Antidepressant Treatment Of Bipolar Depression Research Articles

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

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

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

"How harmful is your mania to you or others?" Sharing decisions about antidepressant treatment in bipolar depression.

"How harmful is your mania to you or others?" Sharing decisions about antidepressant treatment in bipolar depression.

Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data

BackgroundOne previous study suggested that the presence of a manic episode before bipolar depression is related to worse response to antidepressants. MethodTo examine this effect in a larger sample, we used data from the large, multi-site STEP-BD study. We hypothesized that among persons treated with antidepressants for bipolar depression, manic or mixed episodes before depression onset (as compared to euthymia) would predict lower rate of recovery, more sustained depressive symptoms and higher rate of switching into mania/hypomania after antidepressant treatment of bipolar depression. 320 participants were available for analyses (140 male) diagnosed with bipolar I, bipolar II, cyclothymia, bipolar disorder not otherwise specified, or schizoaffective disorder bipolar subtype. Patients were randomly assigned to 3 treatment randomization strata (placebo, bupropion, and paroxetine) as adjuncts to mood stabilizers. ResultsAnalyses were conducted to examine the effect of episode status before the depressive episode on the degree of change in depressive symptoms at 3 and 6 months, the likelihood of depression recovery and the likelihood of anti-depressant induced switching.Presence of a manic episode before depression in patients with bipolar disorder did not significantly predict response to antidepressants. LimitationsThe study was limited by a high rate of attrition, and consideration of only two antidepressant medications. ConclusionsOur findings are in agreement with other past studies suggesting that mania and depression may operate separately for those with bipolar disorder, with differential predictors of the onset and offset of mania versus depression. Future directions may consider vulnerability for these episodes separately.

Bupropion Maintenance Treatment in Refractory Bipolar Depression: A Case Report.

Background:The optimal duration of antidepressant treatment in bipolar depression appears to be controversial due to a lack of quality evidence, and guideline recommendations are either vague or contradictive. This is especially true for second line treatments such as bupropion that had not been subject to rigourous long term studies in Bipolar Disorder.Case presentation:We report the case of a 75 year old woman who presented with treatment refractory bipolar depression. Because of insufficient response to previous mood stabilizer treatment and refractory depressive symptoms, bupropion was added to venlafaxine and lamotrigine. From there onwards, the patient improved continuously without experiencing deterioration of depression or a switch into hypomania. Our patient being on antidepressants for allmost four years experienced an obvious benefit from longterm antidepressant administration.Conclusion:Noradrenergic/dopaminergic mechanisms of action may play a more prominent role in bipolar depression, and may still be underused as a therapeutic strategy in the acute phase as well as in long-term maintenance in at least a subgroup of bipolar patients. There is still a lack of evidence from RCTs, but this case report further supports antidepressant long-term continuation and the usefulness of a noradrenergic/dopaminergic antidepressant in the acute and maintenance treatment of bipolar disorder.

A Comparative Study of Depressive Episode in Major Depressive Disorder and Bipolar Disorder

Distinguishing between major depressive disorder (MDD) and bipolar disorder is important because there are differences in the optimal management of these conditions. Antidepressant treatment of bipolar depression (BPD) can adversely affect long-term prognosis by causingdestabilisation of mood and more frequent depressive episodes, and can lead to the development of treatment resistance. Most people with bipolar disorder experience depression rather than mania as their first episode of illness. It is clinically desirable to recognise, or at least to suspect,bipolar depression at an early stage of a bipolar illness. 
 OBJECTIVE : Comparison of depressive episode in major depressive disorder and bipolar affective disorder in a tertiary care general hospital, psychiatry unit. 
 METHOD : 80 cases of unipolar depression and 54 cases of bipolar depression were compared on the basis of socio-demographic profile, family history of mood disorder and clinical features using Semi structured questionnaire for socio-demographic profile and validated Bengaliversion of Beck Depression Inventory (BDI). 
 RESULTS : Bipolar depression is characterized by early age of onset, more number of previous episodes, positive family history, more severe in nature associated with prominent features of guilt feeling, self dislike, self accusation, suicidal ideas, irritability, social withdrawal, fatigability and loss of libido. Major depressive disorder shows female preponderance, more number of stressful life events before episodes. Body image change, insomnia, anorexia, weight loss, somatic pre-occupation are more in unipolar depression.

Overview of Antidepressant Treatment of Bipolar Depression

Bipolar depression remains a major unresolved challenge for psychiatric therapeutics. It is associated with significant disability and mortality and represents the major proportion of the approximately half of follow-up time spent in morbid states despite use of available treatments. Evidence regarding effectiveness of standard treatments, particularly with antidepressants, remains limited and inconsistent. We reviewed available clinical and research literature concerning treatment with antidepressants in bipolar depression and its comparison with unipolar depression. Research evidence concerning efficacy and safety of commonly used antidepressant treatments for acute bipolar depression is very limited. Nevertheless, an updated meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressan...

Short-term antidepressant treatment of bipolar depression: Are ISBD recommendations useful in clinical practice?

ObjectivesThe study aimed to test the effectiveness of the ISBD Guidelines for short-term AD treatment of BP depression. MethodsThe study sample included 255 patients with mood disorders (154 UP, 49 BP-I, 52 BP-II). Response was defined as a HDRS21 total score<7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. ResultsResponse was achieved by 64.9% of patients with UP disorder, 75.5% of patients with BP-I disorder and 75.0% with BP-II disorder without significant differences (χ²=3.0, p=0.219). The remission rate did not differ significantly among groups (χ²=3.8, p=0.151). The dropout rate was significantly higher for patients with UP (18.2%) than for patients with BP-I (2%) and BP-II (7.7%) disorder (χ²=10.1, p=0.006). Concerning AD safety, one patient with BP-I depression committed a suicide attempt and AD-emerging switch was observed in 2.9% of patients, 2 with BP-I and 1 with BP-II disorder. LimitationsThe observational nature of the study and unblinded outcomes assessment. ConclusionsOur findings confirm the usefulness of ISBD Guidelines for short-term AD treatment of BP depression. These patients appear to have similar response and remission rate to those observed in UP depression and do not exhibit significant switch rates or risk of suicide. Our results are limited to patients with pure bipolar depression (excluding those with broadly defined mixed states), treated with ADs-mood stabilizers combination. We suggest to partially modify ISBD Recommendations 1 and 4, to include potential responders and to improve safety.

Overview of antidepressant treatment of bipolar depression

Bipolar depression remains a major unresolved challenge for psychiatric therapeutics. It is associated with significant disability and mortality and represents the major proportion of the approximately half of follow-up time spent in morbid states despite use of available treatments. Evidence regarding effectiveness of standard treatments, particularly with antidepressants, remains limited and inconsistent. We reviewed available clinical and research literature concerning treatment with antidepressants in bipolar depression and its comparison with unipolar depression. Research evidence concerning efficacy and safety of commonly used antidepressant treatments for acute bipolar depression is very limited. Nevertheless, an updated meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressant treatment are less than appears to be widely believed. The findings encourage additional efforts to test antidepressants adequately in bipolar depression, and to consider options for depression in types I vs. II bipolar disorder, depression with subsyndromal hypomania and optimal treatment of mixed agitated-dysphoric states--both short- and long-term. Many therapeutic trials considered were small, varied in design, often involved co-treatments, or lacked adequate controls.

Antidepressant Treatment for Acute Bipolar Depression: An Update

While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted.

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

P.3.008 Predictors of response to antidepressant treatment in bipolar depression

People in the late stage of bipolar disorder (BD) experience elevated relapse rates and poorer quality of life (QoL) compared with those in the early stages. Existing psychological interventions also appear less effective in this group. To address this need, we developed a new online mindfulness-based intervention targeting quality of life (QoL) in late stage BD. Here, we report on an open pilot trial of ORBIT (online, recovery-focused, bipolar individual therapy).Inclusion criteria were: self-reported primary diagnosis of BD, six or more episodes of BD, under the care of a medical practitioner, access to the internet, proficient in English, 18–65 years of age. Primary outcome was change (baseline – post-treatment) on the Brief QoL.BD (Michalak and Murray, 2010). Secondary outcomes were depression, anxiety, and stress measured on the DASS scales (Lovibond and Lovibond, 1993).Twenty-six people consented to participate (Age M=46.6 years, SD=12.9, and 75% female). Ten participants were lost to follow-up (38.5% attrition). Statistically significant improvement in QoL was found for the completers, t(15)=2.88, 95% CI:.89–5.98, p=.011, (Cohen׳s dz=.72, partial η2=.36), and the intent-to-treat sample t(25)=2.65, 95% CI:.47–3.76, (Cohen׳s dz=.52; partial η2=.22). A non-significant trend towards improvement was found on the DASS anxiety scale (p=.06) in both completer and intent-to-treat samples, but change on depression and stress did not approach significance.This was an open trial with no comparison group, so measured improvements may not be due to specific elements of the intervention. Structured diagnostic assessments were not conducted, and interpretation of effectiveness was limited by substantial attrition.Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective, and ORBIT warrants full development. Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention, adding cautions about the impact of extended meditations, and addition of coaching support/monitoring to optimise engagement.

Ceiling effects in the "Effectiveness of adjunctive antidepressant treatment for bipolar depression" study: was the sky the limit?

Ceiling effects in the "Effectiveness of adjunctive antidepressant treatment for bipolar depression" study: was the sky the limit?

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Objective: Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression. Method: A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania. Results: Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder. Conclusions: These data suggest that minimal manic symptoms at baseline co-existing with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression. (Reprinted with permission from American Journal of Psychiatry 2009; 166:164–172)

Bupropion-Induced Mania and Hypomania: A Report of Two Cases

Bupropion-Induced Mania and Hypomania: A Report of Two Cases

Is There a Role for Antidepressants in the Treatment of Bipolar II Depression?

Is There a Role for Antidepressants in the Treatment of Bipolar II Depression?

Substance Abuse and Switch From Depression to Mania in Bipolar Disorder

Back to table of contents Previous article Next article Letter to the EditorFull AccessSubstance Abuse and Switch From Depression to Mania in Bipolar DisorderJoseph F. Goldberg, M.D.Joseph F. GoldbergSearch for more papers by this author, M.D.Published Online:1 Jul 2010https://doi.org/10.1176/appi.ajp.2010.10030367AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The recent Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) article by Michael J. Ostacher, M.D., M.P.H., et al. (1), published in the March 2010 issue of the Journal, identified an association between current or past substance abuse or dependence in bipolar disorder patients and a greater likelihood for affective polarity switch from depression to mania, hypomania, or mixed state relative to when comorbid substance use disorders were absent (1). Consistent with this finding, previous naturalistic data from a study that I co-authored (2) demonstrated that a history of comorbid alcohol or substance use disorders conferred an approximate 7-fold increased risk in bipolar disorder patients for developing antidepressant-induced mania, regardless of cotherapy with antimanic agents. Using multiple regression, similar findings during antidepressant therapy were reported by Manwani et al. (3). In light of this prior literature, it would have been informative within the STEP-BD database to determine whether the presence or absence of antidepressant use mediated the relationship between a comorbid substance use disorder and affective polarity switch from depression. Although STEP-BD subjects with comorbid substance use disorders were less likely to receive an antidepressant than those without substance use disorders, this comparison in itself does not address the question of whether depressed bipolar subjects with a substance use disorder were more likely to experience a polarity switch in the presence rather than absence of an adjunctive antidepressant.Elsewhere, the STEP-BD randomized acute depression pathway (4) showed no increased risk for mood destabilization with antidepressants among bipolar depressed patients overall, but that investigation has not yet examined whether there may be distinct bipolar subgroups who are prone to affective polarity switch during antidepressant therapy. Insofar as Dr. Ostacher et al. identify bipolar disorder patients with comorbid substance use disorders as especially vulnerable to mood instability, yet no less likely to recover from a depressive episode as those without substance use disorder comorbidity, the potential safety versus efficacy of adjunctive antidepressants in this particular subset of individuals with bipolar depression warrants further examination.New York, N.Y.Dr. Goldberg has served on the speaker's bureaus of AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, and Pfizer; he has received honoraria for lectures for Janssen-Cilag; and he has served as a consultant to or on the scientific advisory board for Cephalon and Eli Lilly.References1 Ostacher MJ , Perlis RH , Nierenberg AA , Calabrese J , Stange JP , Salloum I , Weiss RD , Sachs GS ; for STEP-BD Investigators: Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2010; 167:289–297 Link, Google Scholar2 Goldberg JF , Whiteside JE : The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study. J Clin Psychiatry 2002; 63:791–795 Crossref, Medline, Google Scholar3 Manwani SG , Pardo TB , Albanese MJ , Zablotsky B , Goodwin FK , Ghaemi SN : Substance use disorder and other predictors of antidepressant-induced mania: a retrospective chart review. J Clin Psychiatry 2006; 67:1341–1345 Crossref, Medline, Google Scholar4 Sachs GS , Nierenberg AA , Calabrese JR , Marangell LB , Wisniewski SR , Gyulai L , Friedman ES , Bowden CL , Fossey MD , Ostacher MJ , Ketter TA , Patel J , Hauser P , Rapport D , Martinez JM , Allen MH , Miklowitz DJ , Otto MW , Dennehy EB , Thase ME : Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356:1711–1722 Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byCanadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 201312 December 2012 | Bipolar Disorders, Vol. 15, No. 1 Volume 167Issue 7 July 2010Pages 868-869 Metrics PDF download History Accepted 1 April 2010 Published online 1 July 2010 Published in print 1 July 2010

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression. A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania. Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder. These data suggest that minimal manic symptoms at baseline coexisting with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression.

Risk of Treatment-Emergent Mania Increases After Antidepressant Use

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessRisk of Treatment-Emergent Mania Increases After Antidepressant UseJun YanJun YanSearch for more papers by this authorPublished Online:2 Jan 2009https://doi.org/10.1176/pn.44.1.0010aPsychiatrists must watch for subtle symptoms of mania before prescribing antidepressants for bipolar patients during a depressive episode because of a significant risk of inducing mania in this particular subgroup of patients, a new study suggests.In the clinical trial conducted by the Bipolar Collaborative Network (formerly the Stanley Foundation Bipolar Network), 176 adult patients with bipolar depression were treated with adjunctive antidepressants for 10 weeks. The authors found that patients who experienced treatment-emergent mania—a rapid mood switch from depression to mania or hypomania—had significantly higher levels of motor activity, speech, and language-thought disorder on the Young Mania Rating Scale (YMRS) at baseline, compared with patients who did not have this adverse outcome.The patients who experienced treatment-emergent mania also had a significantly higher total YMRS score at baseline than patients who did not have treatment-emergent mania. By analyzing YMRS items that are found to relate to each other, the authors identified a significant correlation between treatment-emergent mania and higher scores for motor/verbal activation at baseline.Forty-six patients had treatment-emergent mania, specifically defined as a mania severity score of 4 or greater (moderate to severe) on the Clinical Global Impression scale for bipolar disorder (CGI-BP) or a change in score of 6 or 7 (much worse or very much worse) during the 10-week trial.The authors conducted post hoc analyses on data from a randomized, controlled clinical trial that had compared the efficacy and safety among three antidepressants—venlafaxine, sertraline, and bupropion—as an adjunct to a mood stabilizer. The trial was conducted at six sites in the United States, the Netherlands, and Germany. The same group of authors previously reported in the February 2006 American Journal of Psychiatry that venlafaxine was linked to the highest risk of mood switch, and bupropion with the lowest risk.The causes of rapid mood switch associated with antidepressant treatment are not completely understood. Some antidepressants such as tricyclics are known to pose a higher risk for inducing mood switch. Past studies also indicate that patients with the rapid-cycling type of disorder and in mixed episodes are more likely to have a mood switch when they take antidepressants.“It is important to emphasize that large, placebo-controlled studies suggest that antidepressant treatment [as adjunct to mood stabilizers] is no more efficacious than placebo for bipolar patients treated with mood-stabilizing medications,” said Roy Perlis, M.D., M.Sc., in an interview. He is the medical director of the Bipolar Clinical and Research Program and Center for Human Genetic Research at Massachusetts General Hospital and an assistant professor of psychiatry at Harvard Medical School.“So, before we talk about the risk of mood switch, we need to consider whether any amount of risk is worthwhile,” added Perlis, who served as an investigator in the National Institute of Mental Health's Systematic Treatment Enhanced Program for Bipolar Disorder (STEP-BD) trial.Data from the STEP-BD trial indicated that in bipolar patients with simultaneous manic symptoms and full-blown depression, adjunctive antidepressants were not significantly more effective than placebo and may exacerbate mania (Psychiatric News, September 21, 2007).“What the current study makes clear is that, among previously suggested clinical features, few are useful for predicting mood switch. The one set of features... significantly associated with switch were manic symptoms,” said Perlis. In other words, when a patient is depressed, having more manic symptoms is a sign that he or she is closer to a manic or mixed state. “The closer you are to mania, the more likely you are to become manic after [antidepressant] treatment; this is not a big surprise. However, this finding underscores the important point that all depressed patients need to be carefully evaluated for manic/hypomanic symptoms prior to initiating or changing treatment,” he emphasized.The current study was funded by the Stanley Medical Research Institute and published online in AJP in Advance on November 17, 2008.Combined with other similar findings, the authors concluded that“ short-term use of antidepressants may have liabilities—induction of mania or hypomania or persistence of manic or hypomanic symptoms—in bipolar depressed patients who have minimal manic symptoms at baseline.”“A careful examination for... specific symptoms of mania is warranted prior to antidepressant treatment for bipolar depression,” they recommended.“Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression” is posted at<ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2008.08030322v1>.▪ ISSUES NewArchived

The Use of Antidepressants in Bipolar Disorder

Whether or not to use antidepressants in patients with bipolar disorder is a matter of debate. Antidepressant treatment of bipolar depression has been associated with manic switch and cycle acceleration. Furthermore, recent studies have argued against the efficacy of antidepressants in the treatment of bipolar depression. Nevertheless, many clinicians continue to employ antidepressants, especially in the management of severe depression that is unresponsive to mood stabilizers alone. Because of the unclear risk-to-benefit ratio of antidepressants in bipolar disorder, we have performed an updated review of the relevant literature. In this article we examine (1) all randomized controlled trials (RCTs) evaluating the use of antidepressants in the treatment of acute bipolar depression and assessing the risk of antidepressant-induced manic switch and (2) non-RCT trials that evaluate the impact of antidepressant discontinuation after acute antidepressant response. A MEDLINE search of journals, covering the period from January 1966 to July 2007 and supplemented by bibliographic cross-referencing, was performed to identify the relevant studies. The keywords used were antidepressant, bipolar depression, bipolar disorder, switch, manic switch, antidepressant-induced mania, predictors, and antidepressant discontinuation. Criteria used to select studies included (1) English language and (2) studies published in peer-reviewed journals. Randomized, double-blind, placebo-controlled studies have demonstrated that antidepressants exert some efficacy in the treatment of bipolar depression in some populations of patients. Moreover, the risk of manic switch, although not totally countered, appears to be strongly reduced when antidepressants are given in combination with a mood stabilizer and when new-generation antide-pressants are preferred over old tricyclic antidepressants. Finally, some studies have proven that the continuous use of antidepressants after the remission of a major depressive episode helps to prevent further depressive relapses without causing a significant increase in manic relapses. Clearly, there is a place for antidepressants in bipolar disorder; however, it is important to be cautious and evaluate their use on a case-by-case basis. Looking at specific depressive symptoms might help physicians in making the choice of whether to prescribe or not prescribe antidepressants.