In the 50th aniversary of implementation to the clinical practice imipramine – first TCA antidepressant – author analyzed positive and controversial problems related to first and second generation of antidepressants.
Classical tricyclic antidepressants (TCA), still regarded as essential in the treatment of depression, are called by pharmacologists “dirty” due to the complex (not “clean”) mechanism underlying action of these drugs, involving several types of neurotransmission. Numerous side effects are connected with such a complex action. It should be noted that basic TCAs are characterized by a considerable effectiveness, so that imipramine is still used as a reference drug (a “golden standard”) in the evaluation of new drugs efficacy. One of major directions in the development of contemporary psychopharmacology of depression is to synthesize drugs showing a selective effect on neurotransmis-sion, affecting a single, specific system (NA or 5HT). Implementation of such drugs in the clinical practice involves a number of questions, concerning: mechanisms underlying their antidepressant action, pathogenesis of depression (i.e. which of the two neurotransmission systems is changed: NA or 5HT), and effectiveness of drugs selectively enhancing a specific type of neurotransmission. These problems have not been elucidated so far, and research findings reported in the literature are inconsistent. Undoubtedly, antidepressants with selective action are safer than TCAs – however, it is not clear yet whether they are equally effective. It can be hoped that these controversial problems may be settled due to the implementation in clinical practice of antidepressants affecting both the NA and 5HT systems, but having no influence on other types of neurotransmission (DA, ACh, H1 and H2 receptors).
Among controversial problems need further inwestigation author indicates: short and long term influence of antidepressants on the course of bipolar disorder (f.ex. induce switching depression of mania, rapid cycling course), increase the risk of suicide during the first days of treatment.
This paper discusses actual, often controversial, problems related to clinical investigations of antidepressants. Such problems include criteria of results evaluations (50% reduction of pretreatment number of point in the Hamilton Depression Rating Scale is not satisfactory from clinical point of view, this criterion could be replaced by remission), duration of treatment (4-6 weeks observation period is to short for adequate evaluation of treatment effects). Author critically evaluate some aspects pharmacoeconomy and abuse of pharmacoeconomy by pharmaceutical industry.
Objectives: the present study was aimed to investigate possible associations between polymorphisms of dopamine receptors genes type D2 (DRD2, DRD3 and DRD4) and prophylactic efficacy of lithium treatment in patients with bipolar affective disorder.
Material and methods: ninety two patients (54 female, 38 male) diagnosed with bipolar affective disorder. Mean duration of lithium treatment was 14,6±7,5 years (range 5-32 years), and lithium dosage was adjusted to maintain lithium level in the range 0.5-0.8 mmol/l. Patients were divided into three subgroups based on lithium efficacy: excellent lithium responders (n=23), partial responders (n=47) and non-responders (n=22).
Results: no association between studied polymorphisms of dopamine receptors genes DRD2, DRD3, DRD3 and lithium efficacy was found in our group of patients with bipolar affective disorder.
We report on a 46-old patient with chronic hepatitis C in whom seven-month treatment with interferon-alpha plus ribavirin induced persistent psychotic disturbances and significant cognitive impairment that caused marked psychosocial deterioration. The disturbances appeared resistant to therapy with typical neuroleptics and subsequent treatment with clozapine plus quetiapine partially alleviated the symptoms. The latter drugs yielded distinct reduction of tension, auditory hallucinations, improvement of sleep quality and disappearance of suicidal impulses. However, serious impairment of cognitive functions on the level of mild dementia together with psychomotor slowness continued for more than a year. Good psychosocial premorbid functioning, negative personal and family psychiatric history, no substance abuse in the past suggest a relationship between therapy with interferon-alpha plus ribavirin and onset of psychosis and dementia. This may indicate irreversible brain damage in the aftermath of treatment with interferon-alpha plus ribavirin in susceptible individuals.
Epilepsy is a frequent neurological disorder characterized by spontaneous, unpredictable recurrent seizures that affect about 1,5% of worldwide population. Numerous patients do not respond adequately to current antiepileptic drugs. Metabotropic glutamate receptors (mGluRs) have multiple important actions on neuronal excitability. Their function is especially linked with regulation of glutamatergic and GABA-ergic neurotransmission. Bearing in mind that mGluR take part in modulation excitatory and inhibitory systems activity it is no surprising that this family of receptors could be effective target for treatment of epilepsy. This review summarize latest information on the involvement of mGluRs, neurotrophic factors (BDNF), and processes of neurogenesis in the expression of epileptic seizures as well as in the epileptogenesis.
Glutamatergic system is a main excitatory neurotransmitters system of brain. Glutamate receptors are divided into ionotropic (NMDA, AMPA , and kainate receptors) and metabotropic. NMDA receptor participates in neuro-transsmision and is important for synapsis development. Hyperactivity of NMDA receptor causes activation of the cascade cellular processes leading to apopotosis. The last data of many trials confirmed glutamatergic dysfunction hypothesis for schizophrenia.Many genes,G72, DAAO, dysbindyne, neuroregulin, RGS4, and GRIN1, GRM3, have direct connections with glutamatergic system. For excitation NMDA receptor is needed glutamic acid, change of cellular membranes tension, and glycine – co- agonist NMDA receptor. Stable glicyne concentration in neuronal connectivity depended from cell glia, where are situated glicyne transporters. Modulation of glutamatergic function by administration of glycine binding site agonists (glicyne, D- cycloserine, sarcosine), or glycine transporters in addition to antipsychotics can give significant clinical improvement, especially in negative and cognitive symptoms.
Serotonin syndrome is considered as a potentially fatal complication of serotoninergic drug therapy. Sometimes it can be adverse drug reaction that results from therapeutic drug use, but more often it is caused by intentional self-poisoning, or inadvertent interactions between drugs. The symptoms usually involve altered mental status, neuromuscular abnormalities, and autonomic dysfunction. Clinical manifestation of the serotonin syndrome may range from barely perceptible to lethal but in most cases there is a good prognosis when medication is discontinued.
A rewiev of case reports of serotonin syndrome published during last decade was presented and possible patomechanisms were discussed.