The Influence of Electroconvulsive Therapy (ECT) on Brain-Derived Neurotrophic Factor (BDNF) Plasma Level in Patients with Schizophrenia-A Systematic Review and Meta-Analysis.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = -0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.

Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia-A Systematic Review.

The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic treatment which could enhance antipsychotic therapy efficacy whilst simultaneously addressing somatic symptoms in individuals with schizophrenia. A systematic search of the PubMed database up to February 2022 was conducted. Inclusion criteria: randomized controlled trials using augmentation therapy in chronic schizophrenia in adults, written in English, and only studies with psychometric assessments of schizophrenia were incorporated. Exclusion criteria: non-clinical, first episode of schizophrenia, patients on medication other than antipsychotics augmented, and not adjunctive therapy. Overall, 37 studies of 1931 patients with schizophrenia who received a combination of antipsychotic medication with other drugs were selected. A statistically significant reduction of negative and positive symptoms of schizophrenia, measured with the PANSS scale, when using a combination of antipsychotic treatment along with aspirin, simvastatin, N-acetylcysteine, or pioglitazone was found. A combination of antipsychotic medication with aspirin, simvastatin, N-acetylcysteine, or pioglitazone seems to be effective in the reduction of symptoms of schizophrenia in adults, but long-term studies are required to confirm this effect.

Atypical Neuroleptic Malignant Syndrome: Case Reports and Diagnostic Challenges.

Neuroleptic malignant syndrome caused by atypical antipsychotic drugs may present in an atypical manner without symptoms such as hyperthermia and/or muscle rigidity. A detailed description of atypical neuroleptic malignant syndrome induced by atypical antipsychotic drugs, practical information to distinguish neuroleptic malignant syndrome from other related conditions, and the diagnostic criteria that may be used to settle the diagnosis of atypical neuroleptic malignant syndrome are highlighted in this paper. This study was conducted searching PubMed and Science Direct, resulting in 525 articles. 26 case reports that met inclusion criteria were identified. Atypical neuroleptic malignant syndrome was found to develop mainly in male patients suffering from schizophrenia (14 cases) and bipolar disorder (2), and was induced by clozapine (6 cases), olanzapine (5 cases), aripiprazole and quetiapine (4 cases). Muscle rigidity did not develop in patients treated with clozapine and quetiapine, whereas a lack of hyperthermia was common with aripiprazole and clozapine treatment. Atypical neuroleptic malignant syndrome is a difficult matter, especially when symptoms of hyperthermia or muscle rigidity is lacking, but using Levenson's or Adityanjee and Aderibigbe's criteria may increase it detectability, can permit earlier intervention and prevent development of life-threatening typical neuroleptic malignant syndrome.

The role of glutamate receptors and their interactions with dopamine and other neurotransmitters in the development of tardive dyskinesia: preclinical and clinical results.

Tardive dyskinesia is a serious, disabling, movement disorder associated with the ongoing use of antipsychotic medication. Current evidence regarding the pathophysiology of tardive dyskinesia is mainly based on preclinical animal models and is still not completely understood. The leading preclinical hypothesis of tardive dyskinesia development includes dopaminergic imbalance in the direct and indirect pathways of the basal ganglia, cholinergic deficiency, serotonin receptor disturbances, neurotoxicity, oxidative stress, and changes in synaptic plasticity. Although, the role of the glutamatergic system has been confirmed in preclinical tardive dyskinesia models it seems to have been neglected in recent reviews. This review focuses on the role and interactions of glutamate receptors with dopamine, acetylcholine, and serotonin in the neuropathology of tardive dyskinesia development. Moreover, preclinical and clinical results of the differentiated effectiveness of N-methyl-D-aspartate (NMDA) receptor antagonists are discussed with a special focus on antagonists that bind with the GluN2B subunit of NMDA receptors. This review also presents new combinations of drugs that are worth considering in the treatment of tardive dyskinesia.

Lamotrigine, quetiapine and aripiprazole-induced neuroleptic malignant syndrome in a patient with renal failure caused by lithium: a case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) may be induced by atypical antipsychotic drugs (AAPDs) such as aripiprazole, olanzapine, risperidone and quetiapine, either as a single treatment or in combination with other drugs. A case of NMS following the administration of lamotrigine, aripiprazole and quetiapine in a patient with bipolar disorder, and with renal failure caused by toxic lithium levels has not been reported. CASE PRESENTATION: A 51-year-old female patient with a 27-year history of bipolar disorder, being treated with lithium, fluoxetine, olanzapine, gabapentine, perazine and biperiden, was admitted to the hospital due to depressed mood and delusions. A urinary tract infection was diagnosed and antibiotic therapy was initiated. After 5 days of treatment her physical state deteriorated and she developed a fever of 38.4 °C. Her laboratory results revealed a toxic level of lithium (2.34 mmol/l). Acute renal failure was diagnosed and the lithium was withdrawn. After stabilization of her condition, and despite her antipsychotic treatment, further intensification of delusions and depressed mood were observed. All drugs being taken by the patient were withdrawn and lamotrigine and aripiprazole were initiated. Due to the insufficient effectiveness of aripiprazole treatment and because of problems with sleep, quetiapine was added, however further treatment with this drug combination and an increase of quetiapine to 400 mg/d eventually caused NMS. Amantadine, lorazepam and bromocriptine were therefore initiated and the patient's condition improved. CONCLUSION: This case report indicates that concurrent use of multiple antipsychotic drugs in combination with mood stabilizers in patients with organic disorders confers an increased risk of NMS development.