Impact of psychotropic drugs on suicide and suicidal behaviors.

OBJECTIVE: To examine the impact of psychotropic drugs on suicide and suicidal behaviors in bipolar disorders. METHODS: A Medline search of articles published from January 1960 to January 2013 was performed using relevant keywords to identify studies examining the relationship of psychotropic drugs to suicidal behaviors. The publications were further reviewed for relevant references and information. Additionally, the US Food and Drug Administration Center for Drug Evaluation Research website was searched. RESULTS: The available studies used differing methodologies, making interpretation of the findings difficult. Studies suggest that antidepressants may increase suicidal risk in bipolar disorder, this possibly being related to the induction of broadly defined mixed states. There is no evidence that antiepileptic drugs as a class increase suicidal risk in patients with bipolar disorder. Only lithium provides convincing data that it reduces the risk of suicide over the long term. There is little known regarding the effects of antipsychotics, as well as anti-anxiety and hypnotic drugs, on suicidal behavior. CONCLUSIONS: The available evidence for the impact of psychotropics on suicidal risk in patients with bipolar disorder is largely methodologically flawed and, except for a few instances, clinically not useful at this point. Adequately powered, prospective randomized controlled studies are needed to assess the impact of each class of psychotropic and each psychotropic as well as common combination therapies. Until such studies have been carried out, clinicians are urged to exercise caution in using these drugs and rely on the traditional means of carefully assessing and monitoring patients with bipolar disorder who are at high risk for suicide.

Subtypes of antipsychotics and suicidal behavior in bipolar disorder.

OBJECTIVE: Antipsychotics are commonly used in bipolar disorder, with newer (SGA) agents increasingly replacing FGA antipsychotics, particularly in bipolar depression. There are few data on differences between FGA and SGA antipsychotics in terms of their relationship to suicidal behavior in bipolar disorder. METHOD: This was a retrospective chart review of 161 bipolar veterans treated naturalistically with antipsychotics at a university-affiliated VA hospital and clinics for up to 8 years. Charts were reviewed to determine monthly antipsychotic use and occurrence of suicidal behavior: completed suicide, attempted suicide or hospitalization to prevent suicide. Suicidal behavior events were compared across patients during treatment with individual antipsychotics and FGAs or SGAs as a class. RESULTS: Non-lethal suicide events were more common during FGA than SGA monotherapy (9 events/110 months of exposure vs. 6 events/381 months of exposure; χ(2)=9.65, p=0.002). Suicide event rates did not differ between FGAs and SGAs when used in conjunction with mood stabilizers. Event rates were lower with lithium than anticonvulsants when used in conjunction with antipsychotics. No differences were found between olanzapine, risperidone and quetiapine. LIMITATIONS: The retrospective chart review methodology may have led to confounding by indication and diagnostic inaccuracy. No completed suicides occurred. Study participants were primarily male veterans. Results may not be generalizable to SGAs marketed since 2003. CONCLUSIONS: FGA antipsychotic monotherapy may be associated with higher suicidal behavior risk than SGA antipsychotic monotherapy. Antipsychotics used in conjunction with mood stabilizers, particularly lithium, are associated with lower rates, independent of antipsychotic subtype.

Bipolar pharmacotherapy and suicidal behavior Part 2. The impact of antidepressants.

UNLABELLED: Antidepressant-induced mania and cycle acceleration is a potential risk in bipolar patients. Another serious risk of antidepressants, that of increasing suicidal behavior, has been identified in some affectively ill populations. However, there is a dearth of knowledge about the effects of antidepressants on suicidal behavior specifically in bipolar patients. METHODS: Retrospective chart review of 405 veterans with bipolar disorder followed for a mean of three years, with month by month systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Chi-squared comparison of (log) rates of suicidal events during mood stabilizer monotherapy, antidepressant monotherapy, and combination of mood stabilizer and antidepressant. RESULTS: Suicidal behavior event rates (per 100 patient years) were greatest during treatment with antidepressant monotherapy (25.92), least during mood stabilizer monotherapy (3.48), and intermediate during mood stabilizer + antidepressant combination treatment (9.75). These differences were statistically significant. LIMITATIONS: In a clinical setting, antidepressants may have been prescribed because patients were deemed at greater risk of suicidality. CONCLUSIONS: During treatment with antidepressants (even when coupled with mood stabilizers), patients with bipolar disorder have significantly higher rates of non-lethal suicidal behavior compared to those on mood stabilizers without antidepressants, and thus require careful monitoring.

Bipolar pharmacotherapy and suicidal behavior. Part I: Lithium, divalproex and carbamazepine.

INTRODUCTION: The anti-suicidal benefit of lithium on suicidal behavior in bipolar disorder is well-established. Data are mixed on the effects of divalproex and carbamazepine. METHODS: Retrospective chart review study of 405 veterans with bipolar disorder followed for a mean of 3 years, with month by month review of clinical progress notes, and systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of suicide event rates (events/100 patient years) between mood stabilizers and during-vs-after discontinuation of mood stabilizers, with linear regression analysis for influence of potential confounding variables, and robust bootstrap confirmation analysis. RESULTS: No completed suicides occurred during or after discontinuation of monotherapy. Rates of non-lethal suicidal behavior were similar during lithium (2.49), divalproex (4.67) and carbamazepine (3.80) monotherapies. There was a sixteen fold greater, highly statistically significant non-lethal suicidal event rate after discontinuation compared with during mood stabilizer monotherapy (55.89 vs. 3.48 events/100 patient years; Chi2=13.95; df=1; p<0.0002). On compared with off treatment differences were similar for the three different agents. LIMITATIONS: Treatments were uncontrolled in this naturalistic setting, and data were analyzed retrospectively. CONCLUSIONS: Lithium and the anticonvulsants may show similar benefits in protecting bipolar patients from non-lethal suicidal behavior when careful analysis of clinical data is done to confirm medication adherence/non-adherence. Findings in this study were similar to those of a previous study that applied the same methodology in a private practice setting.

Bipolar pharmacotherapy and suicidal behavior Part 3: impact of antipsychotics.

INTRODUCTION: Antipsychotics, particularly second generation agents, are widely used in bipolar disorder, but their effect on suicidal behavior in this population has not been systematically studied. METHODS: Retrospective chart review of 405 veterans with bipolar disorder followed for a mean of three years, with month-by-month systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of rates of suicidal events during mood stabilizer monotherapy, antipsychotic monotherapy, and combination of mood stabilizer and antipsychotic. RESULTS: Non-lethal suicide event rates were 9.4 times greater (chi2=28.29, p<.0001) during antipsychotic monotherapy and 3.5 times greater during mood stabilizer+antipsychotic (chi2=15.13, p=0.0001) than during mood stabilizer monotherapy. LIMITATIONS: Antipsychotics may have been prescribed because patients were at greater risk of suicidal behavior. First and second generation antipsychotics were not distinguished. CONCLUSIONS: Treatment of bipolar patients with antipsychotics is associated with an increase in non-lethal suicidal behavior. Thus, use of antipsychotics for bipolar patients requires careful monitoring for suicidal behavior. Further studies are urgently needed to better characterize this relationship.

The dexamethasone suppression test as a predictor of suicidal behavior in unipolar depression.

BACKGROUND: Non-suppression on the dexamethasone suppression test (DST) in unipolar depression has been found to be associated with completed suicide, with less consistent data for attempted suicide and hospitalizations for suicidality. The purpose of this study was to examine DST non-suppression as a predictor of these three aspects of suicidal behavior. METHODS: Records were reviewed for 101 patients who met criteria for major depressive disorder and/or dysthymic disorder and had a DST performed. All patients were treated naturalistically and were followed for an average of 2 years. DST suppressors and non-suppressors were compared with respect to three outcomes: (1) completed suicide; (2) attempted suicide; and (3) hospitalizations for suicidality. RESULTS: DST non-suppressors were significantly more likely to have completed suicide or be hospitalized for suicidality than DST suppressors, with a non-significant trend for attempts. Total suicidal events were also significantly more frequent in the non-suppressor group. LIMITATIONS: Axis II diagnoses and severity of illness were not assessed. Knowledge of DST results may have influenced the decision to hospitalize patients. CONCLUSIONS: DST non-suppression identifies unipolar depressed patients with a higher risk for future suicide completion or hospitalization for suicidality. Performance of DST upon initiation of treatment may be a useful adjunct in identifying suicidal risk.

Lithium, anticonvulsants and suicidal behavior in bipolar disorder.

BACKGROUND: Lithium has been found to be effective in reducing suicide rates during long term treatment of patients with bipolar disorders. Data on the efficacy of anticonvulsant mood stabilizers in reducing suicide risk are sparse. METHOD: Charts of 140 bipolar patients treated continuously for a minimum of 6 months during a 23-year period of private practice by the senior author were extracted from nearly 4000 patient records. Data extracted from the charts were incidence of completed suicide, number of suicide attempts, and number of hospitalizations for suicidal ideation or behavior per 100 patient-years of either 'on' or 'off' lithium or anticonvulsant mood stabilizer monotherapy. RESULTS: Only one completed suicide (during a period off of lithium) occurred in the patients studied. Incidence of non-lethal suicidal behavior was not different during treatment with lithium, compared with anticonvulsants. Being on a mood stabilizer significantly protected against suicidal behavior. The relative protective effect was more modest than in reports from other treatment settings. LIMITATIONS: This was a retrospective chart review study of naturalistically treated patients. CONCLUSIONS: Treatment of patients with bipolar disorder with either lithium or anticonvulsant mood stabilizers was associated with reduced risk of suicidal behavior. This study did not find evidence for a difference in the protective effect of the two types of mood stabilizing medications against non-lethal suicidal behavior in the naturalistic setting of private practice.