Bipolar Affective Disorder Research Articles

Mood Stabilizers of First and Second Generation.

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.

A Randomized Clinical Trial of Technology-Enhanced Family-Focused Therapy for Youth in the Early Stages of Mood Disorders

Family-focused therapy (FFT) is associated with enhanced outcomes in youth with bipolar and depressive disorders, but has not been evaluated in conjunction with mobile health tools. In symptomatic adolescents whose parents had histories of mood disorders, we examined whether the effects of telehealth-based FFT were augmented by mobile health apps that emphasized mood tracking and family coping skills. Participants (aged 13-19 years) had active mood symptoms and a parent with major depressive or bipolar disorder. Participants received 12 sessions in 18 weeks of telehealth FFT, with random assignment to (1) a mobile app (MyCoachConnect, MCC) that enabled mood tracking, reviews of session content, and text reminders to practice mood management and family communication skills (FFT-MCC); or (2) a mobile app that enabled mood tracking only (FFT-Track). Independent evaluators assessed youth every 9 weeks over 6 months on depressive symptoms (primary outcome), anxiety, and psychosocial functioning. Participants (N = 65; mean age 15.8 ± 1.6 years) significantly improved in depressive symptoms over 6 months (F1,170 = 45.02, p < .0001; ή2 = 0.21, 95% CI = 0.11-0.31), but there were no effects of treatment condition or treatment by time interactions on depression scores. When secondary outcome measures were considered, the subgroup of youth with bipolar spectrum disorders showed greater improvements in anxiety and global functioning in FFT-MCC compared with FFT-Track. Youth in the early stages of mood disorder may benefit from FFT enhanced by mobile health apps. Collaborations between researchers and information technologists on mobile app design and user experience may lead to increases in engagement among adolescents. Technology Enhanced Family Treatment; https://clinicaltrials.gov/; NCT03913013.

Novel Mutation In The APT13A2 Gene Associated With Ataxia, Cerebellar Tremor, Bipolar Disease and Epilepsy (P9-11.010)

<h3>Objective:</h3> To Report a Novel Mutation In The ATP13A2 Gene Causing Cerebellar Ataxia With Bipolar Disorder And Epilepsy Without Parkinsonism. <h3>Background:</h3> ATP13A2 gene mutations are rare and initially were identified in patients with autosomal recessive (AR) juvenile onset of parkinsonism with supranuclear gaze palsy, and dementia, also known as Kufer-Rakeb disease. Subsequently, recognized phenotypic variability of biallelic mutations in this gene widened and include AR hereditary spastic paraplegia or spastic ataxia. Pure cerebellar ataxia is rarely caused by mutations in this gene. <h3>Design/Methods:</h3> Case report and genetic analysis of the ATP13A2 gene in affected proband and both parents. <h3>Results:</h3> The proband is a 40-year-old male of Iranian descent who developed difficulties walking with multiple falls as a teenager. He transitioned from a walker to a wheelchair dependency in his 20s. He was diagnosed with spinocerebellar ataxia with Holmes tremor in both arms. His examination showed vertical ophthalmoplegia without any signs of Parkinsonism or spasticity. The patient had signs of a mild developmental delay and in his 20s he was also diagnosed with bipolar disorder. He developed seizures in his 40s and they were well-controlled on levetiracetam. Brain MRI showed cerebellar atrophy with no iron deposits in basal ganglia. His parents were first cousins. Family history was noticeable for similar problems in two deceased cousins who were also from consanguineous marriages. Genetic testing showed a novel homozygous mutation in exon 26 of ATP13A2, c.2899G&gt;C (p.Asp967His). We did not find this in 100 controls. Both parents were heterozygous at the same codon. We also confirmed the mutation in the CLIA certified laboratory, which is cataloged as rs772870846. In vitro analysis showed this variant being deleterious. <h3>Conclusions:</h3> We report a novel mutation in the ATP13A2 gene with unique constellation of clinical features, further expanding the phenotypic spectrum of movement disorders associated with this genetic condition. <b>Disclosure:</b> Dr. Yousaf has nothing to disclose. Dr. D’Aguiar Rosa has nothing to disclose. Dr. Ghani has nothing to disclose. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Hedera has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for University of Louisville.

Problems of Adaptation and Impairment of Social Functioning of Persons with Bipolar Affective Disorder Type II

The article presents an analysis of the main theoretical approaches to the violation of adaptation and social functioning of patients with bipolar disorder. The main approaches to socio-psychological adaptation in domestic and foreign psychology are presented. The concept of sustainability is disclosed as the ability to recover and grow positively after periods of impaired adaptation. The main areas of disruption of social functioning during the period of pathopsychological manifestations in patients with bipolar affective disorder are outlined: violations of interpersonal and social functioning, professional and educational activities, identity, self-image, emotional regulation, self-service ability. A study is presented that confirms the hypothesis of a decrease in adaptability and social functioning during periods of pathopsychological manifestations (21 people). The presented data can serve as a basis for effective support of patients with bipolar affective disorder.

Nerve Growth Factor in Psychiatric Disorders: A Scoping Review.

Neurotrophins have been implicated in multiple psychiatric disorders. Nerve Growth Factor (NGF) is one of the major neurotrophins that has attracted much research interest. Therefore, we undertook, to the best of our knowledge, the first scoping review encompassing all major psychiatric disorders and their relation to NGF. This review aimed to identify the current position of NGF in psychiatric research and to outline present gaps in knowledge, which can be answered with a more detailed systematic review in the future. Suitable studies were identified using PubMed. A total of 20 studies were included in the review: two on bipolar affective disorder (BPAD), three on schizophrenia, seven on depression, and eight on alcohol use disorder. NGF levels are definitively reduced in BPAD and depression, while NGF levels in schizophrenia decreased further after treatment than in the drug-naïve state. The effect of treatment on NGF levels in depression varied based on treatment modalities and severity of depression. In patients with depression, raised NGF was a predictor of conversion to bipolar disorder (BD). NGF levels were raised in acute alcohol intoxication and withdrawal but normalized slowly as abstinence was maintained. NGF may play a protective role in preventing the toxic ill effect of acute alcohol intoxication on the central nervous system. Based on current knowledge, NGF levels may be a useful biomarker of a chronic mental stress condition. However, further research is needed before it can be used to identify a specific psychiatric illness or predict treatment response.

Binge eating disorder, impulsivity and bipolar spectrum features in a sample of obese candidates for bariatric surgery.

Candidates for bariatric surgery are routinely screened for psychiatric disorders because abnormal eating behaviors are considered common among these patients. This study aimed to evaluate the frequency and persistence, in terms of one month-to-lifetime prevalence ratio, of binge eating disorder (BED) and the potential association with impulsivity features and bipolar spectrum comorbidity in a sample of obese patients undergoing a psychiatric evaluation for bariatric intervention. Overall, 80 candidates to bariatric surgery were assessed consecutively over 12 months within the framework of a collaboration between the University of Pisa Psychiatry and Internal Medicine Departments. Patients were evaluated through structured clinical interviews and self-report questionnaires. The lifetime and last-month frequencies of BED according to DSM-5 criteria were 46.3% and 17.5%, respectively, with a prevalence ratio of 37.8%. Rates of formal bipolar disorder diagnoses were extremely low in patients with or without BED. However, patients with BED showed more severe dyscontrol, attentional impulsivity and bipolar spectrum features than patients with no BED. The relationship of BED, impulsivity, and mood disorders in bariatric patients is more complex than usually reported in the literature. In particular, the presence of bipolar spectrum features should be systematically investigated in these patients because of their essential clinical and therapeutical implications.

Comparison of Depression, Anxiety and Stress in Caregivers of Patients with Schizophrenia and Bipolar Affective Disorder

Objective: To compare depression, anxiety, and stress amongst caregivers of patients with Schizophrenia and Bipolar Affective Disorder&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Psychiatry Department, Fauji Foundation Hospital, Rawalpindi Pakistan, from May to Nov 2021&#x0D; Methodology: One hundred caregivers of patients with Schizophrenia and Bipolar Affective Disorder took part in the study. The “Depression Anxiety Stress Scales” scale assessed depression, anxiety and stress. The difference in both groups was checked by the chi-square test.&#x0D; Results: One hundred caregivers (46 caregivers of patients with Schizophrenia and 54 caregivers of patients with the bipolar affective disorder) were recruited. Among caregivers of patients with Schizophrenia, 29(63%) had significant depression, 33(71%) had anxiety, and an equal proportion had stress. Of those who cared for patients with bipolar affective disorder,16(29.6 %) had depression, 29(53.7 %) had anxiety, and 25(46.29%) had stress. Depression, anxiety, and stress among caregivers had a statistically significant association with clinical diagnosis in our target population (p-valve 0.002, 0.033, 0.007), respectively.&#x0D; Conclusion: Depression, anxiety, and stress are significantly higher among caregivers of patients with Schizophrenia as compared to caregivers of patients with bipolar affective disorder. Our findings have identified a significant need for supporting caregivers of patients with serious mental illness.

Brief intervention reduces prescription of sodium valproate in women of childbearing age.

Sodium valproate's teratogenicity has prompted increasing restrictions to its use. Our initial audit 2years prior demonstrated continuing hazardous prescription to women of childbearing age in a New Zealand psychiatric inpatient unit, consistent with nationwide dispensing data. Following a service-wide educational intervention and application of "black box" warnings, we conducted a follow-up audit of valproate prescription in the same inpatient unit by reviewing records of women admitted over a 10-month period (March 2020-January 2021). Results were compared with local and international guidelines, and against data from our initial audit. Two hundred and sixty-one women of childbearing age were admitted over the sampling period, 26 of whom (10%) were prescribed valproate on discharge. Over three quarters (77%) of these patients had diagnoses other than bipolar affective disorder, valproates only approved psychiatric indication in New Zealand. Following intervention, significant improvements were observed in several key indicators of prescribing quality: pregnancy testing, documentation of contraception status, and discussion of teratogenic risk. Following intervention, re-audit demonstrated reduced prescription of valproate and improved management of its teratogenic risk in women of childbearing age receiving inpatient psychiatric care. These results demonstrate the value of a systematic approach to improve prescribing practice.

Can neurological soft signs and neurocognitive deficits serve as a combined endophenotype for Han Chinese with bipolar disorder?

Bipolar disorder's (BD) potential endophenotypes include neurological soft signs (NSS) and neurocognitive disorders (ND). Few research, meanwhile, has coupled NSS and ND as combined endophenotypes of BD. This study intends to investigate NSS and ND and compare their differences in euthymic patients with bipolar disorder (EBP), their unaffected first-degree relatives (FDR), and healthy controls (HC). Additionally, search for potential endophenotypic subprojects of NSS and ND and construct and verify a composite endophenotypic. The subjects were all Han Chinese and consisted of 86 EBP, 81 FDR, and 81HC. Cambridge Neurological Inventory and MATRICSTM Consensus Cognitive Battery tested NSS and ND independently. All three groups displayed a trapezoidal distribution of NSS levels and cognitive abnormalities, with EBP having the most severe NSS levels and cognitive deficits, followed by FDR and HC. Among them, motor coordination in NSS and Information processing speed (IPS), Verbal learning (VL), and Working memory (WM) in neurocognitive function are consistent with the traits of the endophenotype of BD. The accuracy in differentiating EBP and HC or FDRs and HC was higher when these items were combined as predictor factors than in differentiating EBP and FDR. These results provide more evidence that motor coordination, IPS, VL, and WM may be internal characteristics of bipolar disease. When these characteristics are combined into a complex endophenotype, it may be possible to distinguish BD patients and high-risk groups from normal populations.

The relationship of frustration reactions and gender role behavior in patients with schizophrenia and affective disorders

The study of violations of the adaptive-compensatory mechanisms of patients with mental disorders makes it relevant to study the combined characteristics of gender, psychosexual sphere and response to stress in mental pathology. The aim of the study was to identify the relationship between the types and directions of frustration reactions as unconscious components of coping with gender and gender-role behavior. 183 patients with diagnoses of schizophrenia and schizotypal disorder, recurrent depressive disorder, bipolar affective disorder were examined. In the diagnostic groups, men and women were dominated by persons under the age of 30. The «Method of diagnostics of gender role behavior accentuations» and «Drawing Associations test» were used. The data obtained indicate that among patients with schizophrenia, men with cross-gender role accentuation better assimilate socio-normative patterns of behavior than women with cross-gender role accentuation; in women with schizotypal disorder, the presence of cross-gender accentuation of gender-role behavior is associated with a lower level of social adaptation compared to women without accentuation.Women with schizotypal disorder and more pronounced masculine gender role accentuation have a profile of the direction of emotional reactions in frustrating situations, characteristic of men with schizotypal disorder. In ontogenesis, the interrelationships of stereotypes of emotional response and the level of gender role accentuation change. The revealed sex differences in the profiles of frustration reactions among patients on the schizophrenic spectrum may be partially explained by the gender-role characteristics of patients. In conclusion of the analysis, it can be concluded that the stereotypes of a person’s emotional response and their formation are closely related to gender-role behavior. Knowledge of this kind of interrelationships enables the psychotherapist in the course of treatment to achieve the patient’s understanding of his behavior, including its unconscious aspects.

Exploring the role of serum uric acid as a biomarker in patients with schizophrenia, bipolar affective disorder, and major depressive disorder

BackgroundUric acid plays a pivotal role in the regulation of mood and behavior. The study aimed to elucidate the role of serum uric acid as a biomarker in patients with schizophrenia, bipolar affective disorder (BAD), and major depressive disorder (MDD) and to examine its relation to symptom domains and severity of illness.ResultsA total of 150 participants with schizophrenia, BAD, and MDD and 50 healthy controls were recruited. Patients were assessed using Structured Clinical Interview for DSM-IV Axis I Diagnosis (SCID-I), Positive and Negative Syndrome Scale (PANSS), the Young Mania Rating Scale (YMRS), and the Hamilton Depression Rating Scale (HAM-D). General Health Questionnaire (GHQ-28) was applied to healthy controls. Then, a blood draw from all participants was performed to measure serum uric acid level. According to this study, there was a statistically significant difference between patients with schizophrenia, BAD, MDD, and healthy controls, with regard to serum uric acid level (P = 0.007). On correlating symptom domains and severity of schizophrenia, bipolar, and MDD with serum uric acid level, there was only a statistically significant negative correlation between YMRS and serum uric acid level (P = 0.022).ConclusionsSerum uric acid could be a valuable biomarker in patients with schizophrenia, bipolar, and MDD especially in patients with bipolar disorder.

Lorazepam use during clinical trials of adults with bipolar mania episodes

BackgroundLorazepam has commonly been prescribed to reduce agitation during bipolar 1 mania trials. Its use has varied considerably by trial methodology and in clinical practice. MethodsThe extent and amount of lorazepam treatment was recorded and analyzed from available brief, controlled trials of acute bipolar mania and in clinical reports in adults. ResultsIn 3-week, placebo-controlled clinical trials (n = 19), most manic subjects (79%) were treated with lorazepam to reduce agitation. This treatment was most prominent during the antimanic drug wash-out phase that preceded placebo-controlled trials. Doses of lorazepam administered during the first 7–10 days of the pre-trial and the early trial phases averaged 2.2 mg/day. These doses were one-third the lorazepam/clonazepam doses administered during placebo-controlled, non-washout trials. Far higher benzodiazepine doses for manic agitation were noted in emergency department reports. Intake enrollment was strikingly restricted only in placebo-controlled trials that used pretrial drug wash-out. ConclusionsMedication treatment conclusions from placebo-controlled, drug washout trials are not representative of clinical treatment for acute bipolar mania.

Psychopathology and coping behaviors among wives of patients with bipolar affective disorder

Psychopathology and coping behaviors among wives of patients with bipolar affective disorder

Biography

I am Drew K Swindells, 70 years old and I live in Buckinghamshire in the UK. I’ve been writing poetry for around three years when my girlfriend at the time got me interested.Since then I’ve developed my voice and write mainly about mental health, love, and love lost. I was diagnosed with bipolar affective disorder a long time ago and draw on my experiences and feelings. I use a pen name sometimes ‘the manic poet’ and I also introduce the semi colon into my work (it’s a mental health symbol meaning survival), also ‘gold and silver’ makes some appearances. Through poetry I can express difficult thoughts and feelings.

Lithium and chronic kidney disease: to stop or not to stop?

Lithium is the first-line treatment as a mood stabiliser in bipolar affective disorder, but it is associated with an increased risk of developing chronic kidney disease (CKD). Consideration of ongoing lithium therapy in patients with CKD is a relatively common clinical scenario, but there is a lack of clear clinical guidelines and management practices vary. We discuss two cases of patients on lithium therapy who developed CKD, in order to provide a meaningful context to further explore the clinical framework for decision making and management.

The efficacy of homoeopathic medicine anacardium Orientale as an adjuvant medicine in the treatment of bipolar affective disorder: A randomized controlled trail

Background: Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks which cause the significant psychological distress, affects one’s work, family, social life and may even result in suicide. During the homoeopathic drug proving of Anacardium Orientale, as per the provers Materia Medica the recorded mental symptoms were similar to BPAD symptoms. Hence, this study was done to assess the efficacy of Anacardium Orientale in the treatment of Bipolar Affective disorder as an Adjuvant Medicine.Methodology: Total 30 cases were selected and randomized as Anacardium group and placebo group. For all the cases GB scale score was measured before and after the treatment and BPAD Symptom Severity (SS) Scale was used to check the effectiveness of Anacardium Orientale. A 6-month follow-up was done for every case. Two from each group discontinued the treatment, total 26 patients were taken for statistical analysis.Results: In Anacardium group, 10 patients had shown significant improvement (76.92%) whereas the condition of three patients had not improved (23.07%). According to the treatment outcome Anacardium Oreintale was found more effective in the patient who has current episode mild or moderate depression (F 31.3) and current episode hypomanic (F 31.0) and in patients with current episode mania without psycotic symptoms (F 31.1).Conclusions: After the statistical analysis of the score obtained from Goldberg Scale and BPAD symptom severity scale, Anacardium Orientale the homoeopathic medicine was found effective in the management of bipolar affective disease as an adjuvant medicine than the placebo.

Rhabdomyolysis Caused by a Behavioral Manifestation of Acute Mania

AbstractIntroductionWhile seen in patients with bipolar disorder due to NMS, antipsychotic side effects, or substance use, rhabdomyolysis resulting from behaviors seen in mania has not been reported in recent literature. We present a case of a patient with rhabdomyolysis due to exertion during a manic episode.CaseA 29-year-old male with a history of bipolar disorder type 1 was brought to the ED in June 2022 after he was found on the roof of a local theater sharing excerpts from a book he had written. Temperatures outside were 100–102 Fahrenheit. On presentation, the patient had rapid, pressured speech and demonstrated flight of ideas. He was religiously preoccupied. He had been previously admitted to Psychiatric Emergency Services in April 2022 for mania and was discharged with lithium and lamotrigine. He had been titrating these medications with his outpatient psychiatrist.The patient’s labs showed an elevated creatinine of 1.49, up from his baseline of 1.09. Further workup revealed an elevated CK of 3,538. Additional abnormalities included an AST of 70, calcium of 10.6, total bilirubin of 1.6, and WBC of 15.5. He was afebrile, oriented, and had no obvious signs of infection. The patient received 2 liters of Lactated Ringers (LR) and was admitted to Internal Medicine. Later, he was agitated overnight and received 10mg olanzapine and 2mg lorazepam. Lithium level following fluid resuscitation was 0.6.On interview the next day, the patient described working on a creative religious piece that he wanted to share with others, leading to him climbing on the roof. He had been hyper-focused on this work, with 1–4 hours of sleep nightly. He also had been frequently doing gymnastics, walking long distances, and climbing other buildings. He endorsed diffuse muscle pain, but this was not reproducible on exam.150mL/hr of LR was started, and PO fluid intake was encouraged. He agreed to resume his medications and was started on lithium 900mg and lamotrigine 50mg. His CK continued to downtrend. WBC count decreased and was 12.9 at discharge. Lamotrigine was titrated up to home dose of 100mg. His mania improved, and he was ultimately discharged home with outpatient follow-up.ConclusionRhabdomyolysis results from the release of toxic cellular compounds from muscle fibers. Complications include acute renal failure, hyperkalemia, and compartment syndrome. Causes include substance use, medications, trauma, seizures, ischemia, overexertion, and dehydration. Recently reported cases of mania-associated rhabdomyolysis involve iatrogenic causes, such as neuromuscular malignant syndrome (NMS) and non-NMS antipsychotic side effects.Other causes include high-risk drug use during mania. Rhabdomyolysis due to behavioral manifestations of mania have been documented more rarely in older reports, similarly, addressing excessive exercise and dehydration. Therefore, our case represents a reminder of the medical sequalae resulting from actions undertaken during acute mania. This highlights the importance of implementing effective treatment to prevent such episodes.FundingNo Funding

Ambition and Its Psychopathologies.

Ambition is a uniquely human, complex personality trait. Although the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition mentions ambition only once, in a peripheral comment concerning narcissistic personality disorder, psychopathological states associated with ambition are commonly encountered in everyday life. Ambition has been linked to narcissism, power, and dominance, but it is distinct from each of these concepts. Although the development of ambition is most strongly influenced by social, cultural, and demographic factors, evidence suggests that genetic and biological factors also contribute.This article describes how ambition-related psychopathologies can manifest as 1) misalignment of ambitions and capabilities; 2) "blind ambition"; 3) distortions associated with bipolar and other mood disorders; 4) amalgams of ambition with Machiavellian traits, psychopathy, narcissism, and sadism (i.e., dark triad/tetrad traits); and 5) amotivation/apathy syndrome deficits associated with general medical and psychiatric conditions.The field requires more robust measures for assessing ambition, further delineation of ambition-related psychopathologies, and effective treatments for these conditions.

Tackling Bipolar Disease with Impulsivity: The Role of Endoxifen

Tackling Bipolar Disease with Impulsivity: The Role of Endoxifen

Antidepressants and memory effects of ketamine under the neuromolecular view: A literature review

Objective: Major Depressive Disorder (MDD) has as diagnostics characteristics chronic deep sadness, anhedonia, sleeping disorder, lower energy, and cognition impairment like memory deficits. Among the pharmacological treatments that have been used until the moment, most of them act by monoaminergic pathways. Overall, the antidepressant effects promoted by this kind of medication usually delay starting, resulting in treatment resistance by the patients; moreover, in some cases, this kind of treatment has shown to be inefficient in depression remission. With this, new treatments have been studied for resistant cases and an immediate antidepressant effect, for example, ketamine – whose action occurs in glutamatergic pathways. This study aimed to analyze, from a literature review, the molecular mechanisms involved in the action of ketamine - focusing on the neuroplastic hypothesis of depression. Methods: A literature search was conducted in PubMed, MEDLINE, and SciELO databases using the following terms as descriptors: "ketamine AND depression AND neuroplasticity," with criterion PICO, resulting in 60 bibliographic texts. Results/discussion: The studies analyzed demonstrated that ketamine could exert its antidepressant effects through the inhibition of GABAergic interneurons, activation of TRK-B/AKT/mTORC pathways involved with cell survival/growth through the neurotrophine BDNF and increased activation of AMPAr by glutamate. Furthermore, it is evident that the pharmacodynamics of ketamine involves different molecular cascades present in the impaired neural plasticity pathways in individuals with MDD. Conclusion: Thus, more research on the effectiveness of ketamine is needed to consolidate its use in MDD and to evolve with glutamatergic pharmacological therapy for other mental disorders, such as bipolar and neurodegenerative affective disorders, an example of Alzheimer's disease.