insight, negative attitude or subjective response toward medication, cognitive dysfunction, treatment-related side effects, substance abuse and complicated treatment regimen. Partial compliance is among the most common causes of psychotic relapse and the need for rehospitalisation. The reduced incidence of adverse side effects such as extrapyramidal symptoms with atypical antipsychotic agents has the potential to improve compliance in the maintenance treatment of schizophrenia. Administration of a long-acting injectable antipsychotic provides confirmation of whether patients have taken their medication. Furthermore, it allows physicians to distinguish non-response and non-compliance. Strategies for managing partial compliance include the use of a long-acting injectable atypical antipsychotic, psychoeducation and cognitive-behavioural interventions.]



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BÁNKI M. Csaba

[Schizophrenia is a severe and chronic disorder affecting almost 1% of the population worldwide. Antipsychotic drugs, currently in their secondgeneration (atypical) antipsychotics, represent its first-line treatment. Compliance during long-term maintenance pharmacotherapy is one of the key factors in successful patient management; longacting, injectable antipsychotics may significantly contribute to the improvement of the patients The new form of this drug is the first long-acting, injectable second-generation antipsychotic; administered biweekly it produces stable, reliable clinical efficacy. Low peak plasma concentrations and smaller plasma level fluctuations result in excellent tolerance, less side effects than with per os risperidone and minimal local pain due to its specific technology. There is strong evidence from controlled clinical trials for its prolonged efficacy during long-term administration and for patient satisfaction being usually better than with most other antipsychotics. Switching over to long-acting injectable risperidone often results in further improvement even in previously stable patients. No safety concerns have emerged from published evidence. The long-acting injectable risperidone appears to reduce the rehospitalisation rate, a major factor towards its cost-effectiveness.]

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[The first drug used as an antipsychotic was chlorpromazine in 1952. The effective drugs after chlorpromazine in the treatment of schizophrenia and acute manic episodes were named as “major tranquillants” then neuroleptic drugs and later as first-generation antipsychotics. The discovery of clozapin has opened a new era in psychiatric therapy which was followed by new antipsychotics with less and less neurological sideeffects. These are called atypical neuroleptics or second generation antipsychotics. The author reviews the path that is characterized by the changes in the naming of these drugs and has led to a situation where clinical recommendations - both in Hungary and internationally - are used to distinguish between the second generation antipsychotics as first or second treatment of choice.]

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[INTRODUCTION - In the past 15 years new antipsychotic drugs have come forward with higher efficacy in the treatment of schizophrenia. These new medications are safer and have less side-effects. It is now established that longacting maintenance therapy is favourable than intermittent therapy CASE PRESENTATION - The author introduces the case of a male schizophrenic patient who was hospitalized three times over ten years. He discontinued maintenance therapy because of lack of symptoms first time, then because of severe side-effects and then he stopped seeing his psychiatrist. However after a new acute episode his treatment was changed to longacting injectable risperidone with a success. With maintenance therapy the patient is now symptom-free and went back to work. CONCLUSION - Continuous long-acting injectable therapy proved to be successful in the prevention of symptom recurrence and with its application patient compliance has improved and smaller doses have become sufficient to maintain stedy-state.]

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Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Lege Artis Medicinae

[Psychiatric conditions not only influence the severity of clinical outcome of COVID-19 but also the medication of mental diseases]


[The disease process in psychiatric patients who contracted SARS-CoV-2 infection might become more severe because of their impaired general health, comorbidities and unhealthy lifestyle. However, among all psychiatric conditions statistically significant correlation with severe and lethal outcome have been found only in schizophrenia with possible association of multiple immune dysfunctions. While the antipsychotic clozapine used in treatment resistant schizophrenia seems to decrease the likelihood of recovery of patients who underwent COVID-19 infection, antidepressants treatment for major depression may result in more favourable outcome. Mainly the antidepressant fluvoxamine has been reliably found effective by inhi­biting cytokine storms observed in some COVID-19 infected patients.]

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Symptom profiles and parental bonding in homicidal versus non-violent male schizophrenia patients

HALMAI Tamás, TÉNYI Tamás, GONDA Xénia

Objective - To compare the intensity and the profile of psychotic symptoms and the characteristics of parental bonding of male schizophrenia patients with a history of homicide and those without a history of violent behaviour. Clinical question - We hypothesized more intense psychotic symptoms, especially positive symptoms as signs of a more severe psychopathology in the background of homicidal behaviour. We also hypothesized a more negatively perceived pattern (less Care more Overprotection) of parental bonding in the case of homicidal schizophrenia patients than in non-violent patients and non-violent healthy controls. Method and subjects - Symptom severity and symptom profiles were assessed with the Positive and Negative Syndrome Scale in a group of male schizophrenia patients (n=22) with the history of committed or attempted homicide, and another group (n=19) of male schizophrenia patients without a history of violent behaviour. Care- and Overprotection were assessed using the Parental Bonding Instrument (PBI) in a third group of non-violent healthy controls (n=20), too. Results - Positive, negative and general psychopathology symptoms in the homicidal schizophrenia group were significantly (p<0.005) more severe than in the non-violent schizophrenia group. Non-violent schizophrenia patients scored lower on Care and higher on Overprotection than violent patients and healthy controls. Homicidal schizophrenia patients showed a pattern similar to the one in the healthy control group. Conclusions - It seems imperative to register intense positive psychotic symptoms as predictive markers for later violent behaviour. In the subgroup of male homicidal schizophrenia patients negatively experienced parental bonding does not appear to be major contributing factor to later homicidal behaviour.

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[Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia]

PULAY Attila József, KOLLER Júlia, NAGY László, MOLNÁR Mária Judit, RÉTHELYI János

[Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives - The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multilocus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods - Associations of single nucleotide and indel markers were transferred to gene- and geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results - After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xq13 cytobands were found (p_corr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (P_rep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses. ]

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[Myasthenia in a patient with sarcoidosis and schizophrenia (in English language)]

RÓZSA Csilla, KIS Gábor, KOMOLY Sámuel

[A 44-year-old male patient was hospitalised with paranoid schizophrenia in 1985. Depot neuroleptic treatment was started which successfully prevented further psychotic relapses for the next ten years. His myasthenia gravis started with bulbar signs in 1997 and the symptoms soon became generalized. The diagnosis of myasthenia gravis was confirmed by electromyography, by positive anticholinesterase test and by the detection of anti-acetylcholine receptor antibodies in the serum. Mediastinal CT examination showed enlarged hilar lymph nodes on the left but no thymic pathology was observed. Mediastinoscopy was performed and biopsies were obtained from the affected nodes. Histology revealed sarcoidosis. The patient suffered respiratory crisis following the thoracic intervention (in September 1998). Combined oral corticosteroid (64 mg methylprednisolone/e.o.d.) and azathioprine (150 mg/day) treatment regimen was initiated and complete remission took place in both the myasthenic symptoms and the sarcoidosis. The follow-up CT scans showed no mediastinal pathology (January 2000). During steroid treatment a transient psychotic relapse occured which was successfully managed by supplemental haloperidol medication added to his regular depot neuroleptics. The patient currently takes 150 mg/day azathioprine and receives 40 mg/month flupentixol depot im. His physical and mental status are stable and he has been completely symptome free in the last 24 months. The association of myasthenia gravis and sarcoidosis is very rare. To our best knowledge no case has been reported of a patient suffering from myasthenia gravis, sarcoidosis, and schizophrenia at the same time.]