Manic Switch Research Articles

Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose–response meta-analysis

Question The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose–response relationship for efficacy, acceptability, and metabolic/endocrine profiles. Study selection and analysis Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose–response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs. Findings Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40–60 mg) improved depression (50 mg: SMD −0.60 (95% CI −0.30, –0.89)), anxiety (50 mg: −0.32 (95% CI −0.21, –0.42)), clinical global impression (50 mg: −0.67 (95% CI −0.30, –1.03)) and disability (50 mg: −0.38 (95% CI −0.08, –0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose–effect relationship. Weight increased at doses<60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses>70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)). Conclusions A daily dose of 40–60 mg of lurasidone is a reasonable choice for bipolar depression treatment. Trial registration number INPLASY202430069.

Post-marketing safety concerns with lumateperone: a pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database.

Lumateperone, a novel antipsychotic drug that was granted by the Food and Drug Administration (FDA) approval in December 2019, remains insufficiently explored for its adverse event profile. This study used the FDA Adverse Event Reporting System (FAERS) database to explore its potential safety issues. This study conducted a retrospective analysis of FAERS data from the fourth quarter of 2019 to the third quarter of 2023, extracting reports related to lumateperone. Disproportionality analysis using Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithms was employed to detect signals of adverse events (AEs). Our research processed 4,777 pertinent AE disclosures related to lumateperone, unveiling 125 signals that satisfied both ROR and BCPNN evaluative benchmarks across 26 System Organ Classes (SOCs). Intriguingly, 108 of these signals were categorized as unanticipated, spotlighting notable psychiatric manifestations such as mania (ROR = 73.82, 95% CI = 57.09-95.46; IC = 6.16, IC025 = 4.49), and hypomania (ROR = 34.74, 95% CI = 15.54-77.64; IC = 5.10, IC025 = 3.43), alongside non-psychiatric phenomena like urinary retention (ROR = 3.59, 95% CI = 1.80-7.19; IC = 1.84, IC025 = 0.18) and serotonin syndrome (ROR = 8.69, 95% CI = 4.81-15.72; IC = 3.11, IC025 = 1.45). This research provides real-world safety data on lumateperone post-marketing and is an important supplement to the information from clinical trial studies. Healthcare professionals should be vigilant for the risk of a manic switch in patients with bipolar depression who are administered lumateperone. More epidemiological studies are needed in the future to explore and further evaluate the risk-benefit issue of lumateperone.

Hypomania with Low-Dose Lamotrigine Suggests it Really is an Antidepressant

Depression predominates over any other mood phases in bipolar I disorder, and treatment options remain sparse. Lamotrigine, an anticonvulsant used for the prevention and treatment of bipolar depression, has been reported to induce hypomanic and manic switches. Its multimodal mechanism of action may provide an explanation for its propensity to induce mood switches. The authors report a case of hypomania developing briefly after the introduction of very low-dose adjunctive lamotrigine for the treatment of bipolar depression and review proposed mechanisms of action.

Delta-8-tetrahydrocannabinol Associated Manic Switch: A Case Report.

Delta-8-tetrahydrocannabinol Associated Manic Switch: A Case Report.

Manic switch during vortioxetine treatment: New medicine, new issue

Antidepressants have been linked to manic or hypomanic episodes in patient being treated for unipolar or bipolar depression. Knowledge of the risk of manic or hypomanic switch associated with a specific antidepressant assists clinicians in analyzing the risk-benefit ratio and finally prescribing an antidepressant of choice in a specific instance. Vortioxetine is now frequently utilized in clinical practice to treat unipolar depression. However, there is insufficient data on manic or hypomanic transition during vortioxetine treatment of unipolar depression. The purpose of this case report is to add to the existing literature on the vortioxetine-induced manic switch and the importance of considering risk factors before starting anti-depressants. Vortioxetine should be used with caution in patients with mood disorders.

Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis

Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression. We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726. We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles. This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally. None.

Predictive Value of qEEG in Manic Switch of Depressed Patients.

Backgrounds: More than half of the patients with bipolar disorder (BD) had depressive episodes at the onset of BD. Despite some suggested clinical predictors, there are no certain criteria for predicting which unipolar depression patient switch to manic episodes during the treatment course. Electrophysiological markers can address this issue. Methods: Pretreatment quantitative electroencephalography (qEEG) records of patients diagnosed with major depressive disorder (MDD) or BD at the first visit were included in the study. Patients with MDD were also grouped with manic switch (MS) or MDD based on the diagnosis of later visits. The qEEG spectral power was analyzed across 3 groups, that is, MS, MDD, and BD. Results: Compared to patients whose diagnosis did not change, patients with MS had accelerated high-frequency activities predominantly in the left hemisphere (central-parietal-occipital regions). In contrast, they showed increased slow wave activity predominantly in the right hemisphere (parietal-occipital regions). Conclusion: It can be concluded that searching for electrophysiological markers, which have distinct advantages of repeatability, noninvasiveness, and cost-effectiveness, can facilitate the prediction of the MS.

Revisiting the association between treatment with antidepressants and mania: A nationwide within-individual study of 3554 patients with bipolar disorder.

Antidepressants are commonly used "off-label" for bipolar depression, despite concerns over the risk of potential treatment-emergent mania (or "manic switch"). Treatment-emergent mania is difficult to study with adequate power in clinical trials as it requires a large group of participants and long follow-up. Therefore, naturalistic register-based studies have been applied to assess this phenomenon. Here, we aimed to replicate previous findings and address key methodological limitations that were not previously taken into account. We utilized data from nationwide Danish health registries to identify patients with bipolar disorder treated with an antidepressant, either with or without concomitant treatment with a mood stabilizer (drug treatment proxied via redeemed prescriptions). We plotted the incidence of manic and depressive episodes relative to the initiation of antidepressant treatment and compared the incidence of mania in the period prior to and following initiation of antidepressant treatment (within-individual design). In 3554 patients with bipolar disorder initiating treatment with an antidepressant, the number of manic episodes peaked approximately 3 months prior to initiation of antidepressant treatment, and the number of depressive episodes peaked around the initiation of antidepressant prescription. This temporal pattern suggests that antidepressants were used to treat post-manic depression. Within-individual designs do not control sufficiently for confounding by indication, when the treatment indication is time-varying. Thus, results from prior within-individual studies of antidepressant treatment in the context of bipolar disorder may be invalid due to time-varying confounding by indication.

The mediation role of impulsivity between childhood trauma and dissociative symptomatology in bipolar disorder.

We administered the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11), Dissociative Experience Scale (DES-II), and Alda scale. Spearman correlation analysis assessed the independent variables associated with CTQ and DES-II. We performed a mediation analysis using the bootstrapping technique to verify the hypothesis that impulsivity represented an intervening variable between childhood trauma and dissociation. CTQ and DES-II scores in 100 BD patients were both significantly associated with the number of lifetime affective episodes, a clinical course of mania-depression-euthymia, suicidal ideation, a history of antidepressant-induced manic switch, poor response to mood stabilizers, mixed features, psychotic symptoms, aggressive behavior, and BIS-11 (p<0.01). At the regression analysis, CTQ was associated with DES-II (p<0.001), while DES-II was associated with the CTQ (p<0.001) and BIS-11 (p< 0.001), as well as with aggression (p=0.002). The mediation analysis showed that impulsivity significantly mediated the effect of childhood trauma on dissociative symptomatology (z=25.71; 0.930-1.084). Impulsivity might play a key role in onset and prognosis of BD patients. Our findings may help in increasing the knowledge about the possible association between impulsivity, childhood traumatic experiences and dissociative symptomatology. BD patients with dissociative symptoms might benefit from a tailored treatment which could include a training based on emotional and behavioral regulation.

Antidepressant Treatment and Manic Switch in Bipolar I Disorder: A Clinical and Molecular Genetic Study.

Affective switch is an important clinical issue when treating bipolar disorder. Though commonly seen in clinical practice, the benefits of prescribing antidepressants for bipolar depression are still controversial. To date, there have been few genetic studies and no genome-wide association study (GWAS), focusing on manic switch following bipolar depression. This study aims to investigate the effects of individual genomics and antidepressant medication on the risk of manic switch in bipolar I disorder (BPI). A total of 1004 patients with BPI who had at least one depressive episode with complete data on antidepressant treatment and outcome were included. Clinical assessment of mania and depression was performed by trained psychiatric nurses and psychiatrists using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), and the diagnosis of BPI was made according to DSM-IV criteria. Manic switch was defined as a manic episode occurring within eight weeks of remission from an acute depressive episode. The age at first depressive episode of the study patients was 30.7 years (SD 12.5) and 56% of all patients were female. GWAS was carried out in a discovery group of 746 patients, followed by replication in an independent group of 255 patients. The top SNP rs10262219 on chromosome 7 showed the strongest allelic association with manic switch (p = 2.21 × 10−7) in GWAS, which was however not significantly replicated. Antidepressant treatment significantly (odds ratio 1.7; 95% CI 1.3–2.2; p < 0.001) increased the risk of manic switch. In logistic regression analysis, the CC genotype of rs10262219 (odds ratio 3.0; 95% CI 1.7–5.2) and antidepressant treatment (odds ratio 2.3; 95% CI 1.4–3.7) significantly increased the risk of manic switch with a joint effect (odds ratio 5.9; 95% CI 3.7–9.4). In conclusion, antidepressant medication and rs10262219 variants jointly increased the risk of manic switch after bipolar depression.

Gender Incongruence Unmasked by Manic Switch During COVID-19 Infection.

Gender Incongruence Unmasked by Manic Switch During COVID-19 Infection.

Substance use disorders in bipolar disorders: Clinical correlates and treatment response to mood stabilizers

BackgroundSubstance use disorders (SUD) in bipolar disorders (BD) present relevant impact on psychopathological features and illness course. The present study was aimed at analyzing the clinical correlates of this comorbidity. MethodsIn- and outpatients suffering from BD were recruited. Socio-demographic and clinical characteristics were collected. Subjects underwent a psychopathological assessment evaluating affective temperaments and impulsiveness. The appraisal of treatment response to mood stabilizers was conducted with the Alda Scale. Bivariate analyses were used to compare subjects suffering from BD with (SUD-BD) or without comorbid SUD (nSUD-BD) (p<0.05). A logistic regression model was performed to identify specific correlates of SUD in BD. ResultsAmong the 161 included subjects, 63 (39.1%) were diagnosed with comorbid SUD. SUD-BD subjects showed younger age at onset (p = 0.003) and higher prevalence of BD type I diagnosis (BDI) (p<0.001). Furthermore, lifetime mixed features (p<0.001), psychotic symptoms (p<0.001), suicide attempts (p = 0.002), aggression (p = 0.003), antidepressant-induced manic switch (p = 0.003), and poor treatment response (p<0.001) were more frequent in the SUD-BD subgroup. At the logistic regression, SUD revealed a positive association with BD type I diagnosis (Odds Ratio (OR) 4.77, 95% CI 1.66–13.71, p = 0.004) and mixed features (OR 2.54, 95% CI 1.17–5.53, p = 0.019). LimitationsThe cross-sectional study design and the relatively small sample size may limit the generalizability of the findings. The retrospective evaluation of comorbid SUD could have biased the outcome assessment. ConclusionsSubjects with BD and SUD are characterized by higher clinical severity and require careful assessment of treatment response.

Vortioxetine as adjunctive therapy in the treatment of schizophrenia.

Background:The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking.Objectives:Vortioxetine is a novel antidepressant that has been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis.Design:This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust.Methods:Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression – Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months.Results:Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder–prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment.Conclusion:Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.

Abstract- Poster

Introduction:Electro-convulsive therapy is a brain stimulation technique which results in a seizure activity when electrical stimulus is applied. It is indicated for disorders like depression, bipolar disorder, schizophrenia and catatonia and in cases where pharmacotherapy has failed. It can cause side effects like cardiovascular problems, cognitive impairment and mania.Case report:A 19years old male patient, Mr. A, presented to the OPD with parents. Patient was mute. Informants had complaints of decreased interaction, prefers to be alone, sitting idly, poor self-care since one year and maintaining postures for long hours, not speaking anything, and disturbed sleep since one month. He was diagnosed as Catatonic Schizophrenia and was started on Inj. Lorazepam 2mg BD, ECT was started. After receiving 2 ects patient was showing manic symptoms. He was started on Tab. Olanzapine -10mg and 8 ects were continued.Discussion:ECT is a very effective treatment in cases of catatonia. ECT induced manic switch in depressed patients is considered as Bipolar I. There are no case reports suggesting ECT induced mania in catatonic schizophrenia.Conclusion:It is relatively common to see ECT induced mania in depressed patients, but the case discussed above has a rare nature. The exact mechanism for this remains to be unclear and a matter of research.

Manic Switch During Transcranial Magnetic Stimulation for Bipolar Depression.

Manic Switch During Transcranial Magnetic Stimulation for Bipolar Depression.

Selective serotonin reuptake inhibitors and manic switch: A pharmacovigilance and pharmacodynamical study.

There is still no approved mechanism of manic switch in bipolar disorder, yet many selective serotonin reuptake inhibitors were accused for this important adverse event. Therefore, we aimed to investigate to estimate SSRI's risk for reporting mania and elevated mood using FEARS database and investigate receptor mechanisms involved. Mania and relevant side effects approved by FDA were screened in this dataset from the first quarter of 2004 to the third quarter of 2020. Disproportionality analysis were performed to estimate reporting odds ratio (ROR) and linear regressions were conducted to investigate relationship between ROR and Ki values. Receptor occupancy ratios were calculated from in vitro receptor binding profiles. The pharmacodynamical profile was extracted from the International Union of Basic and Clinical Pharmacology and the British Pharmacology Society dataset. Child and adolescent population was also investigated separately. The analysis showed that the odds of a spontaneous report of mania in the FAERS database involving an SSRI were higher than the odds that such a report involved other types of drugs (ROR: 5.324 [CI: 3.773; 7.514]). The largest effect size in this estimation was found in fluvoxamine (ROR: 13.957 [CI: 10.391; 18.747]). Significant effects were found in regression analysis for Ki values of H1 and M1 receptors on ROR. Receptor occupation was not found to have an effect on ROR. Lower degress of Ki values on M1 and H1 may be plausible pharmacological mechanism. Further pharmacological data and clinical assessments may be important to validate this safety signal.

ADHD and Bipolar Disorder in Adulthood: Clinical and Treatment Implications.

Attention deficit hyperactivity disorder (ADHD) is a condition that usually has its onset in childhood. Although the disorder persists into adulthood in half of cases, adult ADHD is often not recognized due to different psychopathological characteristics, quite often overlapping with other diagnoses such as mood, anxiety and personality disorders. This is especially true for bipolar disorder (BD), which shares several symptoms with adult ADHD. Moreover, besides an overlapping clinical presentation, BD is often co-occurring in adults with ADHD, with comorbidity figures as high as 20%. This review will focus on the comorbidity between ADHD and BD by exploring the magnitude of the phenomenon and evaluating the clinical and functional characteristics associated with ADHD–BD comorbidity in adults. Finally, the review will address the implications of pharmacologically treating the ADHD–BD comorbidity, providing suggestions in how to treat these complex patients and addressing the issue of treatment-induced manic switch with the use of stimulants and other medications for ADHD.

Self-injurious behaviour in patients with bipolar disorder and attention deficit hyperactivity disorder after central stimulant start– a retrospective study based on the lisie cohort

IntroductionCurrently, our understanding remains limited of how co-occurring bipolar disorder and attention deficit hyperactivity disorder (ADHD) should be treated.ObjectivesTo evaluate the impact of central stimulant treatment on self-injurious behaviour in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD.MethodsRetrospective cohort study (LiSIE) into effects and side-effects of lithium as compared to other mood stabilisers. Here, using a mirror-image design, we compared suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after central stimulant treatment start.ResultsOf 1564 eligible patients, 206 patients met inclusion criteria; having a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD at first central stimulant initiation. In these, suicide attempts and non-suicidal self-injury events decreased significantly within both 6 months (p = 0.004) and 2 years (p = 0.028) after central stimulant start. After multiple adjustments, this effect was preserved 2 years after central stimulant start (OR 0.63, 95% CI; 0.40 – 0.98, p = 0.041).ConclusionsCentral stimulant treatment may reduce the risk of self-injurious behavior in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. However, to reduce the risk of manic switches, concomitant mood stabilising treatment remains warranted.DisclosureMichael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astra

Common mechanisms involved in manic switch and pain relief induced by lamotrigine: A case report and a literature review

Common mechanisms involved in manic switch and pain relief induced by lamotrigine: A case report and a literature review

Treatment of Comorbid Psychiatric Disorders with Bipolar Disorder.

Life time psychiatric comorbidities of bipolar disorders are highly prevalent. Anxiety disorders, alcohol-substance use disorders, obsessive-compulsive disorder and attention deficit and hyperactivity disorder are the most common comorbid psychiatric conditions in bipolar disorders. Psychiatric comorbidity of bipolar disorders is strongly associated with poor treatment response, higher recurrence of mood episodes, suicide attempts, rapid-cycling, worse general functioning and quality of life. Therefore, considering the huge impact of comorbidity on the bipolar disorder illness course, treatment is usually challenging. The primary aim of the treatment in psychiatric comorbidity of bipolar disorder should be mood stabilization and prevention of mood episodes. Then, first line treatment options recommended for the specific psychiatric disorders might be preferred for the treatment of bipolar disorder comorbidity. With this rationale, quetiapine can be listed as a first line treatment for anxiety disorders comorbidity in bipolar disorders while serotonergic antidepressants and olanzapine are recommended as second line options. For the treatment of alcohol-substance use disorders comorbidity, first line mood stabilizers such as valproate and lithium and new generation antipsychotic quetiapine seem to be the leading options. Serotonergic antidepressants for obsessive-compulsive disorder and stimulants for the attention-deficit hyperactivity disorders are the key treatment choices. However, both treatment agents might cause to manic switch and mood destabilization. Thus, clinicians should be aware of these complications when prescribing in bipolar disorders comorbidity.