Manic Switch Research Articles

Predictors of switch from depression to mania in bipolar disorder

Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM).8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks.In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch.

Research Roundup

Teens who get sleep or anxiety medications more likely to abuse them Outcomes for ‘ultra‐high risk for psychosis' patients: Nonpsychotic disorders Olanzapine/fluoxetine superior to placebo in treating bipolar I depression in pediatric and adolescent patients Antidepressants for pediatric bipolar depression more likely than antipsychotics to cause manic switch

A case of hypomania with low-dose lamotrigine

Byline: Serap. Oflaz, Eren. Y?ld?zhan, Zeynep. Tatar, Fatma. Akyuz Sir, Lamotrigine is an effective treatment for acute bipolar depression. [sup][1] Although a recent review concluded that the lamotrigine does not increase the incidence of hypomania or manic switches, [sup][2] cases of lamotrigine-induced manic switches in patients with bipolar disorder have been reported. [sup][3],[4] We would like to report a case of hypomanic switches with low doses of lamotrigine. A 42-year-old man was referred to our outpatient clinic because of unhappiness and fatigue since more than a year. He had a 19-year history of bipolar disorder that included three psychiatric hospitalizations for manic episodes with psychotic features. His manic episodes were preceded by depressive episodes, which dominated his clinical course. He had been taking lithium 1200 mg/day and olanzapine 2.5 mg/day regularly as a mood stabilizer for more than 2 years. He had previously taken fluoxetine and bupropion for depression, but they were not effective in relieving his depressive symptoms. The patient had complained of weight gain during follow-up; therefore, olanzapine was discontinued. Lamotrigine 25 mg/day was added at bedtime and increased by 25 mg after 2 weeks. However, after 2 weeks, he reported restlessness, decreased need for sleep (5 h/day), improved mood, increased energy, and distractibility. As a result, the dose was reduced to 25 mg/day, which led to amelioration of the hypomanic symptoms. After 2 weeks, his depressive symptoms re-emerged, and he was prescribed lamotrigine 37.5 mg/day. After 1 week, he complained of the same hypomanic symptoms. A diagnosis of hypomania (lamotrigine induced) was made, and the dose was again decreased to 25 mg/day; his symptoms subsequently improved over 2 weeks. He was regularly taking prophylactic lithium during follow-up, and although his blood lithium level was in the therapeutic range (0.89 mEq/L), he experienced lamotrigine-induced hypomania. Lithium 1200 mg/day and lamotrigine 25 mg/day were continued during the follow-up, and he remained stable without the recurrence of hypomania or depression for approximately 1 year. The temporal correlations between the occurrence of hypomania and increases in lamotrigine doses (37.5 mg and 50 mg) and those between the disappearance of hypomania and decreases in lamotrigine doses (25 mg) suggest that the patient's hypomania was induced by lamotrigine. …

A comparative study on psycho-socio-demographic and clinical profile of patients with bipolar versus unipolar depression.

Background:Several studies have revealed significant differences between bipolar (BP) and unipolar depression (UP). Misdiagnosing BP depression results in suboptimal symptom resolution, induction of manic switch, mixed state, or accelerated cycling. This study compares various psycho-socio-demographic, longitudinal course, and phenomenological factors associated with BP and UP depression.Materials and Methods:We compared 30 UP and 30 BP depression patients using a specially designed intake proforma, International Classification of Diseases-10 diagnostic criteria for research, Hamilton Rating Scale for Depression-21 (HAMD-21), Hypomania Checklist-32 Questionnaire (HCL-32), Brief psychiatric rating scale (BPRS), and Kuppuswami's socioeconomic status scale.Results:BP depression group consisted of mostly males, with earlier age of onset of illness, longer illness duration, frequent episodes, hospitalizations and psychotic symptoms. The total HAM-D score and 4 HAM-D item scores–psychomotor retardation, insight, diurnal variation of symptoms and its severity, and paranoid symptoms were significantly higher in this group. Binary logistic regression identified the age of onset, the total duration of illness, frequency of affective episodes, and presence of delusions as predictors of bipolarity (odds ratio = 1.327; 1.517; 0.062; 0.137).Conclusions:Identification of clinical markers of bipolarity from large scale prospective studies is needed.

The Risk of Switch to Mania in Patients With Bipolar Disorder During Treatment With an Antidepressant Alone and in Combination With a Mood Stabilizer

Objective:This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer.Method:Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0–3 months and 3–9 months after the start of antidepressant treatment with a preceding non-treatment period.Results:Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent...

Risk of manic switch associated with antidepressant therapy in pediatric bipolar depression.

The purpose of this study was to assess the risk of manic switch associated with antidepressants in Medicaid-enrolled pediatric patients with bipolar depression. This retrospective cohort study involved 2003-2007 Medicaid Analytic eXtract (MAX) data from four geographically diverse states. The study sample included children and adolescents (ages 6-18 years) who had received a diagnosis of bipolar disorder on two or more separate occasions or during a hospital discharge, followed by a diagnosis of depression. According to the pharmacotherapy received by these patients in the 30 days around the index bipolar depression diagnosis, patients were categorized into five mutually exclusive groups. Manic switch was defined as having received a diagnosis of mania within 6 weeks after the initiation of bipolar depression treatment. Relative risks of manic switch between antidepressant monotherapy/polytherapy and their alternatives were assessed using Cox proportional hazards model. The robustness of the conventional Cox proportional hazards model toward possible bias caused by unobserved confounders was tested using instrumental variable analysis, and the uncertainty regarding manic switch definition was tested by altering the duration of follow-up. After applying all the selection criteria, 179 antidepressant monotherapy, 1047 second-generation antipsychotic (SGA) monotherapy, 570 mood stabilizer monotherapy, 445 antidepressant polytherapy, and 1906 SGA-mood stabilizer polytherapy users were identified. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49]; antidepressant monotherapy vs. mood stabilizer monotherapy, HR=1.41 [95% CI: 0.52-3.80); antidepressant polytherapy vs. SGA-mood stabilizer polytherapy, HR=1.61 [95% CI: 0.90-2.89]). However, only the comparison between antidepressant monotherapy and SGA monotherapy was statistically significant. The instrumental variable analysis did not detect endogeneity of the treatment variables. Extending the follow-up period from 6 weeks to 8 and 12 weeks generated findings consistent with the main analysis. Study findings indicated a higher risk of manic switch associated with antidepressant monotherapy than with SGA monotherapy in pediatric patients with bipolar depression. The finding supported the clinical practice of cautious prescribing of antidepressants for brief periods.

Low-Dose Manic Switch and High-Dose Antimanic Effect and Extrapyramidal Symptoms by Aripiprazole in a Single Bipolar Patient

A case report of an adult female patient with bipolar depression who developed mania after short-term administration of low-dose aripiprazole (2 mg daily) is reported. Later, the author rechallenged with high-dose aripiprazole (22 mg) for treating mania, but there was no manic switch, unlike when using low-dose aripiprazole. A 1-month follow-up revealed no further symptoms of mania or depression, except dyskinesia and sialorrhea. Clinicians should therefore carefully and vigilantly monitor for both the induction of mania and extrapyramidal symptoms according to the aripiprazole dose.

The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer.

This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer. Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0-3 months and 3-9 months after the start of antidepressant treatment with a preceding non-treatment period. Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3-9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93). In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.

P.2.d.031 Predictors for manic switch at depressive episodes in bipolar disorder: the Systematic Treatment Enhancement Program for Bipolar Disorder

P.2.d.031 Predictors for manic switch at depressive episodes in bipolar disorder: the Systematic Treatment Enhancement Program for Bipolar Disorder

Familiality and Indicators of Risk for Bipolar Disorder in Youth with Attention-Deficit/Hyperactivity Disorder

Our literature review aims to identify risks for pediatric bipolar disorder in youth in the presence of symptoms of attention-deficit/hyperactivity disorder (ADHD). This issue is of clinical and scientific significance as these two disorders share multiple characteristics, as well as high rates of comorbidity with disruptive behavior disorders. Family studies validate that these disorders often co-exist and suggest that a family history heightens the risk for the development of bipolar disorder. Elevated emotional dysregulation scores on the Child Behavioral Check List present another risk factor that is associated with the diagnosis of bipolar disorder in youth. In addition, ADHD children initially presenting with depression are at an increased risk for manic switches; a switch can be predicted by the presence of a family history of mood disorders, emotional and behavioral dysregulation, subthreshold manic symptoms, and psychosis. Taken together, these risk factors can aid clinicians in making an accurate diagnosis of mania in youth with ADHD. [ Psychiatr Ann . 2014; 44(9):423–427.]

Agomelatine-associated manic switch in bipolar depression: A case report

Agomelatine-associated manic switch in bipolar depression: A case report

Near-infrared spectroscopy and plasma homovanillic acid levels in bipolar disorder: a case report

Misdiagnosis of bipolar disorder is a serious, but not unusual problem for patients. Nevertheless, there are few biomarkers for distinguishing unipolar and bipolar disorder. Near-infrared spectroscopy (NIRS) is a noninvasive and useful method for the measurement of hemoglobin concentration changes in the cortical surface area, which enables the assessment of brain function. We measured NIRS and plasma monoamine metabolite levels in a patient with bipolar disorder. A 22-year-old man was admitted due to major depression. At admission, NIRS findings showed oxygenated hemoglobin reincrease in the posttask period, which is characteristic of schizophrenia. After treatment with paroxetine, he became manic with psychotic symptoms. His plasma level of homovanillic acid just before the manic switch was ten times higher than that just after paroxetine initiation. Treatment with lithium and antipsychotics was successful, and plasma homovanillic acid decreased after treatment. In this case, the NIRS findings may predict a possible risk of a manic switch, which is likely induced by paroxetine. NIRS may be able to help distinguish unipolar and bipolar disorder in clinical settings.

Efficacy of Olanzapine for Treating Depressive Episodes in Bipolar Disorder

Purpose: We administered olanzapine to 24 outpatients with bipolar disorder who had experienced a depressive or mixed episode as their most recent episode to evaluate the efficacy and safety of olanzapine in clinical practice. Methods: The duration of study treatment was 8 weeks. Symptoms in each subject were assessed using the Montgomery Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity of Illness, Bipolar Version (CGI-BP) at the start of treatment with olanzapine and at Week 4 and Week 8 of treatment. Results: A total of 17 subjects underwent the assessments at Week 4, and 13 subjects completed the 8-week treatment regimen and the assessments at Week 8. The mean total score and each individual item score of the MADRS were significantly improved at Week 4 and Week 8 compared to those at the start of treatment. The mean CGI-BP Depression and CGI-BP Overall scores were significantly improved at Week 4 and Week 8, while the mean CGI-BP Mania score was not significantly different at Week 4 or Week 8 compared to that at the start of treatment. Adverse drug reactions were reported in 3 subjects during the study: hyperphagia in 2 subjects and light-headed feeling in 1 subject. No manic switches were observed. Discussion: The results of this study confirmed the efficacy and safety of olanzapine in outpatients with bipolar depression in clinical practice.

Eye movement desensitization and reprocessing for posttraumatic stress disorder in bipolar disorder.

There is evidence that posttraumatic stress disorder (PTSD) is more prevalent in patients with bipolar disorder. According to a review, 1 the mean prevalence of PTSD in bipolar patients is 16.0%, which is double the lifetime prevalence of PTSD in the general population. 2 Also bipolar patients with comorbid PTSD exhibit more severe bipolar illness and multiple Axis I disorders, and they disengage more frequently from treatment, suggesting poorer outcome and course of the disorder. 3,4 Trauma-focused cognitive-behavior therapy and eye movement desensization and reprocessing (EMDR) are considered first-line treatments for PTSD. 5 Nonetheless, evidence for the efficacy of PTSD treatment in bipolar disorder is lacking. This is an unsatisfactory situation given the fact that anti depressant pharmacotherapy, often suggested as a second-line treatment for PTSD, has limited application for for bipolar patients because of the possibility of manic switch and adverse long-term outcomes. 6 We report here the successful administration of EMDR to two cases of PTSD in patients with bipolar disorder. A 25-year-old Korean woman was hospitalized for recurrence of a manic episode that initially began three years earlier. Although her affective symptoms had improved, she was troubled by continuing PTSD symptoms that were initiated by multiple rapes 10 years previously. She was additionally diagnosed with PTSD according to DSM-IV criteria and she scored 52 (mild level of PTSD) on the Clinician-administered PTSD scale (CAPS) 7 ; while being maintained on antimanic medi

Bupropion as an Add-on Therapy in Depressed Bipolar Disorder Type I Patients With Comorbid Cocaine Dependence

The treatment of bipolar disorder type I (BD-I) with a comorbid cocaine dependence disorder (CDD) is a challenge in current psychiatric practice. Drugs with proven efficacy in manic/mixed episodes, such as atypical antipsychotics and mood stabilizers, sometimes do not prevent depressive relapses; on the other hand, the use of antidepressants during acute depressive episodes may increase the risk of a manic switch. The aim of the present study was to investigate the short-term efficacy of bupropion augmentation in acutely depressed BD-I patients with co-occurring CDD. Twelve depressed BD-I patients, with a comorbid CDD, treated with valproate 1000 to 1500 mg/d and aripiprazole 10 mg/d, were randomly assigned to receive bupropion 150 mg/d as an open-label add-on therapy (n = 5) or to continue their previous treatment (n = 7). After 4 weeks of observation, patients receiving add-on therapy with bupropion have improved in terms of Hamilton Depression Rating Scale scores and Drug Abuse Screening Test scores, with respect to those of the comparison group, whereas no significant increase of Young Mania Rating Scale scores over time was observed. Our preliminary findings suggest that combining bupropion with mood stabilizers and atypical antipsychotics may be a good therapeutic option in short-term treatment of depressed BD-I patients with comorbid CDD.

Antidepressant-induced mania or hypomania in DSM-5

To the Editor: In contrast to DSM-IV-TR, DSM-5 adds the note to the diagnostic criteria of manic episodes as follows: “A full manic episode that emerges during antidepressant treatment but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and, therefore, a bipolar I diagnosis” (American Psychiatric Association 2013). Also, hypomanic episodes have a similar note in DSM-5 (American Psychiatric Association 2013). These notes seem to widen the concept of bipolar disorder because patients developing mania or hypomania during antidepressant treatment beyond the physiological effect can be diagnosed as bipolar I or II in DSM-5 although they were diagnosed as suffering from substance-induced mood disorder in DSM-IV-TR. Back to DSM-III-R, manic episodes should have been diagnosed in cases that are apparently precipitated by antidepressants because DSM-III-R had a note that “somatic antidepressant treatment that apparently precipitates a mood disturbance should not be considered an etiologic organic factor” in the diagnostic criteria of manic episode (Goodwin and Jamison 2007). According to Dunner (a member of the DSM-IV task force), “There was a sense from the Task Force that bipolar conditions should not be over-diagnosed in the community. Therefore, hypomanic episodes occurring in response to treatment with antidepressant pharmacotherapy would not count toward the diagnosis of bipolar II. However, it is difficult to induce mania or hypomania in a true unipolar depression: “there is likelihood that patients who develop mania or hypomania in response to treatment are actually bipolar.” (American Psychiatric Association 1987). Thereafter, Chun and Dunner (2004) suggest that the rate of antidepressant-induced hypomania in major depressive disorder is very low and that antidepressant treatment cannot make a unipolar patient bipolar. Recently, Dumlu et al. (2011) confirmed that unipolar depression with a history of treatment-induced mania, bipolar I, and bipolar II clustered together in contrast to unipolar depression without manic switch. In this point, DSM-5 seems to be appropriately coming back to DSMIII-R. Nonetheless, beyond the physiological effect in the notes of DSM-5 should be deleted because patients who develop mania or hypomania in response to treatment may be actually bipolar (American Psychiatric Association 1987; Chun and Dunner 2004), and it seems difficult to determine whether manic or hypomanic state persists beyond the physiological effect in individual patients, inducing low reliability.

Mental disorders that exacerbated due to the Fukushima disaster, a complex radioactive contamination disaster.

The Fukushima disaster was caused by an earthquake that occurred on 11 March 2011. Following the serious damage caused by the earthquake and the subsequent tsunami, radioactive contamination occurred because of the meltdown accident at the Fukushima nuclear power plant. We investigated what mental disorders were likely to become exacerbated under these conditions. We surveyed psychiatric outpatients at Fukushima Medical University Hospital for 1 month (31 days) from the day of the earthquake (March–April 2011). The survey revealed that bipolar I disorder was most likely to become exacerbated under the conditions and that the exacerbation exhibited was more likely to involve manic switches than depression. On the basis of the results of our study, particular care must be taken to follow up bipolar I disorder patients after a natural disaster. Our results also suggested the possible origin of bipolar I disorder.

The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.

The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Antidepresan Tedavi İle Hipomanik / Manik Kayma Gösteren Bipolar Bozukluk Hastalarında Sosyodemografik Ve Klinik Özellikler / Sociodemographic and Clinical Features of Antidepressant-Induced Hypomanic and Manic Switches in Patients With Bipolar Disorder

Sociodemographic and clinical features of antidepressant-induced hypomanic and manic switch in patients with bipolar disorder Objective: The aim of this study was to identify sociodemographic, familial, childhood and various clinical characteristics of bipolar disorder patients in whom hypomanic/manic switches had been observed during treatment with antidepressant drugs. Methods: One hundred sixty-one patients diagnosed with bipolar disorder on the basis of DSM-IV-TR were included. The study was a retrospective chart review. The sociodemographic, familial, childhood and various clinical characteristics of patients with manic or hypomanic switches (n=41, 25.4%) observed in association with antidepressant treatment during polyclinic or ward monitoring, or patients without switches (n=120, 74.6%) were compared. Patient data were obtained from Psychiatric Association of Turkey Mood Disorders Branch patient record forms. Results: The first disease episode in the switch group was more commonly a depressive one. Cesarean birth and enuresis nocturna were more common childhood characteristics in the switch group. No difference was determined between the groups in terms of other characteristics. Conclusion: Physicians should be careful in terms of hypomanic/manic switch in patients whose first episode is a depressive one. Our other two findings, cesarian birth and enuresis nocturna, may be significant in terms of suggesting clues for the planning of new studies illuminating the etiology.

One-year outcomes of unipolar depression patients with manic or hypomanic switch during acute antidepressant treatment

Objective. The aim of the study was to investigate one-year outcomes of unipolar depression patients with manic or hypomanic switch during acute antidepressant treatment. Methods. A review of medical records revealed 37 consecutive patients admitted from 1997 to 2002 who underwent an antidepressant-induced manic or hypomanic switch fulfilling DSM-IV criteria. Their clinical courses were retrospectively investigated after discharge. Results. Of the 37 patients, 33 (89.2%) were followed up for 1 year after discharge. None developed a manic episode, while seven developed a hypomanic episode, including 1 patient who was lost after emerging from a hypomanic episode within 6 months after discharge. Only one of those seven patients developed hypomania during acute antidepressant treatment for a recurrent depressive episode under maintenance mood stabilizer treatment. Furthermore, bipolar conversion occurred in four patients within the first 6 months and in another two patients, including 1 with rapid cycling, over the subsequent 6 months after discharge. Of these 33 patients, 28 received continuous maintenance treatment with mood stabilizers for the one-year period after discharge. Conclusions. The subjects were considered to have a bipolar nature according to the prevalence rate of bipolar conversion over a one-year period. Longer follow-up studies appear warranted determine the diagnostic issues of antidepressant-induced switch in unipolar depression.