Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.

Corticosteroids and mania: A systematic review.

OBJECTIVES: Corticosteroids are widely prescribed for a variety of medical conditions. Accumulating evidence suggests that their use may be associated with adverse psychiatric effects, including mania. In this systematic review, we aim to critically evaluate the existing literature on the association between corticosteroid use and the emergence of mania. METHODS: We conducted a comprehensive search of major electronic databases (PubMed, Embase, Cochrane Library) for relevant studies published up to the date of the search (12th January 2023). Inclusion criteria involve studies that investigate the association between corticosteroid use and the emergence of mania in adult patients. The primary outcome is the prevalence of (hypo)mania following corticosteroid administration. Secondary outcomes include potential risk factors, dose-response relationships, and differences among various corticosteroid formulations. RESULTS: The identified studies were subjected to a systematic selection process and data extraction by an independent reviewer. A total of 47 articles met the inclusion criteria for our systematic review. CONCLUSION: Our findings suggest that mania is a common side-effect of corticosteroid use, particularly in prednisone equivalent doses above 40 mg. These findings hold practical significance for clinicians and provide insights into potential interventions, including careful monitoring, dose adjustments, and consideration of psychotropic medications when managing corticosteroid-induced mania.

Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan.

INTRODUCTION: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. METHODS: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). RESULTS: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31-2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55-0.70), divalproex (0.89, 0.83-0.95), and aripiprazole (0.81, 0.66-1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89-1.01), risperidone (0.92, 0.82-1.02), and paliperidone (1.24, 0.88-1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65-0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). CONCLUSION: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality.

A systematic review and network meta-analysis on comparative efficacy, acceptability, and safety of treatments in acute bipolar mania in youths.

BACKGROUND: The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents. METHOD: We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455). RESULTS: Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ2 = 0.0072, I2 = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio. LIMITATIONS: Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered. CONCLUSIONS: Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.

Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies.

This meta-analysis investigated the efficacy, safety, and tolerability of lamotrigine versus placebo in preventing relapse and recurrence of mood episodes in women of childbearing age with bipolar I disorder. Following up to 16 weeks' open-label lamotrigine treatment, responders were randomized to double-blind treatment, including lamotrigine 100-400 mg/day or placebo, in four trials of up to 76 weeks. Women aged 18-45 years who received ≥ 1 dose of study treatment and had ≥ 1 efficacy assessment in the double-blind phase were pooled for efficacy analysis. The primary outcome was median time to intervention for any mood episode (TIME). Of 717 eligible women in the open-label phase, 287 responded and were randomized to lamotrigine (n = 153) or placebo (n = 134). The randomized group had a mean (SD) of 2.0(2.02) manic and 2.5(2.02) depressive episodes in the 3 years before screening. Median TIME was 323 days with lamotrigine and 127 days with placebo (HR 0.69; 95% CI 0.49, 0.96; p = 0.030). Lamotrigine delayed time to intervention for any depressive episode (HR 0.59; 95% CI 0.39, 0.90; p = 0.014) with no treatment difference for manic episodes (HR 0.91; 95% CI 0.52, 1.58; p = 0.732). 2/717 (< 1%) participants experienced serious rash-related adverse events (AEs) during the open-label phase, and 52/717 (7%) had non-serious rash-related events leading to study withdrawal. Incidence of AEs and AEs leading to withdrawal were similar between lamotrigine and placebo groups. Lamotrigine delayed relapse and recurrence of mood episodes, largely by preventing depressive episodes, and was well tolerated in women of childbearing age.

Stimulant Treatment and Potential Adverse Outcomes in Pediatric Populations With Bipolar Disorder: A Systematic Review of the Literature.

OBJECTIVE: To explore outcomes of stimulant treatment for ADHD in pediatric populations with particular attention to bipolar disorder (BPD). METHOD: We conducted a literature search of PubMed articles published prior to August 25, 2022 that focused on BPD, mania, and psychosis prior to, or as result of, stimulant treatment. We excluded studies: (1) unrelated to stimulants, (2) general stimulant research, (3) articles older than 40 years, (4) study protocols, or (5) case reports. RESULTS: A total of 11 articles met all inclusion/exclusion criteria. Some reports found stimulant treatment safe and well-tolerated in children with comorbid BPD and ADHD. Others found evidence of treatment-emergent mania (TEM), discontinuation, and other adverse events with stimulant treatment. CONCLUSION: Poor outcomes associated with stimulant treatment in pediatric populations with BPD necessitate work to identify patients at risk of serious stimulant-related adverse events. Our results were limited by automated search filters and a pediatric, primarily male sample.

Different pharmacokinetics of lithium orotate inform why it is more potent, effective, and less toxic than lithium carbonate in a mouse model of mania.

Lithium carbonate (LiCO) is a mainstay therapeutic for the prevention of mood-episode recurrences in bipolar disorder (BD). Unfortunately, its narrow therapeutic index is associated with complications that may lead to treatment non-compliance. Intriguingly, lithium orotate (LiOr) is suggested to possess unique uptake characteristics that would allow for reduced dosing and mitigation of toxicity concerns. We hypothesized that due to differences in pharmacokinetics, LiOr is more potent with reduced adverse effects. Dose responses were established for LiOr and LiCO in male and female mice using an amphetamine-induced hyperlocomotion (AIH) model; AIH captures manic elements of BD and is sensitive to a dose-dependent lithium blockade. LiCO induced a partial block of AIH at doses of 15 mg/kg in males and 20 mg/kg in females. In contrast, LiOr elicited a near complete blockade at concentrations of just 1.5 mg/kg in both sexes, indicating improved efficacy and potency. Prior application of organic anion transport inhibitors, or inhibition of orotate uptake into the pentose pathway, completely blocked the effects of LiOr on AIH while sparing LiCO effects, confirming differences in transport and compartmentalization between the two compounds. Next, the relative toxicities of LiOr and LiCO were contrasted after 14 consecutive daily administrations. LiCO, but not LiOr, elicited polydipsia in both sexes, elevated serum creatinine levels in males, and increased serum TSH expression in females. LiOr demonstrates superior efficacy, potency, and tolerability to LiCO in both male and female mice because of select transport-mediated uptake and pentose pathway incorporation.

Does celecoxib with sodium valproate have an augmentation effect on acute mania in bipolar disorder? A double-blind controlled clinical trial in Iran.

Inflammatory processes in the brain play a role in acute mania etiopathogenesis. There is little evidence indicating the efficacy of celecoxib adjuvant therapy in treatmenting of manic episodes of bipolar disorder. Therefore, this clinical trial aimed to assess the celecoxib effect on treating acute mania. In a double-blind, placebo-controlled trial, 58 patients meeting the criteria for acute mania were enrolled. After considering eligibility, 45 patients were included in the study and randomly divided into two groups. The first group (23 patients) received sodium valproate 400 mg/day along with celecoxib 400 mg/day, and the second group (22 patients) received sodium valproate 400 mg/day and a placebo. The subjects were evaluated by the Young Mania Rating Scale (YMRS) at the beginning of the study and 9, 18, and 28 days following the initiation of the medication. Evaluation of baseline factors indicated a significant difference in age ( P = 0.01) and psychiatric history ( P = 0.02) between the two groups. However, other factors were similar between groups ( P ≥ 0.05). Comparing the YMRS score between celecoxib and placebo groups revealed no significant difference on days 0, 9, 18, and 28. However, the YMRS score at the end of the study decreased by 16.05 ± 7.65 in the intervention group ( P < 0.001) and 12.50 ± 5.98 in controls ( P < 0.001) compared to the baseline, the trend of change was not significant between the two groups during the time of the study ( F = 0.38; P = 0.84). Although celecoxib adjuvant therapy indicated no considerable side effects, a longer treatment duration may be needed to detect its beneficial effects for treating acute mania in bipolar patients. Trial registration: Iran clinical trial register: IRCT20200306046708N1.

The efficacy and safety of lurasidone in bipolar I depression with and without rapid cycling: A pooled post-hoc analysis of two randomized, placebo-controlled trials.

BACKGROUND: The efficacy and safety of lurasidone monotherapy in patients with bipolar I depression with or without rapid cycling has not been previously investigated. METHODS: We performed subgroup analysis (rapid cycling/non-rapid cycling) of pooled data from two 6-week, randomized, double-blind, placebo-controlled trials of lurasidone monotherapy (20-60 mg/day or 80-120 mg/day). Analyses included mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Safety assessments included the number of treatment-emergent adverse events (TEAEs) and laboratory assessments. RESULTS: Of 1024 patients randomized, 85 were rapid cycling. Mean change in MADRS total score in patients with non-rapid cycling and rapid cycling, respectively, was -14.8 (effect size = 0.47) and - 12.8 (effect size = 0.04) in the lurasidone 20-60 mg/day group, -14.3 (effect size = 0.41) and - 13.0 (effect size = 0.02) in the lurasidone 80-120 mg/day group and -10.6 and -13.3 in the placebo group. The most common TEAE in each subgroup was akathisia in both lurasidone groups. Treatment-emergent mania was reported only in a small number of rapid cycling and non-rapid cycling patients. LIMITATIONS: This was a post-hoc analysis of a short-term study that excluded patients with ≥8 cycles in the past year. CONCLUSIONS: In patients with non-rapid cycling bipolar depression, lurasidone monotherapy significantly improved depressive symptoms relative to placebo at both the 20-60 mg/day and 80-120 mg/day doses. In patients with rapid cycling, both doses of lurasidone displayed depressive symptom score reduction from baseline, but significant improvement was not observed likely due to high levels of improvement on placebo and small sample size.

Comparison of antipsychotic dose equivalents for acute bipolar mania and schizophrenia.

QUESTION: Are antipsychotic dose equivalents between acute mania and schizophrenia the same? STUDY SELECTION AND ANALYSIS: Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia. FINDINGS: We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%). CONCLUSIONS: Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.

Decision-making among adolescents prescribed antipsychotic medications: Interviews to gain perspectives of youth without psychosis or mania.

OBJECTIVES: This study aimed to understand the experiences of youth who had been prescribed antipsychotics but did not have psychosis, mania, autism spectrum disorder, or developmental disability. METHODS: Twenty-three qualitative telephone interviews were conducted with youth aged 11-18 who had been prescribed an antipsychotic medication but did not have a diagnosis of psychotic disorder, bipolar disorder, autism spectrum disorder, or developmental disability. Participants were recruited from four U.S. healthcare systems participating in the pragmatic trial Safer Use of Antipsychotics in Youth (SUAY). Interviews were recorded, transcribed and analyzed using template analysis techniques. RESULTS: Prior to initiating an antipsychotic medication, most participants experienced behavioral health crises; many felt that they had no options other than to start the medication. Other core themes included: (1) antipsychotics had both positive psychosocial outcomes, such as improvement of family life, and adverse effects, such as drowsiness or weight gain, (2) antipsychotics were only one part of a broader treatment plan, (3) efforts were made to maximize benefits and minimize side effects through careful titration, (4) feedback from friends and family was important in the decision to continue. CONCLUSIONS: The findings provide valuable insights into how to engage youth in conversations around the use of antipsychotics.

Bipolar Disorder and Manic-Like Symptoms in Alzheimer's, Vascular and Frontotemporal Dementia: A Systematic Review.

BACKGROUND: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. OBJECTIVES: The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. METHODS: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD, or FTD and BD or (hypo) mania have been included. RESULTS: Manic symptoms seem to be associated to disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincide with or precede cognitive impairment in FTD. Overall, mood stabilizers, and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert neuroprotective activity in patients with AD. CONCLUSION: Prevalence, course, and characteristics of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.

Identifying the neuropsychiatric health effects of low-dose lithium interventions: A systematic review.

BACKGROUND: Lithium is widely evidenced for its neuropsychiatric benefits. Advantages of 'sub-therapeutic' doses are increasingly being reported, which is apposite given enduring concerns around adverse effects of 'therapeutic' doses. We aimed to synthesise all available evidence from interventional studies investigating low-dose lithium (LDL) across neuropsychiatric outcomes. METHODS: Electronic databases were systematically searched to include studies where a group of adult humans were treated with LDL (∼serum level ≤0.6 mmol/L), where data describing a neuropsychiatric outcome were reported either before and after treatment, and/or between lithium and a comparator. RESULTS: 18 articles were examined and grouped according to outcome domain (cognition, depression, mania, and related constructs e.g., suicidality). Significant benefits (versus placebo) were identified for attenuating cognitive decline, and potentially as an adjunctive therapy for people with depression/mania. Across studies, LDL was reported to be safe. CONCLUSIONS: Despite the paucity and heterogeneity of studies, LDL's apparent pro-cognitive effects and positive safety profile open promising avenues in the fields of neurodegeneration, and augmentation in affective disorders. We urge future examinations of LDL's potential to prevent cognitive/affective syndromes.

Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.

Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005-2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR] = 1.3, 95% CI = 1.04-1.62, p = 0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR = 1.46, 95% CI = 1.05-2.02, p = 0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.

Secondary Mania induced by TNF-α inhibitors: A systematic review.

A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor-α (TNF-α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in patients with or without bipolar disorders remains controversial. Thus, we conducted a systematic review to study the anti-TNF-α medication-induced manic or hypomanic episodes. PubMed, Scopus, Medline, and Embase databases were screened for a comprehensive literature search from inception until November 2020, using The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Out of the initial 75 references, the screening resulted in the inclusion of four case reports (each describing one patient) and a cohort study (in which 40 patients out of 7600-0.53% - experienced elated mood episodes after infliximab administration). Of these 44 patients, 97.7% experienced a manic episode and 2.3% hypomania. 93.2% of patients had no history of psychiatric disorder or psychotropic treatment. Only 6.8% had a history of psychiatric disorders with the affective spectrum (4.6% dysthymia and 2.3% bipolar disorder). The time of onset of manic or hypomanic symptoms varied across TNF-α inhibitors with an early onset for Infliximab and a later onset for Adalimumab and Etanercept. These findings suggest that medications targeting the TNF-α pathway may trigger a manic episode in patients with or without affective disorders. However, prospective studies are needed to evaluate the relative risk of such side effects and identify the population susceptible to secondary mania.

Lurasidone-Induced Manic Switch in an Adolescent with Bipolar I Disorder: a Case Report.

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression.

Bipolar disorder and Susac syndrome: a case report.

Susac-syndrome is a rare autoimmune disease that manifests with mood alterations in up to 15% of cases and is usually treated with corticosteroids. We present the case of a 41-year-old woman with a first manic episode and history of Susac-syndrome, secondary Cushing's syndrome after receiving high doses of corticosteroids and a previous depressive episode. Differentiating between primary and secondary mania is difficult, as people with bipolar disorder are prone to multiple psychiatric and nonpsychiatric comorbidities, in this case, the differential diagnosis included secondary mania, corticoid-induced manic episode and primary bipolar disorder. Upon admission, corticosteroid treatment was suspended, and the patient was started on lithium and risperidone. Secondary causes of mania were discarded and, assessing temporal and dosage criteria, it was deemed unlikely that the present episode was corticosteroid-induced. One-year outpatient follow-up pointed towards a primary bipolar type I disorder, as a separate entity from her Susac-syndrome. Corticosteroid use or abrupt withdrawal pose an underestimated risk of inducing depressive or manic symptoms, which may unmask affective disorders in susceptible individuals. Many medical conditions share CNS involvement and/or high-dose/prolonged corticosteroid treatment. In such cases, psychiatric manifestations such as mania or depression should be regarded as secondary and studied to determine the existence of medical complications before considering primary psychiatric conditions.

[Drug-induced mania and hypomania: analysis of a case of lamotrigine-induced mania]. / Manía e hipomanía inducida por fármacos: análisis de un caso de manía inducida por lamotrigina.

INTRODUCTION: Lamotrigine is an antiepileptic medication approved as a mood stabilizer for the prevention of depressive episodes in bipolar disorder. Among its adverse reactions, it may present maniac symptoms, despite being an idiosyncratic adverse effect and low incidence. CASE REPORT: We present the case of a 58-year-old patient, diagnosed with bipolar disorder since her youth and who has required multiple therapeutic schemes. After a pharmacological change from lithium to lamotrigine in progressive ascending doses, she presented a mania decompensation, temporally consistent with the initiation of lamotrigine, and that was accentuated with increasing dose. The symptoms disappear when lamotrigine is withdrawn and a pharmacological approach is carried out. When evaluating the case according to the causality criteria of Naranjo et al, we found a possible result. CONCLUSION: Although lamotrigine-induced manifest symptoms have been previously documented, it is important to take this adverse effect into account, given the affective and behavioral repercussions. Further studies are needed to understand the bilateral relationship of this effect from a clinical and neurobiological point of view.

TITLE: Manía e hipomanía inducida por fármacos: análisis de un caso de manía inducida por lamotrigina.Introducción. La lamotrigina es un antiepiléptico aprobado como estabilizador del ánimo para la prevención de episodios depresivos en el trastorno bipolar. Entre sus reacciones adversas puede presentar sintomatología maniforme inducida, a pesar de ser un efecto adverso de carácter idiosincrático y baja incidencia. Caso clínico. Presentamos el caso de una paciente de 58 años, con diagnóstico de trastorno bipolar desde su juventud y que, a lo largo de la evolución de su patología, ha precisado múltiples esquemas terapéuticos. Tras un cambio farmacológico de litio a lamotrigina en dosis ascendentes progresivas, presenta descompensación maniforme, concordante temporalmente con el inicio de la lamotrigina y que se acentúa con el aumento de la dosis. La sintomatología desaparece al retirar la lamotrigina y realizar un abordaje farmacológico. Al evaluar el caso según los criterios de causalidad de Naranjo et al, encontramos un resultado posible. Conclusión. Aunque se ha documentado previamente sintomatología maniforme inducida por lamotrigina, es importante tener en cuenta este efecto adverso, dada la repercusión a nivel afectivo y conductual. Son necesarios más estudios para entender la relación bilateral de este efecto desde un punto de vista clínico y neurobiológico.

Oseltamivir-Induced Mania in a Patient With Influenza A.

ABSTRACT: Oseltamivir is an antiviral drug often preferred in treating viral infections. Its use has increased owing to annual influenza outbreaks and the COVID-19 pandemic. Although its adverse effects are often seen in the gastrointestinal system, it has other adverse effects that can prevent its use, for example, neuropsychiatric events. In this case report, we present a manic episode case caused by the use of oseltamivir.