Negative (deficit) symptoms of schizophrenia are a significant cause of poor social functioning and a low quality of life, and their treatment is difficult. The aim of this paper is to review the literature of the last two decades as well as current recommendations regarding their treatment. The introduction of the second-generation antipsychotic drugs (SGA) in mid-1990s brought hope for higher efficacy in the treatment of negative symptoms and improvement of cognitive dysfunctions when compared with the typical neuroleptics. Two decades of treatment experience have proven that all the SGAs are more efficacious than typical neuroleptics, although this difference is moderate. Amisulpride and ziprasidone show a significant efficiency in this respect. Combining other drugs with antipsychotics (add-on strategy) is the most common approach in the treatment of negative symptoms. Antidepressant drugs are the most widely used. Reduction in negative symptoms has been observed after their administration, particularly following mianserin and mitrazapine. Some efficacy has been found for drugs acting as agonists of the glycine site of the NMDA receptor (glycine, D-serine, D-cycloserine) and as glycine transporter's inhibitors (sarcosine), according to a postulate of NMDA glutamate receptor dysfunction in schizophrenia. Good results were observed after the application of drugs affecting the cholinergic system, immunological system, inflammatory processes and hormonal substances – when combined with antipsychotic drugs. Among the non-pharmacological methods, physical activity and brain stimulating methods have shown promising results. Unfortunately, currently available therapeutic methods do not provide a satisfying outcome in the treatment of negative symptoms. Further research in this field is one of the most important challenges of modern psychiatry.
Objectives. The article presents the results of two prospective clinical studies using glutamatergic system modulators – glycine and sarcosine, as conducted in the Department of Affective and Psychotic Disorders at the Medical University of Lodz.
Material and methods. In both studies, participants were previously diagnosed with schizophrenia with predominantly negative symptoms. The inclusion criteria included a stable mental state and established dosing of antipsychotic drugs. In both projects we monitored the efficacy of glutamatergic drugs on the symptomatology of schizophrenia with the PANSS scale as the primary assessment tool.
Results. In the first project – designed as an open-label study – we monitored the effect of glycine (0.8 g/kg of body mass, max. 60 g per day), NMDA receptor co-agonist during the 6-week administration of this amino acid. We noted a significant score reduction in negative symptoms and general psychopathology subscales and in total PANSS. In the second project a randomized, double-blind placebo-controlled 6-month trial, we evaluated the efficacy of sarcosine (2 grams per day), glycine transporter type 1 inhibitor. In this study we demonstrated a significant improvement in negative symptoms and general psychopathology, as well as in the total PANSS score in the sarcosine group. In the placebo group, changes were insignificant.
Conclusions. Glycine and sarcosine were effective and well tolerated by the patients.
Coexistence of depression and pain is frequently observed in clinical practice. It has been estimated that approximately 50% of patients report pain which is usually medically unexplainable during depressive episodes. On that account, these symptoms are referred to as unexplained painful physical symptoms – UPPS. The perception of pain is based on the interaction of several brain structures and some of them are also known to be involved in the regulation of mood. Descending serotoninergic and noradrenergic neurons play an important role in the modulation of nociceptive signals. Tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and selective serotonin and noradrenaline inhibitors (SNRI), besides their anti-depressive efficacy, also have a beneficial effect on chronic pain of different aetiology. Clinical studies have shown that the SNRI duloxetine exerted a better effect on UPPS in patients with major depression than placebo. However, a head-to-head comparison of duloxetine and paroxetine as well escitalopram and nortriptyline demonstrated a similar effect on UPPS. Further studies are necessary for a better understanding of this important issue.
Clozapine is considered to be the precursor of second generation antipsychotics. It was introduced to pharmacotherapy of schizophrenia in 1970s. Subsequently, due to several cases of agranulocytosis clozapine was withdrawn from the market. However, evidence suggesting better efficacy of clozapine, in comparison to other antipsychotics, led to reintroduction of this medication. The obligatory monitoring of white blood cell (WBC) count and absolute neutrophil count (ANC) significantly reduced the risk of agranulocytosis. Currently, clozapine is frequently used particularly in schizophrenic patients, who did not respond to other antipsychotics. Benefits related to its use may be interfered due to side effects including also life threating complications. The aim of this review is to present recent data regarding the prevalence, and the management of common side effects of clozapine. Life threating complications like agranulocytosis, myocarditis, thromboembolism and metabolic side effects including weight gain and diabetes observed during treatment with clozapine are discussed in details. Finally the list of very rare side effects of clozapine was presented.
Herpes Simplex viruses are among the most widespread human pathogens. It is estimated that over one-third of the global population is infected by HSV. In Poland, 89.9% of the population has the specific antibodies for HSV-1 virus, women being at a greater risk of exposure. In this paper, we present a case study of a patient with bipolar disorder, who experienced a remission of herpes lesions during lithium therapy and a relapse after the discontinuation of treatment.