Antidepressants and suicidal behavior in bipolar disorder

Patients with bipolar disorder are at very high risk for suicidal ideation, non-fatal suicidal behaviors and suicide and are frequently treated with antidepressants. However, no prospective, randomized, controlled study specifically evaluating an antidepressant on suicidality in bipolar disorder has yet been completed. Indeed, antidepressants have not yet been shown to reduce suicide attempts or suicide in depressive disorders and may increase suicidal behavior in pediatric, and possibly adult, major depressive disorder. Available data on the effects of antidepressants on suicidality in bipolar disorder are mixed. Considerable research indicates that mixed states are associated with suicidality and that antidepressants, especially when administered as monotherapy, are associated with both suicidality and manic conversion. In contrast, growing research suggests that antidepressants administered in combination with mood stabilizers may reduce depressive symptoms in patients with bipolar depression. Further, the only prospective, long-term study evaluating antidepressant treatment and mortality in bipolar disorder, although open-label, found antidepressants and/or antipsychotics in combination with lithium, but not lithium alone, reduced suicide in bipolar and unipolar patients (Angst F, et al. J Affect Disord 2002: 68: 167–181). We conclude that antidepressants may induce suicidality in a subset of persons with depressive (and probably anxious) presentations; that this induction may represent a form of manic conversion, and hence a bipolar phenotype, and that lithium's therapeutic properties may include the ability to prevent antidepressant-induced suicidality.     

Self-esteem, social adjustment and suicidality in affective disorders.

Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients.     

Comorbid anxiety in bipolar disorder: does it have an independent effect on suicidality?

Objective:  Comorbid anxiety disorder is reported to increase suicidality in bipolar disorder. However, studies of the impact of anxiety disorders on suicidal behavior in mood disorders have shown mixed results. The presence of personality disorders, often comorbid with anxiety and bipolar disorders, may explain these inconsistencies. This study examined the impact of comorbid Cluster B personality disorder and anxiety disorder on suicidality in bipolar disorder.
Methods:  A total of 116 depressed bipolar patients with and without lifetime anxiety disorder were compared. Multiple regression analysis tested the association of comorbid anxiety disorder with past suicide attempts and severity of suicidal ideation, adjusting for the effect of Cluster B personality disorder. The specific effect of panic disorder was also explored.
Results:  Bipolar patients with and without anxiety disorders did not differ in the rate of past suicide attempt. Suicidal ideation was less severe in those with anxiety disorders. In multiple regression analysis, anxiety disorder was not associated with past suicide attempts or with the severity of suicidal ideation, whereas Cluster B personality disorder was associated with both. The results were comparable when comorbid panic disorder was examined.
Conclusions:  Comorbid Cluster B personality disorder appears to exert a stronger influence on suicidality than comorbid anxiety disorder in persons with bipolar disorder. Assessment of suicide risk in patients with bipolar disorder should include evaluation and treatment of Cluster B psychopathology.     

Rapid mood switching and suicidality in familial bipolar disorder

Objectives: Rapidly alternating or mixed mood states in bipolar disorder are associated with a particularly high risk for suicidal behavior. Are individuals with these patterns of illness more likely to develop suicidal intentions, or are they less able to resist them? This analysis examines the specific contribution of rapid switching and other variables to the relative likelihood of having or acting on self‐reported suicidal thought and action, in a large group of individuals with bipolar disorder. Methods: The analysis included 1574 family members with bipolar disorder interviewed for a multi‐site bipolar disorder genetic linkage study. Two models were tested, using the same set of demographic and clinical data points as independent variables. One model tested the influence of rapid switching and other variables on self‐reported suicidal thought or action (i.e., suicidality), while the other tested the influences on suicidal action only among those who reported a history of suicidality. Results: Over 75% of subjects had contemplated suicide and 38% reported a history of suicidal behavior. A history of rapid switching was associated with higher likelihood of a history of suicidality, as was panic disorder. Familial suicidal behavior, as well as drug abuse, increased the likelihood of suicidal action among suicidal individuals, but did not increase the likelihood of becoming suicidal. Female sex, early age at onset, and several demographic factors were associated with both facets of suicidality. Conclusions: Factors associated with high acuity of distress, such as panic attacks and unstable moods, appear to enhance the risk of suicidality in general. Factors that affected the threshold for action without increasing suicidality overall can also be seen as markers of impulsive decision‐making. Of the two distinct kinds of suicidal risk, the latter – the likelihood of action given intent – appears to be the more familial.     

Differences in cholesterol and metabolic syndrome between bipolar disorder men with and without suicide attempts

Patient with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome (MetS) and its components compared to general population. Among psychiatric disorders, bipolar disorder ranks highest in suicidality with a relative risk ratio of completed suicide of about 25 compared to the general population. Regarding the biological hypotheses of suicidality, low blood cholesterol level has been extensively explored, although results are still conflicting. The aim of this study was to investigate whether there were differences in the serum cholesterol levels in hospitalized bipolar disorder men patients with history of suicide attempts (N = 20) and without suicide attempts (N = 20). Additionally, we investigated if there were differences in the prevalence of MetS according to NCEP ATP-III criteria in these two groups of patients. Results of the study indicated significantly lower serum cholesterol levels (p = 0.013) and triglyceride levels (p = 0.047), in the bipolar disorder men with suicide attempts in comparison to bipolar disorder men without suicide attempts. The overall prevalence of MetS was 11/40 (27.5%). On this particular sample it was higher in the non-attempters 8/20 (40.0%) than in attempters 3/20 (15.0%) bipolar men group, but without statistical significance. Lower concentrations of serum cholesterol might be useful biological markers of suicidality in men with bipolar disorder.     

Are antidepressants associated with new-onset suicidality in bipolar disorder? A prospective study of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

OBJECTIVE: Depressive episodes are common in bipolar disorder, and the disorder is characterized by high suicide rates. Recent analyses indicate a possible association of antidepressant treatment and suicidality in children and adults with depressive or anxiety disorders. However, few data are available to inform the suicidality risk assessment of antidepressant use specifically in bipolar disorder. METHOD: Of the first 2000 participants followed for 18 months in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 425 experienced a prospectively observed, new-onset major depressive episode without initial suicidal ideation. Standardized ratings of suicidality and antidepressant exposure at index depressive episode and next evaluation were used to investigate the primary hypothesis that new-onset suicidality was associated with increased antidepressant exposure (antidepressant initiation or dose increase). Secondary analysis investigated correlates of new-onset suicidality and antidepressant exposure. Data were collected from November 8, 1999, to April 24, 2002. RESULTS: Twenty-four participants (5.6%) developed new-onset suicidality at follow-up, including 2 suicide attempts. There was no association of new-onset suicidality with increased antidepressant exposure or any change in antidepressant exposure, and no association with initiation of antidepressant treatment. New-onset suicidality was associated with neuroticism, prior attempt, and higher depressive or manic symptom ratings at index episode. Increased antidepressant exposure was negatively associated with higher manic symptom rating at index episode; control for this sole empirically identified confound did not alter the primary results. CONCLUSIONS: Although careful monitoring for suicidality is always warranted in bipolar disorder, this cohort study provides no evidence that increased antidepressant exposure is associated with new-onset suicidality in this already high-risk population. Correlates of both suicidality and antidepressant exposure indicate directions for further research.     

Routine use of the Beck Scale for Suicide Ideation in a psychiatric emergency department

BACKGROUND: U.S. suicide rates are estimated to be 11 per 100,000 people, and improved screening in emergency departments may reduce suicide rates. METHOD: This study examined the relationship between clinician rating of suicide ideation and Beck Scale for Suicide Ideation (BSI) scores when clinicians had access to the BSI results and whether BSI scores and/or clinician ratings of suicidality are associated with patient disposition from the psychiatric emergency department. RESULTS: Of 735 patients, 665 (90%) had documentation of suicide ideation in the chart; 246 (37%) were rated as suicidal; 487 (66%) patients completed the BSI forms; 300 patients (62%) scored positive on the BSI. Logistic regression analysis for BSI scores and clinician ratings of suicidality showed similar results, except clinicians were more likely to rate males as suicidal, while BSI scores did not vary according to sex. Hospitalization occurred more often for patients with mood disorder who had positive BSI scores, while hospitalization occurred more often for patients with a diagnosis of bipolar disorder or schizophrenia who were rated by clinicians as suicidal. CONCLUSIONS: There were important demographic and diagnostic differences revealed by logistic regression analysis of BSI scores and clinician-rated suicidality, and these differences may be associated with disposition for patients presenting with suicide ideation.     

Hopelessness and suicidal risk in bipolar disorder. A study in clinically nonsyndromal patients

Objective

Attempted suicide and death due to suicide are not uncommon among patients with bipolar disorder. Although some risk factors for suicidality in bipolar patients have been identified, little is known about hopelessness and other possible trait or diathesis-related factors. Consequently, the objective of this study was to investigate variables associated with suicidal risk in clinically nonsyndromal bipolar patients.

Methods

A sample of 102 outpatients with a diagnosis of bipolar disorder according to International Classification of Diseases, 10th Revision criteria during nonsyndromal stage were evaluated. On the basis of suicidal history, patients were divided into suicide attempt, suicidal ideation, and nonsuicidal groups. Sociodemographic, clinical, and psychopathological variables were assessed.

Results

As compared with the nonsuicidal group, female sex, combined psychopharmacologic treatment, and hopelessness were independently associated with suicide attempt. Hopelessness and insight into having a mental disorder were independently associated with history of suicidal ideation.

Conclusions

Patients with bipolar disorder and suicidal history are characterized by the presence of hopelessness, which probably confers greater vulnerability for suicidal behavior in the presence of stress factors. This identification of the risk profile for suicidal behavior in nonsyndromal bipolar patients adds complementary information to risk factors established for suicidality during acute phases of the disease, allows for differentiated preventive and treatment approaches of patients at risk, and suggests psychotherapy as an advisable intervention in this group of patients.     

Mental Health Collaborative Care and its Role in Primary Care Settings

Bipolar depression is considered the most difficult-to-treat phase of bipolar disorder, in relation to its pervasiveness and efficacy and/or tolerability limitations of available treatments. Indeed, most mood stabilizers and atypical antipsychotics are not as effective in ameliorating depressive compared with manic symptoms, and entail substantial tolerability limitations. However, the use of antidepressants is highly controversial, as their efficacy appears less robust in bipolar compared with unipolar depression. In addition, antidepressants, in spite of generally having adequate somatic tolerability, in BD may be associated with a higher risk of manic/hypomanic switch, suicidality and rapid cycling. Among alternative pharmacological strategies, compounds with stimulant and pro-dopaminergic effects, such as methylphenidate, modafinil, armodafinil and pramipexole, have showed potential antidepressant activity, even though their use in clinical practice has been limited by the paucity of controlled evidence. This article seeks to review available evidence about the use of the aforementioned compounds in the treatment of bipolar depression. Findings from reviewed studies suggested that pro-dopaminergic compounds, such as pramipexole and stimulants/stimulant-like agents, deserve consideration as adjunctive therapies in bipolar depressed patients, at least in some subgroups of patients. Nevertheless, caution regarding their use is recommended as further clinical trials with larger samples and longer follow-up periods are necessary to clarify the roles of these medications in bipolar depression.     

Insomnia symptoms predict emotional dysregulation,impulsivity and suicidality in depressive bipolar II patients with mixed features

IntroductionInsomnia symptoms are very common in Bipolar Disorder. Our aim was to assess the potential association between insomnia, emotion dysregulation and suicidality in subjects with Bipolar Disorder.MethodsSeventy-seven subjects with Bipolar Disorder type II with a depressive episode with mixed features were recruited. Patients were assessed with SCID-DSM-5, the Insomnia Severity Index (ISI), the Difficulties in Emotion Regulation Scale (DERS), the Scale for Suicide Ideation (SSI) while evaluating manic and depressive symptoms.ResultsSubjects with insomnia symptoms compared to those without showed higher scores in the DERS scale and subscales, including impulsivity, and in the SSI scale. Insomnia symptoms significantly predicted the severity of depressive symptoms, emotion dysregulation, and suicidality in subjects with bipolar disorder. In particular, insomnia was related to difficulties in some areas of emotion regulation including impulsivity. Emotion dysregulation significantly mediated the association between insomnia and depressive symptoms (Z = 2.9, p = 0.004). Furthermore, emotional impulsivity mediated the association between insomnia symptoms and suicidality (Z = 2.2, p = 0.03).ConclusionIn our study, subjects with bipolar disorder suffering from insomnia experienced a greater severity of depressive symptoms and suicidality compared to subjects without insomnia. Insomnia was associated with emotion dysregulation, impulsivity and suicidality. Further research is necessary to investigate if these latter features may benefit from early insomnia treatment in subjects with bipolar disorder.     

Suicidality in pediatric bipolar disorder: predictor or outcome of family processes and mixed mood presentation?

Algorta GP, Youngstrom EA, Frazier TW, Freeman AJ, Youngstrom JK, Findling RL. Suicidality in pediatric bipolar disorder: predictor or outcome of family processes and mixed mood presentation?
Bipolar Disord 2011: 13: 76–86. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: Pediatric bipolar disorder (PBD) involves a potent combination of mood dysregulation and interpersonal processes, placing these youth at significantly greater risk of suicide. We examined the relationship between suicidal behavior, mood symptom presentation, family functioning, and quality of life (QoL) in youth with PBD. Methods: Participants were 138 youths aged 5–18 years presenting to outpatient clinics with DSM‐IV diagnoses of bipolar I disorder (n = 27), bipolar II disorder (n = 18), cyclothymic disorder (n = 48), and bipolar disorder not otherwise specified (n = 45). Results: Twenty PBD patients had lifetime suicide attempts, 63 had past or current suicide ideation, and 55 were free of suicide ideation and attempts. Attempters were older than nonattempters. Suicide ideation and attempts were linked to higher depressive symptoms, and rates were even higher in youths meeting criteria for the mixed specifier proposed for DSM‐5. Both suicide ideation and attempts were associated with lower youth QoL and poorer family functioning. Parent effects (with suicidality treated as outcome) and child effects (where suicide was the predictor of poor family functioning) showed equally strong evidence in regression models, even after adjusting for demographics. Conclusions: These findings underscore the strong association between mixed features and suicidality in PBD, as well as the association between QoL, family functioning, and suicidality. It is possible that youths are not just a passive recipient of family processes, and their illness may play an active role in disrupting family functioning. Replication with longitudinal data and qualitative methods should investigate both child and parent effect models.     

Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

OBJECTIVE: The authors provide a detailed perspective on the correlates of comorbid anxiety in a large, well-characterized sample of bipolar disorder patients. METHOD: Anxiety and its correlates were examined in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS: Lifetime comorbid anxiety disorders were common, occurring in over one-half of the sample, and were associated with younger age at onset, decreased likelihood of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Although substance abuse disorders were particularly prevalent among patients with anxiety disorders, comorbid anxiety appeared to exert an independent, deleterious effect on functioning, including history of suicide attempts (odds ratio=2.45, 95% CI=1.4-4.2). CONCLUSIONS: An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated, highlighting the need for greater clinical attention to anxiety in this population, particularly for enhanced clinical monitoring of suicidality. In addition, it is important to determine whether effective treatment of anxiety symptoms can lessen bipolar disorder severity, improve response to treatment of manic or depressive symptoms, or reduce suicidality.     

Managing bipolar disorder from urgent situations to maintenance therapy

Treatment for bipolar disorder consists of 2 goals: 1) managing urgent situations and 2) transitioning patients into maintenance therapy. Patients with bipolar disorder who present in urgent situations, including symptoms of suicidality, aggression, occupational impairment, legal involvement, and psychosis, require quick and efficient identification and resolution of symptoms. Once patients are stabilized, clinicians must then implement maintenance therapy to manage behavioral symptoms, promote optimal functioning, and ultimately, to reach full, functional recovery.     

Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study

Mahon K, Burdick KE, Wu J, Ardekani BA, Szeszko PR. Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study.
Bipolar Disord 2012: 14: 80–89. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S. Background: Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well‐investigated. Methods: Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract‐Based Spatial Statistics method in the FSL software package. Results: Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity. Conclusions: Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder.     

Bipolar disorder and suicide: Research synthesis and clinical translation

Attempted suicide and suicide are prevalent in individuals with bipolar disorder (BD). Extant evidence indicates that history of suicide attempts, percentage of time spent in a depressed state, and hostility are factors associated with suicide attempts and completed suicide. Childhood adversity (eg, sexual and physical abuse) is emerging as a risk factor for suicide attempts in adults with BD. The pertinacity of medical comorbidity (eg, obesity, metabolic syndrome) in the bipolar population is further underscored by its preliminary association with suicidality. Biomarkers such as cerebrospinal fluid monoamine metabolite levels may be predictive of suicide attempts and lethality in BD. Compelling evidence supports an antisuicide effect of long-term lithium prophylaxis; lithium’s salutary effect is mediated primarily by reduced lethality of suicidal acts. Conventional unimodal antidepressants may engender or exacerbate suicidality in susceptible individuals with BD. A nascent database suggests that adjunctive psychosocial interventions may further reduce suicide risk in bipolar individuals.     

Suicidality in bipolar compared to unipolar depressed inpatients

The aim of the present analyses was to evaluate differences in suicidality (past suicide attempts, suicidal thoughts at time of admission and completed suicides during the hospital stay) between bipolar and unipolar depressed inpatients. Apart from a higher frequency of past suicide attempts in bipolar depressed patients (26.6% in bipolar vs. 17.8% in unipolar patients), findings do not indicate any further differences in suicidality (suicidal thoughts (about 40% in both groups) and completed suicides during the hospital stay (0.8% in both groups)) between bipolar and unipolar patients. Factors with a predictive value for suicidal thoughts at the time of admission were a positive family history for affective disorders, past suicide attempts, and the depressive and paranoid hallucinatory syndrome (all associated with an increased risk). Female gender, an older age at hospitalisation and a longer duration of the illness were found to be associated with a lower probability for having suicidal tendencies at the time of admission. The risk for committing suicide during the hospital stay was increased if the patients had a history of past suicide attempts and suicidal thoughts at the time of admission. A more pronounced depressive syndrome at time of admission was slightly associated with a lower risk of committing suicide. Received: 25 April 2000 / Accepted: 28 June 2000     

Newer prophylactic agents for bipolar disorder and their influence on suicidality.

Different from lithium, there is little known so far on the effect of (newer) anticonvulsants on suicidality in bipolar patients. We evaluated data of 128 patients with bipolar disorders for suicidal ideation. These patients were treated with various mood-stabilizing medications for at least 3 months. No suicide attempt or completed suicide occurred in this cohort during prospective follow up for an average of 13.3 +/- 12.1 years. Compared to lithium, the relative risk of suicidal ideation was numerically slightly higher for valproate, carbamazepine and a small group treated with either levetiracetam, oxcarbazepine or topiramate, but lower in patients treated with lamotrigine, without reaching statistical significance. Confounding variables in more intensive care of these patients participating in a naturalistic study may blur small differences and contribute to a generally favorable outcome.     

Suicidality and its association with insight and neurocognition in taiwanese patients with bipolar I disorder in remission

The aims of this study were to examine the relationships between suicidality, insight, and neurocognition in patients with bipolar I disorder who were in a remitted state. Using the Violence and Suicide Assessment Scale, we evaluated 96 patients with bipolar I disorder in remission to determine their suicidal ideations and attempts over the previous year. We also evaluated their level of insight by using the Schedule of Assessment of Insight (SAI) and its expanded version (SAI-E), as well as their neurocognitive function by a series of neurocognitive function tests. Insight and neurocognitive functions of bipolar subjects who had and who had no suicidal ideations or attempts over the previous year were compared. The results indicated that the remitted bipolar subjects who had suicidal ideations or attempts over the previous year had higher insight scores on all 3 SAI dimensions and on the SAI-E compared with those who had no suicidal ideations or attempts. However, no difference in any neurocognitive function was found between the 2 groups of remitted bipolar subjects. The results of this study suggest clinicians need to be particularly alert to the potential for suicide in bipolar patients with a high level of insight.