Current issue

2023, volume 39, issue 1

Review article

Sixty-year history of dopaminergic mechanism of antipsychotic drugs

Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2023, 39 (1): 9-17

Objective. Sixty-year history of the role of the dopaminergic system in the antipsychotic drugs' action.

Literature review. Sixty years ago, an article suggested the role of the dopaminergic system in the mechanism of action of neuroleptic (antipsychotic) drugs. The author was Arvid Carlsson who in 2000 was awarded the Nobel Prize for his research on the pathogenic and therapeutic role of dopamine. A portrait of this researcher was sketched. Next, the development of the dopaminergic theory of antipsychotic drugs was presented. A concept of dopaminergic receptor blockade was depicted and the dopaminergic D2 receptors were identified as a main element of antipsychotic drug action. A novel finding was the discovery of partial agonists of D2 receptors. The effect on the dopaminergic system and interactions with other neurotransmitters have formed the basis for the identification of three generations of antipsychotic drugs. The first generation of antipsychotics was characterised by the blockade of dopaminergic D2 receptors and the second generation additionally by the blockade of serotonergic 5-HT2 receptors. The third generation includes drugs characterised by partial agonism for D2 receptors and those acting on dopaminergic D3 receptors and serotonergic receptors 5-HT1A and 5-HT7. These groups differ as to the therapeutic spectrum, covering various domains of schizophrenia as well as other psychiatric disturbances, mainly bipolar mood disorder.

Conclusions. The effect on the dopaminergic system is the main therapeutic mechanism of antipsychotic drugs. Suggestions of a possible antipsychotic effect due to a predominant influence on other neurotransmitter systems (glutamatergic, serotonergic, cholinergic) have not been sufficiently confirmed.

Review article

New antipsychotic medications

Krzysztof Wojtasik-Bakalarz, Marcin Siwek
Farmakoterapia w Psychiatrii i Neurologii 2023, 39 (1): 19-38

Objectives. The objective of this article was to present information concerning mechanisms of action, pharmacokinetics, clinical efficacy and tolerance of newly approved antipsychotic medication – lurasidone, brexpiprazole, cariprazine, lumateperone and pimavanserin – and to compare them with previously available ones.

Literature review. We reviewed data from preclinical and clinical trials, literature reviews and meta-analyses concerning newly approved antipsychotic medication. We summarised information about pharmacodynamic effects, pharmacokinetics, clinical efficacy and tolerance of described medications.

Conclusions. Newly approved antipsychotic medication seem to give hope of improvement of treatment efficacy, especially with regards to negative, cognitive and depress­ive symptoms of schizophrenia. They also seem to be better tolerated than previously available antipsychotics.

Review article

Lumateperone in the treatment of psychiatric disorders – a review of the literature

Ada Kaczmarek, Wiktor Szymajda, Katarzyna Dettlaff
Farmakoterapia w Psychiatrii i Neurologii 2023, 39 (1): 39-52

Objectives. The treatment of psychiatric disorders, including schizophrenia and bipolar disorder, is constantly changing. There are new medications that reduce treatment-related side effects and present new mechanisms of action. This article aims to describe characteristics, mechanism of action, and medical use, but also the safety of lumateperone – a drug classified as antipsychotic medication, which was approved by the FDA (Food and Drug Administration) for the treatment of patients with schizophrenia and depressive episodes associated with bipolar disorder in 2019.

Literature review. The review includes up-to-date publications concerning the efficacy of lumateperone in the treatment of psychiatric disorders – schizophrenia, bipolar disorder, but also insomnia, and dementia. The pharmacokinetic and pharmacodynamic characteristics of lumateperone and its precise mechanism of action were presented. The adverse reactions and possible drug interactions were likewise discussed.

Conclusions. Lumateperone is a medication with an interesting mechanism of action, which is unique compared to other antipsychotic drugs. The analysis of clinical trials suggests that lumateperone is an effective and safe medication for the treatment of schizophrenia, as well as bipolar affective disorder. There are high hopes for the use of lumateperone in the treatment of insomnia and dementia.

Review article

Brexanolone and current methods of treating postpartum and perinatal depression

Aleksandra Oracz, Stefan Modzelewski, Kamila Iłendo, Aleksandra Sokół
Farmakoterapia w Psychiatrii i Neurologii 2023, 38 (1): 53-64

Objective. Postpartum depression (PPD) is estimated to affect between 6.5 and 12.9% of women who have given birth. If untreated, the disorder can lead to serious consequences for the patient and her offspring – comprom­ising the formation of the relationship between mother and child. Drugs used to treat postpartum depression should be selected individually to achieve the best pos­sible therapeutic effect, taking into account the severity of the depression, the risk of side effects and other factors determining the course of therapy. In our work, we compare selected treatments for PPD with an indication of the side effects associated with medication.
The paper aims to evaluate brexanolone, a drug that is a synthetic form of the hormone allopregnanolone, a progesterone derivative, comparing it with the main pharmacological treatments for PPD, detailing the mechanisms of action of the above-mentioned groups of drugs and the side effects they induce.

Literature review. The literature was reviewed in terms of the efficacy and safety of drugs used in PPD.

Conclusions. Pharmacological treatment should be avoided if the patient’s condition allows it.
If necessary, SSRIs are the first choice drugs. If these are contraindicated, the use of TCAs may be considered, and in the most severe and resistant to treatment cases, the use of electroconvulsive therapy or a neurosteroid that acts on GABAergic conductivity of the CNS – allopregnanolone (as a drug, allopregnanolone is referred to as brexanolone).
Sertraline appears to be the safest drug for women who are pregnant or in the postpartum period. An al­ternative to sertraline in lactating mothers is paroxetine or nortriptyline therapy. In our opinion, brexanolone will not replace SSRIs, due to the long duration of inpatient infusions and the indication for use only after delivery and not during pregnancy. It is important to bear in mind that this is a relatively new drug, so its action profile and potential side effects will only become apparent in future studies, so according to the current state of knowledge it should only be used when necessary.

Review article

The pathogenesis of anxiety syndromes in the concepts of Jaak Panksepp and Joseph LeDoux: implications for pharmacotherapy and psychotherapy

Sławomir Murawiec, Justyna Danel
Farmakoterapia w Psychiatrii i Neurologii 2023, 39 (1): 65-78

Objectives. This paper describes two theories of the pathogenesis of anxiety disorders (by Jaak Panksepp and Joseph LeDoux) and analyses the impact of theory assumptions on the clinical aspects of pharmacotherapy and psychotherapy.

Literature review. In studying anxiety, Panksepp emphasises its evolutionary and neurobiological dimensions. He formulates his assumptions based on empirical research. He describes seven basic emotional systems, including at least two responsible for the response of individuals to danger, which proceeds unconsciously. Within the single fear system, LeDoux and Pine describe a two-system concept, consisting of a system based on a cognitive appraisal and a system based on defensive behaviours and physiological responses. Targeted anxiolytic treatment should be accompanied by the recognition of the pathomechanism of anxiety and the use of the best possible therapeutic method. Depending on the genesis of the patient’s response to danger, different therapeutic approaches can be used.

Conclusions. Both Panksepp and LeDoux refer to the original patterns of response to danger. However, the detailed exploration and characterisation of the neurobiology of the human brain, including the use of functional imaging, may make it possible to tailor anti-anxiety therapies (both pharmacotherapy and psychotherapy) to the individual patient.