Tardive dyskinesia (TD) is a late-appearing and sometimes persistent complication of longterm treatment with antipsychotics (AP) charakterised by abnormal postures and involuntary movements of the face or longue, trunk and extremities. We reffered the pathophisiologic hypotheses proposed to explain TD and clinical data about risk of TD in patients under treatment with classical neuroleptics and novel antipsychotics (SGA). Very few evidence-based treatment options for TD have been estabilished as effective. The strategies which has been used to help manage TD, are discussed (switch on different AP, supplementary drugs with target activity in neurotransmission and antioxidants). The results of studies suggest, that clozapine and probably SGAS suppress pre-existing TD therefore atypical antipsychotics should be the fi rst antipsychotics used in patients whe have experienced TD a result of treatment with conventional neuroleptics.
Neurotrophic factors (NTFs) have the unique potential to support neuronal structure, neuronal function, and stimulation of nerve growth in physiological environment and in case of injured nervous system. Numerous studies conducted over the last 20 years have provided evidence for the therapeutic potential of NTFs. However therapeutic use of NTFs still is hampered by many obstacles. Major problems are inability to cross the blood-brain-barrier and adverse effects resulting from the broad exposure of the nervous system and other structures to NTFs action. Viral vectors hopefully allow the targeted delivery of NTFs while providing a long-lasting supply in therapeutic doses. In this review, we consider some of experiments in animal model with use of NTFs. These insights had let to the first clinical trials with NTFs. Clinical trials to be continued over the next years will allow to determine whether NTFs are efficient in prevention and therapy of neurodegenerative diseases such as Alzheimer disease, Parkinson’s disease, Huntington disease or multiple sclerosis.
Aim: The recent studies suggest a signifi cant role of stressful live events (sLE) in the pathogenesis of depressive symptoms. The aim of this study was to analyze antidepressants treatment effi cacy in correlation of presence and severity of stressful live events occurring 6 month prior to depression episode.
Material and methods: We analyzed 95 patients in the age between 19-68 years old (mean 38), suffering from depressive disorder of at least moderate severity, diagnosed according to DSM-IV and ICD-10 criteria by two different psychiatrists. Patients were randomized to one of the 2 different treatment regimes, and were observed during 8 weeks. The treatment recommended dosage ranges were: escitalopram 10-20 mg/day (n=55) and nortriptyline 75-150mg/day (n=40). The Hamilton Rating Scale (HAMD-17) was used for the assessment of the severity of depressive symptoms. Response for treatment was defi ned as ≥ 50% score reduction from baseline on HAMD17. Based on BLEQ questionnaire two different patient subgroups was distinguished: patients with mild stressful live events (sLE ≤ 6) and those with more severe sLE (sLE ≥ 6). Statistical analysis was performed using Statistica 7.1 program.
Results: The analysis showed no signifi cant differences were observed beetwen effi cacy of escitalopram and nortryptyline in both subgroups: sLE ≤ 6 (p=0,106) and sLE ≥ 6 (p= 0,02).
The GABA system plays the pivotal role in anxiety disorders. Most of antiepileptic drugs increase the GABA neurotransmission which may suggest a potential anxiolytic properties. A Medline search using key words: panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder and carbamazepine, valproates gabapentine, pregabaline, tiagabine, topiramate, levetiracetam found 35 articles (randomised, control studies, open studies and case reports). Randomized, placebo controlled studies confi rmed the efficacy of pregabaline in generalized anxiety disorder and. social phobia and gabapentine in social phobia. Results of open studies need a confi rmation in randomized controlled trials to determine the place of antiepileptic drugs in pharmacotherapy of anxiety disorders.
Polyunsaturated fatty acids (PUFA), particularly arachidonic, eicosapentaenoic, dokosahexaenoic acids are the key structural elements of neuronal membranes. They constitute about 15-30% of the dry brain weight and that fact is largely responsible for the unique physical and chemical features of the neuronal phospholipid bilayers which cover many intracellular organelle and take part in information exchange processes. PUFA’s concentration changes in brain phospholipids infl uence many key cellular processes: membrane fl uidity, tertiary structure of receptor and transport proteins, receptor-ligand interacions and induce neurotransmission disturbances. Developing brain utilises vast quantities of PUFA’s, which are essential for neuronal development, migration, synaptogenesis, synaptic plasticity and neurogenesis. PUFA’s are also substrates for eicosanoids production, which are very short-living and extremely reactive substances playing many biological as well as signalling functions. Phospholipids processing by phospholipases is also connected with second messenger signalling activity and transduction of information received by many groups of metabotropic receptors. PUFAs concentration and metabolism disturbances have been observed repeatedly in schizophrenic patients. These changes were most frequent and intense on early stages of the disease. The above mentioned disturbances along with the key role of PUFAs in neurodevelopment and brain maturation contributed to the formulation of membrane phospholipids composition (MPC) hypothesis of schizophrenia, which may constitute a biochemical foundation for neuroimaging and neuronal cytoarchitecture disturbances observed in that chronic and devastating disease. The paper discusses the role of PUFA in brain, their metabolism and lipid abnormalities observed in schizophrenia. The main assumptions of David Horrobin’s MPC hypothesis of schizophrenia are also presented.